Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study
To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP). We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups. In total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10. CP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP.
Authors: Hagn-Meincke, Rasmus;Van Den Eeden, Stephen K;Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC),;et al.
Pancreatology. 2024 May;24(3):384-393. Epub 2024-02-28.
Pharmacy Assistance Programs for Oral Anticancer Drugs: A Narrative Review
Oral anticancer medications (OAMs) are high priced with a significant cost-sharing burden to patients, which can lead to catastrophic financial, psychosocial, and clinical repercussions. Cost-conscious prescribing and inclusion of low-cost alternatives can help mitigate this burden, but cost transparency at the point of prescribing remains a major barrier to doing so. Pharmacy assistance programs, including co-payment cards and patient assistance programs administered by manufacturers and foundation-based grants, remain an essential resource for patients facing prohibitive co-payments for OAMs. However, access to these programs is fraught with complexities, including lack of trained financial navigators, limited transparency on eligibility criteria, onerous documentation burdens, and limits in available funding. Despite these drawbacks and the potential for such programs to incentivize manufacturers to keep list prices high, assistance programs have been demonstrated to improve financial well-being for patients with cancer. The increasing development of integrated specialty pharmacies with dedicated, trained pharmacy staff can help improve and standardize access to such programs, but these services are disproportionately available to patients seen at tertiary care centers. Multistakeholder interventions are needed to mitigate the burden of cost sharing for OAMs, including increased clinician knowledge of financial resources and novel assistance mechanisms, investment of institutions in trained financial navigation services and centralized platforms to identify assistance programs, and policies to cap out-of-pocket spending and improve transparency of rates charged by pharmacy benefit managers to a health plan.
Authors: Ragavan, Meera V;Swartz, Scott;Clark, Mackenzie;Chino, Fumiko
JCO Oncol Pract. 2024 Apr;20(4):472-482. Epub 2024-01-19.
Characterizing the spectrum of bladder health and lower urinary tract symptoms among men: Results from the CARDIA study
To operationalize a new definition for bladder health, we examined the distribution and impact of lower urinary tract symptoms (LUTS), along with risk factors, among men in the Coronary Artery Risk Development in Young Adults (CARDIA) study. LUTS were defined by American Urologic Association Symptom Index (AUASI) scores and impact on quality of life (QoL). Separate questions assessed urinary incontinence (UI) and postvoid dribbling. We performed cluster analyses using AUASI scores, with and without urine incontinence and postvoid dribbling, and impact collected in 2010-11. We performed analyses to evaluate sociodemographic and cardiovascular risk factors between clusters. Among CARDIA men (mean age: 50.0, SD = 3.6; range: 42-56 years) with complete LUTS data (n = 929), we identified and compared four clusters: men who reported no or very mild symptoms and no impact on well-being (bladder health, n = 696, 75%), men with moderate symptoms and moderate impact on well-being (moderate symptoms/impact, n = 84, 9%), men with high symptoms and high impact on well-being (severe symptoms/impact, n = 117, 13%), and a separate group that reported moderate symptoms and UI with a high impact on well-being (UI + moderate symptoms/severe impact, n = 32, 3%). Exploration of the groupings showed a large percentage of postvoid dribbling across groups (overall 69%). Sociodemographic and cardiovascular risk factors were not associated with symptom/impact groups. Bladder health clustered into four categories. A majority of middle-aged men in the community showed no or mild bladder symptoms without impact on QoL. Postvoid dribbling is pervasive but did not cluster with a specific LUTS or impact category.
Authors: Markland, Alayne D;Hellemann, Gerhard;Shan, Liang;Brady, Sonya S;Huling, Jared D;Schreiner, Pamela J;Sidney, Stephen;Van Den Eeden, Stephen K;Lewis, Cora E
Neurourol Urodyn. 2024 Apr;43(4):840-848. Epub 2024-02-26.
Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Incident Diabetes: The Study of Women’s Health Across the Nation (SWAN)
To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. We followed 2,952 participants in the Study of Women’s Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log-based discrete-time survival models anchored at baseline. Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87-0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] -92.3 to -1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> -1.5 to -0.2 nmol/L] HR 0.33, 95% CI 0.23-0.48; Q3 [> -0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25-0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30-0.63). Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity.
Authors: Hedderson, Monique M;Capra, Angela;Lee, Catherine;Habel, Laurel A;Lee, Jennifer;Gold, Ellen B;Badon, Sylvia E;Mitro, Susanna D;El Khoudary, Samar R
Diabetes Care. 2024 Apr 01;47(4):676-682.
A novel body composition risk score (B-Score) and overall survival among patients with nonmetastatic breast cancer
Measurements (amount, distribution, and radiodensity) of muscle and adipose tissue were reported to be individually associated with overall survival in patients with breast cancer. However, they were not typically combined to develop an overall risk score, which can identify patients at high risk of death and prioritize patients in need of dietary and lifestyle interventions. Thus, we aimed to develop a novel composite body composition risk score (B-Score). We included 3105 patients with stage II or III breast cancer at Kaiser Permanente Northern California and Dana Farber Cancer Institute. From CT scans at diagnosis, we assessed areas and radiodensity of muscle and adipose tissue at the third lumber vertebrae. We considered skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI) and SAT radiodensity as they were independent prognostic factors for overall survival. Each measurement was dichotomized using optimal stratification, with low SMI (<40.1 cm2/m2), high SATI (≥75.7 cm2/m2), and high SAT radiodensity (≥-97.2HU) considered risk factors. We calculated B-Score as the sum of these factors and estimated its association with overall survival using Cox proportional hazards regression with adjustment for clinicopathologic factors. Mean (standard deviation) age was 53.9 (11.8) years, 70.3% were Non-Hispanic White, and 60.5% were stage II. Most patients (60.6%) had only one body composition risk factor (B-Score = 1). Compared to those with no risk factors (B-Score = 0), the risk of death increased with more body composition risk factors: the adjusted hazard ratios were 1.10 (95% CI: 0.85, 1.42), 1.47 (95% CI: 1.12, 1.92), and 2.11 (95% CI: 1.26, 3.53) for B-Scores of 1, 2, and 3, respectively (Ptrend < 0.001). More unfavorable body composition characteristics were associated with increased risks of overall mortality in a dose-response manner. Considering body composition measurements together as a composite score (B-Score) may improve risk stratification and inform dietary and lifestyle interventions following breast cancer diagnosis.
Authors: Cheng, En;Caan, Bette J;Chen, Wendy Y;Prado, Carla M;Cespedes Feliciano, Elizabeth M
Clin Nutr. 2024 Apr;43(4):981-987. Epub 2024-03-06.
Skeletal muscle and visceral adipose radiodensities are pre-surgical, non-invasive markers of aggressive kidney cancer
Most studies on body composition in kidney cancer have been conducted among patients with metastatic disease. Given that aggressive tumours can adversely impact body composition and even non-metastatic tumours can be aggressive, we evaluated associations between pre-surgical body composition features and tumour pathological features in patients with non-metastatic clear cell renal cell cancer (ccRCC). The Resolve Cohort consists of 1239 patients with non-metastatic ccRCC who underwent nephrectomy at Memorial Sloan Kettering Cancer Center between 2000 and 2020. The cross-sectional areas and radiodensities of skeletal muscle, visceral adipose, and subcutaneous adipose tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. Pearson’s correlation coefficients describe inter-relationships among BMI and body composition variables, while odds ratios (OR) and 95% confidence intervals (CI) estimate associations between continuous body composition features (per 1-standard deviation) and advanced stage (Stage III vs. Stages I-II) and high Fuhrman grade (Grades 3-4 vs. 1-2) from multivariable logistic regression models that considered the potential impact of biological sex, contrast enhanced CTs, and early age at onset of ccRCC. The cohort was predominantly male (69%), white (89%), and had a median age of 58. The proportion of patients presenting with advanced stage and high-grade disease were 31% and 51%, respectively. In models that adjusted for demographics and all body composition variables simultaneously, decreasing skeletal muscle radiodensity (i.e., more fat infiltration) but increasing visceral adipose tissue radiodensity (i.e., more lipid depletion) were associated with advanced tumour features. Per 8.4 HU decrease in skeletal muscle radiodensity, the odds of presenting with advanced stage was 1.61 (95% CI: 1.34-1.93). Per 7.22 HU increase in visceral adipose tissue radiodensity, the odds of presenting with advanced stage was 1.45 (95% CI: 1.22-1.74). Skeletal muscle index (i.e., sarcopenia) was not associated with either tumour feature. Similar associations were observed for Fuhrman grade, a more direct marker of tumour aggressiveness. Associations did not differ by sex, contrast use, or age at onset of ccRCC. Lipid infiltrated skeletal muscle, but lipid depleted visceral adipose tissue were independently associated with advanced tumour features in non-metastatic ccRCC. Findings highlight the importance of evaluating the full range of body composition features simultaneously in multivariable models. Interpreting pre-surgical CTs for body composition for patients may be a novel and non-invasive way to identify patients with aggressive renal tumours, which is clinically relevant as renal biopsies are not routinely performed.
Authors: Furberg, Helena;Caan, Bette;Mourtzakis, Marina;et al.
J Cachexia Sarcopenia Muscle. 2024 Apr;15(2):726-734. Epub 2024-01-24.
Postoperative chemotherapy relative dose intensity and overall survival in patients with colon cancer
Quantifying the association of chemotherapy relative dose intensity (RDI) with overall survival may enable supportive care interventions that improve chemotherapy RDI to estimate their magnitude of potential clinical benefit. This cohort study included 533 patients with stage II-III colon cancer who initiated a planned regimen of 12 cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposure was chemotherapy RDI. The primary outcome was overall survival. Restricted cubic splines estimated hazard ratios (HR). Chemotherapy regimen RDI was associated with overall survival in an L-shaped pattern (linear P = 0.006; nonlinear P = 0.057); the risk of death was flat above 85% but increased linearly below 85%. For example, a decrease in RDI from 85 to 75% was associated with an increased risk of death [HR: 1.20 (95% CI: 1.08, 1.52)], whereas an increase in RDI from 85 to 95% was not associated with the risk of death [HR: 1.06 (95% CI: 0.82, 1.38)]. If chemotherapy RDI is considered a potential surrogate of overall survival, supportive care interventions that improve chemotherapy RDI might confer a potential clinical benefit in this population.
Authors: Brown, Justin C;Meyerhardt, Jeffrey A;Yang, Shengping;Caan, Bette J
Cancer Chemother Pharmacol. 2024 Mar 23.
Evaluation of Pre-Analytical Variables for Human Papillomavirus Primary Screening from Self-Collected Vaginal Swabs
Human papillomavirus (HPV) primary screening is an effective approach to assessing cervical cancer risk. Self-collected vaginal swabs have shown promise to expand testing access, but there are limited data defining analytical performance criteria necessary for adoption of self-collected specimens, especially for those occurring outside the clinic, where the swab remains dry during transport. Here, we evaluated the performance of self-collected vaginal swabs for HPV detection using the Cobas 6800. There was insignificant variability between swabs self-collected by the same individual (n = 15 participants collecting 5 swabs per participant), measured by amplification of HPV and human β-globin control DNA. Comparison of self-collected vaginal swab and provider-collected cervical samples (n = 144 paired collections) proved highly concordant for HPV detection (total agreement = 90.3%; positive percentage agreement = 84.2%). There was no relationship between the number of dry storage days and amplification of HPV (n = 68; range, 4 to 41 days). Exposure of self-collected dry swabs to extreme summer and winter temperatures did not affect testing outcomes. We assessed a second internal control (RNase P) in a subset and demonstrate that lack of amplification for β-globin from self-collected specimens was consistent with poor, but not absent, cellularity. These data suggest that self-collected vaginal samples enable accurate clinical HPV testing, and that extended ambient dry storage or exposure to extreme temperatures does not influence HPV detection. Furthermore, lack of β-globin amplification in HPV-negative samples accurately identified participants who required recollection.
Authors: Qi, Michelle;Naranjo, Anissa R;Duque, Abigail J;Lorey, Thomas S;Schapiro, Jeffrey M;Suh-Burgmann, Betty J;Rummel, Michael;Salipante, Stephen J;Wentzensen, Nicolas;Greene, Dina N
J Mol Diagn. 2024 Mar 15.
Low physical function Post-Cancer diagnosis is associated with higher mortality risk in postmenopausal women
Postmenopausal women with cancer experience an accelerated physical dysfunction beyond that expected through aging alone due to cancer and its treatments. The aim of this study is to determine whether declines in physical function after cancer diagnosis are associated with all-cause mortality and cancer-specific mortality. This prospective cohort study included 8,068 postmenopausal women enrolled in the Women’s Health Initiative (WHI) who were diagnosed with cancer and had physical function assessed within 1-year of cancer diagnosis. Self-reported physical function was measured using the 10-item physical function subscale of the RAND 36-Item Health Survey. Cause of death was determined by medical record review with central adjudication and linkage to the National Death Index. Death was adjudicated through February 2022. Over a median follow-up of 7.7 years from cancer diagnosis 3,316 (41.1%) women died. Our results showed that for every 10% decline in the physical function score after cancer diagnosis, all-cause mortality and cancer-specific mortality were significantly reduced by 12% (HR, 0.88; 95% CI, 0.87 to 0.89) and (HR, 0.88; 95%CI, 0.86 to 0.91), respectively. Further categorical analyses showed a significant dose-response relationship between post-diagnosis physical function categories and mortality outcomes (trend test P < .001), where the median survival time for women in the lowest physical function quartile was 9.1 (8.6, 10.6) years compared to 18.4 (15.8, 22.0) years for women in the highest physical function quartile. Postmenopausal women with low physical function after cancer diagnosis may be at higher risk of mortality from all causes and cancer-related mortality.
Authors: Gonzalo-Encabo, Paola;Kroenke, Candyce H;Dieli-Conwright, Christina M;et al.
J Natl Cancer Inst. 2024 Mar 06.
Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer
It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor-negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor-negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P < .001) compared with patients with ERBB2-negative and hormone receptor-negative tumors. Within the hormone receptor-negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03). These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.
Authors: Khoury, Thaer;Kwan, Marilyn L;Ergas, Isaac J;Kushi, Lawrence H;Kushi, Lawrence H;et al.
JAMA Netw Open. 2024 Mar 04;7(3):e243345. Epub 2024-03-04.
Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California
Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis (‘late VTE’) is scarce, particularly in young survivors. We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.
Authors: Abrahão, Renata;Kushi, Lawrence H;Keegan, Theresa H M;et al.
Thromb Res. 2024 Mar;235:1-7. Epub 2024-01-15.
Evaluation of algorithms using automated health plan data to identify breast cancer recurrences
We updated algorithms to identify breast cancer recurrences from administrative data, extending previously developed methods. In this validation study, we evaluated pairs of breast cancer recurrence algorithms (vs. individual algorithms) to identify recurrences. We generated algorithm combinations that categorized discordant algorithm results as no recurrence [High Specificity and PPV (positive predictive value) Combination] or recurrence (High Sensitivity Combination). We compared individual and combined algorithm results to manually abstracted recurrence outcomes from a sample of 600 people with incident stage I-IIIA breast cancer diagnosed between 2004 and 2015. We used Cox regression to evaluate risk factors associated with age- and stage-adjusted recurrence rates using different recurrence definitions, weighted by inverse sampling probabilities. Among 600 people, we identified 117 recurrences using the High Specificity and PPV Combination, 505 using the High Sensitivity Combination, and 118 using manual abstraction. The High Specificity and PPV Combination had good specificity [98%, 95% confidence interval (CI): 97-99] and PPV (72%, 95% CI: 63-80) but modest sensitivity (64%, 95% CI: 44-80). The High Sensitivity Combination had good sensitivity (80%, 95% CI: 49-94) and specificity (83%, 95% CI: 80-86) but low PPV (29%, 95% CI: 25-34). Recurrence rates using combined algorithms were similar in magnitude for most risk factors. By combining algorithms, we identified breast cancer recurrences with greater PPV than individual algorithms, without additional review of discordant records. Researchers should consider tradeoffs between accuracy and manual chart abstraction resources when using previously developed algorithms. We provided guidance for future studies that use breast cancer recurrence algorithms with or without supplemental manual chart abstraction.
Authors: Aiello Bowles, Erin J;Kushi, Lawrence H;Kantor, Elizabeth D;et al.
Cancer Epidemiol Biomarkers Prev. 2024 Mar 01;33(3):355-364.
The economics of nature’s healing touch: A systematic review and conceptual framework of green space, pharmaceutical prescriptions, and healthcare expenditure associations
Green spaces play a crucial role in promoting sustainable and healthy lives. Recent evidence shows that green space also may reduce the need for healthcare, prescription medications, and associated costs. This systematic review provides the first comprehensive assessment of the available literature examining green space exposure and its associations with healthcare prescriptions and expenditures. We applied Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to search MEDLINE, Scopus, and Web of Science for observational studies published in English through May 6, 2023. A quality assessment of the included studies was conducted using the Office of Health Assessment and Translation (OHAT) tool, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessment was used to evaluate the overall quality of evidence. Our search retrieved 26 studies that met the inclusion criteria and were included in our review. Among these, 20 studies (77 % of the total) showed beneficial associations of green space exposure with healthcare prescriptions or expenditures. However, most studies had risks of bias, and the overall strength of evidence for both outcomes was limited. Based on our findings and related bodies of literature, we present a conceptual framework to explain the possible associations and complex mechanisms underlying green space and healthcare outcomes. The framework differs from existing green space and health models by including upstream factors related to healthcare access (i.e., rurality and socioeconomic status), which may flip the direction of associations. Additional research with lower risks of bias is necessary to validate this framework and better understand the potential for green space to reduce healthcare prescriptions and expenditures.
Authors: Patwary, Muhammad Mainuddin;Van Den Eeden, Stephen K;Van Den Eeden, Stephen K;et al.
Sci Total Environ. 2024 Mar 01;914:169635. Epub 2023-12-28.
Use of Cancer-Directed therapy at the end of life among adolescents and young adults
Adolescents and young adults (AYAs) frequently receive chemotherapy near death. We know less about use of targeted agents and immunotherapy or trends over time. We conducted a retrospective cohort study of 1,836 AYAs with cancer who died between 2009-2019 after receiving care at one of three sites (Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California). We reviewed electronic health data and medical records to examine use of cancer-directed therapy in the last 90 days of life, including chemotherapy, targeted therapy, immunotherapy, and investigational drugs. Over the study period, 35% of AYAs received chemotherapy in the last 90 days of life; 24% received targeted therapy, 7% immunotherapy, and 5% investigational drugs. Fifty-six percent received at least one form of systemic cancer-directed therapy in the last 90 days of life. After adjustment for patient sex, race, ethnicity, age, site of care, diagnosis, and years from diagnosis to death, the proportion of AYAs receiving targeted therapy (odds ratio (OR) 1.05 per year of death, 95% confidence interval (CI) 1.02-1.10, P = .006), immunotherapy (OR 1.27, 95%CI 1.18-1.38, P<.0001), and any cancer-directed therapy (OR1.04, 95%CI 1.01-1.08, P=.01) in the last 90 days of life increased over time. More than half of AYAs receive cancer therapy in the last 90 days of life, and use of novel agents such as targeted therapy and immunotherapy are increasing over time. While some AYAs may wish to continue cancer therapy while living with advanced disease, efforts are needed to ensure that use of cancer-directed therapy meets preferences of AYAs approaching death.
Authors: Mack, Jennifer W;Kushi, Lawrence H;Uno, Hajime;et al.
J Natl Cancer Inst. 2024 Feb 20.
Quality of End-of-Life Care Among Adolescents and Young Adults With Cancer
Adolescents, young adults with cancer receive limited psychosocial and spiritual support near death.
Authors: Mack, Jennifer W;Kushi, Lawrence;Kushi, Lawrence;et al.
J Clin Oncol. 2024 Feb 20;42(6):621-629. Epub 2023-10-27.
Lay healthcare worker financial toxicity intervention: a pilot financial toxicity screening and referral program
Financial toxicity is a source of significant distress for patients with urologic cancers, yet few studies have addressed financial burden in this patient population. We developed a financial toxicity screening program using a lay health worker (LHW) and social worker (SW) to assess and mitigate financial toxicity in a single academic medical clinic. As part of a quality improvement project, the LHW screened all newly diagnosed patients with advanced stages of prostate, kidney, or urothelial cancer for financial burden using three COST tool questions and referred patients who had significant financial burden to an SW who provided personalized recommendations. The primary outcome was feasibility defined as 80% of patients with financial burden completing the SW consult. Secondary outcomes were patient satisfaction, change in COST Tool responses, and qualitative assessment of financial resources utilized. The LHW screened a total of 185 patients for financial toxicity; 82% (n = 152) were male, 65% (n = 120) White, and 75% (n = 139) reported annual household income >$100,000 US Dollars; 60% (n = 114) had prostate cancer. A total of 18 (9.7%) participants screened positive for significant financial burden and were referred to the SW for consultation. All participants (100%) completed and reported satisfaction with the SW consultation and had 0.83 mean lower scores on the COST Tool post-intervention assessment compared to pre-intervention (95% confidence interval [0.26, 1.41]). This multidisciplinary financial toxicity intervention using an LHW and SW was feasible, acceptable, and associated with reduced financial burden among patients with advanced stages of urologic cancers. Future work should evaluate the effect of this intervention among cancer patients in diverse settings.
Authors: Parikh, Divya A;Rodriguez, Gladys M;Ragavan, Meera;Kerr, Elizabeth;Asuncion, Mary Khay;Hansen, Jennifer;Srinivas, Sandy;Fan, Alice C;Shah, Sumit;Patel, Manali I
Support Care Cancer. 2024 Feb 16;32(3):161. Epub 2024-02-16.
Predicting Risk of Colorectal Cancer After Adenoma Removal in a Large, Community-based Setting
Colonoscopy surveillance guidelines categorize individuals as high or low risk for future colorectal cancer (CRC) based primarily on their prior polyp characteristics, but the approach is imprecise, and consideration of other risk factors may improve post-polypectomy risk stratification. Among patients who underwent a baseline colonoscopy with removal of a conventional adenoma in 2004-2016, we compared the performance for post-polypectomy CRC risk prediction (through 2020) of a comprehensive model featuring patient age, diabetes diagnosis, and baseline colonoscopy indication and prior polyp findings (i.e., adenoma with advanced histology, polyp size ≥10 mm, and sessile serrated adenoma or traditional serrated adenoma) to a polyp model featuring only polyp findings. Models were developed using Cox regression. Performance was assessed using area under the receiver-operating characteristic curve (AUC) and calibration by the Hosmer-Lemeshow goodness-of-fit test. Among 95,001 patients randomly divided 70:30 into model development (n=66,500) and internal validation cohorts (n=28,501); 495 CRCs were subsequently diagnosed, 354 in the development cohort and 141 in the validation cohort. Models demonstrated adequate calibration and the comprehensive model demonstrated superior predictive performance to the polyp model in the development cohort (AUC: 0.71, 95% confidence interval [CI]: 0.68-0.74 vs. AUC: 0.61, 95% CI: 0.58-0.64, respectively) and validation cohort (AUC: 0.70, 95% CI: 0.65-0.75 vs. AUC: 0.62, 95% CI: 0.57-0.67, respectively). A comprehensive CRC risk prediction model featuring patient age, diabetes diagnosis, and baseline colonoscopy indication and polyp findings was more accurate at predicting post-polypectomy CRC diagnosis than a model based on polyp findings alone.
Authors: Lee, Jeffrey K;Levin, Theodore R;Corley, Douglas A;Corley, Douglas A;et al.
Am J Gastroenterol. 2024 Feb 14.
Differences in Smoking Behavior by Nativity, Race/Ethnicity, and Education Among Women Diagnosed with Breast Cancer
We evaluated smoking differences across nativity and race/ethnicity among women diagnosed with breast cancer. In our Northern Californian pooled population of 5,653 [670 Asian, 690 Hispanic, and 4,300 Non-Hispanic White (White)] women diagnosed with breast cancer, we evaluated smoking differences across nativity, race/ethnicity, and acculturation and effect modification of nativity by race/ethnicity and education. Foreign-born women currently smoked less than US-born women [odds ratio (OR) = 0.46, 95% confidence limit (CL): 0.29, 0.72]. Hispanic (OR = 0.50, 95% CL: 0.32, 0.78) women currently smoked less than White women. Among those who ever smoked (n = 2,557), foreign-born women smoked 5.23 fewer pack-years (PY) than US-born women (95% CL: -2.75, -7.70). Furthermore, Asian (-4.60, 95% CL: -0.81, -8.39) and Hispanic (-6.79, 95% CL: -4.14, -9.43) women smoked fewer PY than White women. Associations were generally suggestive of greater smoking with greater acculturation (immigration age, US years, survey language). Finally, associations for nativity differed by education but not race/ethnicity, with a higher likelihood of smoking in US-born women only among those with less than a bachelor’s degree (OR = 2.84, 95% CL: 2.15, 3.77) (current smoking: p = 0.01, PY: p = 0.05). Asian and Hispanic (vs. White) and foreign-born (vs. US-born) breast cancer survivors reported fewer smoking behaviors. Smoking differences across nativity and education were driven by higher rates of smoking in US-born women with lower educational attainment. Smoking behavioral patterns were similar among breast cancer survivors and the general population, informing potential smoking interventions.
Authors: Uong, Stephen P;Torres, Jacqueline M;Alexeeff, Stacey E;Morey, Brittany N;Caan, Bette J;Kushi, Lawrence H;Kroenke, Candyce H
Cancer Epidemiol Biomarkers Prev. 2024 Feb 12.
Implementation of a hepatocellular carcinoma surveillance program in a community-based integrated health system in patients with hepatitis C cirrhosis
Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes. In this retrospective cohort study, we assessed pre- and post-inclusion HCC surveillance patterns among 597 patients with HCV cirrhosis enrolled in a program at an integrated health system between 2013-20. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre and post enrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging exam (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality. The surveillance program significantly improved surveillance completion (77.6% vs. 5.0%, p<0.001) and proportion time covered (80.9% vs. 15.8%, p<0.001). Compared to prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs. 44.8%, p<0.001), early-stage (85.2% vs. 44.8%, p<0.001), with smaller maximum diameter (median 2.3 cm vs. 3.2 cm) and more likely to undergo curative therapy (92.5% vs. 72.4% p=0.010). Survival was improved compared to prevalent cases HR 0.23 (0.11-0.51) after adjusting for age and MELD score. Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with HCV cirrhosis. These findings may inform similar interventions by other healthcare systems.
Authors: Bui, Hien;Kumar, Nikhilesh G;Singal, Amit G;Boparai, Jasdeep;Tran, Don;Mukhtar, Nizar A;Saxena, Varun;Balasubramanian, Sripriya
Am J Gastroenterol. 2024 Feb 09.
Mobile app activity engagement by cancer patients and their caregivers informs remote monitoring
Mobile phone applications (“apps”) are potentially an effective, low-burden method to collect patient-reported outcomes outside the clinical setting. Using such apps consistently and in a timely way is critical for complete and accurate data capture, but no studies of concurrent reporting by cancer patient-caregiver dyads have been published in the peer-reviewed literature. This study assessed app engagement, defined as adherence, timing, and attrition with two smartphone applications, one for adult cancer patients and one for their informal caregivers. This was a single-arm, pilot study in which adult cancer patients undergoing IV chemotherapy or immunotherapy used the DigiBioMarC app, and their caregivers used the TOGETHERCare app, for approximately one month to report weekly on the patients’ symptoms and wellbeing. Using app timestamp metadata, we assessed user adherence, overall and by participant characteristics. Fifty patient-caregiver dyads completed the study. Within the one-month study period, both adult cancer patients and their informal caregivers were highly adherent, with app activity completion at 86% for cancer patients and 84% for caregivers. Caregivers completed 86% of symptom reports, while cancer patients completed 89% of symptom reports. Cancer patients and their caregivers completed most activities within 48 h of availability on the app. These results suggest that the DigiBioMarC and TOGETHERCare apps can be used to collect patient- and caregiver-reported outcomes data during intensive treatment. From our research, we conclude that metadata from mobile apps can be used to inform clinical teams about study participants’ engagement and wellbeing outside the clinical setting.
Authors: Yunis, Reem;Fonda, Stephanie J;Aghaee, Sara;Kubo, Ai;Davis, Sharon W;Liu, Raymond;Neeman, Elad;Oakley-Girvan, Ingrid
Sci Rep. 2024 Feb 09;14(1):3375. Epub 2024-02-09.
Projected colorectal cancer incidence and mortality based on observed adherence to colonoscopy and sequential stool-based screening
Modeling supporting recommendations for colonoscopy and stool-based colorectal cancer (CRC) screening tests assumes 100% sequential participant adherence. The impact of observed adherence on the long-term effectiveness of screening is unknown. We evaluated the effectiveness of a program of screening-colonoscopy every ten years versus annual high-sensitivity guaiac-based fecal occult blood testing (HSgFOBT) using observed sequential adherence data. MIcrosimulation SCreening ANalysis (MISCAN) model using observed sequential screening adherence, HSgFOBT positivity, and diagnostic-colonoscopy adherence in HSgFOBT-positive individuals from the National Colonoscopy Study (NCS; single screening-colonoscopy versus ≥4 HSgFOBT sequential rounds). We compared CRC incidence and mortality over 15 years with no screening, or ten-yearly screening-colonoscopy versus annual HSgFOBT with 100% and differential observed adherence from the trial. Without screening, simulated incidence and mortality over 15 years were 20.9 (95% probability interval, 15.8-26.9) and 6.9 (5.0-9.2) per 1000 participants, respectively. In the case of 100% adherence, only screening-colonoscopy was predicted to result in lower incidence; however, both tests lowered simulated mortality to a similar level (2.1 [1.6-2.9] for screening-colonoscopy; 2.5 [1.8-3.4] for HSgFOBT). Observed adherence for screening-colonoscopy (83.6%) was higher than observed sequential HSgFOBT adherence (73.1% first round; 49.1% by round 4), resulting in lower simulated incidence and mortality for screening-colonoscopy (14.4 [10.8-18.5] and 2.9 [2.1-3.9], respectively) than HSgFOBT (20.8 [15.8-28.1] and 3.9 [2.9-5.4], respectively), despite a 91% adherence to diagnostic-colonoscopy with FOBT positivity. The relative risk of CRC mortality for screening-colonoscopy versus HSgFOBT was 0.75 (95%PI, 0.68-0.80). Findings were similar in sensitivity analyses with alternative assumptions for repeat colonoscopy, test performance, risk, age, and projection horizon. Where sequential adherence to stool-based screening is suboptimal and colonoscopy is accessible and acceptable – as observed in NCS – offering screening-colonoscopy can increase screening effectiveness.
Authors: Meester, Reinier G S;Corley, Douglas A;Zauber, Ann G;et al.
Am J Gastroenterol. 2024 Feb 06.
Unsatisfactory Fecal Immunochemical Tests for Colorectal Cancer Screening: Prevalence, Reasons, and Subsequent Testing
Fecal immunochemical test (FIT) is an effective colorectal cancer screening modality. Little is known about prevalence, reasons, and testing after unsatisfactory FIT, or a FIT that cannot be processed by the laboratory due to inadequate stool specimen or incomplete labeling. Our retrospective cohort study examined unsatisfactory FIT among average-risk individuals aged 50-74 years in a large, integrated, safety-net health system who completed an index FIT from 2010 to 2019. We determined prevalence of unsatisfactory FIT and categorized reasons hierarchically. We used multivariable logistic regression models to identify factors associated with: (i) unsatisfactory FIT; and (ii) subsequent testing within 15 months of the unsatisfactory FIT. Of 56,980 individuals completing an index FIT, 10.2% had an unsatisfactory FIT. Reasons included inadequate specimen (51%), incomplete labeling (27%), old specimen (13%), and broken/leaking container (8%). Unsatisfactory FIT was associated with being male [OR, 1.10; confidence interval (CI), 1.03-1.16], Black (OR, 1.46; CI, 1.33-1.61), Spanish speaking (OR, 1.12; CI, 1.01-1.24), on Medicaid (OR, 1.42; CI, 1.28-1.58), and received FIT by mail (OR, 2.66; CI, 2.35-3.01). Among those with an unsatisfactory FIT, fewer than half (41%) completed a subsequent test within 15 months (median, 4.4 months). Adults aged 50-54 years (OR, 1.16; CI, 1.01-1.39) and those who received FIT by mail (OR, 1.92; CI, 1.49-2.09) were more likely to complete a subsequent test. One in ten returned a FIT that could not be processed, mostly due to patient-related reasons. Fewer than half completed a subsequent test after unsatisfactory FIT. Screening programs should address these breakdowns such as specimen collection and labeling to improve real-world effectiveness. See related In the Spotlight, p. 183.
Authors: Liu, Po-Hong;Levin, Theodore R;Halm, Ethan A;et al.
Cancer Epidemiol Biomarkers Prev. 2024 Feb 06;33(2):215-223.
Traditional Mexican dietary pattern and cancer risk among women of Mexican descent
To examine the association of a traditional Mexican diet score with risk of total, breast, and colorectal cancer among women of Mexican ethnic descent in the Women’s Health Initiative (WHI). Participants were WHI enrollees who self-identified as being of Mexican descent. Data from food frequency questionnaires self-administered at study baseline were used to calculate the MexD score, with higher scores indicating greater adherence to an a priori-defined traditional Mexican diet (high in dietary fiber, vegetables, and legumes). Incident cancers were self-reported by participants from 1993 to 2020 and adjudicated by trained physicians. We used multivariable-adjusted Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Among 2,343 Mexican descent women (median baseline age: 59 years), a total of 270 cancers (88 breast, 37 colorectal) occurred during a mean follow-up of 14.4 years. The highest tertile of MexD score was associated with a lower risk of all-cancer incidence (HR: 0.67; 95% CI 0.49-0.91; p-trend: 0.01) and colorectal cancer (HR: 0.38; 95% CI 0.14-0.998; p-trend < 0.05), with each unit increase in the MexD score associated with a 6% lower risk of all-cancer incidence (HR: 0.94; 95% CI 0.88-0.99). There was no statistically significant association with risk of breast cancer. Consumption of a traditional Mexican diet was associated with a significantly lower risk of all-cancer incidence and colorectal cancer. Confirmation of these findings in future studies is important, given the prevalence of colorectal cancer and a growing U.S. population of women of Mexican descent.
Authors: Loroña, Nicole C;Santiago-Torres, Margarita;Lopez-Pentecost, Melissa;Garcia, Lorena;Shadyab, Aladdin H;Sun, Yangbo;Kroenke, Candyce H;Snetselaar, Linda G;Stefanick, Marcia L;Neuhouser, Marian L
Cancer Causes Control. 2024 Feb 02.
Circulating immune signatures across clinical stages of chronic pancreatitis: a pilot study
This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP). We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to characterise immune signatures across CP subgroups. A total of 135 CP subjects (evenly distributed between clinical stages) and 50 controls were studied. Interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble intercellular adhesion molecule 1 (sICAM-1) were significantly elevated in CP subjects compared to controls. The levels of IL-6 and IL-8 increased with advancing disease stages, with the highest levels observed in CP with diabetes and EPD (clinical stage 3). Furthermore, hepatocyte growth factor and macrophage-derived chemokine were significantly increased in clinical stage 3 compared to controls. Our study reveals a progressive elevation in pro-inflammatory cytokines and chemokines with advancing clinical stages of CP. These findings indicate potential targets for the development of disease-modifying interventions.
Authors: Hagn-Meincke, Rasmus;Van Den Eeden, Stephen K;Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC),;et al.
Eur J Gastroenterol Hepatol. 2024 Feb 01;36(2):177-183. Epub 2023-11-30.
Stressful life events, social support, and epigenetic aging in the Women’s Health Initiative
Elevated psychosocial stress has been linked with accelerated biological aging, including composite DNA methylation (DNAm) markers that predict aging-related outcomes (“epigenetic age”). However, no study has examined whether stressful life events (SLEs) are associated with epigenetic age acceleration in postmenopausal women, an aging population characterized by increased stress burden and disease risk. We leveraged the Women’s Health Initiative, a large muti-ancestry cohort of postmenopausal women with available psychosocial stress measures over the past year and epigenomic data. SLEs and social support were ascertained via self-report questionnaires. Whole blood DNAm array (450 K) data were used to calculate five DNAm-based predictors of chronological age, health span and life span, and telomere length (HorvathAge, HannumAge, PhenoAge, GrimAge, DNAmTL). After controlling for potential confounders, higher SLE burden was significantly associated with accelerated epigenetic aging, as measured by GrimAge (β: 0.34, 95% CI: 0.08, 0.59) and DNAmTL (β: -0.016, 95% CI: -0.028, -0.004). Exploratory analyses showed that SLEs-GrimAge associations were stronger in Black women as compared to other races/ethnicities and in those with lower social support levels. In women with lower social support, SLEs-DNAmTL associations showed opposite association in Hispanic women as compared to other race/ethnicity groups. Our findings suggest that elevated stress burden is associated with accelerated epigenetic aging in postmenopausal women. Lower social support and/or self-reported race/ethnicity may modify the association of stress with epigenetic age acceleration. These findings advance understanding of how stress may contribute to aging-related outcomes and have important implications for disease prevention and treatment in aging women.
Authors: Skinner, Harlyn G;Kroenke, Candyce H;Zannas, Anthony S;et al.
J Am Geriatr Soc. 2024 Feb;72(2):349-360. Epub 2023-12-27.
Endoscopic Evaluation of PET/CT Abnormalities in the Gastrointestinal Tract: Yield and Approach
Unexpected hypermetabolic activity is often encountered in the gastrointestinal tract when PET/CT is performed for various indications, prompting endoscopic evaluation. Our aim was to characterize the types of lesions seen in segments of the gastrointestinal tract with unexpected PET/CT abnormalities as well as clinically significant lesions seen on endoscopy which did not produce a PET/CT abnormality to guide the endoscopist tasked with evaluating these imaging findings. We retrospectively reviewed a database of endoscopies performed at City of Hope Comprehensive Cancer Center between January 1, 2016 and September 30, 2021 for an indication of “abnormal PET.” We divided the gastrointestinal tract into segments and defined categories of endoscopic/histologic findings for each segment. We counted the number of segments with an abnormal PET/CT finding and corresponding endoscopic/histologic abnormality as well as the number of segments with an endoscopic/histologic abnormality but normal PET/CT. PET/CT identified 209 segments with hypermetabolic activity, 109 of which had corresponding endoscopic/histologic abnormalities. In the jejunum and ileum, all corresponding lesions were malignant. Seventy-three percent of corresponding lesions in the stomach were H. pylori positive. PET/CT failed to detect 34.7% of clinically significant lesions diagnosed endoscopically, including 1 malignancy in the transverse colon and many inflammatory or low-risk premalignant lesions. PET/CT abnormalities seen in the small bowel should be evaluated urgently as nearly all correlates were malignant, while abnormalities in the stomach should prompt workup for H. pylori. Most lesions missed by PET/CT were inflammatory or low-risk premalignant yet clinically significant, confirming the need to inspect the entirety of the upper or lower gastrointestinal tract during endoscopy.
Authors: Trieu, Harry;De Silva, Sadie;Manoukian, Saro;Rajan, Anand;Mannan, Rifat;Liang, Yu;Lee, Jeffrey K;Lin, James;Kidambi, Trilokesh D
Dig Dis Sci. 2024 Feb;69(2):552-561. Epub 2023-12-16.
Assessment of breast cancer chemotherapy dose reduction in an integrated healthcare delivery system
Most cytotoxic drugs are dosed using body surface area (BSA), yet not all cancer patients receive the full BSA-determined dose. Prior work suggests that breast cancer patients who are obese are more likely to experience dose reduction than normal weight patients. However, the factors driving dose reduction remain unclear. In 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California, we evaluated the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. Study participants were a part of the Pathways Study, diagnosed between 2006 and 2013 and treated with cyclophosphamide + doxorubicin, followed by paclitaxel (ACT). Dose reduction was assessed using first cycle dose proportion (FCDP) and average relative dose intensity (ARDI), a metric of dose intensity over the course of chemotherapy. Overall, 8% of participants received a FCDP < 90% and 21.2% had an ARDI < 90%, with dose reduction increasing with body mass index. In adjusted logistic regression models, obese women had 4.1-fold higher odds of receiving an ARDI < 90% than normal weight women (95% CI: 1.9-8.9; p-trend = 0.0006). Increasing age was positively associated with an ADRI < 90%, as was the presence of comorbidity. Dose reduction was less common in later calendar years. Results offer insight on factors associated with chemotherapy dosing for a common breast cancer regimen. Larger studies are required to evaluate relevance to other regimens, and further work will be needed to determine whether dose reductions impact outcomes in obese women.
Authors: Kantor, Elizabeth D;Ergas, Isaac J;Kolevska, Tatjana;Kushi, Lawrence H;Kushi, Lawrence H;et al.
Breast Cancer Res Treat. 2024 Feb;203(3):565-574. Epub 2023-11-04.
Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study
Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder lacking therapies and biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proinflammatory cytokine elevated during inflammation that binds fatty acids (FAs) like linoleic acid. We hypothesized that systemic NGAL could serve as a biomarker for CP and, with FAs, provide insights into inflammatory and metabolic alterations. NGAL was measured by immunoassay and FA composition was measured by gas chromatography in plasma ( n = 171) from a multicenter study, including controls ( n = 50), acute and recurrent acute pancreatitis (AP/RAP) ( n = 71), and CP ( n = 50). Peripheral blood mononuclear cells (PBMCs) from controls ( n = 16), AP/RAP ( n = 17), and CP ( n = 15) were measured by CyTOF. Plasma NGAL was elevated in subjects with CP compared to controls (AUC = 0.777) or AP/RAP (AUC = 0.754) in univariate and multivariate analyses with sex, age, BMI, and smoking (control AUC = 0.874; AP/RAP AUC = 0.819). NGAL was elevated in CP and diabetes compared to CP without diabetes (p < 0.001). NGAL + PBMC populations distinguished CP from controls (AUC = 0.950) or AP/RAP (AUC = 0.941). Linoleic acid was lower while dihomo-γ-linolenic and adrenic acids were elevated in CP (p < 0.05). Linoleic acid was elevated in CP with diabetes compared to CP subjects without diabetes (p = 0. 0471). Elevated plasma NGAL and differences in NGAL + PBMCs indicate an immune response shift that may serve as biomarkers of CP. The potential interaction of FAs and NGAL levels provide insights into the metabolic pathophysiology and improve diagnostic classification of CP.
Authors: Gumpper-Fedus, Kristyn;Van Den Eeden, Stephen K;Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC),;et al.
Clin Transl Gastroenterol. 2024 Jan 26.
Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial
Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients. Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program. Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06). Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.
Authors: Caan, Bette J;Lee, Catherine;Quesenberry, Charles P;Cespedes Feliciano, Elizabeth M;Schmitz, Kathryn H;et al.
Cancer. 2024 Jan 24.
A polygenic score associated with fracture risk in breast cancer patients treated with aromatase inhibitors
Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.
Authors: Hook, Christine;Lee, Catherine;Lo, Joan C;Kushi, Lawrence H;Kwan, Marilyn L;Yao, Song;et al.
NPJ Breast Cancer. 2024 Jan 20;10(1):9. Epub 2024-01-20.
Advances in Adherence Reporting of Resistance Training in a Clinical Trial during Adjuvant Chemotherapy for Colon Cancer
Detailed reporting of individually tailored exercise prescriptions (ExRx) used in clinical trials is essential to describe feasibility, tolerability, and efficacy of the intervention and to inform translation to clinical care. This paper outlines the methodology used to develop a resistance training (RT) ExRx for people with colon cancer receiving chemotherapy and reports adherence to the randomized controlled trial testing the impact of RT on relative dose intensity of chemotherapy and patient-reported toxicities. Participants randomized to the exercise arm (n = 90) were included. To promote muscle hypertrophy, the ExRx was twice-weekly, moderate to heavy loads (65-85% 1-RM), high sets (3-5), and intermediate repetitions (6-10) of five large multi-joint movements with adjustable dumbbells. Attendance (achieved frequency) and adherence (achieved volume) were calculated. Group-based trajectory modeling was used to identify clusters of individuals with similar adherence patterns and compared baseline characteristics across adherence groups. The median attendance was 69.1%. Adherence was 60.6%, but higher for those receiving 3 versus 6 months of chemotherapy (80.4 vs. 47.4%; p < 0.05). Participants engaged in a median of 1.4 days of RT each week, lifting 62% of the 1-RM load, for 3.0 sets and 7.5 repetitions per set. Three distinct adherence groups were identified: 13% "non-starter", 37% "tapered off", and 50% "consistent exercisers". Females were more likely to be in the "non-starter" and "tapered off" groups. This paper outlines suggested methods for reporting ExRx of RT in oncology clinical trials and provides insight into the tolerance of ExRx of RT during chemotherapy treatment for colon cancer. These findings aim to foster constructive dialogue, and offer a premise for designing future research to elucidate the benefits of exercise during chemotherapy.
Authors: Campbell, Kristin L;Lee, Catherine;Sternfeld, Barbara;Caan, Bette J;Schmitz, Kathryn H;et al.
Med Sci Sports Exerc. 2024 Jan 18.
Sex-Dependent Prognosis of Patients with Advanced Soft Tissue Sarcoma
To examine whether overall survival (OS) differs for male and female patients with advanced soft-tissue sarcoma (STS). The study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 and 3 locally advanced or metastatic STS whose tumor underwent next-generation sequencing. We used Cox regression modeling to examine association of sex and OS adjusting for other important factors. Among 388 eligible patients, 174 had leiomyosarcoma (LMS), 136 had undifferentiated pleomorphic sarcoma (UPS), and 78 had liposarcoma. OS for male versus female patients appeared to be slightly better among the full cohort [HR = 0.89; 95% confidence interval (CI), 0.66-1.20]; this association appeared to be stronger among the subsets of patients with LMS (HR = 0.76; 95% CI, 0.39-1.49) or liposarcoma (HR = 0.74; 95% CI, 0.32-1.70). Better OS for male versus female patients was also observed among all molecular subgroups except mutRB1 and mutATRX, especially among patients whose tumor retained wtTP53 (HR = 0.73; 95% CI, 0.44-1.18), wtCDKN2A (HR = 0.85; 95% CI, 0.59-1.23), wtRB1 (HR = 0.73; 95% CI, 0.51-1.04), and among patients whose tumor had mutPTEN (HR = 0.37; 95% CI, 0.09-1.62). OS also appeared to be better for males in the MSK-IMPACT and TCGA datasets. A fairly consistent pattern of apparent better OS for males across histologic and molecular subgroups of STS was observed. If confirmed, our results could have implications for clinical practice for prognostic stratification and possibly treatment tailoring as well as for future clinical trials design.
Authors: Pan, Minggui;Habel, Laurel A;Ganjoo, Kristen N;et al.
Clin Cancer Res. 2024 Jan 17;30(2):413-419.
Randomized trial of patient outreach approaches to de-implement outdated colonoscopy surveillance intervals
Guidelines now recommend patients with low-risk adenomas receive colonoscopy surveillance in 7-10 years and those with the previously recommended 5-year interval be reevaluated. We tested three outreach approaches for transitioning patients to the 10-year interval recommendation. Design: 3-arm pragmatic randomized trial comparing telephone, secure messaging, and mailed letter outreach. Kaiser Permanente Northern California, a large integrated healthcare system. Patients aged 54-70 years with 1-2 small (<10 mm) tubular adenomas at baseline colonoscopy, due for 5-year surveillance in 2022, without high-risk conditions, and with access to all three outreach modalities. Patients were randomly assigned to outreach arm (telephone [n=200], secure message [n=203], and mailed letter [n=201]) stratified by age, sex, race, and ethnicity. Outreach in each arm was performed by trained medical assistants (unblinded) communicating in English with 1 reminder attempt at 2-4 weeks. Participants could change their assigned interval to 10 years or continue their planned 5-year interval. 60-day response rates were higher for telephone (64.5%) and secure messaging outreach (51.7%) versus mailed letter (31.3%). Also, more patients adopted the 10-year surveillance interval in the telephone (37.0%) and secure messaging arms (32.0%) compared to mailed letter (18.9%) and rate differences were significant for telephone (18.1%; 97.5% CI: 8.3%, 27.9%) and secure message outreach (13.1%; 97.5% CI: 3.5%, 22.7%) versus mailed letter outreach. Telephone and secure messaging were more effective than mailed letter outreach for de-implementing outdated colonoscopy surveillance recommendations among individuals with a history of low-risk adenomas in an integrated healthcare setting.
Authors: Lee, Jeffrey K;Velayos, Fernando S;Quesenberry, Charles P;Corley, Douglas A;Levin, Theodore R;Levin, Theodore R;et al.
Clin Gastroenterol Hepatol. 2024 Jan 06.
Access to Financial Assistance Programs and Their Impact on Overall Spending on Oral Anticancer Medications at an Integrated Specialty Pharmacy.
PURPOSE: Financial assistance (FA) programs are increasingly used to help patients afford oral anticancer medications (OAMs), but access to such programs and their impact on out-of-pocket (OOP) spending has not been well explored. This study aimed to (1) characterize the impact of receipt of FA on both OOP spending and likelihood of catastrophic spending on OAMs and (2) evaluate racial/ethnic disparities in access to FA programs. n METHODS: Patients with a cancer diagnosis prescribed an OAM anytime between January 1, 2021, and December 31, 2021 were included in this retrospective, single-center study at an integrated specialty pharmacy affiliated with a tertiary academic cancer center. Fixed-effect regression models were used to characterize the impact of receipt of FA on overall spending and likelihood of catastrophic spending on OAMs, as well as explore the association of race/ethnicity with receipt of FA. n RESULTS: Across 1,186 patients prescribed an OAM, 37% received FA. Receipt of FA was associated with lower annual spending on OAMs (β = -$1,236 US dollars [USD; 95% CI, -$1,841 to -$658], n CONCLUSION: FA programs can mitigate high OOP spending but not for patients who spend at catastrophic levels. There are racial/ethnic and language disparities in access to such programs. Future studies should evaluate access to FA programs across diverse delivery settings.
Authors: Ragavan, Meera V;Swartz, Scott;Clark, Mackenzie;Lo, Mimi;Gupta, Arjun;Chino, Fumiko;Lin, Tracy Kuo
JCO Oncol Pract. 2024 Jan 04:OP2300446. doi: 10.1200/OP.23.00446..
Risk of adverse birth outcomes after adolescent and young adult cancer
Many women diagnosed with cancer as adolescents and young adults (AYAs, age 15-39 years) want biological children after cancer but lack information on the potential impact of their cancer history on future reproductive outcomes. We investigated the risk of adverse birth outcomes among AYA cancer survivors. We identified insured women diagnosed with AYA breast cancer, thyroid cancer, gynecologic cancers, lymphoma, or melanoma from 2003 to 2016 in the state of North Carolina or the Kaiser Permanente health care systems in northern and southern California. Post-diagnosis births to cancer survivors were each matched with up to 5 births to women without cancer. Risk ratios for preterm birth (<37 completed weeks), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and small for gestational age (SGA, <10th percentile of weight for gestational age) were estimated using modified Poisson regression. Analyses included 1648 births to 1268 AYA cancer survivors and 7879 births to 6066 women without cancer. Overall, risk of preterm birth, very preterm birth, low birth weight, and SGA did not significantly differ between births to women with and without cancer. However, births to women with gynecologic cancers had a significantly increased risk of low birth weight (risk ratio = 1.82; 95% confidence interval: 1.03 to 3.21) and suggested increased risk of preterm birth (risk ratio = 1.59; 95% confidence interval: 0.99 to 2.54). Chemotherapy exposure was not associated with increased risk of adverse birth outcomes. Women with gynecologic cancers, but not other cancers, had an increased risk of adverse birth outcomes compared to women without cancer.
Authors: Anderson, Chelsea;Kwan, Marilyn L;Kushi, Lawrence H;Nichols, Hazel B;et al.
JNCI Cancer Spectr. 2024 Jan 04;8(1).
Financial strain across 25 years and women’s bladder health: A life course perspective
A small number of cross-sectional studies have found that financial insecurity-a social determinant of health-is associated with lower urinary tract symptoms. This study aimed to examine (1) whether women in the Coronary Artery Risk Development in Young Adult Study with higher levels of financial strain, assessed at 7 time points across 25 years beginning in 1985-1986, were more likely to report lower urinary tract symptoms and impact after the 2010-2011 financial strain assessment and (2) whether healthcare access and comorbidities mediated potential associations. This prospective cohort study recruited Black and White participants aged 18 to 30 years at baseline (1985-1986) from the populations of 4 US cities. The analytical sample was composed of women with complete data for analyses involving financial strain trajectories across 7 assessments (n=841) and mediation tests of data collected at 4 assessments (n=886). The outcome variable was previously developed through a cluster analysis of urinary incontinence severity, urinary incontinence impact, other lower urinary tract symptoms severity, and their impact in 2012-2013, which yielded 4 lower urinary tract symptoms and impact cluster categories: women with no symptom or very mild symptoms and no impact vs women with mild, moderate, or severe symptoms and impact. Financial strain was defined as finding it “very hard,” “hard,” or “somewhat hard” (vs “not very hard”) to pay for the very basics, such as food, heating, and medical care. Using proportional odds logistic regression, cluster categories were regressed on the financial strain trajectory group, adjusting for age, race, education, and parity. For mediation analyses, separate financial strain variables (difficulty paying for the very basics, such as food and heating, and difficulty paying for medical care) were created by combining 1995-1996 and 2000-2001 values. Two healthcare access variables (difficulty receiving care and underutilization of care) and a single comorbidity index (smoking, physical inactivity, body mass index, hypertension, diabetes mellitus, and depressive symptoms) were created by combining 2005-2006 and 2010-2011 values. Regression analyses and structural equation modeling were used to test whether healthcare access and comorbidities mediated associations between financial strain and lower urinary tract symptoms and impact cluster categories. In comparison to women who were consistently not financially strained, women who were consistently strained (odds ratio, 2.10; 95% confidence interval, 1.13-3.91), shifted into being strained (odds ratio, 2.00; 95% confidence interval, 1.29-3.10), or experienced >1 shift in strain (odds ratio, 1.99; 95% confidence interval, 1.46-2.71) had roughly twice the odds of reporting greater lower urinary tract symptoms and impact. Underutilization of healthcare and comorbidities mediated the association between difficulty paying for medical care and lower urinary tract symptoms and impact. In the structural equation model, difficulty paying for medical care and underutilization of care were associated (β=.31; P<.01), as was underutilization of care and greater lower urinary tract symptoms and impact (β=.09; P<.01). Moreover, difficulty paying for medical care and the comorbidity index were associated (β=.34; P<.01), as was the comorbidity index and greater lower urinary tract symptoms and impact (β=.24; P<.01). Collectively, these mediation pathways eliminated a direct association between difficulty paying for medical care and lower urinary tract symptoms and impact. Underutilization of healthcare and comorbidities explained an association between financial strain (difficulty paying for medical care) and lower urinary tract symptoms and impact. Research is needed to confirm the findings and examine other mechanisms that may further explain the association. Accumulated evidence may inform future policies and practices.
Authors: Brady, Sonya S;Arguedas, Andrés;Huling, Jared D;Hellemann, Gerhard;Lewis, Cora E;Fok, Cynthia S;Van Den Eeden, Stephen K;Markland, Alayne D
Am J Obstet Gynecol. 2024 Jan;230(1):77.e1-77.e12. Epub 2023-09-29.
Job strain, occupation, and bladder health among women
Lower urinary tract symptoms (LUTS) are common among employed women. An underexplored topic is whether characteristics of women’s occupations may influence LUTS. The present study examined whether job strain and its individual components (psychological demands, decision latitude) were associated with greater LUTS and their impact and whether, compared to managerial and professional occupations, occupations characterized by manual labor, sales, service, nursing, and teaching were associated with greater LUTS and their impact. Coronary Artery Risk Development in Young Adults cohort study data were analyzed. Job strain and occupation were assessed in 1987-88 and 1995-96. In 2012-13, LUTS and their impact were assessed. LUTS/impact category (a composite variable ranging from bladder health to mild, moderate, and severe LUTS/impact) was regressed on job strain and occupation in separate analyses, adjusting for age, race, parity, education, and financial hardship (n = 1006). Job strain and its individual components were not associated with LUTS/impact. In comparison to managerial and professional occupations, service occupations in 1987-88 and 1995-96 were both associated with greater odds of LUTS/impact in proportional odds logistic regression analyses. Employment as a nurse, health assistant, or health aide in 1995-96 was associated with greater odds of any LUTS/impact versus bladder health. Support positions in 1987-88 and sales positions in 1995-96 were associated with greater odds of moderate or severe LUTS/impact versus bladder health or mild LUTS/impact. Future research should examine characteristics of workplaces that may promote or constrain bladder health (e.g., time and autonomy to void when desired, infrastructure to void).
Authors: Brady, Sonya S;Arguedas, Andrés;Huling, Jared D;Hellemann, Gerhard;Lewis, Cora E;Fok, Cynthia S;Van Den Eeden, Stephen K;Markland, Alayne D
Neurourol Urodyn. 2024 Jan;43(1):69-80. Epub 2023-10-04.
Caregiving and all-cause mortality in postmenopausal women: findings from the Women’s Health Initiative
Caregiving is commonly undertaken by older women. Research is mixed, however, about the impact of prolonged caregiving on their health, well-being, and mortality risk. Using a prospective study design, we examined the association of caregiving with mortality in a cohort of older women. Participants were 158,987 postmenopausal women aged 50-79 years at enrollment into the Women’s Health Initiative (WHI) who provided information on current caregiving status and caregiving frequency at baseline (1993-1998) and follow-up (2004-2005). Mortality was ascertained from baseline through March of 2019. Cox regression with caregiving status defined as a time-varying exposure was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality, adjusting for sociodemographic factors, smoking, and history of diabetes, hypertension, cardiovascular disease (CVD), and cancer. Stratified analyses explored whether age, race-ethnicity, depressive symptoms, frequency of caregiving, optimism, and living status modified the association between caregiver status and mortality. At baseline, 40.7% of women (mean age 63.3 years) self-identified as caregivers. During a mean 17.5-year follow-up, all-cause mortality (50,526 deaths) was 9% lower (multivariable-adjusted HR = 0.91, 95% CI: 0.89-0.93) in caregivers compared to non-caregivers. The inverse association between caregiving and all-cause mortality did not differ according to caregiving frequency or when stratified by age, race-ethnicity, depressive symptoms, optimism, or living status (interaction p > 0.05, all). Caregiving was inversely associated with CVD and cancer mortality. Among postmenopausal women residing across the United States, caregiving was associated with lower mortality. Studies detailing the type and amount of caregiving are needed to further determine its impact on older women.
Authors: Chavan, Prachi P;Kroenke, Candyce H;Wactawski-Wende, Jean;et al.
J Am Geriatr Soc. 2024 Jan;72(1):24-36. Epub 2023-11-08.
Evaluation of the international Ki67 working group cut point recommendations for early breast cancer: comparison with 21-gene assay results in a large integrated health care system
The International Ki67 Working Group (IKWG) has developed training for immunohistochemistry (IHC) scoring reproducibility and recommends cut points of ≤ 5% and ≥ 30% for prognosis in ER+, HER2-, stage I/II breast cancer. We examined scoring reproducibility following IKWG training and evaluated these cut points for selecting patients for further testing with the 21-gene Recurrence Score (RS) assay. We included 307 women aged 50+ years with node-negative, ER+PR+HER2- breast cancer and with available RS results. Slides from the diagnostic biopsy were stained for Ki67 and scored using digital image analysis (IA). Two IHC pathologists underwent IKWG training and visually scored slides, blinded to each other and IA readings. Interobserver reproducibility was examined using intraclass correlation (ICC) and Kappa statistics. Depending on reader, 8.8-16.0% of our cohort had Ki67 ≤ 5% and 11.4-22.5% had scores ≥ 30%. The ICC for Ki67 scores by the two pathologists was 0.82 (95% CI 0.78-0.85); it was 0.79 (95% CI 0.74-0.83) for pathologist 1 and IA and 0.76 (95% CI 0.71-0.80) for pathologist 2 and IA. For Ki67 scores ≤ 5%, the percentages with RS < 26 were 92.6%, 91.8%, and 90.9% for pathologist 1, pathologist 2, and IA, respectively. For Ki67 scores ≥ 30%, the percentages with RS ≥ 26 were 41.5%, 51.4%, and 27.5%, respectively. The IKWG's Ki67 training resulted in moderate to strong reproducibility across readers but cut points had only moderate overlap with RS cut points, especially for Ki67 ≥ 30% and RS ≥ 26; thus, their clinical utility for a 21-gene assay testing pathway remains unclear.
Authors: Shim, Veronica C;Lee, Catherine;Habel, Laurel A;Habel, Laurel A;et al.
Breast Cancer Res Treat. 2024 Jan;203(2):281-289. Epub 2023-10-17.
Risk Factors for Recurrent Emergency Care Utilization for Flares in Inflammatory Bowel Disease
Patients with inflammatory bowel disease (IBD) need frequent emergency care due to flares of their disease. However, understanding which patients are most vulnerable to repeat emergency care due to recurrent flares of their disease remains poor. This was a retrospective cohort study of Kaiser Permanente Northern California health plan members aged ≥18 years between 2009 and 2018. Our primary outcome was occurrence of repeat emergency department (ED) visits with a primary diagnosis code of IBD in the 6 months following their index ED visit. Baseline characteristics and clinical service use patterns were extracted. We used multivariable negative binomial regression analysis to measure the incident risk of a recurrent ED visit within 6 months. We found 2111 patients who met eligibility criteria, of whom 56.7% were female and 39.7% were non-White. During the 6-month observation period, 19.3% (n = 408) returned to the ED for a second IBD flare. In adjusted analyses, we found older age (incident risk ratio [IRR] 0.44, 95% confidence interval [CI] 0.31-0.62 for age 60+ compared to 18-30), higher neighborhood household income (IRR 0.80, 95% CI 0.65-0.98 for income ≥$85,000), and diagnosis of alcohol use disorder were associated with a lower risk of repeat ED utilization (IRR 0.62, 95% CI 0.41-0.93), while presence of mood disorder (IRR 1.26, 95% CI 1.03-1.58), history of opiate prescription (IRR 1.38, 95% CI 1.10-1.73), and corticosteroid prescription (IRR 1.57, 95% CI 1.27-1.95) were associated with increased risk of repeat ED utilization. Prompt outpatient follow-up was not associated with a lower odds of recurrent ED utilization (IRR 0.93, 95% CI 0.75-1.15). Our study identified multiple patient characteristics associated with higher recurrent short-term use of the ED for IBD care. Although we did not find prompt outpatient follow-up after initial ED visit to be protective, targeted interventions directed at high-risk individuals based on mood disorders, opiate use, or steroid use may help to optimize care and health care utilization.
Authors: Hassid, Benjamin G;Wei, Julia;Sax, Dana;Velayos, Fernando S
Acad Emerg Med. 2024 Jan;31(1):28-35. Epub 2023-11-05.
Discrimination and bladder health among women in the CARDIA cohort study: Life course and intersectionality perspectives
This study examines whether discriminatory experiences are associated with lower urinary tract symptoms (LUTS) and their impact among 972 women in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study, which recruited participants from 4 cities in the United States. Exposure to discrimination was assessed 3 times (1992-93, 2000-01, 2010-11) and averaged across assessments. Participants separately reported whether they experienced discrimination on the basis of their gender, race or color, and socioeconomic position or social class. For each social identity, discrimination was assessed in 6-7 settings (e.g., when getting a job, medical care, or housing). At different time points, women who reported discriminatory experiences for a given social identity were asked how frequently the discrimination occurred and how stressful experience(s) were. Following the 2010-11 assessment, data on LUTS and their impact were collected. Women were classified into bladder health versus mild, moderate, or severe symptoms/impact clusters. More Black than White women reported discriminatory experiences across all social identities and most settings. Perceived stress of discriminatory experiences did not differ between Black and White women. In analyses stratified by race and social identity, White women reported LUTS/impact with discriminatory experiences in more settings, more frequent discriminatory experiences across settings, and each additional social identity for which discrimination was experienced. Black women reported LUTS/impact with more frequent discriminatory experiences across settings. For Black women, greater perceived stress of both gender and race discrimination were associated with LUTS/impact. For White women, only greater perceived stress of race discrimination was associated with LUTS/impact. This is one of the first studies to examine discrimination in relation to LUTS/impact. Additional research is needed to better understand differences in how discriminatory experiences based on potentially intersecting identities may be related to bladder health among women.
Authors: Brady, Sonya S;Arguedas, Andrés;Huling, Jared D;Hellemann, Gerhard;Lewis, Cora E;Fok, Cynthia S;Van Den Eeden, Stephen K;Markland, Alayne D
Soc Sci Med. 2024 Jan;341:116547. Epub 2023-12-26.
Leisure time television watching, computer use and risks of breast, colorectal and prostate cancer: A Mendelian randomisation analysis
Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. We used univariable and multivariable two-sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self-reported leisure television watching and computer use were identified from a recent genome-wide association study (GWAS). Data related to cancer risk were obtained from cancer GWAS consortia. A series of sensitivity analyses were applied to examine the robustness of the results to the presence of confounding. A 1-standard deviation (SD: 1.5 h/day) increment in hours of television watching increased risk of breast cancer (OR per 1-SD: 1.15, 95% confidence interval [CI]: 1.05-1.26) and colorectal cancer (OR per 1-SD: 1.32, 95% CI: 1.16-1.49) while there was little evidence of an association for prostate cancer risk (OR per 1-SD: 0.94, 95% CI: 0.84-1.06). After adjusting for years of education, the effect estimates for television watching were attenuated (breast cancer, OR per 1-SD: 1.08, 95% CI: 0.92-1.27; colorectal cancer, OR per 1-SD: 1.08, 95% CI: 0.90-1.31). Post hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed for each cancer site according to sex (colorectal cancer), anatomical subsites and cancer subtypes. There was little evidence of associations between genetically predicted computer use and cancer risk. Our univariable analysis identified some positive associations between hours of television watching and risks of breast and colorectal cancer. However, further adjustment for additional lifestyle factors especially years of education attenuated these results. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development.
Authors: Papadimitriou, Nikos;Sakoda, Lori C;Murphy, Neil;et al.
Cancer Med. 2023 Dec 28.
Mode of Detection of Second Breast Cancers in Patients Undergoing Surveillance After Treatment of Ductal Carcinoma in Situ
For patients undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS), the NCCN Guidelines for Breast Cancer recommend annual breast imaging and physical examination every 6 to 12 months for 5 years, and then annually. The aim of our study was to evaluate the modes of detection (imaging, patient reported, or physical examination) of second cancers in a cohort of patients undergoing surveillance after primary DCIS treatment to better inform surveillance recommendations. We performed a retrospective cohort study of patients with DCIS treated between January 1, 2008, and December 31, 2011, within a large integrated health care system. Information on patient demographics, index DCIS treatment, tumor characteristics, and mode of detection of second breast cancer was obtained from the electronic health record or chart review. Our study cohort consisted of 1,550 women, with a median age of 59 years at diagnosis. Surgical treatment of DCIS included lumpectomy (75.0%; n=1,162), unilateral mastectomy (21.1%; n=327), or bilateral mastectomy (3.9%; n=61), with or without sentinel lymph node biopsy. Additionally, 44.4% (n=688) and 28.3% (n=438) received radiation and endocrine therapies, respectively. Median follow-up was 10 years, during which 179 (11.5%) women were diagnosed with a second breast cancer. Of the second cancers, 43.0% (n=77) were ipsilateral and 54.8% (n=98) contralateral, and 2.2% (n=4) presented with distant metastases; 61.5% (n=110) were invasive, 36.3% (n=65) were DCIS, and 2.2% (n=4) were Paget’s disease. Second breast cancers were imaging-detected in 74.3% (n=133) of cases, patient-detected in 20.1% (n=36), physician-detected in 2.2% (n=4), and detected incidentally on imaging or pathology from procedures unrelated to oncologic care in 3.4% (n=6). In our cohort of patients undergoing surveillance following diagnosis and treatment of DCIS, 2% of second breast cancers were detected by a clinical breast examination. This suggests that survivorship care should prioritize mammography and patient education regarding breast self-examination and symptoms that warrant evaluation to detect second breast cancers.
Authors: Waites, Bethany T;Lyon, Liisa;Kuehner, Gillian;Odele, Patience;Habel, Laurel A;Liu, Raymond
J Natl Compr Canc Netw. 2023 Dec 28;22(1). Epub 2023-12-28.
What Matters Most: The Documented Goals, Values and Motivators of Advanced Cancer Patients
Goals of care conversations are essential to delivery of goal concordant care. Infrequent and inconsistent goals of care documentation potentially limit delivery of goal concordant care. At Kaiser Permanente San Francisco Cancer Center, a standardized documentation template was designed and implemented to increase goals of care documentation by oncologists. The centralized, prompt-based template included value clarification of the goals and values of advanced cancer patients beyond treatment preferences. Documented conversations using the template during the initial pilot period were reviewed to characterization the clinical context in which conversations were recorded. Common goals and motivators were also identified. A total of 178 advanced cancer patients had at least 1 documented conversation by a medical oncologist using the goals of care template. Oncologists consistently documented within the template goals of therapy and motivating factors in decision making. The most frequently documented goals of care were “Avoiding Pain and Suffering,” “Physical Independence,” and “Living as Long as Possible.” The least recorded goal was “Comfort Focused Treatment Only.” Review of oncologist documented goals of care conversations using a prompt-based template allowed for characterization of the clinical context, therapy goals and motivators of advanced cancer patients. Communication of goals of care conversations by oncologists using a standardized prompt-based template within a centralized location has the potential to improve delivery of goal concordant care.
Authors: Aller, Ashley;Liu, Raymond;Liu, Raymond;et al.
Am J Hosp Palliat Care. 2023 Dec 19:10499091231223144.
Incidence and Survival for Patients Diagnosed With Breast, Colorectal, and Lung Cancer in an Integrated System
Documenting trends in cancer incidence and survival is a national priority. This study estimated age- and sex-adjusted incidence and 5-year relative survival among patients with cancer diagnosed within Kaiser Permanente compared to Surveillance, Epidemiology, and End Results (SEER) estimates. The cohort included Kaiser Permanente health plan members diagnosed with breast (BC), colorectal (CRC), or lung cancer (LC) between January 1, 1999 and December 31, 2018. Incidence was computed as age-adjusted rates per 100,000 member-years. SEER*Stat was used to compute 5-year relative survival. Kaiser Permanente BC incidence rates were persistently higher than SEER from 2004 (126.5 [95% confidence interval (CI) = 123.2-129.9] vs 122.6 [95% CI = 121.3-123.2]) through 2013 (132.06 [95% CI = 129.5-135.7] vs 126.7 [95% CI = 125.9-127.5]). Kaiser Permanente CRC and LC incidence rates were lower than SEER for all years except 2008, showing a spike in CRC incidence (51.5 [95% CI = 49.9-53.0] vs 46.1 [95% CI = 45.7-46.4]). Kaiser Permanente BC, CRC, and LC survival estimates for all stages were higher than SEER. Incidence rates for all-stage and localized-stage BC were consistently higher for Kaiser Permanente than for SEER. CRC and LC rates were lower. Kaiser Permanente survival rates were consistently higher than for SEER. The strengths of these findings are associated with the ability to capture “gold-standard” cancer registry data on defined Kaiser Permanente populations. However, findings should be interpreted cautiously given differences in the underlying populations and secular and regional differences between Kaiser Permanente and SEER. The Kaiser Permanente population is younger and more racially diverse than SEER aggregate populations, and Kaiser Permanente members are insured with access to preventive care (eg, smoking cessation programs, cancer screening).
Authors: Hahn, Erin E;Ritzwoller, Debra P;Munoz-Plaza, Corrine E;Gander, Jennifer;Kushi, Lawrence H;McMullen, Carmit;Oshiro, Caryn;Roblin, Douglas W;Wernli, Karen J;Staab, Jenny
Perm J. 2023 Dec 15;27(4):129-135. Epub 2023-09-19.
Environmental and Occupational Exposures and Prognosis in Patients with Non-Muscle Invasive Bladder Cancer in the Be-Well Study
Bladder cancer is primarily diagnosed as non-muscle invasive bladder cancer (NMIBC) with high recurrence and progression rates. Environmental and occupational exposures to carcinogens are well-known risk factors for developing bladder cancer, yet their effects on prognosis remain unknown. In the Be-Well Study, a population-based prospective cohort study of 1,472 patient with newly diagnosed NMIBC from 2015 to 2019, we examined history of environmental and occupational exposures in relation to tumor stage and grade at initial diagnosis by multivariable logistic regression, and subsequent recurrence and progression by Cox proportional hazards regression. Exposure to environmental and occupational carcinogens was significantly associated with increased risk of progression (HR = 1.79; 95% CI: 1.04, 3.09), specifically increased progression into muscle-invasive disease (HR = 2.28; 95% CI: 1.16, 4.50). Exposure to asbestos and arsenic were associated with increased odds of advanced stage at diagnosis (asbestos: OR = 1.43; 95% CI: 1.11, 1.84; arsenic, OR = 1.27; 95% CI: 1.01, 1.63), and formaldehyde exposure was associated with increased risk of recurrence (HR = 1.38; 95% CI: 1.12, 1.69). Our findings suggest that history of these exposures may benefit current risk stratification systems to tailor clinical care and improve prognosis in patients with NMIBC.
Authors: Wang, Zinian;Ergas, Isaac J;Quesenberry, Charles P;Kushi, Lawrence H;Tang, Li;et al.
Am J Epidemiol. 2023 Dec 05.
The Health Inequality Impact of Liquid Biopsy to Inform First-Line Treatment of Advanced Non-Small Cell Lung Cancer: A Distributional Cost-Effectiveness Analysis.
OBJECTIVES: To perform a distributional cost-effectiveness analysis of liquid biopsy (LB) followed by, if needed, tissue biopsy (TB) (LB-first strategy) relative to a TB-only strategy to inform first-line treatment of advanced non-small cell lung cancer (aNSCLC) from a US payer perspective by which we quantify the impact of LB-first on population health inequality according to race and ethnicity. n METHODS: With a health economic model, quality-adjusted life-years (QALYs) and costs per patient were estimated for each subgroup. Given the lifetime risk of aNSCLC, and assuming equally distributed opportunity costs, the incremental net health benefits of LB-first were calculated, which were used to estimate general population quality-adjusted life expectancy at birth (QALE) by race and ethnicity with and without LB-first. The degree of QALYs and QALE differences with the strategies was expressed with inequality indices. Their differences were defined as the inequality impact of LB-first. n RESULTS: LB-first resulted in an additional 0.21 (95% uncertainty interval: 0.07-0.39) QALYs among treated patients, with the greatest gain observed among Asian patients (0.31 QALYs [0.09-0.61]). LB-first resulted in an increase in relative inequality in QALYs among patients, but a minor decrease in relative inequality in QALE. n CONCLUSIONS: LB-first to inform first-line aNSCLC therapy can improve health outcomes. With current diagnostic performance, the benefit is the greatest among Asian patients, thereby potentially widening racial and ethnic differences in survival among patients with aNSCLC. Assuming equally distributed opportunity costs and access, LB-first does not worsen and, in fact, may reduce inequality in general population health according to race and ethnicity.
Authors: Jansen, Jeroen P;Ragavan, Meera V;Chen, Cheng;Douglas, Michael P;Phillips, Kathryn A
Value Health. 2023 Dec;26(12):1697-1710. doi: 10.1016/j.jval.2023.08.010. Epub 2023 Sep 22.
What Constitutes Quality of Life? Perspectives of Adolescents and Young Adults With Advanced Cancer
Adolescents and young adults (AYAs) with advanced cancer identify maintaining a good quality of life (QoL) as a central goal of end-of-life care. QoL is a dynamic and subjective overarching concept that refers to an individual’s relative satisfaction with their own life. Despite its importance to AYAs with advanced cancer, a patient-centered definition of QoL is lacking in this population. This qualitative secondary analysis of semistructured interviews was conducted across 3 institutions and 1 online support community among AYA patients with advanced cancer, family caregivers, and health care providers who cared for living or recently deceased AYAs. Interviewees were asked about priorities in receipt of care. Interviews were transcribed using NVivo software for primary analysis, and previously coded excerpts were screened for references to QoL. Relevant excerpts were sorted into organizing domains. Participants included 23 AYA patients, 28 family caregivers, and 29 health care providers (including physicians, nurses, nurse practitioners, social workers, and psychologists). Four domains of QoL were identified: psychosocial and physical well-being, dignity, normalcy, and personal and family relationships. Within each domain there was agreement across AYAs, caregivers, and health care providers, with nuanced perspectives provided by AYAs of different ages. Personal and family relationships was the most frequently referenced domain of QoL among all participants. A common feature of each domain was that adaptation to current circumstances impacted perspectives on QoL. Patients valued active participation in the development of a care plan that supported these domains. AYAs with advanced cancer, their caregivers, and health care providers agree on several broad domains of QoL in this population. To provide high-quality, patient-centered care, care plans should integrate these domains to enable AYAs to maximize their QoL throughout their advanced cancer care.
Authors: Hinkle, Jane;Kushi, Lawrence H;Mack, Jennifer W;et al.
J Natl Compr Canc Netw. 2023 Dec;21(12):1243-1250.
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
Authors: Wang, Anqi;Van Den Eeden, Stephen K;Haiman, Christopher A;et al.
Nat Genet. 2023 Dec;55(12):2065-2074. Epub 2023-11-09.
Hypothetical interventions on diet quality and lifestyle factors to improve breast cancer survival: the Pathways Study
The number of breast cancer survivors is increasing, yet evidence to inform dietary and lifestyle guidelines is limited. This analysis included 3,658 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive breast cancer. A healthy plant-based dietary index score (hPDI), an American Cancer Society (ACS) nutrition guidelines score, a 2015 Healthy Eating Index score (HEI), hours per week of moderate to vigorous physical activity (PA), and lifetime cumulative pack-years of cigarette smoking (SM) were each measured at diagnosis, 6, 24, and 72 months. Using g-computation, 5- and 10-year risk ratios (RR), risk differences, and 95% confidence intervals (CI) for all-cause mortality under hypothetical interventions on diet quality, PA, and SM, compared with the natural course (no intervention) were calculated. Hypothetical moderate to extreme interventions on hPDI, ACS, and HEI, each in combination with PA and SM, showed 11% to 56%, 9% to 38%, and 9% to 49% decreases in 5-year risks of all-cause mortality compared with no intervention, respectively [(hPDI: RRmoderate = 0.89, 95% CI: 0.82-0.94; RRextreme = 0.44, 95% CI: 0.26-0.67), (ACS: RRmoderate = 0.91, 95% CI: 0.85-0.96; RRextreme = 0.62, 95% CI: 0.43-0.82), (HEI: RRmoderate = 0.91, 95% CI: 0.84-0.95; RRextreme = 0.51, 95% CI: 0.33-0.72)]. While 10-year relative risks were slightly attenuated, absolute risk reductions were more pronounced. Interventions to improve diet quality, increase PA, or reduce SM at the time of diagnosis may improve survival among breast cancer survivors. We estimate that over 10% of deaths could be delayed by even moderate adoption of these behaviors.
Authors: Ergas, Isaac J;Bradshaw, Patrick T;Cespedes Feliciano, Elizabeth M;Roh, Janise M;Kwan, Marilyn L;Laraia, Barbara;Madsen, Kristine A;Yao, Song;Thomsen, Catherine;Kushi, Lawrence H
Cancer Epidemiol Biomarkers Prev. 2023 Dec 01;32(12):1716-1725.
D3-creatine dilution, computed tomography and dual-energy X-ray absorptiometry for assessing myopenia and physical function in colon cancer: A cross-sectional study
Low skeletal muscle mass (myopenia) is common in cancer populations and is associated with functional decline and mortality, but prior oncology studies did not assess total body skeletal muscle mass. Instead, they measured surrogates such as cross-sectional area (CSA) of skeletal muscle at L3 from computed tomography (CT) or appendicular lean mass (ALM) from dual-energy X-ray absorptiometry (DXA). D3-creatine (D3Cr) dilution is a non-invasive method to assess total body skeletal muscle mass, which has been examined in a variety of populations but not in cancer. To compare the associations of D3Cr muscle mass, CT CSA, and DXA ALM with myopenia and physical function, we conducted a cross-sectional study among 119 patients with colon cancer (2018-2022). For each technique (D3Cr, CT and DXA), myopenia was defined as the lowest sex-specific quartile of its measurement. Physical function was measured by the short physical performance battery and grip strength. We calculated Pearson correlations (r) among three techniques, computed Cohen’s kappa coefficients (κ) to assess the agreement of myopenia, and estimated Pearson correlations (r) of three techniques with physical function. All analyses were sex-specific. Sixty-one (51.3%) participants were male, the mean (standard deviation) age was 56.6 (12.9) years, and most (68.9%) had high physical function (short physical performance battery: ≥11 points). Correlations and myopenia agreement among three techniques were greater in men than women; for example, regarding D3Cr muscle mass versus CT CSA, r was 0.73 (P < 0.001) for men versus 0.45 (P < 0.001) for women, and κ was 0.82 (95% CI: 0.65, 0.99) for men versus 0.24 (95% CI: -0.08, 0.52) for women. Among men, higher D3Cr muscle mass was significantly correlated with faster gait speed (r = 0.43, P < 0.01) and stronger grip strength (r = 0.32, P < 0.05); similar correlations were observed for CT CSA and DXA ALM. However, among women, no measure of muscle or lean mass was significantly associated with physical function. This is the first study using D3-creatine dilution method to assess muscle mass in a cancer population. Regardless of the techniques used for muscle or lean mass assessment, we observed stronger correlations, greater myopenia agreement, and more significant associations with physical function in men with colon cancer than women. D3Cr, CT and DXA are not interchangeable methods for assessing myopenia and physical function, especially in women with colon cancer. Future studies should consider relative advantages of these techniques and examine the D3-creatine dilution method in other cancer types.
Authors: Cheng, En;Sternfeld, Barbara;Cespedes Feliciano, Elizabeth M;Cespedes Feliciano, Elizabeth M;et al.
J Cachexia Sarcopenia Muscle. 2023 Dec;14(6):2768-2778. Epub 2023-10-30.
AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn’s Disease
Biomarkers are used frequently for evaluation and monitoring of patients with Crohn’s disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn’s Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 μg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.
Authors: Ananthakrishnan, Ashwin N;Adler, Jeremy;Chachu, Karen A;Nguyen, Nghia H;Siddique, Shazia M;Weiss, Jennifer M;Sultan, Shahnaz;Velayos, Fernando S;Cohen, Benjamin L;Singh, Siddharth;AGA Clinical Guidelines Committee. Electronic address: clinicalpractice@gastro.org,
Gastroenterology. 2023 Dec;165(6):1367-1399.
Reply to Uchiyama et al
Authors: Li, Dan;Shah, Shailja C;Corley, Douglas A
Gastroenterology. 2023 Dec;165(6):1585-1586. Epub 2023-09-28.
A Multicenter Virtual Multidisciplinary Sarcoma Case Conference Improves Outcome for a Rare Soft Tissue Sarcoma (Dermatofibrosarcoma Protuberans)
The purpose of this study is to analyze the impact of a virtual multidisciplinary sarcoma case conference (VMSCC) on the outcomes of dermatofibrosarcoma protuberans (DFSP). We compared margin status after surgery and disease-free survival (DFS) on two cohorts of patients with DFSP, one diagnosed from 2010 to 2015 and one from 2016 to 2020 (before and after virtual multidisciplinary sarcoma case conference (VMSCC) within Kaiser Permanente Northern California (KPNC), using Kaplan-Meier curves and Cox proportional hazard regression models. There was no significant difference between the two cohorts on demographics, tumor location, type of surgery, receipt of radiation, receipt of imatinib, or size of tumor. However, the percent of patients with positive margin after final surgery and the percent of local recurrence were significantly different: 6.5% and 6.3% for the 2010-2015 cohort, and .8% and 0% for the 2016-2020 cohort, respectively. Our data suggest that the outcomes of DFSP improved significantly after the implementation of VMSCC.
Authors: Chang, Amber L;Kwak, Hyunjee V;Pan, Minggui;Peng, Peter D;Morse, Lee J;Chang, C K
Am Surg. 2023 Dec;89(12):5240-5245. Epub 2022-11-28.
Leisure-time physical activity, daily sitting time, and mortality among US skin cancer survivors
To investigate the long-term effect of sitting time and physical activity after a skin cancer diagnosis. A cohort of a nationally representative sample of skin cancer survivors (n=862) and non-cancer adults (n=13691) ≥50 years from the US National Health and Nutrition Examination Survey. Mortality data were linked through December 31, 2019. During up to 13.2 years of follow-up (median, 6.3 years; 94,093 person-years), 207 deaths (cancer: 53) occurred in skin cancer survivors and 1970 (cancer: 414) in non-cancer adults. After adjusting for covariates and skin cancer type, being active was associated with lower risks of all-cause (HR=0.69; 95% CI: 0.47 to 1.00) and non-cancer (HR=0.59; 95% CI: 0.36 to 0.97) mortality compared to being inactive among skin cancer survivors. Meanwhile, sitting 8 h/d was associated with higher risks of all-cause (HR=1.72; 95% CI: 1.11 to 2.67) and non-cancer (HR=1.76; 95% CI: 1.07 to 2.92) mortality compared to sitting <6 h/d. In the joint analysis, inactive skin cancer survivors sitting >8 h/d had the highest mortality risks from all-cause (HR=2.26; 95% CI: 1.28 to 4.00) and non-cancer (HR=2.11; 95% CI,1.10 to 4.17). Additionally, the associations of LTPA and sitting time with all-cause and cause-specific mortality did not differ between skin cancer survivors and non-cancer adults (all P for interaction>0.05) CONCLUSION: The combination of prolonged sitting and lack of physical activity was associated with elevated risks of all-cause and non-cancer deaths among US skin cancer survivors. Skin cancer survivors could benefit from maintaining a physically active lifestyle.
Authors: Cao, Chao;Wang, Nan;Liu, Raymond;Patel, Alpa V;Friedenreich, Christine M;Yang, Lin
Support Care Cancer. 2023 Nov 24;31(12):718. Epub 2023-11-24.
Data gaps and opportunities for modeling cancer health equity
Population models of cancer reflect the overall US population by drawing on numerous existing data resources for parameter inputs and calibration targets. Models require data inputs that are appropriately representative, collected in a harmonized manner, have minimal missing or inaccurate values, and reflect adequate sample sizes. Data resource priorities for population modeling to support cancer health equity include increasing the availability of data that 1) arise from uninsured and underinsured individuals and those traditionally not included in health-care delivery studies, 2) reflect relevant exposures for groups historically and intentionally excluded across the full cancer control continuum, 3) disaggregate categories (race, ethnicity, socioeconomic status, gender, sexual orientation, etc.) and their intersections that conceal important variation in health outcomes, 4) identify specific populations of interest in clinical databases whose health outcomes have been understudied, 5) enhance health records through expanded data elements and linkage with other data types (eg, patient surveys, provider and/or facility level information, neighborhood data), 6) decrease missing and misclassified data from historically underrecognized populations, and 7) capture potential measures or effects of systemic racism and corresponding intervenable targets for change.
Authors: Trentham-Dietz, Amy;Tiro, Jasmin A;et al.
J Natl Cancer Inst Monogr. 2023 Nov 08;2023(62):246-254.
Clinical Adjuncts to Lung Cancer Screening: A Narrative Review
The updated US Preventive Services Task Force guidelines on lung cancer screening have significantly expanded the population of screening eligible adults, among whom the balance of benefits and harms associated with lung cancer screening vary considerably. Clinical adjuncts are additional information and tools that can guide decision-making to optimally screen individuals who are most likely to benefit. Proposed adjuncts include integration of clinical history, risk prediction models, shared-decision-making tools, and biomarker tests at key steps in the screening process. Although evidence regarding their clinical utility and implementation is still evolving, they carry significant promise in optimizing screening effectiveness and efficiency for lung cancer.
Authors: Susai, Cynthia J;Velotta, Jeffrey B;Sakoda, Lori C
Thorac Surg Clin. 2023 Nov;33(4):421-432. Epub 2023-05-12.
Common Instances of Low-value Care in Inflammatory Bowel Diseases
Value-based care focuses on improving the quality, effectiveness, and efficiency of healthcare while controlling costs. Low value care implies services or interventions that provide little or no benefit to patients, have the potential to cause harm, incur unnecessary cost to patients, or waste limited healthcare resources. In this review, we discuss common instances of low value care along the spectrum of management in IBD. These include low value care in (1) diagnosis and monitoring of IBD: utilization of serological markers to screen and diagnose IBD, over-reliance on symptoms for monitoring disease, failure to employ treat-to-target strategies in symptomatic patients with IBD, and annual surveillance colonoscopies in patients at low risk of developing dysplasia; (2) treatment of IBD: use of 5-aminosalicylates (5-ASA) in Crohn’s disease, continuation of 5-ASA after escalation to immunosuppressive therapy, chronic corticosteroid use without steroid-sparing strategies, step therapy for Crohn’s disease, failure to optimize TNF antagonists in patients with active disease and subsequently de-intensification of therapies in those who have achieved stable remission; and (3) management of hospitalized patients with IBD: routine cross-sectional imaging for patients with IBD presenting to the emergency department, withholding pharmacological prophylaxis for venous thromboembolism in patients hospitalized with IBD flare, and prolonged use of high dose intravenous corticosteroids in patients with acute severe ulcerative colitis. This review is meant to bring attention to value-based care in IBD and provide guidance to treating practitioners. Future studies on systematic evaluation of high- and low-value care in patients with IBD are warranted.
Authors: Singh, Siddharth;Velayos, Fernando S;Rubin, David T
Clin Gastroenterol Hepatol. 2023 Oct 23.
Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
Authors: Thomas, Minta;Sakoda, Lori C;Lee, Jeffrey K;Corley, Douglas A;Hsu, Li;et al.
Nat Commun. 2023 Oct 02;14(1):6147. Epub 2023-10-02.
Impact of a scalable training program on the quality of colonoscopy performance and risk of post-colonoscopy colorectal cancer
Endoscopist adenoma detection rates (ADRs) vary widely and are associated with patients’ risk of postcolonoscopy colorectal cancers (PCCRCs). However, few scalable physician-directed interventions demonstrably both improve ADR and reduce PCCRC risk. Among patients undergoing colonoscopy, we evaluated the influence of a scalable online training on individual-level ADRs and PCCRC risk. The intervention was a 30-minute, interactive, online training, developed using behavior change theory, to address factors that potentially impede detection of adenomas. Analyses included interrupted time series analyses for pretraining versus posttraining individual-physician ADR changes (adjusted for temporal trends) and Cox regression for associations between ADR changes and patients’ PCCRC risk. Across 21 endoscopy centers and all 86 eligible endoscopists, ADRs increased immediately by an absolute 3.13% (95% confidence interval [CI], 1.31-4.94) in the 3-month quarter after training compared with .58% per quarter (95% CI, .40-.77) and 0.33% per quarter (95% CI, .16-.49) in the 3-year pretraining and posttraining periods, respectively. Posttraining ADR increases were higher among endoscopists with pretraining ADRs below the median. Among 146,786 posttraining colonoscopies (all indications), each 1% absolute increase in screening ADR posttraining was associated with a 4% decrease in their patients’ PCCRC risk (hazard ratio, .96; 95% CI, .93-.99). An ADR increase of ≥10% versus <1% was associated with a 55% reduced risk of PCCRC (hazard ratio, .45; 95% CI, .24-.82). A scalable, online behavior change training intervention focused on modifiable factors was associated with significant and sustained improvements in ADR, particularly among endoscopists with lower ADRs. These ADR changes were associated with substantial reductions in their patients' risk of PCCRC.
Authors: Corley, Douglas A;Jensen, Christopher D;Lee, Jeffrey K;Contreras, Richard;Fireman, Bruce H;Quesenberry, Charles P;et al.
Gastrointest Endosc. 2023 Oct;98(4):609-617. Epub 2023-04-23.
Germline Genetic Testing Among Women ≤ 45 Years of Age with Ductal Carcinoma In Situ Versus Invasive Breast Cancer in a Large Integrated Health Care System
We compared the results of hereditary cancer multigene panel testing among patients ≤ 45 years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in a large integrated health care system. A retrospective cohort study of hereditary cancer gene testing among women ≤ 45 years of age diagnosed with DCIS or IBC at Kaiser Permanente Northern California between September 2019 and August 2020 was performed. During the study period, institutional guidelines recommended the above population be referred to genetic counselors for pretesting counseling and testing. A total of 61 DCIS and 485 IBC patients were identified. Genetic counselors met with 95% of both groups, and 86.4% of DCIS patients and 93.9% of IBC patients (p = 0.0339) underwent gene testing. Testing differed by race/ethnicity (p = 0.0372). Among those tested, 11.76% (n = 6) of DCIS patients and 16.71% (n = 72) of IBC patients had a pathogenic variant (PV) or likely pathogenic variant (LPV) based on the 36-gene panel (p = 0.3650). Similar trends were seen in 13 breast cancer (BC)-related genes (p = 0.0553). Family history of cancer was significantly associated with both BC-related and non-BC-related PVs in IBC, but not DCIS. In our study, 95% of patients were seen by a genetic counselor when age was used as an eligibility criterion for referral. While larger studies are needed to further compare the prevalence of PVs/LPVs among DCIS and IBC patients, our data suggest that even in younger patients, the prevalence of PVs/LPVs in BC-related genes is lower in DCIS patients.
Authors: Hsu, Diana S;Jiang, Sheng-Fang;Habel, Laurel A;Hoodfar, Elizabeth;Karlea, Audrey;Manace-Brenman, Leslie;Dzubnar, Jessica M;Shim, Veronica C
Ann Surg Oncol. 2023 Oct;30(11):6454-6461. Epub 2023-06-29.
Transportation barriers and endoscopic procedures: barriers, legal challenges, and strategies for GI endoscopy units
Authors: American Society for Gastrointestinal Endoscopy Quality Assurance in Endoscopy Committee,;Kwok, Karl;Levin, Theodore R;Dominitz, Jason A;Panganamamula, Kashyap;Feld, Andrew D;Bardall, Bruce;Newbury, Kara;Day, Lukejohn W
Gastrointest Endosc. 2023 Oct;98(4):475-481. Epub 2023-08-24.
Elucidating the Risk of Colorectal Cancer for Variants in Hereditary Colorectal Cancer Genes
Authors: Mahmood, Khalid;Thomas, Minta;Qu, Conghui;Gecco-Ccfr Consortium,;Hsu, Li;Buchanan, Daniel D;Peters, Ulrike
Gastroenterology. 2023 Oct;165(4):1070-1076.e3. Epub 2023-07-14.
An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles
New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test’s ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.
Authors: Bresalier, Robert S;Levin, Bernard;Members of the World Endoscopy Colorectal Cancer Screening New Test Evaluation Expert Working Group,;et al.
Gut. 2023 Oct;72(10):1904-1918. Epub 2023-07-18.
AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study
In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.
Authors: Mehta, Neil;Kotwani, Prashant;Norman, Joshua;Shui, Amy;Li, Po-Yi;Saxena, Varun;Chan, Wesley;Yao, Francis Y
Liver Transpl. 2023 Oct 01;29(10):1041-1049. Epub 2023-04-27.
Colorectal Cancer Screening Decision Based on Predicted Risk: Protocol for a Pilot Randomized Controlled Trial
Incidence of and mortality from colorectal cancer (CRC) can be effectively reduced by screening with the fecal immunochemical test (FIT) or colonoscopy. Individual risk to develop CRC within 15 years varies from <1% to >15% among people aged 50 to 75 years. Communicating personalized CRC risk and appropriate screening recommendations could improve the risk-benefit balance of screening test allocations and optimize the use of limited colonoscopy resources. However, significant uncertainty exists regarding the feasibility and efficacy of risk-based screening. We aim to study the effect of communicating individual CRC risk and a risk-based recommendation of the FIT or colonoscopy on participants’ choice of screening test. We will also assess the feasibility of a larger clinical trial designed to evaluate the impact of personalized screening on clinical outcomes. We will perform a pilot randomized controlled trial among 880 residents aged 50 to 69 years eligible to participate in the organized screening program of the Vaud canton, Switzerland. Participants will be recruited by mail by the Vaud CRC screening program. Primary and secondary outcomes will be self-assessed through questionnaires. The risk score will be calculated using the open-source QCancer calculator that was validated in the United Kingdom. Participants will be stratified into 3 groups-low (<3%), moderate (3% to <6%), and high (≥6%) risk-according to their 15-year CRC risk and randomized within each risk stratum. The intervention group participants will receive a newly designed brochure with their personalized risk and screening recommendations. The control group will receive the usual brochure of the Vaud CRC screening program. Our primary outcome, measured using a self-administered questionnaire, is appropriate screening uptake 6 months after the intervention. Screening will be defined as appropriate if participants at high risk undertake colonoscopy and participants at low risk undertake the FIT. We will also measure the acceptability of the risk score and screening recommendations and the psychological factors influencing screening behavior. We will also assess the feasibility of a full-scale randomized controlled trial. We expect that a total sample of 880 individuals will allow us to detect a difference of 10% (α=5%) between groups. The main outcome will be analyzed using a 2-tailed chi-squared test. We expect that appropriate screening uptake will be higher in the intervention group. No difference in overall screening uptake is expected. We will test the impact of personalized risk information and screening recommendations on participants' choice of screening test in an organized screening program. This study should advance our understanding of the feasibility of large-scale risk-based CRC screening. Our results may provide insights into the optimization of CRC screening by offering screening options with a better risk-benefit balance and optimizing the use of resources. ClinicalTrials.gov NCT05357508; https://www.clinicaltrials.gov/study/NCT05357508. DERR1-10.2196/46865.
Authors: Plys, Ekaterina;Bulliard, Jean-Luc;Chaouch, Aziz;Durand, Marie-Anne;van Duuren, Luuk A;Brändle, Karen;Auer, Reto;Froehlich, Florian;Lansdorp-Vogelaar, Iris;Corley, Douglas A;Selby, Kevin
JMIR Res Protoc. 2023 Sep 07;12:e46865. Epub 2023-09-07.
Changes in physical function in older women with endometrial cancer with or without adjuvant therapy
To evaluate changes in physical function (PF) for older women with endometrial cancer (EC) + / - adjuvant therapy in the Women’s Health Initiative Life and Longevity after Cancer cohort. This study examined women ≥ 70 years of age with EC with available treatment records. Change in PF was measured using the RAND-36 and compared between groups using Wilcoxon rank-sum tests. Multivariable median regression was used to compare the changes in scores while adjusting for confounding variables. Included in the study were 287 women, 150 (52.3%) women who did not receive adjuvant therapy and 137 (47.7%) who received adjuvant therapy. When comparing PF scores, there was a statistically significant difference in the median percent change in functional decline, with a greater decline in those who received adjuvant therapy (- 5.9% [- 23.5 to 0%]) compared to those who did not (0 [- 18.8 to + 6.7%]), p = 0.02). Results were not statistically significant after multivariable adjustment, but women who underwent chemotherapy had a greater percent change (median ∆ - 13.8% [- 35.5 to 0%]) compared to those who received radiation alone (median ∆ - 5.9% [- 31.3 to 0%]) or chemotherapy and radiation (median ∆ - 6.5% [- 25.8 to + 5.7%]. Older women with EC who received adjuvant therapy experienced greater change in PF than those who did not receive adjuvant therapy, particularly women who received chemotherapy. These results were not statistically significant on multivariate analysis. EC survivors may experience changes in PF because of chemotherapy and/or radiation therapy. Additional supportive care may need to be provided to older women to mitigate functional decline.
Authors: Quick, Allison M;Cespedes Feliciano, Elizabeth M;Paskett, Electra;et al.
J Cancer Surviv. 2023 Sep 05.
Psychiatric Diagnoses, Medication, and Service Use Among Patients Who Receive Emergency Care for Inflammatory Bowel Diseases
This study examined relative psychiatric burden among patients who presented to the emergency department once or more than once for inflammatory bowel disease visits. Results highlight the need for integration of psychiatric and gastrointestinal care among high-risk inflammatory bowel disease patients.
Authors: He, Jimmy Z;Hirschtritt, Matthew E;Wei, Julia;Ramalingam, Nirmala D;Kahane, Shellie M;Velayos, Fernando S;Hassid, Benjamin G
Inflamm Bowel Dis. 2023 Sep 04.
The costs and inequities of precision medicine for patients with prostate cancer: A call to action.
Financial toxicity is a growing problem in the delivery of cancer care and contributes to inequities in outcomes across the cancer care continuum. Racial/ethnic inequities in prostate cancer, the most common cancer diagnosed in men, are well described, and threaten to widen in the era of precision oncology given the numerous structural barriers to accessing novel diagnostic studies and treatments, particularly for Black men. Gaps in insurance coverage and cost sharing are 2 such structural barriers that can perpetuate inequities in screening, diagnostic workup, guideline-concordant treatment, symptom management, survivorship, and access to clinical trials. Mitigating these barriers will be key to achieving equity in prostate cancer care, and will require a multi-pronged approach from policymakers, health systems, and individual providers. This narrative review will describe the current state of financial toxicity in prostate cancer care and its role in perpetuating racial inequities in the era of precision oncology.
Authors: Ragavan, Meera V;Borno, Hala T
Urol Oncol. 2023 Sep;41(9):369-375. doi: 10.1016/j.urolonc.2023.04.012. Epub 2023 May 9.
Exposure to Perfluoroalkyl Substances and Associations with Pubertal Onset and Serum Reproductive Hormones in a Longitudinal Study of Young Girls in Greater Cincinnati and the San Francisco Bay Area
Per- and polyfluoroalkyl substances (PFAS), endocrine disrupting chemicals with worldwide exposure, cause changes in mammary gland development in rodents. A few human studies report delay in pubertal events with increasing perfluorooctanoic acid (PFOA) exposure, but to our knowledge none have examined reproductive hormone levels at thelarche. In a cohort of Greater Cincinnati (GC) and San Francisco Bay Area (SFBA) girls recruited at 6-8 years of age, clinical examinations were conducted annually or semiannually with sequential Tanner staging. PFAS concentrations were measured in the first serum sample of 704 girls. In 304 GC girls, estradiol (E2), estrone (E1), testosterone (T), and dihydroepiandrosterone sulfate (DHEAS) were measured in serum at four time points around puberty. Relationships between PFAS and age at thelarche, pubarche, and menarche were analyzed using survival and structural equation models. The association between PFAS and reproductive hormones was assessed using linear regression models. Median PFOA serum concentrations in GC (N=353, 7.3 ng/mL) and the SFBA (N=351, 5.8 ng/mL) were higher than in the U.S. In multivariable Cox proportional hazard models [adjusted for race, body mass index (BMI)], increasing serum log-transformed PFOA was associated with a delay in pubarche [hazard ratio (HR)=0.83; 95% CI: 0.70, 0.99] and menarche (HR=0.04; 95% CI: 0.01, 0.25). Structural equation models indicated a triangular relationship between PFOA, BMI percentile, and the age at the pubertal milestone. Increased PFOA had a statistically significant direct effect of delay on all three milestones, as did BMI. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) also were associated with later thelarche, and Me-PFOSA-AcOH also with later pubarche. PFOA was inversely associated with DHEAS (p<0.01), E1 (p=0.04), and T (p=0.03) concentrations at 6 months prior to puberty. PFAS may delay pubertal onset through the intervening effects on BMI and reproductive hormones. The decreases in DHEAS and E1 associated with PFOA represent biological biomarkers of effect consistent with the delay in onset of puberty. https://doi.org/10.1289/EHP11811.
Authors: Pinney, Susan M;Fassler, Cecily S;Windham, Gayle C;Herrick, Robert L;Xie, Changchun;Kushi, Lawrence H;Biro, Frank M
Environ Health Perspect. 2023 Sep;131(9):97009. Epub 2023-09-26.
O-RADS US v2022: An Update from the American College of Radiology’s Ovarian-Adnexal Reporting and Data System US Committee
First published in 2019, the Ovarian-Adnexal Reporting and Data System (O-RADS) US provides a standardized lexicon for ovarian and adnexal lesions, enables stratification of these lesions with use of a numeric score based on morphologic features to indicate the risk of malignancy, and offers management guidance. This risk stratification system has subsequently been validated in retrospective studies and has yielded good interreader concordance, even with users of different levels of expertise. As use of the system increased, it was recognized that an update was needed to address certain clinical challenges, clarify recommendations, and incorporate emerging data from validation studies. Additional morphologic features that favor benignity, such as the bilocular feature for cysts without solid components and shadowing for solid lesions with smooth contours, were added to O-RADS US for optimal risk-appropriate scoring. As O-RADS US 4 has been shown to be an appropriate cutoff for malignancy, it is now recommended that lower-risk O-RADS US 3 lesions be followed with US if not excised. For solid lesions and cystic lesions with solid components, further characterization with MRI is now emphasized as a supplemental evaluation method, as MRI may provide higher specificity. This statement summarizes the updates to the governing concepts, lexicon terminology and assessment categories, and management recommendations found in the 2022 version of O-RADS US.
Authors: Strachowski, Lori M;Suh-Burgmann, Elizabeth J;Andreotti, Rochelle F;et al.
Radiology. 2023 Sep;308(3):e230685.
Cancer Patients’ Preferences and Perceptions of Advantages and Disadvantages of Telehealth Visits During the COVID-19 Pandemic
We aimed to ascertain oncology patients’ perceptions of telehealth versus in-person (IP) visits for different types of clinical encounters. We surveyed adults undergoing cancer treatment at Kaiser Permanente Northern California infusion centers between November 2021 and May 2022 using a self-administered questionnaire. Patients were asked about visit modality preferences (video, phone, and IP) for six types of clinical discussions, overall advantages and disadvantages of telehealth (video or phone) versus IP modalities, and barriers to video visit use. The 839 patients who completed surveys in English were 63% female; median age 63 years; 64% White; and 73% college-educated (45% ≥bachelor’s degree). For the first postdiagnosis discussion visit, 83% of patients preferred IP, followed by video (27%) and phone (18%). For follow-up visits, 52% of patients preferred IP, 50% video, and 37% phone. For discussions of bad news and sensitive topics, respectively, 68% and 62% preferred IP, 44% and 48% video, and 32% and 41% phone visits. Delivery of good news was acceptable through IP (49%), video (52%), or phone (49%) visits. Perceived advantages of IP visits were greater feelings of connection with their doctor (58%), confidence in physical examinations (73%), and ease in showing things (67%) and talking (51%) to the doctor. Advantages of telehealth visits included saved time (72%) and money (38%), less infection exposure (64%), less travel concerns (45%), and ability to include more people (28%). Of 24% of patients who felt video visits would be hard, 51% cited poor internet, 41% lack of an adequate device, and 28% difficulty signing on. Our results support continued use and reimbursement for telehealth visits with patients with cancer for most types of clinical encounters, including clinical trials.
Authors: Kumar, Deepika;Gordon, Nancy;Zamani, Constanza;Sheehan, Tammy;Martin, Ernesto;Egorova, Olga;Payne, Jessica;Kolevska, Tatjana;Neeman, Elad;Liu, Raymond
JCO Clin Cancer Inform. 2023 Sep;7:e2300040.
Challenges and Opportunities of Epidemiological Studies to Reduce the Burden of Cancers in Young Adults
There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health services research in the AYA population. We consider research that uses data from cancer registries, vital records, healthcare utilization, and surveys, and the accompanying challenges and opportunities of each. To illustrate the strengths of each data source, we present example research questions or areas that are aligned with these data sources and salient to AYAs. Integrating the respective strengths of cancer registry, vital records, healthcare data, and survey-based studies sets the foundation for innovative and impactful research on AYA cancer treatment and survivorship to inform a comprehensive understanding of diverse AYA needs and experiences.
Authors: Nichols, Hazel B;Lee, Catherine;Quesenberry, Charles P;Kushi, Lawrence H;Kushi, Lawrence H;et al.
Curr Epidemiol Rep. 2023 Sep;10(3):115-124. Epub 2022-03-29.
Exploring Stakeholders’ Perspectives on Implementing Universal Germline Testing for Colorectal Cancer: Findings From a Clinical Practice Survey
New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders’ perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers. A cross-sectional survey was sent to 317 active members of CGA-IGC. The survey included sections on demographics, clinical practice specialty, established institutional practices for testing, and questions pertaining to support of and barriers to implementing UGT for patients with CRC. Eighty CGA-IGC members (25%) participated, including 42 genetic counselors (53%) and 14 gastroenterologists (18%). Forty-seven (59%) reported an academic medical center as their primary work setting, and most participants (56%) had more than 10 years of clinical practice. Although most participants (73%) supported UGT, 54% indicated that changes in practice would be required before adopting UGT, and 39% indicated that these changes would be challenging to implement. There was support for both genetics and nongenetics providers to order genetic testing, and a majority (57%) supported a standardized multigene panel rather than a customized gene panel. Key barriers to UGT implementation included limited genetics knowledge among nongenetics providers, time-consuming processes for obtaining consent, ordering tests, disclosing results, and lack of insurance coverage. This study demonstrates wide support among hereditary GI cancer experts for implementation of UGT for patients with CRC. However, alternative service delivery models using nongenetics providers should be considered to address the logistical barriers to UGT implementation, particularly the growing demand for genetic testing.
Authors: Rodgers-Fouche, Linda;Li, Dan;Hodan, Rachel;et al.
JCO Precis Oncol. 2023 Sep;7:e2300440.
Genome-wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer
We used a genome-wide discovery approach to identify methylation markers associated with metastasis in men with localized prostate cancer (PCa), as better identification of those at high risk of metastasis can inform treatment decision-making. We identified men with localized PCa at Kaiser Permanente California (January 1, 1997-December 31, 2006) who did not receive curative treatment and followed them for 10 years to determine metastasis status. Cases were chart review-confirmed metastasis, and controls were matched using density sampling. We extracted DNA from the cancerous areas in the archived diagnostic tissue blocks. We used Illumina’s Infinium MethylationEPIC BeadChip for methylation interrogation. We used conditional logistic regression and Bonferroni’s correction to identify methylation markers associated with metastasis. In a separate validation cohort (2007), we evaluated the added predictive utility of the methylation score beyond clinical risk score. Among 215 cases and 404 controls, 31 CpG sites were significantly associated with metastasis status. Adding the methylation score to the clinical risk score did not meaningfully improve the c-statistic (0.80-0.81) in the validation cohort, though the score itself was statistically significant (p < 0.01). In the validation cohort, both clinical risk score alone and methylation marker score alone are well calibrated for predicted 10-year metastasis risks. Adding the methylation score to the clinical risk score only marginally improved predictive risk calibration. Our findings do not support the use of these markers to improve clinical risk prediction. The methylation markers identified may inform novel hypothesis in the roles of these genetic regions in metastasis development.
Authors: Chao, Chun R;Slezak, Jeff;Siegmund, Kimberly;Cannavale, Kimberly;Shu, Yu-Hsiang;Chien, Gary W;Chen, Xu-Feng;Shi, Feng;Song, Nan;Van Den Eeden, Stephen K;Huang, Jiaoti
Cancer Med. 2023 Sep;12(18):18837-18849. Epub 2023-09-11.
Declines in colorectal cancer incidence and mortality rates slow among older adults
Authors: Murphy, Caitlin C;Lee, Jeffrey K;Liang, Peter S;May, Folasade P;Zaki, Timothy A
Clin Gastroenterol Hepatol. 2023 Jun 10.
ASGE Guideline on the role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: Summary and Recommendations
This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the diagnosis of malignancy in patients with biliary strictures of undetermined etiology. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and addresses the role of fluoroscopic-guided biopsies, brush cytology, cholangioscopy, and endoscopic ultrasound (EUS) in the diagnosis of malignancy in patients with biliary strictures. In the endoscopic work-up of these patients, we suggest the use of fluoroscopic-guided biopsies in addition to brush cytology over brush cytology alone, especially for hilar strictures. Especially for patients with, non-diagnostic sampling we suggest the use of cholangioscopic and EUS-guided biopsies; the former for non-distal and the latter for distal strictures or those with suspected spread to surrounding lymph nodes and other structures.
Authors: Fujii-Lau, Larissa L;Law, Joanna K;ASGE Standards of Practice Committee Chair (2020-2023),;et al.
Gastrointest Endosc. 2023 Jun 10.
ASGE Guideline on role of endoscopy in the diagnosis of malignancy in biliary strictures of undetermined etiology: Methodology and Review of Evidence
Biliary strictures of undetermined etiology pose a diagnostic challenge for endoscopists. Despite advances in technology, diagnosing malignancy in biliary strictures often requires multiple procedures. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the available literature on strategies used to diagnose undetermined biliary strictures. Using a systematic review and meta-analysis of each diagnostic modality, including fluoroscopic-guided biopsies, brush cytology, cholangioscopy, and endoscopic ultrasound fine needle aspiration or biopsy, the American Society of Gastrointestinal Endoscopy (ASGE) Standards of Practice committee provides this guideline on modalities used to diagnose biliary strictures of undetermined etiology. This document summarizes the methods used in the GRADE analysis to make recommendations, while the “Summary and Recommendations” document contains a concise summary of our findings and final recommendations.
Authors: Fujii-Lau, Larissa L;Law, Joanna K;ASGE Standards of Practice Committee Chair (2020-2023),;et al.
Gastrointest Endosc. 2023 Jun 10.
Adverse Childhood Experiences and Lower Urinary Tract Symptoms and Impact Among Women
This study utilizes CARDIA (Coronary Artery Risk Development in Young Adults) cohort study data to examine whether (1) family-based adverse childhood experiences, recalled by women aged 32 to 47, are associated with lower urinary tract symptoms and their impact, a composite variable with 4 levels (bladder health and mild, moderate, or severe lower urinary tract symptoms/impact), and (2) extensiveness of women’s social networks in adulthood attenuates an association between adverse childhood experiences and lower urinary tract symptoms/impact. In 2000-2001, frequency of adverse childhood experiences exposure was retrospectively assessed. In 2000-2001, 2005-2006, and 2010-2011, extensiveness of social networks was assessed; scores were averaged. In 2012-2013, lower urinary tract symptoms/impact data were collected. Logistic regression analyses examined whether adverse childhood experiences, extensiveness of social networks, and their interaction were associated with lower urinary tract symptoms/impact, adjusting for age, race, education, and parity (n=1,302). Recall of more frequent family-based adverse childhood experiences was associated with report of more lower urinary tract symptoms/impact over 10 years later (OR=1.26, 95% CI=1.07, 1.48). Social networks during adulthood appeared to attenuate the association between adverse childhood experiences and lower urinary tract symptoms/impact (OR=0.64, 95% CI=0.41, 1.02). Among women with less extensive social networks, estimated probability of experiencing moderate or severe lower urinary tract symptoms/impact vs bladder health or mild lower urinary tract symptoms/impact was 0.29 and 0.21 for those reporting an adverse childhood experiences frequency corresponding to more than “a little” vs “rarely or none of the time,” respectively. Among women with more extensive social networks, estimated probabilities were 0.20 and 0.21, respectively. Family-based adverse childhood experiences are related to lower urinary tract symptoms/impact vs bladder health in adulthood. Additional research is needed to corroborate the potentially attenuating effect of social networks.
Authors: Brady, Sonya S; Arguedas, Andrés; Huling, Jared D; Shan, Liang; Lewis, Cora E; Fok, Cynthia S; Van Den Eeden, Stephen K; Markland, Alayne D
J Urol. 2023 Jun;209(6):1167-1175. Epub 2023-02-22.
Private Payer and Medicare Coverage Policies for Use of Circulating Tumor DNA Tests in Cancer Diagnostics and Treatment.
BACKGROUND: Circulating tumor DNA (ctDNA) is used to select initial targeted therapy, identify mechanisms of therapeutic resistance, and measure minimal residual disease (MRD) after treatment. Our objective was to review private and Medicare coverage policies for ctDNA testing. n METHODS: Policy Reporter was used to identify coverage policies (as of February 2022) from private payers and Medicare Local Coverage Determinations (LCDs) for ctDNA tests. We abstracted data regarding policy existence, ctDNA test coverage, cancer types covered, and clinical indications. Descriptive analyses were performed by payer, clinical indication, and cancer type. n RESULTS: A total of 71 of 1,066 total policies met study inclusion criteria, of which 57 were private policies and 14 were Medicare LCDs; 70% of private policies and 100% of Medicare LCDs covered at least one indication. Among 57 private policies, 89% specified a policy for at least 1 clinical indication, with coverage for ctDNA for initial treatment selection most common (69%). Of 40 policies addressing progression, coverage was provided 28% of the time, and of 20 policies addressing MRD, coverage was provided 65% of the time. Non-small cell lung cancer (NSCLC) was the cancer type most frequently covered for initial treatment (47%) and progression (60%). Among policies with ctDNA coverage, coverage was restricted to patients without available tissue or in whom biopsy was contraindicated in 91% of policies. MRD was commonly covered for hematologic malignancies (30%) and NSCLC (25%). Of the 14 Medicare LCD policies, 64% provided coverage for initial treatment selection and progression, and 36% for MRD. n CONCLUSIONS: Some private payers and Medicare LCDs provide coverage for ctDNA testing. Private payers frequently cover testing for initial treatment, especially for NSCLC, when tissue is insufficient or biopsy is contraindicated. Coverage remains variable across payers, clinical indications, and cancer types despite inclusion in clinical guidelines, which could impact delivery of effective cancer care.
Authors: Douglas, Michael P;Ragavan, Meera V;Chen, Cheng;Kumar, Anika;Gray, Stacy W;Blakely, Collin M;Phillips, Kathryn A
J Natl Compr Canc Netw. 2023 Jun;21(6):609-616.e4. doi: 10.6004/jnccn.2023.7011..
Maternal mental health and offspring brain development: An umbrella review of prenatal interventions
The idea that risk for psychiatric disorders may be transmitted intergenerationally via prenatal programming places interest in the prenatal period as a critical moment during which intervention efforts may have a strong impact, yet studies testing whether prenatal interventions also protect offspring are limited. The present umbrella review of systematic reviews and meta-analyses (SRMAs) of randomized controlled trials aimed to synthesize the available evidence and highlight promising avenues for intervention. Overall, the literature provides mixed and limited evidence in support of prenatal interventions. Thirty SRMAs were included. Of the 23 SRMAs that reported on prenatal depression interventions, 16 found a significant effect (average standard mean difference = -0.45, SD = 0.25). Similarly, 13 of the 20 SRMAs that reported on anxiety outcomes documented significant reductions (average standard mean difference = -0.76, SD = 0.95 or -0.53/0.53 excluding one outlier). Only 4 SRMAs reported child outcomes, and only 2 (of 10) analyses showed significant effects of prenatal interventions (massage and telephone support on neonatal resuscitation [relative risk = 0.43] and neonatal intensive care unit admissions [relative risk = 0.91]). Notably missing, perhaps due to our strict inclusion criteria (inclusion of randomized controlled trials only), were interventions focusing on key facets of prenatal health (e.g., whole diet, sleep). Structural interventions (housing, access to health care, economic security) were not included, although initial success has been documented in non-SRMAs. Most notably, none of the SRMAs focused on offspring mental health or neurodevelopmental outcomes. Given the possibility that interventions deployed in this period will positively impact the next generation, randomized trials that focus on offspring outcomes are urgently needed.
Authors: Lugo-Candelas, Claudia; Talati, Ardesheer; Glickman, Caila; Hernandez, Mariely; Scorza, Pamela; Monk, Catherine; Kubo, Ai; Wei, Chiaying; Sourander, Andre; Duarte, Cristiane S
Biol Psychiatry. 2023 May 15;93(10):934-941. Epub 2023-02-06.
CT Use Reduction In Ostensive Ureteral Stone (CURIOUS)
Computed tomography (CT) is performed in over 90% of patients diagnosed with ureteral stones, but only 10% of patients presenting to the emergency department (ED) with acute flank pain are hospitalized for a clinically important stone or non-stone diagnosis. Hydronephrosis can be accurately detected using point-of-care ultrasound and is a key predictor of ureteral stone and risk of subsequent complications. The absence of hydronephrosis is insufficient to exclude a stone. We created a sensitive clinical decision rule to predict clinically important ureteral stones. We hypothesized that this rule could identify patients at low risk for this outcome. We conducted a retrospective cohort study in a random sample of 4000 adults who presented to one of 21 Kaiser Permanente Northern California EDs and underwent a CT for suspected ureteral stone from 1/1/2016 to 12/31/2020. The primary outcome was clinically important stone, defined as stone resulting in hospitalization or urologic procedure within 60 days. We used recursive partition analysis to generate a clinical decision rule predicting the outcome. We estimated the C-statistic (area under the curve), plotted the receiver operating characteristic (ROC) curve for the model, and calculated sensitivity, specificity, and predictive values of the model based on a risk threshold of 2%. Among 4000 patients, 354 (8.9%) had a clinically important stone. Our partition model resulted in four terminal nodes with risks ranging from 0.4% to 21.8%. The area under the ROC curve was 0.81 (95% CI 0.80, 0.83). Using a 2% risk cut point, a clinical decision tree including hydronephrosis, hematuria, and a history of prior stones predicted complicated stones with sensitivity 95.5% (95% CI 92.8%-97.4%), specificity 59.9% (95% CI 58.3%-61.5%), positive predictive value 18.8% (95% CI 18.1%-19.5%), and negative predictive value 99.3% (95% CI 98.8%-99.6%). Application of this clinical decision rule to imaging decisions would have led to 63% fewer CT scans with a miss rate of 0.4%. A limitation was the application of our decision rule only to patients who underwent CT for suspected ureteral stone. Thus, this rule would not apply to patients who were thought to have ureteral colic but did not receive a CT because ultrasound or history were sufficient for diagnosis. These results could inform future prospective validation studies.
Authors: Durant, Edward J; Engelhart, Darcy C; Ma, Annie A; Warton, E Margaret; Arasu, Vignesh A; Bernal, Raymond; Rauchwerger, Adina S; Reed, Mary E; Vinson, David R
Am J Emerg Med. 2023 May;67:168-175. Epub 2023-02-24.
Association of Surgical Timing with Outcomes in Early Stage Lung Cancer
Optimal time to surgery for lung cancer is not well established. We aimed to assess whether time to surgery correlates with outcomes. We assessed patients 18-84 years old who were diagnosed with stage I/II lung cancer at our integrated healthcare system from 2009 to 2019. Time to surgery was defined to start with disease confirmation (imaging or biopsy) prior to the surgery scheduling date. Outcomes of unplanned return to care within 30 days of lung cancer surgery, all-cause mortality, and disease recurrence were compared based on time to surgery before and after 2, 4, and 12 weeks. Of 2861 included patients, 70% were over 65 years old and 61% were female. Time to surgery occurred in 1-2 weeks for 6%, 3-4 weeks for 31%, 5-12 weeks for 58%, and 13-26 weeks for 5% of patients. Patients with time to surgery > 4 (vs. ≤ 4) weeks had greater risk of both death (hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.39) and recurrence (HR 1.33, 95% CI 1.10-1.62). Associations were not statistically significant when dichotomizing time to surgery at 2 or 12 weeks for death (2 week HR 1.23, 95% CI 0.93-1.64; 12 week HR 1.35, 95% CI 0.97-1.88) and recurrence (2 week HR 1.54, 95% CI 0.85-2.80; 12 week HR 2.28, 95% CI 0.80-6.46). Early stage lung cancer patients with time to surgery within 4 weeks experienced lower rates of recurrence. Optimal time to surgical resection may be shorter than previously reported.
Authors: Banks, Kian C; Dusendang, Jennifer R; Schmittdiel, Julie A; Hsu, Diana S; Ashiku, Simon K; Patel, Ashish R; Sakoda, Lori C; Velotta, Jeffrey B
World J Surg. 2023 May;47(5):1323-1332. Epub 2023-01-25.
Test performance metrics for breast, cervical, colon and lung cancer screening: a systematic review
Multiple quality metrics have been recommended to ensure consistent, high-quality execution of screening tests for breast, cervical, colorectal, and lung cancers. However, minimal data exist evaluating the evidence base supporting these recommendations and the consistency of definitions and concepts included within and between cancer types. We performed a systematic review for each cancer type using MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 2010 to April 2020 to identify guidelines from screening programs or professional organizations containing quality metrics for tests used in breast, cervical, colorectal, and lung cancer screening. We abstracted metrics’ definitions, target performance levels, and related supporting evidence for test completeness, adequacy (sufficient visualization or collection), accuracy, and safety. We identified 11 relevant guidelines with 20 suggested quality metrics for breast cancer, 5 guidelines with 9 metrics for cervical cancer, 13 guidelines with 18 metrics for colorectal cancer (CRC), and 3 guidelines with 7 metrics for lung cancer. These included 54 metrics related to adequacy (n = 6), test completeness (n = 3), accuracy (n = 33), and safety (n = 12). Target performance levels were defined for 30 metrics (56%). Ten (19%) were supported by evidence, all from breast and CRC, with no evidence cited to support metrics from cervical and lung cancer screening. Considerably more guideline-recommended test performance metrics exist for breast and CRC screening than cervical or lung cancer. The domains covered are inconsistent among cancers, and few targets are supported by evidence. Clearer evidence-based domains and targets are needed for test performance metrics. PROSPERO 2020 CRD42020179139.
Authors: Selby, Kevin; Corley, Douglas A; et al.
J Natl Cancer Inst. 2023 Apr 11;115(4):375-384.
Provider- and Facility-Level Variation in Pre-Cancerous Cervical Biopsy Diagnoses
Reproducibility of cervical biopsy diagnoses is low and may vary based on where the diagnostic test is performed and by whom. Our objective was to measure multilevel variation in diagnoses across colposcopists, pathologists, and laboratory facilities. We cross-sectionally examined variation in cervical biopsy diagnoses within the 5 sites of the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR I) consortium within levels defined by colposcopists, pathologists, and laboratory facilities. Patients aged 18 to 65 years with a colposcopy with biopsy performed were included, with diagnoses categorized as normal, cervical intraepithelial neoplasia grade 1 (CIN1), grade 2 (CIN2), and grade 3 (CIN3). Using Markov Chain Monte-Carlo methods, we fit mixed-effects logistic regression models for biopsy diagnoses and presented median odds ratios (MORs), which reflect the variability within each level. Median odds ratios can be interpreted as the average increased odds a patient would have for a given outcome (e.g., CIN2 or CIN3 vs normal or CIN1) when switching to a provider with higher odds of diagnosing that outcome. The MOR is always 1 or greater, and a value of 1 indicates no variation in outcome for that level, with higher values indicating greater variation. A total of 130,110 patients were included who received care across 82 laboratory facilities, 2,620 colposcopists, and 489 pathologists. Substantial variation in biopsy diagnoses was found at each level, with the most occurring between laboratory facilities, followed by pathologists and colposcopists. Substantial variation in biopsy diagnoses of CIN2 or CIN3 (vs normal or CIN1) was present between laboratory facilities (MOR: 1.26; 95% credible interval = 1.19-1.36). Improving consistency in cervical biopsy diagnoses is needed to reduce underdiagnosis, overdiagnosis, and unnecessary treatment resulting from variation in cervical biopsy diagnoses.
Authors: Del Vecchio, Natalie J; Corley, Douglas A; Silverberg, Michael; et al.
J Low Genit Tract Dis. 2023 Apr 01;27(2):113-119. Epub 2023-01-17.
Molecular Characteristics of Early-onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison to Later-onset Cases: Molecular Characteristics and Early-onset Colorectal Tumor Subsites
Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management. Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases. The proportions of MSI-high, CIMP-high, and BRAF -mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF -mutated) (all Ptrend <0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors ( P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend <0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend. Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.
Authors: Ugai, Tomotaka; Sakoda, Lori C; Ogino, Shuji; et al.
Am J Gastroenterol. 2023 Apr 01;118(4):712-726. Epub 2022-12-30.
Overall and Annual Post-Colonoscopy Colorectal Cancer Rates in a Large Integrated Healthcare Setting: A Cross-sectional Study
Authors: Lee, Jeffrey K; H-E Kang, James; Merchant, Sophie A; Jensen, Christopher D; Burr, Nicholas E; Corley, Douglas A
Clin Gastroenterol Hepatol. 2023 Mar 23.
Development of cardiometabolic risk factors following endocrine therapy in women with breast cancer
Studies comparing the effect of aromatase inhibitor (AI) and tamoxifen use on cardiovascular disease (CVD) risk factors in hormone-receptor positive breast cancer (BC) survivors report conflicting results. We examined associations of endocrine therapy use with incident diabetes, dyslipidemia, and hypertension. The Pathways Heart Study examines cancer treatment exposures with CVD-related outcomes in Kaiser Permanente Northern California members with BC. Electronic health records provided sociodemographic and health characteristics, BC treatment, and CVD risk factor data. Hazard ratios (HR) and 95% confidence intervals (CI) of incident diabetes, dyslipidemia, and hypertension in hormone-receptor positive BC survivors using AIs or tamoxifen compared with survivors not using endocrine therapy were estimated using Cox proportional hazards regression models adjusted for known confounders. In 8,985 BC survivors, mean baseline age and follow-up time was 63.3 and 7.8 years, respectively; 83.6% were postmenopausal. By treatment, 77.0% used AIs, 19.6% used tamoxifen, and 16.0% used neither. Postmenopausal women who used tamoxifen had an increased rate (HR: 1.43, 95% CI: 1.06-1.92) of developing hypertension relative to those who did not use endocrine therapy. Tamoxifen use was not associated with incident diabetes, dyslipidemia, or hypertension in premenopausal BC survivors. Postmenopausal AI users had higher hazard rates of developing diabetes (HR: 1.37, 95% CI: 1.05-1.80), dyslipidemia (HR: 1.58, 95% CI: 1.29-1.92) and hypertension (HR: 1.50, 95% CI: 1.24-1.82) compared with non-endocrine therapy users. Hormone-receptor positive BC survivors treated with AIs may have higher rates of developing diabetes, dyslipidemia, and hypertension over an average 7.8 years post-diagnosis.
Authors: Rillamas-Sun, Eileen; Kwan, Marilyn L; Iribarren, Carlos; Neugebauer, Romain; Rana, Jamal S; Nguyen-Huynh, Mai; Kushi, Lawrence H; Greenlee, Heather; et al.
Res Sq. 2023 Mar 22.
Leisure time sedentary behaviour and risks of breast, colorectal, and prostate cancer: A Mendelian randomization analysis
Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. We examined potential causal associations between self-reported leisure television watching and computer use and risks of breast, colorectal, and prostate cancer using a two-sample Mendelian randomization framework. Genetic variants were identified from a recent genome-wide association study (GWAS). Cancer data were obtained from cancer GWAS consortia. Additional sensitivity analyses were applied to examine the robustness of the results. A 1-standard deviation increment in hours of television watching increased risk of breast (OR: 1.15, 95% confidence interval [CI]: 1.05,1.26) and colorectal cancer (OR: 1.32, 95%CI: 1.16,1.49) with little evidence of an association for prostate cancer risk. In multivariable models adjusted for years of education, the effect estimates for television watching were attenuated (breast cancer, OR: 1.08, 95%CI: 0.92,1.27; colorectal cancer, OR: 1.08, 95%CI: 0.90,1.31). Post-hoc analyses showed that years of education might have a possible confounding and mediating role in the association between television watching with breast and colorectal cancer. Consistent results were observed by sex (colorectal cancer), anatomical subsites, and cancer subtypes. There was little evidence of associations between computer use and cancer risk. We found evidence of positive associations between hours of television watching and risks of breast and colorectal cancer. However, these findings should be interpreted cautiously given the complex role of education. Future studies using objective measures of exposure can provide new insights into the possible role of sedentary behaviour in cancer development. Evidence from observational studies that examined associations between sedentary behaviours and common cancers is mixed and causality is uncertain. In our Mendelian randomization analyses, higher levels of leisure television watching were found to increase the risks of breast and colorectal cancer, suggesting that the that the promotion of lowering sedentary behaviour time could be an effective strategy in the primary prevention of these commonly diagnosed cancers. Cancer Epidemiology.
Authors: Papadimitriou, Nikos; Sakoda, Lori C; Murphy, Neil; et al.
medRxiv. 2023 Mar 22.
Resiliency among Women’s Health Initiative women aged 80 and older by race, ethnicity, and neighborhood socioeconomic status
A comprehensive examination of resilience by race, ethnicity, and neighborhood socioeconomic status (NSES) among women aged ≥80 is needed, given the aging of the US population, increasing longevity, and growing racial and ethnic diversity. Participants were women aged ≥80 enrolled in the Women’s Health Initiative (WHI). Resilience was assessed with a modified version of the Brief Resilience Scale. Descriptive statistics and multiple linear regression examined the association of demographic, health, and psychosocial variables with resilience by race, ethnicity, and NSES. Participants (n=29,367, median age=84.3) were White (91.4%), Black (3.7%), Hispanic (1.9%), and Asian (1.7%) women. There were no significant differences by race and ethnicity on mean resiliency scores (p=0.06). Significant differences by NSES were observed regarding mean resiliency scores between those with low NSES (3.94±0.83, out of 5) and high NSES (4.00±0.81). Older age, higher education, higher self-rated health, lower stress, and living alone were significant positive correlates of resilience in the sample. Social support was correlated with resilience among White, Black, and Asian women, but not for Hispanic women. Depression was a significant correlate of lower resilience, except among Asian women. Living alone, smoking, and spirituality were significantly associated with higher resilience among women with moderate NSES. Multiple factors were associated with resilience among women aged ≥80 in the WHI. Despite some differing correlates of resilience by race, ethnicity, and NSES, there were many similarities. These results may aid in the design of resilience interventions for the growing, increasingly diverse population of older women.
Authors: Krok-Schoen, Jessica L; Kroenke, Candyce H; Jackson, Rebecca D; et al.
J Gerontol B Psychol Sci Soc Sci. 2023 Mar 18.
TRENDS IN SMOKING-SPECIFIC LUNG CANCER INCIDENCE RATES WITHIN A U.S. INTEGRATED HEALTH SYSTEM, 2007-2018
At least 10% of lung cancers arise in adults who have never smoked. Data remain inconclusive on whether lung cancer incidence has been increasing among never-smoking adults. How have age-adjusted incidence rates of lung cancer changed temporally, especially among never-smoking adults? Trends in lung cancer incidence were examined using linked electronic health record and cancer registry data on a dynamic cohort of adults aged ≥30 years at risk for incident lung cancer between 1/1/2007 and 12/31/2018 from an integrated healthcare system in northern California. Truncated age-adjusted lung cancer incidence rates and average annual percentage change (AAPC) in rates were estimated, overall and separately for ever- and never-smoking adults by age, sex, and race/ethnicity. Our cohort included 3,751,348 (52.5% female; 48.0% non-Hispanic White; 63.1% never-smoking) adults, among whom 18,627 (52.7% female; 68.6% non-Hispanic White; 15.4% never-smoking) were diagnosed with lung cancer. The overall lung cancer incidence rate declined from 91.1 to 63.7 per 100,000 person-years between 2007-2009 and 2016-2018 (AAPC, -3.9%; 95% CI, -4.2%, -3.6%). Among ever-smoking adults, incidence rates declined overall from 167.0 to 113.4 per 100,000 person-years (AAPC, -4.2%; 95% CI, -4.4%, -3.9%) and, to varying degrees, within all age, sex, and racial/ethnic groups. Among never-smoking adults, incidence rates were relatively constant, with three-year period estimates ranging from 19.9 to 22.6 per 100,000 person-years (AAPC, 0.9%; 95% CI, -0.3%, 2.1%). Incidence rates for never-smoking adults appeared stable over time within age, sex, and racial/ethnic groups, except for those of Asian and Pacific Islander (API) origin (AAPC, 2.0%; 95% CI, 0.1%, 3.9%), whose rates were about twice as high compared to their counterparts. These observed trends underscore the need to further elucidate the etiology of lung cancer in never-smoking adults, including why incidence is higher and rising in never-smoking API adults.
Authors: Sakoda, Lori C; Alabaster, Amy; Sumner, Eric T; Gordon, Nancy P; Quesenberry, Charles P; Velotta, Jeffrey B
Chest. 2023 Mar 17.
Quality Indicators for Adolescents and Young Adults with Advanced Cancer: A Modified Delphi Process with Patients, Family Members, and Clinicians
Quality measures have been devised for end-of-life care of older adults with cancer, but are lacking for adolescents and young adults (AYAs). We previously conducted interviews with AYAs, family caregivers, and clinicians to identify priority domains for high quality care of AYAs with advanced cancer. The goal of this study was to use a modified Delphi process to form consensus around the highest priority quality indicators. A modified Delphi process was conducted with 10 AYAs with recurrent or metastatic cancer, 11 family caregivers, and 29 multidisciplinary clinicians, using small group web conferences. Participants were asked to rate the importance of each of 41 potential quality indicators, rank the 10 most important, and engage in discussion to reconcile differences. Of 41 initial indicators, 34 were rated as highly important (rating 7, 8, or 9 on a 9-point scale) by >70% of participants. The panel was unable to reach consensus around the 10 most important indicators. Instead, participants recommended retaining a larger set of indicators to reflect potential for different priorities across the population, resulting in a final set of 32 indicators. Recommended indicators broadly encompassed attention to physical symptoms; quality of life; psychosocial and spiritual care; communication and decision-making; relationships with clinicians; care and treatment; and independence. A patient- and family-centered process for quality indicator development led to strong endorsement of multiple potential indicators by Delphi participants. Further validation and refinement will be performed using a survey of bereaved family members.
Authors: Mack, Jennifer W; Kushi, Lawrence H; Wiener, Lori; et al.
J Pain Symptom Manage. 2023 Mar 16.
Risk-stratified screening for colorectal cancer using genetic and environmental risk factors: A cost-effectiveness analysis based on real-world data
Previous studies on the cost-effectiveness of personalized colorectal cancer (CRC) screening were based on hypothetical performance of CRC risk prediction and did not consider the association with competing causes of death. In this study, we estimated the cost-effectiveness of risk-stratified screening using real-world data for CRC risk and competing causes of death. Risk predictions for CRC and competing causes of death, from a large community-based cohort, were used to stratify individuals into risk groups. A microsimulation model was used to optimize colonoscopy screening for each risk group by varying the start age (40-60 years), end age (70-85 years), and screening interval (5-15 years). The outcomes included personalized screening ages and intervals, and cost-effectiveness compared to uniform colonoscopy screening (ages 45-75, every 10 years). Key assumptions were varied in sensitivity analyses. Risk-stratified screening resulted in substantially different screening recommendations, ranging from a one-time colonoscopy at age 60 for low-risk individuals to a colonoscopy every five years from ages 40-85 for high-risk individuals. Nevertheless, on a population-level, risk-stratified screening would increase net quality adjusted life years gained (QALYG) by only 0.7% at equal costs to uniform screening, or, reduce average costs by 1.2% for equal QALYG. The benefit of risk-stratified screening improved when it was assumed to increase participation or costs less per genetic test. Personalized screening for CRC, accounting for competing causes of death risk, could result in highly tailored individual screening programs. However, average improvements across the population in QALYG and cost-effectiveness compared with uniform screening are small.
Authors: van den Puttelaar, Rosita; Lee, Jeffrey K; Sakoda, Lori C; Corley, Douglas A; Lansdorp-Vogelaar, Iris; et al.
Clin Gastroenterol Hepatol. 2023 Mar 09.
Increased Risk of Hospitalization, Surgery and Venous Thromboembolism Among Patients with Inflammatory Bowel Disease and Malnutrition in a Large, Community-Based Healthcare System
Patients with inflammatory bowel disease (IBD) constitute a high-risk population for malnutrition. Routine screening with standardized tools is recommended but can be challenging. Outcome data specific to IBD are sparse. We performed a retrospective cohort study (2009-2019) and electronically screened a large community-based population with IBD for malnutrition risk by extracting height and longitudinal weight, data elements used in the Malnutrition Universal Screening Tool (MUST). We used Cox Proportional Hazards regression to evaluate whether an electronic medical record (EMR)-derived modified MUST malnutrition risk score was associated with IBD-related hospitalization, surgery, and venous thromboembolism (VTE).Results: Malnutrition risk was categorized as low in 10,844 IBD patients (86.5%), medium in 1135 patients (9.1%), and high in 551 patients (4.4%). In the one year follow up period, medium and high malnutrition risk, compared to low risk, were associated with IBD-related hospitalization (medium risk adjusted HR 1.80, 95% CI 1.34-2.42; high risk adjusted HR 1.90, 95% CI 1.30-2.78) and IBD-related surgery (medium risk adjusted HR 2.28, 95% CI 1.60-3.26; high risk adjusted HR 2.38, 95% CI 1.52-3.73). Only high malnutrition risk was associated with VTE (adjusted HR 2.79, 95% CI 1.33-5.87). Malnutrition risk is significantly associated IBD-related hospitalization, surgery, and venous thromboembolism. Application of the MUST score to the EMR can efficiently identify patients at risk for malnutrition and adverse outcomes, permitting concentration of nutritional and non-nutritional resources to those at greatest risk.
Authors: Fine, Liat S; Zhu, Shiyun; Shirazi, Aida; Lee, Jeffrey K; Velayos, Fernando S
Am J Gastroenterol. 2023 Mar 09.
Validation of a genetic-enhanced risk prediction model for colorectal cancer in a large community-based cohort
Polygenic risk scores (PRS) which summarize individuals’ genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance. The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group). In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91-1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71-0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity. The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort. The proposed model has potential utility in risk-stratified colorectal cancer prevention.
Authors: Su, Yu-Ru; Sakoda, Lori C; Lee, Jeffrey K; Corley, Douglas A; Hsu, Li; et al.
Cancer Epidemiol Biomarkers Prev. 2023 Mar 06;32(3):353-362.
Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation and immune response
Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. These findings can guide potential prevention treatments.
Authors: Carreras-Torres, Robert; Sakoda, Lori C; Gauderman, W James; et al.
Cancer Epidemiol Biomarkers Prev. 2023 Mar 06;32(3):315-328.
Dietary inflammatory and insulinemic potential, risk of hepatocellular carcinoma and chronic liver disease mortality
Diet modulates inflammation and insulin response and may be an important modifiable factor in the primary prevention of hepatocellular carcinoma (HCC) and chronic liver disease (CLD). We developed the empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores to assess the inflammatory and insulinemic potentials of diet. We prospectively examined the associations of EDIP and EDIH at baseline with the following HCC risk and CLD mortality. We followed 485 931 individuals in the National Institutes of Health-American Association of Retired Persons Diet and Health Study since 1995. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). We confirmed 635 incident HCC cases and 993 CLD deaths. Participants in the highest compared with those in the lowest EDIP quartile had a 1.35 times higher risk of developing HCC (95% CI = 1.08 to 1.70, Ptrend = .0005) and a 1.70 times higher CLD mortality (95% CI = 1.41 to 2.04, Ptrend < .0001). For the same comparison, participants with the highest EDIH were at increased risk of HCC (HR = 1.53, 95% CI = 1.20 to 1.95, Ptrend = .0004) and CLD mortality (HR = 1.72, 95% CI = 1.42 to 2.01, Ptrend < .0001). Similar positive associations of scores with HCC risk and CLD mortality were observed for both women and men. Moreover, individuals in both the highest EDIP and EDIH tertiles had a 92% increased HCC risk (95% CI = 1.43 to 2.58) and 98% increased CLD mortality (95% CI = 1.27 to 3.08) compared with those in both lowest tertiles. Our findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking diet to HCC development and CLD mortality.
Authors: Long, Lu; Lee, Jeffrey K; Zhang, Xuehong; et al.
JNCI Cancer Spectr. 2023 Mar 01;7(2).
A novel smartphone application for the informal caregivers of cancer patients: Usability study
Informal caregivers are a critical source of support for cancer patients. However, their perspectives are not routinely collected, despite health impacts related to the burden of caregiving. We created the TOGETHERCare smartphone application (app) to collect observer-reported outcomes regarding the cancer patient’s health and caregiver’s perceptions of their own mental and physical health, and to provide tips and resources for self-care and patient care. We enrolled 54 caregivers between October 2020 and March 2021 from Kaiser Permanente Northern California (KPNC), an integrated healthcare system. Fifty caregivers used the app for approximately 28 days. Usability and acceptability were assessed using questions from the Mobile App Rating Scale (MARS), the System Usability Scale (SUS), the Net Promoter Score (NPS), and semi-structured interviews. The caregivers’ mean age was 54.4 years, 38% were female and 36% were non-White. The SUS total mean score was 83.4 (SD = 14.2), for a percentile rank of 90-95 (“excellent”). Median MARS responses to the functionality questions were also high. The NPS score of 30 at the end of the study indicated that most caregivers would recommend the app. Themes from semi-structured interviews were consistent across the study period and indicated that the app was easy to use and helpful. Caregivers indicated a need for feedback from the app, suggested some changes to the wording of questions, the app’s visuals, and timing of notifications. This study demonstrated that caregivers are willing to complete frequent surveys about themselves and their patients. The app is unique because it provides a remote method to collect caregivers’ observations about the patient that may be useful for clinical care. To our knowledge, TOGETHERCare is the first mobile app developed specifically to capture adult cancer patient symptoms from the informal caregiver’s perspective. Future research will examine whether use of this app can help improve patient outcomes.
Authors: Oakley-Girvan, Ingrid; Yunis, Reem; Fonda, Stephanie J; Neeman, Elad; Liu, Raymond; Aghaee, Sara; Ramsey, Maya E; Kubo, Ai; Davis, Sharon W
PLOS Digit Health. 2023 Mar;2(3):e0000173. Epub 2023-03-03.
Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases
The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.
Authors: Ugai, Tomotaka; Sakoda, Lori C; Ogino, Shuji; et al.
J Gastroenterol. 2023 Mar;58(3):229-245. Epub 2023-01-17.
Association of Inflammatory Biomarkers With Survival Among Patients With Stage III Colon Cancer
The association of chronic inflammation with colorectal cancer recurrence and death is not well understood, and data from large well-designed prospective cohorts are limited. To assess the associations of inflammatory biomarkers with survival among patients with stage III colon cancer. This cohort study was derived from a National Cancer Institute-sponsored adjuvant chemotherapy trial Cancer and Leukemia Group B/Southwest Oncology Group 80702 (CALGB/SWOG 80702) conducted between June 22, 2010, and November 20, 2015, with follow-up ending on August 10, 2020. A total of 1494 patients with plasma samples available for inflammatory biomarker assays were included. Data were analyzed from July 29, 2021, to February 27, 2022. Plasma inflammatory biomarkers (interleukin 6 [IL-6], soluble tumor necrosis factor α receptor 2 [sTNF-αR2], and high-sensitivity C-reactive protein [hsCRP]; quintiles) that were assayed 3 to 8 weeks after surgery but before chemotherapy randomization. The primary outcome was disease-free survival, defined as time from randomization to colon cancer recurrence or death from any cause. Secondary outcomes were recurrence-free survival and overall survival. Hazard ratios for the associations of inflammatory biomarkers and survival were estimated via Cox proportional hazards regression. Of 1494 patients (median follow-up, 5.9 years [IQR, 4.7-6.1 years]), the median age was 61.3 years (IQR, 54.0-68.8 years), 828 (55.4%) were male, and 327 recurrences, 244 deaths, and 387 events for disease-free survival were observed. Plasma samples were collected at a median of 6.9 weeks (IQR, 5.6-8.1 weeks) after surgery. The median plasma concentration was 3.8 pg/mL (IQR, 2.3-6.2 pg/mL) for IL-6, 2.9 × 103 pg/mL (IQR, 2.3-3.6 × 103 pg/mL) for sTNF-αR2, and 2.6 mg/L (IQR, 1.2-5.6 mg/L) for hsCRP. Compared with patients in the lowest quintile of inflammation, patients in the highest quintile of inflammation had a significantly increased risk of recurrence or death (adjusted hazard ratios for IL-6: 1.52 [95% CI, 1.07-2.14]; P = .01 for trend; for sTNF-αR2: 1.77 [95% CI, 1.23-2.55]; P < .001 for trend; and for hsCRP: 1.65 [95% CI, 1.17-2.34]; P = .006 for trend). Additionally, a significant interaction was not observed between inflammatory biomarkers and celecoxib intervention for disease-free survival. Similar results were observed for recurrence-free survival and overall survival. This cohort study found that higher inflammation after diagnosis was significantly associated with worse survival outcomes among patients with stage III colon cancer. This finding warrants further investigation to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes. ClinicalTrials.gov Identifier: NCT01150045.
Authors: Cheng, En; Caan, Bette J; Cespedes Feliciano, Elizabeth M; Meyerhardt, Jeffrey A; et al.
JAMA Oncol. 2023 Mar 01;9(3):404-413.
Long-term Trajectories of Physical Function Decline in Women With and Without Cancer
Patients with cancer experience acute declines in physical function, hypothesized to reflect accelerated aging driven by cancer-related symptoms and effects of cancer therapies. No study has examined long-term trajectories of physical function by cancer site, stage, or treatment compared with cancer-free controls. Examine trajectories of physical function a decade before and after cancer diagnosis among older survivors and cancer-free controls. This prospective cohort study enrolled patients from 1993 to 1998 and followed up until December 2020. The Women’s Health Initiative, a diverse cohort of postmenopausal women, included 9203 incident cancers (5989 breast, 1352 colorectal, 960 endometrial, and 902 lung) matched to up to 5 controls (n = 45 358) on age/year of enrollment and study arm. Cancer diagnosis (site, stage, and treatment) via Medicare and medical records. Trajectories of self-reported physical function (RAND Short Form 36 [RAND-36] scale; range: 0-100, higher scores indicate superior physical function) estimated from linear mixed effects models with slope changes at diagnosis and 1-year after diagnosis. This study included 9203 women with cancer and 45 358 matched controls. For the women with cancer, the mean (SD) age at diagnosis was 73.0 (7.6) years. Prediagnosis, physical function declines of survivors with local cancers were similar to controls; after diagnosis, survivors experienced accelerated declines relative to controls, whose scores declined 1 to 2 points per year. Short-term declines in the year following diagnosis were most severe in women with regional disease (eg, -5.3 [95% CI, -6.4 to -4.3] points per year in regional vs -2.8 [95% CI, -3.4 to -2.3] for local breast cancer) or who received systemic therapy (eg, for local endometrial cancer, -7.9 [95% CI, -12.2 to -3.6] points per year with any chemotherapy; -3.1 [95% CI, -6.0 to -0.3] with radiation therapy alone; and -2.6 [95% CI, -4.2 to -1.0] with neither, respectively). While rates of physical function decline slowed in the later postdiagnosis period (eg, women with regional colorectal cancer declined -4.3 [95% CI, -5.9 to -2.6] points per year in the year following diagnosis vs -1.4 [95% CI, -1.7 to -1.0] points per year in the decade thereafter), survivors had estimated physical function significantly below that of age-matched controls 5 years after diagnosis. In this prospective cohort study, survivors of cancer experienced accelerated declines in physical function after diagnosis, and physical function remained below that of age-matched controls even years later. Patients with cancer may benefit from supportive interventions to preserve physical functioning.
Authors: Cespedes Feliciano, Elizabeth M; Quesenberry, Charles; Caan, Bette J; Anderson, Garnet L; et al.
JAMA Oncol. 2023 Mar 01;9(3):395-403.
Post-Colonoscopy Colorectal Cancer Etiologies in a Large Integrated US Health Care Setting
Authors: Leung, Lawrence Jun; Lee, Jeffrey K; Merchant, Sophie A; Jensen, Christopher D; Alam, Asim; Corley, Douglas A
Gastroenterology. 2023 Mar;164(3):470-472.e3. Epub 2022-12-01.
Pregnancy attempts among adolescent and young adult cancer survivors
To examine whether demographic and cancer-related characteristics and factors such as fertility discussion with a medical provider and fertility preservation use are associated with attempting pregnancy after adolescent and young adult cancer. Cross-sectional online survey. Not applicable. Women with lymphoma, breast cancer, thyroid cancer, or gynecologic cancer diagnosed at 15-39 years from 2004 to 2016 were identified from the North Carolina Cancer Registry and the Kaiser Permanente Northern and Southern California health care systems and responded to an online survey addressing survivorship concerns, including fertility and reproductive outcomes. Demographic characteristics, cancer characteristics, fertility discussion with a medical provider or fertility specialist between cancer diagnosis and starting cancer treatment, use of fertility preservation strategies (freezing embryos or oocytes) after cancer diagnosis. Pregnancy attempt after cancer diagnosis, defined by either a pregnancy or 12 months of trying to become pregnant without pregnancy. Among 801 participants who had not reached their desired family size at diagnosis, 77% had a fertility discussion with any medical provider between cancer diagnosis and treatment initiation, and 8% used fertility preservation after cancer diagnosis. At survey (median =7 years after diagnosis; interquartile range, 4-10), 32% had attempted pregnancy. Neither fertility discussion with any medical provider nor fertility counseling with a fertility specialist was significantly associated with pregnancy attempts. However, the use of fertility preservation was significantly associated with attempting pregnancy (prevalence ratios = 1.74; 95% confidence interval: 1.31-2.32). Other characteristics positively associated with pregnancy attempts included younger age at diagnosis, longer time since diagnosis, having a partner (at diagnosis or at survey), and having a history of infertility before cancer diagnosis. Use of fertility preservation strategies was uncommon in our cohort but was associated with attempting pregnancy after cancer. Ensuring access to fertility preservation methods may help adolescent and young adult cancer survivors to plan and initiate future fertility.
Authors: Anderson, Chelsea; Fitz, Victoria; Deal, Allison; Getahun, Darios; Kwan, Marilyn L; Mersereau, Jennifer E; Kushi, Lawrence H; Chao, Chun R; Nichols, Hazel B
Fertil Steril. 2023 Mar;119(3):475-483. Epub 2022-12-17.
Neighborhood Racial and Economic Privilege and Timing of Pubertal Onset in Girls
Early puberty is associated with adverse health outcomes over the life course, and Black and Hispanic girls experience puberty earlier than girls of other racial/ethnic backgrounds. Neighborhood racial and economic privilege may contribute to these disparities by conferring differential exposure to mechanisms (e.g., stress, obesity, endocrine disruptors) underlying early puberty. We examined associations between neighborhood privilege, measured by the Index of Concentration at the Extremes (ICE), and age at pubic hair onset (pubarche) and breast development onset (thelarche) in a large multiethnic cohort. A cohort of 46,299 girls born 2005-2011 at Kaiser Permanente Northern California medical facilities were followed until 2021. Pubertal development was assessed routinely by pediatricians using the Sexual Maturity Rating scale. ICE quintiles for race/ethnicity, income, and income + race/ethnicity were calculated using American Community Survey 2010 5-year estimates and linked to census tract at birth. We fit multilevel Weibull regression models accommodating left, right, and interval censoring for all analyses. ICE measures were monotonically associated with pubertal onset, with the strongest associations observed for ICE-race/ethnicity. Adjusting for maternal education, age at delivery, and parity, girls from the least versus most privileged ICE-race/ethnicity quintiles were at increased risk for earlier pubarche (hazard ratio: 1.30, 95% confidence interval: 1.21, 1.38) and thelarche (hazard ratio: 1.45, 95% confidence interval: 1.36, 1.54). These associations remained significant after adjusting for girls’ race/ethnicity and childhood body mass index. Additionally, adjustment for ICE partially attenuated Black-White and Hispanic-White disparities in pubertal onset. Neighborhood privilege may contribute to pubertal timing and related disparities.
Authors: Acker, Julia; Mujahid, Mahasin; Aghaee, Sara; Gomez, Scarlett; Shariff-Marco, Salma; Chu, Brandon; Deardorff, Julianna; Kubo, Ai
J Adolesc Health. 2023 Mar;72(3):419-427. Epub 2022-12-15.
Natural history of multiple recurrences in intermediate-risk non-muscle invasive bladder cancer: lessons from a prospective cohort
To describe the risk of multiple recurrences in intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) and their impact on progression. Prognostic studies of IR-NMIBC have focused on initial recurrences, yet little is known about subsequent recurrences and their impact on progression. IR-NMIBC patients from the Be-Well Study, a prospective cohort study of NMIBC patients diagnosed from 2015 to 2019 at Kaiser Permanente Northern California, were identified. The frequency of first, second, and third intravesical recurrences of urothelial carcinoma were characterized using conditional Kaplan-Meier analyses and random-effects shared-frailty models. The association of multiple recurrences with progression was examined. In 291 patients with IR-NMIBC (median follow-up 38 months), the 5-year risk of initial recurrence was 54.4%. After initial recurrence (n = 137), 60.1% of patients had a second recurrence by 2 years. After second recurrence (n = 70), 51.5% of patients had a third recurrence by 3 years. In multivariable analysis, female sex (Hazard Ratio 1.51, P< .01), increasing tumor size (HR 1.14, P< .01) and number of prior recurrences (HR 1.24, P< .01) were associated with multiple recurrences; whereas maintenance BCG (HR 0.66, P = .03) was associated with reduced recurrences. The 5-year risk of progression varied significantly (P< .01) by number of recurrences: 9.5%, 21.9%, and 37.9% for patients with 1, 2, and 3+ recurrences, respectively. Multiple recurrences are common in IR-NMIBC and are associated with progression. Female sex, larger tumors, number of prior recurrences, and lack of maintenance BCG were associated with multiple recurrences. Multiple recurrences may prove useful as a clinical trial endpoint for IR-NMIBC.
Authors: Sharma, Vidit; Kushi, Lawrence H; Quesenberry, Charles P; Kwan, Marilyn L; et al.
Urology. 2023 Mar;173:134-141. Epub 2022-12-24.
Change in four measures of physical function among older adults during lung cancer treatment: A mixed methods cohort study.
INTRODUCTION: Functional outcomes during non-small cell lung cancer (NSCLC) treatment are critically important to older adults. Yet, data on physical function and which measures best capture functional change remain limited. n MATERIALS AND METHODS: This multisite, mixed methods cohort study recruited adults ≥65 years with advanced NSCLC starting systemic treatment (i.e., chemotherapy, immunotherapy, and/or targeted therapy) with non-curative intent. Participants underwent serial geriatric assessments prior to starting treatment and at one, two, four, and six months, which included the Karnofsky Performance Scale (KPS, range: 0-100%), instrumental activities of daily living (IADL, range: 0-14), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Physical Functioning subscale (EORTC QLQ-C30 PF, range: 0-100), and Life-Space Assessment (LSA, range: 0-120). For all measures, higher scores represent better functioning. In a qualitative substudy, 20 patients completed semi-structured interviews prior to starting treatment and at two and six months to explore how treatment affected their daily functioning. We created joint displays for each interview participant that integrated their longitudinal KPS, IADL, EORTC QLQ-C30 PF, and LSA scores with patient quotes describing their function. n RESULTS: Among 87 patients, median age was 73 years (range 65-96). Mean pretreatment KPS score was 79% (standard deviation [SD] 13), EORTC QLQ-C30 PF was 69 (SD 23), and LSA was 67 (SD 28); median IADL was 13 (interquartile range [IQR] 10-14). At two months after treatment initiation, 70% of patients experienced functional decline on at least one measure, with only 13% of these patients recovering at six months. At two and six months, decline in LSA was the most common (48% and 35%, respectively). Joint displays revealed heterogeneity in how well each quantitative measure of physical function captured the qualitative patient experience. n DISCUSSION: Functional decline during NSCLC treatment is common among older adults. LSA is a useful measure to detect subtle functional decline that may be missed by other measures. Given heterogeneity in how well each quantitative measure captures changes in physical function, there is value to including more than one functional measure in geriatric oncology research studies.
Authors: Singhal, Surbhi;Mohile, Supriya G;Wong, Melisa L;et al.
J Geriatr Oncol. 2023 Mar;14(2):101366. doi: 10.1016/j.jgo.2022.08.015. Epub 2022 Sep 1.
Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry
Genetic factors play an important role in prostate cancer (PCa) susceptibility. To discover common genetic variants contributing to the risk of PCa in men of African ancestry. We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry. Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4). This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.
Authors: Chen, Fei; Van Den Eeden, Stephen K; Haiman, Christopher A; et al.
Eur Urol. 2023 Feb 27.
Impact of Racial/Ethnic Discrimination on Quality of Life among Breast Cancer Survivors: The Pathways Study
Although racial/ethnic disparities in health-care access, treatment, and cancer outcomes are well documented, the impact of racial/ethnic discrimination on cancer survivorship is unclear. We examined associations between quality of life (QoL) and self-reported discrimination among 3,991 women with breast cancer recruited during 2006-2013 from the Pathways Study in the Kaiser Permanente Northern California integrated health-care system, using linear regression models. Overall, 31% of women reported experiencing racial/ethnic discrimination, with differences by race/ethnicity (82% among non-Hispanic Black women vs. 19% among non-Hispanic White women) and nativity (40% among foreign-born Hispanic women vs. 76% among US-born Asian-American women). Experiencing racial/ethnic discrimination was associated with lower QoL in fully adjusted models. The mean QoL score was 119.6 (95% confidence interval (CI): 102.0, 137.1) for women who did not report discrimination, 115.5 (95% CI: 98.0, 133.0) for those who reported some discrimination/less than the median level, and 110.2 (95% CI: 92.7, 127.7) for those who reported more discrimination/greater than or equal to the median level. Discrimination was associated with lower QoL among women who used passive coping strategies or lived in neighborhoods with high neighborhood socioeconomic status, neighborhoods with high levels of segregation, or non-ethnic enclaves. Among breast cancer survivors, clinically meaningful differences in QoL scores were associated with racial/ethnic discrimination. Additional studies are needed to understand potential pathways through which these social factors affect survivorship outcomes.
Authors: Shariff-Marco, Salma; Sangaramoorthy, Meera; Ellis, Libby; Thomsen, Catherine; Roh, Janise M; Kroenke, Candyce; Valice, Emily; Kwan, Marilyn L; Ambrosone, Christine; Kushi, Lawrence; Gomez, Scarlett Lin
Am J Epidemiol. 2023 Feb 24;192(3):367-376.
Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis
Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
Authors: Watts, Eleanor L; Schaefer, Catherine A; Van Den Eeden, Stephen K; Travis, Ruth C; et al.
Int J Epidemiol. 2023 Feb 08;52(1):71-86.
Body Mass Index and Molecular Subtypes of Colorectal Cancer
Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease. We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables. Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control). In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.
Authors: Murphy, Neil; Sakoda, Lori C; Campbell, Peter T; et al.
J Natl Cancer Inst. 2023 Feb 08;115(2):165-173.
Successful Design and Implementation of a POEM Program for Achalasia in an Integrated Healthcare System
Per Oral Endoscopic Myotomy (POEM) is a minimally invasive treatment for achalasia with results comparable to laparoscopic Heller myotomy (LHM). Studies have described the development of proficiency for endoscopists learning to perform POEM, and societies have defined educational and technical objectives for advanced endoscopy fellows in training. However, there is limited guidance on the organizational strategy and educational plan necessary to develop an achalasia service with POEM expertise. We aim to outline the steps for design and implementation of a successful POEM program. We reported our experience developing a multi-disciplinary clinical program for POEM and the steps taken to achieve procedural proficiency. We also reported our technical success (successful tunneling into the gastric cardia and myotomy of LES muscle fibers) and clinical success (post-procedure Eckardt score ≤ 3) at 3-6 months and 12 months post-procedure. Adverse events were classified per the ASGE lexicon for endoscopic adverse events. After creating a multi-disciplinary clinical program for achalasia and completing procedural proficiency for POEM, our technical success rate was 100% and clinical success rate 90% for the first 41 patients. One adverse event (2.4%) occurred, moderate in severity per the American Society of Gastrointestinal Endoscopy (ASGE) lexicon for adverse endoscopic events. In this study, we outlined the steps involved to establish a POEM service in a large integrated healthcare system. Prior competency in interventional endoscopy, procedural training models, POEM observation and education, proctorship, and interdisciplinary patient care are recommended.
Authors: Leung, Lawrence Jun; Ma, Gene K; Lee, Jeffrey K; Fukami, Norio; Chang, Howard; Svahn, Jonathan; Xu, Ming-Ming; Lam, Steven; Risbud, Amita; Jue, Terry L
Dig Dis Sci. 2023 Feb 01:1-9.
Association of Long-term Exposure to Particulate Air Pollution With Cardiovascular Events in California
Long-term exposure to fine particulate air pollution (PM2.5) is a known risk factor for cardiovascular events, but controversy remains as to whether the current National Ambient Air Quality Standard (12 μg/m3 for 1-year mean PM2.5) is sufficiently protective. To evaluate the associations between long-term fine particulate air pollution and cardiovascular events using electronic health record and geocoded address data. This retrospective cohort study included adults in the Kaiser Permanente Northern California integrated health care system during 2007 to 2016 and followed for up to 10 years. Study participants had no prior stroke or acute myocardial infarction (AMI), and lived in Northern California for at least 1 year. Analyses were conducted January 2020 to December 2022. Long-term exposure to PM2.5. Individual-level time-varying 1-year mean PM2.5 exposures for every study participant were updated monthly from baseline through the end of follow-up, accounting for address changes. Incident AMI, ischemic heart disease (IHD) mortality, and cardiovascular disease (CVD) mortality. Cox proportional hazards models were fit with age as time scale, adjusted for sex, race and ethnicity, socioeconomic status, smoking, body mass index, baseline comorbidities, and baseline medication use. Associations below the current regulation limit were also examined. The study cohort included 3.7 million adults (mean [SD] age: 41.1 [17.2] years; 1 992 058 [52.5%] female, 20 205 [0.5%] American Indian or Alaskan Native, 714 043 [18.8%] Asian, 287 980 [7.6%] Black, 696 796 [18.4%] Hispanic, 174 261 [4.6%] multiracial, 1 904 793 [50.2%] White). There was a 12% (95% CI, 7%-18%) increased risk of incident AMI, a 21% (95% CI, 13%-30%) increased risk of IHD mortality, and an 8% (95% CI, 3%-13%) increased risk of CVD mortality associated with a 10 μg/m3 increase in 1-year mean PM2.5. PM2.5 exposure at moderate concentrations (10.0 to 11.9 μg/m3) was associated with increased risks of incident AMI (6% [95% CI, 3%-10%]) and IHD mortality (7% [95% CI, 2%-12%]) compared with low concentrations (less than 8 μg/m3). In this study, long-term PM2.5 exposure at moderate concentrations was associated with increased risks of incident AMI, IHD mortality, and CVD mortality. This study’s findings add to the evidence that the current regulatory standard is not sufficiently protective.
Authors: Alexeeff, Stacey E; Deosaransingh, Kamala; Van Den Eeden, Stephen; Schwartz, Joel; Liao, Noelle S; Sidney, Stephen
JAMA Netw Open. 2023 Feb 01;6(2):e230561. Epub 2023-02-01.
Association between dietary inflammatory potential and mortality after cancer diagnosis in the Women’s Health Initiative
Chronic inflammation is implicated in cancer prognosis and can be modulated by diet. We examined associations between post-diagnosis dietary inflammatory potential and mortality outcomes among post-menopausal women diagnosed with cancer in the Women’s Health Initiative (WHI). Energy-adjusted dietary inflammatory index scores (E-DII) were calculated from dietary and supplemental intake data collected on the first food frequency questionnaire following the diagnosis of primary invasive cancer for 3434 women in the WHI. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for risk of death from any cause, cancer, cardiovascular disease (CVD) and other causes by post-diagnosis quartiles of E-DII. Subgroup analyses by cancer stage and grade were performed. There were 1156 deaths after a median 13 years of follow-up from the date of a cancer diagnosis. In the multivariable-adjusted analyses, a more anti-inflammatory diet plus supplements after cancer diagnosis was associated with lower all-cause mortality, cancer mortality, CVD mortality and mortality from other causes with HRsQ1vs.Q4 ranging from 0.47 to 0.68 (all P-trends < 0.05). Associations were stronger for cancers diagnosed at more distant stages or moderately differentiated grades. A more anti-inflammatory diet plus supplements after a cancer diagnosis may improve survival for post-menopausal cancer survivors.
Authors: Zheng, Jiali; Tabung, Fred K; Zhang, Jiajia; Caan, Bette; Hebert, James R; Kroenke, Candyce H; Ockene, Judith; Shivappa, Nitin; Steck, Susan E
Br J Cancer. 2023 Feb;128(4):606-617. Epub 2022-12-08.
Gaps in the screening process for women diagnosed with cervical cancer in four diverse US health care settings
Potential care gaps in the cervical cancer screening process among women diagnosed with cervical cancer in an era with increased human papillomavirus (HPV) testing have not been extensively evaluated. Women diagnosed with cervical cancer between ages 21 and 65 at four study sites between 2010 and 2014 were included. Screening histories were ascertained from 0.5 to 4 years prior to cervical cancer diagnosis. We identified potential care gaps in the screening history for each woman and classified them into one of three mutually exclusive types: lack of a screening test, screening test failure, and diagnostic/treatment care gap. Distributions of care gaps were tabulated by stage, histology, and study site. Multivariable nominal logistic regression was used to examine the associations between demographic and cancer characteristics and type of care gap. Of 499 women evaluated, 46% lacked a screening test in the time window examined, 31% experienced a screening test failure, and 22% experienced a diagnostic/treatment care gap. More than half of the women with advanced cancer and squamous cell carcinoma lacked a screening test compared to 31% and 24% of women with localized cancer and adenocarcinoma, respectively. Women aged 21-29 at diagnosis were more likely to experience screening test failure and diagnostic/treatment care gap, while those aged 50-65 were more likely to lack a screening test, compared to women aged 30-39. Our findings demonstrate a continuing need to develop interventions targeting unscreened and under-screened women and improve detection and diagnosis of adenocarcinoma in women undergoing cervical cancer screening and diagnostic follow-up.
Authors: Chao, Chun R; Silverberg, Michael J; Corley, Douglas A; Wheeler, Cosette M; et al.
Cancer Med. 2023 Feb;12(3):3705-3717. Epub 2022-09-15.
Characterizing mechanism-based pain phenotypes in patients with chronic pancreatitis: a cross-sectional analysis of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies
Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.
Authors: Saloman, Jami L; Van Den Eeden, Stephen K; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer,; et al.
Pain. 2023 Feb 01;164(2):375-384. Epub 2022-06-07.
Biopsy of Non-tumor Sites After Biopsy of a Colorectal Cancer is not Associated With Metachronous Cancers: A Case-control Study
Recent research has demonstrated biologic plausibility for iatrogenic tumor seeding via colonoscopy as a cause of metachronous colorectal cancers (CRC). This study evaluated the association between biopsy of non-tumor sites after CRC biopsy and risk of metachronous CRC in a large community-based health care organization. This was a retrospective case-control study of adults with an initial CRC diagnosed by colonoscopy between January 2006 and June 2018 who underwent curative resection. Cases developed a second primary (metachronous) CRC diagnosed 6 months to 4 years after the initial CRC, and were matched by age, sex, diagnosis of inflammatory bowel disease, race, and ethnicity with up to 5 controls without a second CRC diagnosis. The exposure was biopsy in the colonic segment of the metachronous CRC (or corresponding segment in controls) after tumor biopsy, ascertained with blinding to case status. Associations were evaluated using conditional logistic regression and adjusted for potential cofounders. Among 14,119 patients diagnosed with an initial CRC during colonoscopy, 107 received a second CRC diagnosis. After exclusions for recurrent or synchronous CRC, 45 cases and 212 controls were included. There was no significant association between biopsy of non-tumor sites after initial CRC biopsy and risk of metachronous CRC in the segment of the additional biopsy site (adjusted odds ratio, 2.29; 95% confidence interval, 0.77-6.81). Metachronous cancers are not significantly associated with biopsy of non-tumor sites after biopsy of the primary cancer. Although the sample size does not allow definite exclusion of any association, these findings do not support iatrogenic tumor seeding as a common risk factor for metachronous CRC.
Authors: Lam, Angela Y; Lee, Jeffrey K; Merchant, Sophie; Jensen, Christopher D; Sedki, Mai; Corley, Douglas A
Clin Gastroenterol Hepatol. 2023 Feb;21(2):487-496.e3. Epub 2022-05-26.
A prospective study of lifestyle factors and bone health in breast cancer patients who received aromatase inhibitors in an integrated healthcare setting
Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture. Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37). Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy. Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies.
Authors: Kwan, Marilyn L; Lo, Joan C; Laurent, Cecile A; Roh, Janise M; Tang, Li; Ambrosone, Christine B; Kushi, Lawrence H; Quesenberry, Charles P; Yao, Song
J Cancer Surviv. 2023 Feb;17(1):139-149. Epub 2021-02-09.
Impact of a Comprehensive Financial Resource on Financial Toxicity in a National, Multiethnic Sample of Adult, Adolescent/Young Adult, and Pediatric Patients With Cancer.
PURPOSE: Financial toxicity is a well-recognized problem for patients with cancer. However, a crucial gap remains in describing and implementing mitigation strategies. We conducted a national survey of a multiethnic adolescent/pediatric and adult patient population served by Family Reach, a nonprofit organization focused on removing financial barriers to cancer care, to evaluate the impact of a comprehensive financial resource on patient-reported financial toxicity. n METHODS: An electronic survey was administered to characterize patients’ current financial health and the impact of Family Reach’s resources on financial toxicity. The survey was e-mailed to all patients or caregivers who received resources from Family Reach between January 1, 2020, and June 30, 2020. Factors associated with higher financial stress and higher potential impact of resources on financial burden were evaluated through separate multivariate regression models. Qualitative responses were analyzed using manual coding and thematic analysis. n RESULTS: Three hundred thirty socioeconomically and racially diverse respondents (overall response rate 40%; 46% non-Hispanic White; 48% with incomes below the federal poverty line) completed the survey and were included in the analysis. More than half of respondents reported high financial stress in the previous week. Hispanic ethnicity, Black race, and low annual household income were associated with higher financial toxicity. A greater amount of financial assistance was associated with a higher confidence rating that resources provided would decrease financial stress. In open-ended comments, respondents highlighted the impact of the COVID-19 pandemic and resulting job loss on financial toxicity, the importance of financial navigation, the benefits of financial assistance, and anxiety about long-term financial health. n CONCLUSION: A comprehensive financial resource, particularly financial assistance, alleviated financial toxicity in a multiethnic national sample of patients with cancer. Ongoing work is critical to address sustainable funding sources and financial navigation to support patients during treatment and survivorship.
Authors: Ragavan, Meera V;Mora, Rosa V;Winder, Kate;Incudine, Andrea;Cunningham, Rosie;Stivers, Tom;Borno, Hala T
JCO Oncol Pract. 2023 Feb;19(2):e286-e297. doi: 10.1200/OP.22.00350. Epub 2022 Nov 15.
Whole exome sequencing and replication for breast cancer among Hispanic/Latino women identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer
Breast cancer (BC) is one of the most common cancers globally. Genetic testing can facilitate screening and risk-reducing recommendations, and inform use of targeted treatments. However, genes included in testing panels are from studies of European-ancestry participants. We sequenced Hispanic/Latina (H/L) women to identify BC susceptibility genes. We conducted a pooled BC case-control analysis in H/L women from the San Francisco Bay area, Los Angeles County, and Mexico (4,178 cases and 4,344 controls). Whole exome sequencing was conducted on 1,043 cases and 1,188 controls and a targeted 857-gene panel on the remaining samples. Using ancestry-adjusted SKAT-O analyses, we tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. We calculated odds ratios (OR) for BC using ancestry-adjusted logistic regression models. We also tested the association of single variants with BC risk. We saw a strong association of LoF variants in FANCM with ER-negative BC (p=4.1×10 -7 , OR [CI]: 6.7 [2.9-15.6]) and a nominal association with overall BC risk. Among known susceptibility genes, BRCA1 (p=2.3×10 -10 , OR [CI]: 24.9 [6.1-102.5]), BRCA2 (p=8.4×10 -10 , OR [CI]: 7.0 [3.5-14.0]), and PALB2 (p=1.8×10 -8 , OR [CI]: 6.5 [3.2-13.1]) were strongly associated with BC. There were nominally significant associations with CHEK2, RAD51D , and TP53 . In H/L women, LoF variants in FANCM were strongly associated with ER-negative breast cancer risk. It previously was proposed as a possible susceptibility gene for ER-negative BC, but is not routinely tested in clinical practice. Our results demonstrate that FANCM should be added to BC gene panels.
Authors: Nierenberg, Jovia L; Kushi, Lawrence H; Neuhausen, Susan L; et al.
medRxiv. 2023 Jan 28.
MiXcan: a framework for cell-type-aware transcriptome-wide association studies with an application to breast cancer
Human bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. Conventional transcriptome-wide association study approaches predict genetically regulated gene expression at the tissue level, without considering cell-type heterogeneity, and test associations of predicted tissue-level expression with disease. Here we develop MiXcan, a cell-type-aware transcriptome-wide association study approach that predicts cell-type-level expression, identifies disease-associated genes via combination of cell-type-level association signals for multiple cell types, and provides insight into the disease-critical cell type. As a proof of concept, we conducted cell-type-aware analyses of breast cancer in 58,648 women and identified 12 transcriptome-wide significant genes using MiXcan compared with only eight genes using conventional approaches. Importantly, MiXcan identified genes with distinct associations in mammary epithelial versus stromal cells, including three new breast cancer susceptibility genes. These findings demonstrate that cell-type-aware transcriptome-wide analyses can reveal new insights into the genetic and cellular etiology of breast cancer and other diseases.
Authors: Song, Xiaoyu; Alexeeff, Stacey E; Sakoda, Lori C; Habel, Laurel A; Sieh, Weiva; et al.
Nat Commun. 2023 Jan 23;14(1):377. Epub 2023-01-23.
Combining Asian-European Genome-Wide Association Studies of Colorectal Cancer Improves Risk Prediction Across Race and Ethnicity
Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expanded PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS were 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1,681-3,651 cases and 8,696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They were significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values<0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
Authors: Thomas, Minta; Sakoda, Lori C; Lee, Jeffrey K; Corley, Douglas A; Hsu, Li; et al.
medRxiv. 2023 Jan 19.
Diet Quality, Ultra-Processed Food Consumption, and Quality of Life in a Cross-Sectional Cohort of Adults and Teens with Celiac Disease
Celiac disease (CeD), a common autoimmune condition, requires strict adherence to a gluten-free diet (GFD). Adherence to the GFD has been associated with quality of life (QOL). However, there may be other diet-related concerns, like overall diet patterns, including diet quality or ultra-processed food (UPF) consumption, that could be associated with QOL among people with CeD following a GFD which has not been examined. Determined diet quality based on 24-h diet recalls of a cross-sectional prospectively recruited sample of 80 participants (50 adults and 30 teens) with biopsy-confirmed CeD (“Study Sample”) using the Healthy Eating Index (HEI) and Alternate Mediterranean Diet (AMED) score. Assessed the amount of UPF consumed using Nova, a food processing classification system. Measured QOL using Celiac Disease-Specific Quality of Life (CDQOL) and Celiac Disease Pediatric-Specific Quality of Life (CDPQOL). Compared the Study Sample’s diet patterns with National Health and Nutrition Examination Survey (NHANES) groups (25 adults reporting prior CeD and GFD; 51 adults with new CeD and no GFD; 15,777 adults & 2,296 teens without CeD). Assessed the relationship of the Study Sample’s diet patterns to CDQOL/CDPQOL using ANCOVA. The Study Sample’s diet patterns were suboptimal but generally favorable compared with all NHANES groups. Compared to Study Adults with the highest tertile of UPF, those with the lowest tertile had significantly higher CDQOL [mean: 67.6 vs 78.3, p<0.001]. Compared to Study Teens with the lowest tertile of AMED, those with the highest tertile had significantly higher CDPQOL [mean: 67.0 vs 79.9, p<0.01]. Maintaining high diet quality and minimizing UPF may be important for CeD-specific QOL among individuals with CeD maintaining a GFD. This article is protected by copyright. All rights reserved.
Authors: Cadenhead, Jennifer W; Martínez-Steele, Euridice; Contento, Isobel; Kushi, Lawrence H; Lee, Anne R; Nguyen, Thanh Thanh T; Lebwohl, Benjamin; Green, Peter H R; Wolf, Randi L
J Hum Nutr Diet. 2023 Jan 18.
Participant blinding and gastrointestinal illness in a randomized, controlled trial of an in-home drinking water intervention.
We conducted a randomized, triple-blinded home drinking water intervention trial to determine if a large study could be undertaken while successfully blinding participants. Households were randomized 50:50 to use externally identical active or sham treatment devices. We measured the effectiveness of blinding of participants by using a published blinding index in which values >0.5 indicate successful blinding. The principal health outcome measured was “highly credible gastrointestinal illness” (HCGI). Participants (n=236) from 77 households were successfully blinded to their treatment assignment. At the end of the study, the blinding index was 0.64 (95% confidence interval 0.51-0.78). There were 103 episodes of HCGI during 10,790 person-days at risk in the sham group and 82 episodes during 11,380 person-days at risk in the active treatment group. The incidence rate ratio of disease (adjusted for the clustered sampling) was 1.32 (95% CI 0.75, 2.33) and the attributable risk was 0.24 (95% CI -0.33, 0.57). These data confirm that participants can be successfully blinded to treatment group assignment during a randomized trial of an in-home drinking water intervention.
Authors: Colford, John M Jr; Rees, Judy R; Wade, Timothy J; Khalakdina, Asheena; Hilton, Joan F; Ergas, Isaac J; Burns, Susan; Benker, Anne; Ma, Catherine; Bowen, Cliff; Mills, Daniel C; Vugia, Duc J; Juranek, Dennis D; Levy, Deborah A
Emerg Infect Dis. 2002 Jan;8(1):29-36.
Detected Prenatal Perfluorooctanoic Acid (PFOA) Exposure is Associated with Decreased Fetal Head Biometric Parameters in Participants Experiencing Higher Perceived Stress During Pregnancy in the MADRES Cohort
Authors: Alicia K. Peterson; Sandrah P. Eckel; Rima Habre; Tingyu Yang; Dema Faham; Monica Amin; Brendan H. Grubbs; Shohreh F. Farzan; Kurunthachalam Kannan; Morgan Robinson; Deborah Lerner; Laila A. Al-Marayati; Daphne K. Walker; Edward G. Grant; Carrie V. Breton; Theresa M. Bastain
Environ Adv. 2022 Oct;9:100032. doi: 10.1016/j.envadv.2022.100286. Epub 2022 Sep 8.
Prenatal Perfluorooctanoic Acid (PFOA) Exposure is Associated with Lower Infant Birthweight Within the MADRES Pregnancy Cohort.
Authors: Peterson Alicia K; Eckel Sandrah P; Habre Rima; Yang Tingyu; Faham Dema; Farzan Shohreh F; Grubbs Brendan H; Kannan Kurunthachalam; Robinson Morgan; Lerner Deborah; Al-Marayati Laila A; Walker Daphne K; Grant Edward G; Bastain Theresa M; Breton Carrie V
Front. Epidemiol. 2022 Jul 13;2:934715. doi: 10.3389/fepid.2022.934715. Epub 2022 Jul 13.
Migraine and its association with pubertal maturation and behavioral traits among adolescent girls
To determine if the ages at pubertal milestones are associated with the prevalence of adolescent migraine. Migraine headaches are a common disease in adolescent girls. Past studies have evaluated the relationship between age of onset of menarche and migraine headache, but none have studied earlier pubertal milestones such as thelarche and pubarche. In this cross-sectional study, a previously validated questionnaire was administered to girls (15-18 years) in Breast Cancer and the Environment Research Program puberty cohort to ascertain if they met criteria for migraine over the past year. Ages of pubertal development were ascertained by serial examinations beginning at 6-8 years of age and ending in late puberty. Logistic regression analyses determined if age of onset of each pubertal milestone (thelarche, pubarche, menarche separately) was associated with adolescent migraine after adjusting for other risk factors. Of 761girls, 222 (29.2%) met the criteria for migraine. Later thelarche was associated with a lower odds of adolescent migraine (OR 0.83; 95% CI 0.72-0.97, p = 0.019). In models further adjusted for BASC-2 internalizing problems (n = 490), both later thelarche (OR 0.78; 95% CI 0.64-0.96, p = 0.016) and later menarche (OR 0.81; 95%CI 0.67-0.98, p = 0.026) were associated with a lower migraine prevalence. Internalizing problems (OR 1.05; 95% CI 1.03-1.07) externalizing problems (OR 1.05; 95% CI 1.02-1.07) and behavioral symptoms (OR 1.05; 95% CI 1.03-1.08) were associated with increased prevalence of migraine in separate models. Age of onset of thelarche and menarche, and internalizing, externalizing, and behavioral symptoms were all associated with adolescent migraine.
Authors: Martin, Vincent T; Fassler, Cecily S; Brunst, Kelly J; Ying, Jun; Teitelbaum, Susan; Windham, Gayle C; Deardorff, Julianna; Wolff, Mary S; Kushi, Lawrence H; Biro, Frank M; Pinney, Susan M
Acta Neurol Belg. 2023 Jan 11.
Sleep duration, plasma metabolites, and obesity and diabetes: A metabolome-wide association study in US women
Short and long sleep duration are associated with adverse metabolic outcomes, such as obesity and diabetes. We evaluated cross-sectional differences in metabolite levels between women with self-reported habitual short (<7 h), medium (7-8 h), and long (?9 h) sleep duration to delineate potential underlying biological mechanisms. In total, 210 metabolites were measured via liquid chromatography-mass spectrometry in 9207 women from the Nurses' Health Study (NHS; N = 5027), the NHSII (N = 2368), and the Women's Health Initiative (WHI; N = 2287). Twenty metabolites were consistently (i.e. praw < .05 in ?2 cohorts) and/or strongly (pFDR < .05 in at least one cohort) associated with short sleep duration after multi-variable adjustment. Specifically, levels of two lysophosphatidylethanolamines, four lysophosphatidylcholines, hydroxyproline and phenylacetylglutamine were higher compared to medium sleep duration, while levels of one diacylglycerol and eleven triacylglycerols (TAGs; all with ?3 double bonds) were lower. Moreover, enrichment analysis assessing associations of metabolites with short sleep based on biological categories demonstrated significantly increased acylcarnitine levels for short sleep. A metabolite score for short sleep duration based on 12 LASSO-regression selected metabolites was not significantly associated with prevalent and incident obesity and diabetes. Associations of single metabolites with long sleep duration were less robust. However, enrichment analysis demonstrated significant enrichment scores for four lipid classes, all of which (most markedly TAGs) were of opposite sign than the scores for short sleep. Habitual short sleep exhibits a signature on the human plasma metabolome which is different from medium and long sleep. However, we could not detect a direct link of this signature with obesity and diabetes risk.
Authors: Fritz, Josef; Cespedes Feliciano, Elizabeth M; Vetter, Céline; et al.
Sleep. 2023 Jan 11;46(1).
Risk of colorectal cancer and colorectal cancer mortality beginning ten years after a negative colonoscopy, among screen-eligible adults 76-85 years old
Few empirical data are available to inform older adults’ decisions about whether to screen or continue screening for colorectal cancer based on their prior history of screening, particularly among individuals with a prior negative exam. Using a retrospective cohort of older adults receiving healthcare at three Kaiser Permanente integrated healthcare systems in Northern California (KPNC), Southern California (KPSC), and Washington (KPWA), we estimated the cumulative risk of colorectal cancer incidence and mortality among older adults who had a negative colonoscopy 10 years earlier, accounting for death from other causes. Screen-eligible adults ages 76 to 85 years who had a negative colonoscopy 10 years earlier were found to be at a low risk of colorectal cancer diagnosis, with a cumulative incidence of 0.39% [95% CI, 0.31%-0.48%) at 2 years that increased to 1.29% (95% CI, 1.02%-1.61%) at 8 years. Cumulative mortality from colorectal cancer was 0.04% (95% CI, 0.02%-0.08%) at 2 years and 0.46% (95% CI, 0.30%-0.70%) at 8 years. These low estimates of cumulative colorectal cancer incidence and mortality occurred in the context of much higher risk of death from other causes. Knowledge of these results could bear on older adults’ decision to undergo or not undergo further colorectal cancer screening, including choice of modality, should they decide to continue screening. See related commentary by Lieberman, p. 6.
Authors: Dalmat, Ronit R; Corley, Douglas A; Levin, Theodore R; Chubak, Jessica; et al.
Cancer Epidemiol Biomarkers Prev. 2023 Jan 09;32(1):37-45.
Impact and recovery from COVID-19-related disruptions in colorectal cancer screening and care in the US: A scenario analysis
Many colorectal cancer-related procedures were suspended during the COVID-19 pandemic. In this study, we predict the impact of resulting delays in screening (colonoscopy, FIT, and sigmoidoscopy) and diagnosis on colorectal cancer-related outcomes, and compare different recovery scenarios. Using the MISCAN-Colon model, we simulated the US population and evaluated different impact and recovery scenarios. Scenarios were defined by the duration and severity of the disruption (percentage of eligible adults affected), the length of delays, and the duration of the recovery. During recovery (6, 12 or 24 months), capacity was increased to catch up missed procedures. Primary outcomes were excess colorectal cancer cases and -related deaths, and additional colonoscopies required during recovery. With a 24-month recovery, the model predicted that the US population would develop 7,210 (0.18%) excess colorectal cancer cases during 2020-2040, and 6,950 (0.65%) excess colorectal cancer-related deaths, and require 108,500 (8.6%) additional colonoscopies per recovery month, compared with a no-disruption scenario. Shorter recovery periods of 6 and 12 months, respectively, decreased excess colorectal cancer-related deaths to 4,190 (0.39%) and 4,580 (0.43%), at the expense of 260,200-590,100 (20.7%-47.0%) additional colonoscopies per month. The COVID-19 pandemic will likely cause more than 4,000 excess colorectal cancer-related deaths in the US, which could increase to more than 7,000 if recovery periods are longer. Our results highlight that catching-up colorectal cancer-related services within 12 months provides a good balance between required resources and mitigation of the impact of the disruption on colorectal cancer-related deaths.
Authors: van den Puttelaar, Rosita; Lansdorp-Vogelaar, Iris; Hahn, Anne I; Rutter, Carolyn M; Levin, Theodore R; Zauber, Ann G; Meester, Reinier G S
Cancer Epidemiol Biomarkers Prev. 2023 Jan 09;32(1):22-29.
Cigarette Smoking and Risk of SARS-CoV-2 infection and Disease Severity Among Adults in an Integrated Health Care System in California
The relationship between tobacco smoking status and SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) severity is highly debated. We conducted a retrospective cohort study of?>2.4 million adults in a large healthcare system to evaluate whether smoking is associated with SARS-CoV-2 infection and disease severity. This retrospective cohort study of 2,427,293 adults in KPNC from March 5, 2020 (baseline) to December 31, 2020 (pre-vaccine) included smoking status (current, former, never), socio-demographics, and comorbidities from the electronic health record. SARS-CoV-2 infection (identified by a positive PCR test) and COVID-19 severity (hospitalization, ICU admission or death???30 days of COVID-19 diagnosis) were estimated in time-to-event analyses using Cox proportional hazard regression models adjusting for covariates. Secondary analyses examined COVID-19 severity among patients with COVID-19 using logistic regression. During the study, 44,270 patients had SARS-CoV-2 infection. Current smoking was associated with lower adjusted rates of SARS-CoV-2 infection (aHR?=?0.64 95% CI: 0.61-0.67), COVID-19-related hospitalization (aHR?=?0.48 95% CI: 0.40-0.58), ICU admission (aHR?=?0.62 95% CI: 0.42-0.87), and death (aHR?=?0.52 95% CI: 0.27-0.89) than never-smoking. Former smoking was associated with a lower adjusted rate of SARS-CoV-2 infection (aHR?=?0.96 95% CI: 0.94-0.99) and higher adjusted rates of hospitalization (aHR?=?1.10 95% CI: 1.03-1.08) and death (aHR?=?1.32 95% CI: 1.11-1.56) than never-smoking. Logistic regression analyses among patients with COVID-19 found lower odds of hospitalization for current versus never-smoking and higher odds of hospitalization and death for former versus never-smoking. In the largest US study to date on smoking and COVID-19, current and former smoking showed lower risk of SARS-CoV-2 infection than never-smoking, while a history of smoking was associated with higher risk of severe COVID-19. In this cohort study of 2.4 million adults, adjusting for socio-demographics and medical comorbidities, current tobacco smoking was associated with a lower risk of both SARS-CoV-2 infection and severe COVID-19 illness compared to never-smoking. A history of smoking was associated with a slightly lower risk of SARS-CoV-2 infection and a modestly higher risk of severe COVID-19 illness compared to never-smoking. The lower observed COVID-19 risk for current versus never-smoking deserves further investigation. Results support prioritizing individuals with smoking-related comorbidities for vaccine outreach and treatments as they become available.
Authors: Young-Wolff, Kelly C; Slama, Natalie; Alexeeff, Stacey E; Sakoda, Lori C; Fogelberg, Renee; Myers, Laura C; Campbell, Cynthia I; Adams, Alyce S; Prochaska, Judith J
Nicotine Tob Res. 2023 Jan 05;25(2):211-220.
Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
Authors: Fernandez-Rozadilla, Ceres; Corley, Douglas; Sakoda, Lori; Peters, Ulrike; et al.
Nat Genet. 2023 Jan;55(1):89-99. Epub 2022-12-20.
Association of Social Support with Mild Cognitive Impairment and Dementia Among Older Women: The Women’s Health Initiative Memory Study
Social support may be a modifiable risk factor for cognitive impairment. However, few long-term, large prospective studies have examined associations of various forms of social support with incident mild cognitive impairment (MCI) and dementia. To examine associations of perceived social support with incident MCI and dementia among community-dwelling older women. This prospective cohort study included 6,670 women from the Women’s Health Initiative Memory Study who were cognitively unimpaired at enrollment. We used Cox proportional hazards models to assess associations between perceived social support with incident MCI, dementia, or either MCI/dementia during an average 10.7 (SD = 6.1)-year follow-up. Modelling was repeated for emotional/information support, affection support, tangible support, and positive social interaction subscales of social support. Among 6,670 women (average age = 70 years [SD = 3.8]; 97.0% non-Hispanic/Latina; 89.8% White), greater perceived social support was associated with lower risk of MCI/dementia after adjustment for age, ethnicity, race, hormone therapy, education, income, diabetes, hypertension, and body mass index (Tertile [T]3 versus T1: HR = 0.85, 95% CI 0.74-0.99; ptrend = 0.08). Associations were significant for emotional/information support (T3 versus T1: HR = 0.84, 95% CI 0.72-0.97; ptrend = 0.04) and positive social interaction (T3 versus T1: HR = 0.85, 95% CI 0.73-0.99; ptrend = 0.06) subscales. Associations were attenuated and not significant after adjustment for depressive symptom severity. Perceived social support, emotional/information support, and positive social interaction were associated with incident MCI/dementia among older women. Results were not significant after adjustment for depressive symptom severity. Improving social support may reduce risk of MCI and dementia in older women.
Authors: Posis, Alexander Ivan B; Kroenke, Candyce H; Shadyab, Aladdin H; et al.
J Alzheimers Dis. 2023;91(3):1107-1119.
Informative presence in electronic health record data: a challenge in implementing study exclusion criteria
Authors: Chubak, Jessica; Dalmat, Ronit R; Weiss, Noel S; Doria-Rose, V Paul; Corley, Douglas A; Kamineni, Aruna
Epidemiology. 2023 Jan 01;34(1):29-32. Epub 2022-09-20.
“The simple life experiences that every other human gets”: Desire for normalcy among adolescents and young adults with advanced cancer
Adolescents and young adults (AYAs) with advanced cancer identify normalcy as an important component of quality end-of-life care. We sought to define domains of normalcy and identify ways in which clinicians facilitate or hinder normalcy during advanced cancer care. This was a secondary analysis of a qualitative study that aimed to identify priority domains for end-of-life care. Content analysis of semi-structured interviews among AYAs aged 12-39 years with advanced cancer, caregivers, and clinicians was used to evaluate transcripts. Coded excerpts were reviewed to identify themes related to normalcy. Participants included 23 AYAs with advanced cancer, 28 caregivers, and 29 clinicians. Participants identified five domains of normalcy including relationships, activities, career/school, milestones, and appearance. AYAs and caregivers identified that clinicians facilitate normalcy through exploration of these domains with AYAs, allowing flexibility in care plans, identification of short-term and long-term goals across normalcy domains, and recognizing losses of normalcy that occur during cancer care. AYAs with cancer experience multiple threats to normalcy during advanced cancer care. Clinicians can attend to normalcy and improve AYA quality of life by acknowledging these losses through ongoing discussions on how best to support domains of normalcy and by reinforcing AYA identities beyond a cancer diagnosis.
Authors: Umaretiya, Puja J; Kushi, Lawrence H; Mack, Jennifer W; et al.
Pediatr Blood Cancer. 2023 Jan;70(1):e30035. Epub 2022-10-29.
Development of a Clinical Prediction Model for Diabetes in Chronic Pancreatitis: The PREDICT3c Study
Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP. This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was evaluated by cross validation. Exploratory analyses were stratified according to the timing of development of diabetes relative to the diagnosis of pancreatitis. Independent correlates of diabetes in CP included risk factors for type 2 diabetes (older age, overweight/obese status, male sex, non-White race, tobacco use) as well as pancreatic disease-related factors (history of acute pancreatitis complications, nonalcoholic etiology of CP, exocrine pancreatic dysfunction, pancreatic calcification, pancreatic atrophy) (AUROC 0.745). Type 2 diabetes risk factors were predominant for diabetes occurring before pancreatitis, and pancreatic disease-related factors were predominant for diabetes occurring after pancreatitis. Multiple factors are associated with diabetes in CP, including canonical risk factors for type 2 diabetes and features associated with pancreatitis severity. This study lays the groundwork for the future development of models integrating clinical and nonclinical data to identify patients with CP at risk for diabetes and identifies modifiable risk factors (obesity, smoking) on which to focus for diabetes prevention.
Authors: Jeon, Christie; Van Den Eeden, Stephen K; Goodarzi, Mark O; et al.
Diabetes Care. 2023 Jan 01;46(1):46-55.
Fostering a High-Functioning Team in Cancer Care Using the 4R Oncology Model: Assessment in a Large Health System and a Blueprint for Other Institutions
Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system. 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. We formed an internally and externally recognized team of 24 specialties committed to a shared goal of delivering multidisciplinary care at the optimal time and sequence from a patient-centric viewpoint. The team conducted 40 optimizations of interdependent care (22 for breast, seven for lung, and 11 for both cancers) at four points in the care continuum and established an ongoing teamwork adaptation process. Half of the optimizations entailed low effort, while 30% required high level of effort; 78% resulted in improved process efficiency. 4R facilitated development of a large high-functioning team and enabled 40 optimizations of interdependent care along the cancer care continuum in a feasible way. 4R may be an effective approach for fostering high-functioning teams, which could contribute to improving viability of the oncology workforce. Our intervention and taxonomy of results serve as a blueprint for other institutions motivated to strengthen teamwork to improve patient-centered care.
Authors: Liu, Raymond; Gordon, Nancy; Sakoda, Lori C; Trosman, Julia R; et al.
JCO Oncol Pract. 2023 Jan;19(1):e125-e137. Epub 2022-09-30.
The New Kids on the Block: Emerging Complementary Colonoscopy Quality Metrics
Authors: Lam, Angela Y; Lee, Jeffrey K
Clin Gastroenterol Hepatol. 2023 Jan;21(1):26-28. Epub 2022-05-10.
Survival Associated With Consolidated Multidisciplinary Care in Head and Neck Cancer: A Retrospective Cohort Study
To compare survival among patients with head and neck cancer before and after implementing a weekly multidisciplinary clinic and case conference. A retrospective cohort study with chart review was conducted of 3081 patients (1431 preimplementation, 1650 postimplementation) diagnosed with stage I-IVB tumors in the oral cavity, oropharynx, hypopharynx, nasopharynx, or larynx. Pre- and postimplementation differences in overall and disease-specific survival 1, 2, and 3 years after diagnosis were assessed with unadjusted Kaplan-Meier curves and multivariable Cox proportional hazard regression models adjusted for demographic characteristics, comorbidity burden, smoking status, tumor site and stage, p16 status for oropharyngeal squamous cell cancer, and initial treatment modality. Patients less commonly presented with oropharyngeal squamous cell cancer and advanced tumors (III-IVB) and received primary treatment with surgery alone or with adjuvant therapy preimplementation than postimplementation. Overall survival at 3 years was 77.1% and 79.9% (P = .07) and disease-specific survival was 84.9% and 87.5% (P = .05) among pre- and postimplementation patients, respectively. At 3 years, preimplementation patients had slightly poorer overall (hazard ratio, 1.20; 95% CI, 1.02-1.40) and disease-specific (hazard ratio, 1.26; 95% CI, 1.03-1.54) adjusted survival than postimplementation patients. In unadjusted and adjusted analyses, survival improvements were more pronounced among patients with advanced disease. A multidisciplinary clinic and case conference were associated with improved outcomes among patients with head and neck cancer, especially those with advanced tumors. All patients with head and neck cancer should receive multidisciplinary team management, especially those with advanced tumors.
Authors: Meltzer, Charles; Nguyen, Nathalie T; Zhang, Jie; Aguilar, Jillian; Blatchins, Maruta A; Quesenberry, Charles P; Wang, Yan; Sakoda, Lori C
Otolaryngol Head Neck Surg. 2023 Jan;168(1):82-90.
Medical imaging utilization and associated radiation exposure in children with down syndrome
To evaluate the frequency of medical imaging or estimated associated radiation exposure in children with Down syndrome. This retrospective cohort study included 4,348,226 children enrolled in six U.S. integrated healthcare systems from 1996-2016, 3,095 of whom were diagnosed with Down syndrome. We calculated imaging rates per 100 person years and associated red bone marrow dose (mGy). Relative rates (RR) of imaging in children with versus without Down syndrome were estimated using overdispersed Poisson regression. Compared to other children, children with Down syndrome received imaging using ionizing radiation at 9.5 times (95% confidence interval[CI] = 8.2-10.9) the rate when age <1 year and 2.3 times (95% CI = 2.0-2.5) between ages 1-18 years. Imaging rates by modality in children <1 year with Down syndrome compared with other children were: computed tomography (6.6 vs. 2.0, RR = 3.1[95%CI = 1.8-5.1]), fluoroscopy (37.1 vs. 3.1, RR 11.9[95%CI 9.5-14.8]), angiography (7.6 vs. 0.2, RR = 35.8[95%CI = 20.6-62.2]), nuclear medicine (6.0 vs. 0.6, RR = 8.2[95% CI = 5.3-12.7]), radiography (419.7 vs. 36.9, RR = 11.3[95%CI = 10.0-12.9], magnetic resonance imaging(7.3 vs. 1.5, RR = 4.2[95% CI = 3.1-5.8]), and ultrasound (231.2 vs. 16.4, RR = 12.6[95% CI = 9.9-15.9]). Mean cumulative red bone marrow dose from imaging over a mean of 4.2 years was 2-fold higher in children with Down syndrome compared with other children (4.7 vs. 1.9mGy). Children with Down syndrome experienced more medical imaging and higher radiation exposure than other children, especially at young ages when they are more vulnerable to radiation. Clinicians should consider incorporating strategic management decisions when imaging this high-risk population.
Authors: Marlow, Emily C;Ducore, Jonathan M;Kwan, Marilyn L;Bowles, Erin J A;Greenlee, Robert T;Pole, Jason D;Rahm, Alanna K;Stout, Natasha K;Weinmann, Sheila;Smith-Bindman, Rebecca;Miglioretti, Diana L
PLoS One. 2023;18(9):e0289957. Epub 2023-09-06.
Metabolic abnormalities and survival among patients with non-metastatic breast cancer
Research on the impact of metabolic abnormalities on breast cancer prognosis is limited by small samples and assessment of laboratory values at a single time point, often prior to cancer diagnosis and treatment. In this population-based cohort, time-updated laboratory values were adjusted for cancer treatment to assess the association between metabolic risk factors (glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides) and breast cancer survival. 13,434 women diagnosed with stage I-III breast cancer from 2005-15 at Kaiser Permanente were included. All outpatient fasting glucose, HDL-C, LDL-C, and triglyceride values from diagnosis through 2019 or death were extracted from electronic medical records. Risk of breast cancer-specific mortality was evaluated with Cox proportional hazards models adjusted for metabolic labs, demographics, body mass index, diabetes, dyslipidemia and anti-hypertensive medications, tumor characteristics (stage, ER and HER2 receptor status) and cancer treatment (use of chemotherapy, tamoxifen, and aromatase inhibitors). Mean (SD) age at diagnosis was 62.3 (11.8) years. Over a median follow-up of 8.6 years, 2,876 patients died; 1,080 of breast cancer. Patients with low HDL-C (≤ 45 vs. > 45 mg/dL) had higher breast cancer-specific mortality (HR, 1.77; 95% CI, 1.53-2.05), as did those with elevated fasting glucose (> 99 vs. 60-99 mg/dL) (HR, 1.19; 95% CI, 1.03-1.37). Elevated levels of triglycerides and LDL-C were not associated with breast cancer-specific mortality. High fasting glucose and low HDL-C evaluated over time after cancer diagnosis were associated with higher breast cancer mortality independent of cancer treatments and changes in other metabolic risk factors. Future studies should address whether pharmacologic or lifestyle treatment of glucose and lipids after breast cancer diagnosis can optimize survival outcomes.
Authors: Zimbalist, Alexa S; Caan, Bette J; Chen, Wendy Y; Mittendorf, Elizabeth A; Dillon, Deborah A R; Quesenberry, Charles; Cespedes Feliciano, Elizabeth M
BMC Cancer. 2022 Dec 29;22(1):1361. Epub 2022-12-29.
Social Support, social ties, and cognitive function of women with breast cancer: findings from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) Study
This study examined associations between self-reported cognitive functioning and social support as well as social ties among women with breast cancer. The study included 3351 women from the Women’s Health Initiative Life and Longevity After Cancer cohort who were diagnosed with breast cancer stages I-III. Social support was assessed using a modified Medical Outcomes Study (MOS) Social Support Survey, and marital status was obtained from the baseline questionnaire. We also assessed social ties (e.g., number of friends, relatives, living children) and cognitive function (Functional Assessment of Cancer Therapy-Cognitive Function [FACT-COG]) on the year-1-follow up questionnaire. Multivariable quantile regression was used to estimate the changes in median cognitive scores. Kruskal-Wallis tests were used to assess the association of cognitive function with social ties. The majority of participants were non-Hispanic White (93.3%), presently married (49%), with at least a 4-year college degree (53.2%), and had been diagnosed with localized breast cancer (79%). A 10-point higher social support score correlated to a 0.32 higher (better) median cognitive score (p < 0.001). Women who were presently married tended to have better cognition than women who were divorced/separated or widowed (p = 0.01). Significant associations were also present for having close relatives (p < 0.001) or friends (p < 0.001), with cognitive scores being higher in those with at least one close relative or friend compared to none. Women reporting higher social support and greater numbers of friends or relatives have higher cognitive functioning. Compared to divorced or separated women, married women were likely to have higher cognitive functioning. These findings suggest that social support assessments have the potential to help identify women at higher risk of cognitive decline.
Authors: Yang, Yesol; Kroenke, Candyce H; Paskett, Electra D; et al.
Support Care Cancer. 2022 Dec 16;31(1):48. Epub 2022-12-16.
Incidence of Parkinson disease in North America
Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.
Authors: Willis, A W; Roberts, E; Beck, J C; Fiske, B; Ross, W; Savica, R; Van Den Eeden, S K; Tanner, C M; Marras, C; Parkinson’s Foundation P4 Group,
NPJ Parkinsons Dis. 2022 Dec 15;8(1):170. Epub 2022-12-15.
Reply to M.S. Ewer et al
Authors: Greenlee, Heather; Rillamas-Sun, Eileen; Cheng, Richard; Iribarren, Carlos; Rana, Jamal S; Nguyen-Huynh, Mai; Kushi, Lawrence H; Kwan, Marilyn L
J Clin Oncol. 2022 Dec 10;40(35):4159-4160. Epub 2022-07-25.
Association of Global Cognitive Function with Psychological Distress and Adherence to Public Health Recommendations during the COVID-19 Pandemic: The Women’s Health Initiative
The association of cognitive function with symptoms of psychological distress during the coronavirus disease 2019 (COVID-19) pandemic or adherence to COVID-19 protective health behaviors is not well-understood. We examined 2 890 older women from the Women’s Health Initiative cohort. Prepandemic (ie, within 12 months prior to pandemic onset) and peripandemic global cognitive function scores were assessed with the modified Telephone Interview for Cognitive Status (TICS-m). Anxiety, stress, and depressive symptom severity during the pandemic were assessed using validated questionnaires. We examined adherence to protective behaviors that included safe hygiene, social distancing, mask wearing, and staying home. Multivariable models were adjusted for age, race, ethnicity, education, region of residence, alcohol intake, and comorbidities. Every 5-point lower prepandemic TICS-m score was associated with 0.33-point mean higher (95% confidence interval [CI], 0.20, 0.45) perceived stress and 0.20-point mean higher (95% CI, 0.07, 0.32) depressive symptom severity during the pandemic. Higher depressive symptom severity, but not anxiety or perceived stress, was associated with a 0.69-point (95% CI, -1.13, -0.25) mean decline in TICS-m from the prepandemic to peripandemic period. Every 5-point lower peripandemic TICS-m score was associated with 12% lower odds ratio (OR, 0.88; 95% CI, 0.80, 0.97) of practicing safe hygiene. Among older women, we observed that: (a) lower prepandemic global cognitive function was associated with higher stress and depressive symptom severity during the pandemic; (b) higher depressive symptom severity during the pandemic was associated with cognitive decline; and (c) lower global cognitive function during the pandemic was associated with lower odds of practicing safe hygiene.
Authors: Shadyab, Aladdin H; Kroenke, Candyce H; Baker, Laura D; et al.
J Gerontol A Biol Sci Med Sci. 2022 Dec 06;77(Suppl 1):S42-S50.
Associations between changes in loneliness and social connections, and mental health during the COVID-19 Pandemic: The Women’s Health Initiative
Older women have faced significant disruptions in social connections during the coronavirus disease 2019 pandemic. Whether loneliness increased or whether a change in loneliness from pre- to intrapandemic period was associated with mental health during the pandemic is unknown. Older women (n = 27 479; mean age 83.2 [SD: 5.4] years) completed surveys in mid-2020, including questions about loneliness, living arrangements, changes in social connections, and mental health. Loneliness was also previously assessed in 2014-2016. We examined whether loneliness changed from the pre- to intrapandemic period and explored factors associated with this change. In multivariable models, we investigated the association of changes in loneliness and social connections with mental health. Loneliness increased from pre- to intrapandemic levels. Factors associated with worsening loneliness included older age, experiencing stressful life events, bereavement, histories of vascular disease and depression, and social connection disruptions. Factors associated with a decrease in loneliness included identifying as Black, engaging in more frequent physical activity, being optimistic, and having a higher purpose in life. A 3-point increase in loneliness scores was associated with higher perceived stress, higher depressive, and higher anxiety symptoms. Social connection disruptions showed modest or no associations with mental health. Loneliness increased during the pandemic in older women and was associated with higher stress, depressive, and anxiety symptoms. Our findings point to opportunities for interventions targeting lifestyle behaviors, well-being, disrupted social connections, and paying closer attention to those with specific medical and mental health histories that may reduce loneliness and improve mental health.
Authors: Goveas, Joseph S; Kroenke, Candyce H; Anderson, Garnet L; et al.
J Gerontol A Biol Sci Med Sci. 2022 Dec 06;77(Suppl 1):S31-S41.
Adipose tissue radiodensity and mortality among patients with nonmetastatic breast cancer
Computed tomography (CT) scans can measure quantity and distribution of adipose tissue, which are associated with breast cancer prognosis. As a novel prognostic marker, radiodensity of adipose tissue has been examined in multiple cancer types, but never in breast cancer. Lower density indicates larger adipocytes with greater lipid content, whereas higher density can reflect inflammation, fibrosis, vascularity, or even metabolic changes; and both may impact breast cancer prognosis. We included 2868 nonmetastatic patients with breast cancer diagnosed between January 2005 and December 2013 at Kaiser Permanente Northern California, an integrated healthcare system. From CT scans at diagnosis, we assessed the radiodensity of subcutaneous (SAT) and visceral adipose tissue (VAT) at the third lumbar vertebra and categorized their radiodensity into three levels: low (<1 standard deviation [SD] below the mean), middle (mean ± 1 SD), and high (>1 SD above the mean). Using multivariable Cox proportional hazards regression with adjustment for clinicopathological characteristics including body mass index, we calculated hazard ratios (HRs [95% confidence intervals]) for the associations of adipose tissue radiodensity with overall mortality and breast-cancer-specific mortality. Median age at diagnosis of breast cancer was 56.0 years, most (63.3%) were non-Hispanic White and nearly half (45.6%) were stage II. Compared to middle SAT radiodensity, high SAT radiodensity was significantly associated with increased risk of overall mortality (HR: 1.45 [1.15-1.81]), non-significantly with breast-cancer-specific mortality (HR: 1.32 [0.95-1.84]). Neither low SAT radiodensity nor high or low VAT radiodensity was significantly associated with overall or breast-cancer-specific mortality. High radiodensity of SAT at diagnosis of nonmetastatic breast cancer was associated with increased risk of overall mortality, independent of adiposity and other prognostic factors. Considering both radiodensity and quantity of adipose tissue at different locations could deepen understanding of the role of adiposity in breast cancer survival.
Authors: Cheng, En; Caan, Bette J; Chen, Wendy Y; Irwin, Melinda L; Prado, Carla M; Cespedes Feliciano, Elizabeth M
Clin Nutr. 2022 Dec;41(12):2607-2613. Epub 2022-10-04.
Racial differences in anthropometric measures as risk factors for triple-negative breast cancer
The incidence of triple-negative breast cancer (TNBC) is higher in Black women compared to White women which is not explained by racial differences in body mass index (BMI). As BMI has limitations as an anthropometric measure, we used different anthropometric measures to examine associations with TNBC by race. Of 161,808 postmenopausal participants in Women’s Health Initiative, eligible were a subsample of 121,744 White and Black postmenopausal women enrolled from 1993 to 1998, 50-79 years of age with anthropometric measures who were followed for breast cancer incidence until March 2019. At entry, BMI, waist circumference (WC), and waist-hip ratio (WHR) were measured using standardized methods. Breast cancers were verified by central medical record review. Associations between anthropometric measures and triple-negative breast cancer risk were examined using Cox proportional hazards regression models. After 17.6 years (median) follow-up, there were 87 Black women and 529 White women with incident triple-negative breast cancer. Overall, there were no significant associations between anthropometric measures and risk of triple-negative breast cancer. However, compared to White women with normal BMI, White women with obesity (BMI ≥ 30) (HR 0.76, 95% CI 0.60, 0.96) were significantly associated with a lower risk of triple-negative breast cancer. And larger waist circumference (HR per centimeter 0.99, 95% CI 0.99, 1.00) was significantly associated with a lower risk of triple-negative breast cancer among White women. Overall, among postmenopausal women, anthropometric measures were not associated with risk of TNBC. The association among White women with larger waist circumference and women with obesity with a lower risk of triple-negative breast cancer needs further confirmation.
Authors: Wang, Fengge; Kroenke, Candyce H; Pan, Kathy; Shadyab, Aladdin H; Chlebowski, Rowan T; Wactawski-Wende, Jean; Qi, Lihong; Luo, Juhua
Cancer Causes Control. 2022 Dec;33(12):1413-1419. Epub 2022-09-21.
Management of ovarian and breast cancer risk in non-BRCA HBOC pathogenic variant carriers in a large California health care system
To describe breast and ovarian cancer risk reduction strategies in the clinical management of women who test positive for non-BRCA hereditary breast and ovarian cancer (HBOC) pathogenic variants compared to those who test positive for pathogenic BRCA variants or have negative germline panel testing. Examination of imaging and preventive surgeries in women undergoing HBOC genetic testing from 1/1/2015 to 12/31/2018, with follow up to 03/31/2020 in Kaiser Permanente Northern California. A total of 13,271 tests which included HBOC genes were identified. Rate of bilateral salpingo-oophorectomy after genetic testing were similar for BRCA and the non-BRCA moderate risk ovarian pathogenic variants (PVs) (47.4% vs 54%, p = 0.25). Rates were lower for low risk or unknownrisk non-BRCA PVs (12.8%, p < 0.001, 5.3% (p < 0.001). Rates of surveillance for ovarian cancer with ultrasound and CA 125 in the first year was 63.3% and 64.7% for BRCA PV, 37.5% and 27.1%, for non-BRCA moderate risk PVs and 13.7% and 4.6%, for low-risk PVs. Bilateral mastectomy rates were 19.7% for BRCA PV, 10.1% (p = 0.028) for non-BRCA breast high risk PVs, for moderate risk PVs 7.7% (p < 0.001) and for unknown risk 0.4% (p < 0.001). MRI surveillance rates in the first year similarly were 47.4% for non-BRCA BRCA PV, 43% for breast high risk PV, 39.4% for moderate risk and 4.9% for unknown risk PV. Surgical and surveillance strategies are underutilized for HBOC PV, however there is concordance of uptake of preventive strategies with specific risk associated with non-BRCA PVs.
Authors: Powell, C Bethan; Laurent, Cecile; Garcia, Christine; Hoodfar, Elizabeth; Karlea, Audrey; Kobelka, Christine; Lee, Jaimie; Roh, Janise; Kushi, Lawrence H
Gynecol Oncol. 2022 Dec;167(3):467-475. Epub 2022-10-08.
Limitations to Health Care Quality Measurement: Assessing Hospital Variation in Risk of Cardiac Events After Noncardiac Surgery
Limited sample size, incomplete measures, and inadequate risk adjustment adversely influence accurate health care quality measurements, surgical quality measurements, and accurate comparisons among hospitals. Since these measures are linked to resources for quality improvement and reimbursement, improving the accuracy of measurement has substantial implications for patients, clinicians, hospital administrators, insurers, and purchasers. The team examined risk-adjusted differences of postoperative cardiac events among 20 geographically dispersed, community-based medical centers within an integrated health care system and compared it with the National Surgical Quality Improvement Program (NSQIP) hospital-specific differences. The exposure included the hospital at which patients received noncardiac surgical care, with stratification of patients by the acuity of surgery (elective vs. urgent/emergent). Among 157,075 surgery patients, the unadjusted risk of cardiac event per 1000 ranged among hospitals from 2.1 to 6.9 for elective surgery and from 10.3 to 44.5 for urgent/emergent surgery. Across the 20 hospitals, hospital rankings estimated in the present analysis differed significantly from ranking reported by NSQIP (P for difference: elective, P?=?0.0001; urgent/emergent, P?
Authors: Yap, Edward N; Dusendang, Jennifer R; Ng, Kevin P; Keny, Hemant V; Solomon, Matthew D; Cohn, Bradley R; Corley, Douglas A; Herrinton, Lisa J
Popul Health Manag. 2022 Dec;25(6):712-720. Epub 2022-09-12.
Body composition from single versus multi-slice abdominal computed tomography: Concordance and associations with colorectal cancer survival
Computed tomography (CT) scans are routinely obtained in oncology and provide measures of muscle and adipose tissue predictive of morbidity and mortality. Automated segmentation of CT has advanced past single slices to multi-slice measurements, but the concordance of these approaches and their associations with mortality after cancer diagnosis have not been compared. A total of 2871 patients with colorectal cancer diagnosed during 2012-2017 at Kaiser Permanente Northern California underwent abdominal CT scans as part of routine clinical care from which mid-L3 cross-sectional areas and multi-slice T12-L5 volumes of skeletal muscle (SKM), subcutaneous adipose (SAT), visceral adipose (VAT) and intermuscular adipose (IMAT) tissues were assessed using Data Analysis Facilitation Suite, an automated multi-slice segmentation platform. To facilitate comparison between single-slice and multi-slice measurements, sex-specific z-scores were calculated. Pearson correlation coefficients and Bland-Altman analysis were used to quantify agreement. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for death adjusting for age, sex, race/ethnicity, height, and tumour site and stage. Single-slice area and multi-slice abdominal volumes were highly correlated for all tissues (SKM R = 0.92, P < 0.001; SAT R = 0.97, P < 0.001; VAT R = 0.98, P < 0.001; IMAT R = 0.89, P < 0.001). Bland-Altman plots had a bias of 0 (SE: 0.00), indicating high average agreement between measures. The limits of agreement were narrowest for VAT ( ± 0.42 SD) and SAT ( ± 0.44 SD), and widest for SKM ( ± 0.78 SD) and IMAT ( ± 0.92 SD). The HRs had overlapping CIs, and similar magnitudes and direction of effects; for example, a 1-SD increase in SKM area was associated with an 18% decreased risk of death (HR = 0.82; 95% CI: 0.72-0.92), versus 15% for volume from T12 to L5 (HR = 0.85; 95% CI: 0.75-0.96). Single-slice L3 areas and multi-slice T12-L5 abdominal volumes of SKM, VAT, SAT and IMAT are highly correlated. Associations between area and volume measures with all-cause mortality were similar, suggesting that they are equivalent tools for population studies if body composition is assessed at a single timepoint. Future research should examine longitudinal changes in multi-slice tissues to improve individual risk prediction.
Authors: Anyene, Ijeamaka; Caan, Bette; Williams, Grant R; Popuri, Karteek; Lenchik, Leon; Giri, Smith; Chow, Vincent; Beg, Mirza Faisal; Cespedes Feliciano, Elizabeth M
J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2974-2984. Epub 2022-09-02.
Risk of nonalcoholic fatty liver disease and associations with gastrointestinal cancers
Metabolic syndrome may contribute to the rising incidence of multiple gastrointestinal (GI) cancers in recent birth cohorts. However, other than hepatocellular carcinoma, the association between nonalcoholic fatty liver disease (NAFLD) and risk of non-liver GI cancers is unexplored. We prospectively examined the associations of NAFLD risk with GI cancers among 319,290 participants in the UK Biobank (2006-2019). Baseline risk for NAFLD was estimated using the Dallas Steatosis Index, a validated prediction tool. Multivariable Cox models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) according to NAFLD risk categories: low (<20%), intermediate (20%-49%), and high (≥50%). We also examined the associations by age of cancer diagnosis (earlier onset [<60] vs. ≥60). A total of 273 incident liver cancer and 4789 non-liver GI cancer cases were diagnosed. Compared with individuals at low risk for NAFLD, those at high risk had 2.41-fold risk of liver cancer (RR = 2.41, 95% CI: 1.73-3.35) and 23% increased risk of non-liver GI cancers (RR = 1.23, 95% CI: 1.14-1.32) (all ptrend < 0.001). Stronger associations were observed for men and individuals who were obese (all pinteraction < 0.05). NAFLD-associated elevated risk was stronger for earlier-onset cancers. For each 25% increase in NAFLD risk, the RRs for earlier-onset cancers were 1.32 (95% CI: 1.05-1.66) for esophageal cancer, 1.35 (95% CI: 1.06-1.72) for gastric cancer, 1.34 (95% CI: 1.09-1.65) for pancreatic cancer, and 1.10 (95% CI: 1.01-1.20) for colorectal cancer. Conclusion: NAFLD risk was associated with an increased risk of liver and most GI cancers, especially those of earlier onset.
Authors: McHenry, Scott; Zong, Xiaoyu; Shi, Mengyao; Fritz, Cassandra D L; Pedersen, Katrina S; Peterson, Linda R; Lee, Jeffrey K; Fields, Ryan C; Davidson, Nicholas O; Cao, Yin
Hepatol Commun. 2022 Dec;6(12):3299-3310. Epub 2022-10-11.
Analysis of Serious Adverse Event Reporting for Patients Enrolled in Cancer Clinical Trials During the COVID-19 Pandemic.
Authors: Ragavan, Meera V;Legaspi, Nichole;LaLanne, Alyssa;Hong, Julian C;Small, Eric J;Borno, Hala T
JAMA Oncol. 2022 Dec 01;8(12):1849-1851. doi: 10.1001/jamaoncol.2022.4919..
Associations between childhood obesity and pubertal timing stratified by sex and race/ethnicity
Earlier puberty has been associated with numerous adverse mental, emotional, and physical health outcomes. Obesity is a known risk factor for earlier puberty in girls, but research with boys has yielded inconsistent findings. We examined sex- and race/ethnicity-specific associations between childhood obesity and puberty in a multiethnic cohort of 129,824 adolescents born at a Kaiser Permanente Northern California medical facility between 2003 and 2011. We used Weibull regression models to explore associations between childhood obesity and breast development onset (thelarche) in girls, testicular enlargement onset (gonadarche) in boys, and pubic hair development onset (pubarche) in both sexes, adjusting for important confounders. Clear dose-response relationships were observed. Boys with severe obesity had the greatest risk for earlier gonadarche (hazard ratio = 1.23, 95% confidence limit: 1.15, 1.32) and pubarche (hazard ratio = 1.44, 95% confidence limit: 1.34, 1.55), while underweight boys had delayed puberty compared with peers with normal body mass index. A similar dose-response relationship was observed in girls. There were significant interactions between childhood body mass index and race/ethnicity. Childhood obesity is associated with earlier puberty in both boys and girls, and the magnitude of the associations may vary by race/ethnicity. Prevention of childhood obesity may delay pubertal timing and mitigate health risks associated with both conditions.
Authors: Aghaee, Sara; Deardorff, Julianna; Quesenberry, Charles P; Greenspan, Louise C; Kushi, Lawrence H; Kubo, Ai
Am J Epidemiol. 2022 Nov 19;191(12):2026-2036.
Association of serum folate levels during pregnancy and prenatal depression
To evaluate the association between serum folate levels during pregnancy and prenatal depression and the extent to which obesity may modify this relationship. This secondary data analysis leveraged data from a previous study of pregnant Kaiser Permanente Northern California participants who completed a survey and provided a serum sample between 2011 and 2013. Serum folate was assessed using the Center for Disease Control’s Total Folate Serum/Whole Blood Microbiological Assay Method. A score of 15 or greater on the Center for Epidemiologic Studies Depression Scale was defined as prenatal depression. We used Poisson regression to estimate risk of prenatal depression given prenatal serum folate status (low/medium tertiles vs. high tertile) in the full sample and in subsamples of women with pre-pregnancy body mass index in the (a) normal range and (b) overweight/obese range. Of the sample, 13% had prenatal depression. Combined low/medium folate tertiles was associated with prenatal depression (adjusted relative risk [aRR]?=?1.97, 95% confidence interval [CI]: 0.93-4.18), although results did not reach statistical significance. This relationship was stronger among women with overweight/obesity than women with normal weight (aRR: 2.61, 95% CI: 1.01-6.71 and aRR: 1.50, 95% CI: 0.34-6.66, respectively). Results suggest an association between lower pregnancy folate levels and prenatal depression that may be stronger among women with overweight or obesity. Future studies need to clarify the temporal sequence of these associations.
Authors: Avalos, Lyndsay A; Nance, Nerissa; Caan, Bette; Sujan, Ayesha C; Uriu-Adams, Janet Y; Li, De-Kun; Quesenberry, Charles P; Hedderson, Monique M
J Matern Fetal Neonatal Med. 2023 Dec;36(1):1-4. Epub 2022-11-17.
Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk
Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene-environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case-control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E-4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E-4), and Aspartylglucosaminidase (AGA: p = 4.5E-4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.
Authors: Haas, Cameron B; Sakoda, Lori C; Hsu, Li; et al.
Sci Rep. 2022 Nov 07;12(1):18852. Epub 2022-11-07.
Evaluation of Harms Reporting in U.S. Cancer Screening Guidelines
Cancer screening should be recommended only when the balance between benefits and harms is favorable. This review evaluated how U.S. cancer screening guidelines reported harms, within and across organ-specific processes to screen for cancer. To describe current reporting practices and identify opportunities for improvement. Review of guidelines. United States. Patients eligible for screening for breast, cervical, colorectal, lung, or prostate cancer according to U.S. guidelines. Information was abstracted on reporting of patient-level harms associated with screening, diagnostic follow-up, and treatment. The authors classified harms reporting as not mentioned, conceptual, qualitative, or quantitative and noted whether literature was cited when harms were described. Frequency of harms reporting was summarized by organ type. Harms reporting was inconsistent across organ types and at each step of the cancer screening process. Guidelines did not report all harms for any specific organ type or for any category of harm across organ types. The most complete harms reporting was for prostate cancer screening guidelines and the least complete for colorectal cancer screening guidelines. Conceptualization of harms and use of quantitative evidence also differed by organ type. This review considers only patient-level harms. The authors did not verify accuracy of harms information presented in the guidelines. The review identified opportunities for improving conceptualization, assessment, and reporting of screening process-related harms in guidelines. Future work should consider nuances associated with each organ-specific process to screen for cancer, including which harms are most salient and where evidence gaps exist, and explicitly explore how to optimally weigh available evidence in determining net screening benefit. Improved harms reporting could aid informed decision making, ultimately improving cancer screening delivery. National Cancer Institute.
Authors: Kamineni, Aruna; Corley, Douglas A; Burnett-Hartman, Andrea N; et al.
Ann Intern Med. 2022 Nov;175(11):1582-1590. Epub 2022-09-27.
Smoking Behaviors and Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer in the Be-Well Study
Tobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear. To examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions. The Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022. Use of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records. Hazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression. A total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003). These findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.
Authors: Kwan, Marilyn L; Young-Wolff, Kelly C; Ergas, Isaac J; Quesenberry, Charles P; Kushi, Lawrence H; Tang, Li; et al.
JAMA Netw Open. 2022 Nov 01;5(11):e2244430. Epub 2022-11-01.
Quantifying Frailty Requires a Conceptual Model Before a Statistical Model-Reply
Authors: Le, Sidney T; Liu, Vincent X; Cespedes Feliciano, Elizabeth M
JAMA Surg. 2022 Nov 01;157(11):1065-1066.
Physician Adenoma Detection Rates and Colorectal Cancer-Reply
Authors: Corley, Douglas A; Schottinger, Joanne; Jensen, Christopher
JAMA. 2022 10 11;328(14):1462-1463.
Assessment of genetic susceptibility to multiple primary cancers through whole-exome sequencing in two large multi-ancestry studies
Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored. To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large multi-ancestry populations (6429 cases, 165,853 controls). We created two groupings of individuals diagnosed with multiple primary cancers: (1) an overall combined set with at least two cancers across any of 36 organ sites and (2) cancer-specific sets defined by an index cancer at one of 16 organ sites with at least 50 cases from each study population. We then investigated whether variants identified from exome sequencing were associated with these sets of multiple cancer cases in comparison to individuals with one and, separately, no cancers. We identified 22 variant-phenotype associations, 10 of which have not been previously discovered and were significantly overrepresented among individuals with multiple cancers, compared to those with a single cancer. Overall, we describe variants and genes that may play a fundamental role in the development of multiple primary cancers and improve our understanding of shared mechanisms underlying carcinogenesis.
Authors: Cavazos, Taylor B; Alexeeff, Stacey; Van Den Eeden, Stephen; Corley, Douglas A; Kushi, Lawrence H; Habel, Laurel A; Sakoda, Lori C; Witte, John S; et al.
BMC Med. 2022 10 06;20(1):332. Epub 2022-10-06.
Patient, Family, and Clinician Perspectives on Location of Death for Adolescents and Young Adults With Cancer
Adolescents and young adults (AYAs) with cancer have high rates of hospital deaths. It is not clear if this reflects their preferences or barriers to dying at home. Between December 2018 and January 2021, we conducted in-depth interviews with AYAs (age 12-39 years) with stage IV or recurrent cancer, family caregivers including bereaved caregivers, and clinicians of AYAs with cancer. Patients were asked about their priorities for care including location of death, caregivers were asked what was most important in the care of their AYA family member, and clinicians were asked to reflect on priorities identified through caring for AYAs. Directed content analysis was applied to interview data, and themes regarding location of death were developed. Eighty individuals (23 AYAs, 28 caregivers, and 29 clinicians) participated in interviews. Most AYAs and caregivers preferred a home death. However, some AYAs and caregivers opted for a hospital death to alleviate caregiver burden or protect siblings from the perceived trauma of witnessing a home death. Lack of adequate services to manage intractable symptoms at home and insufficient caregiver support led some AYAs/caregivers to opt for hospital death despite a preference for home death. Participants acknowledged the value of hospice while also pointing out its limitations in attaining a home death. Although most AYAs prefer to die at home, this preference is not always achieved. Robust home-based services for effective symptom management and caregiver support are needed to close the gap between preferred and actual location of death for AYAs.
Authors: Odejide, Oreofe O; Kushi, Lawrence H; Mack, Jennifer W; et al.
JCO Oncol Pract. 2022 Oct;18(10):e1621-e1629. Epub 2022-08-18.
Developing Meaningful Health Care Quality Metrics: An Example From Colonoscopy and Adenoma Detection
Authors: Corley, Douglas
Ann Intern Med. 2022 10;175(10):1479-1480. Epub 2022-09-27.
Sociodemographic and clinical characteristics associated with never-smoking status in patients with lung cancer: findings from a large integrated health system
Evidence is limited characterizing sociodemographically diverse patient populations with lung cancer in relation to smoking status. In a cross-sectional analysis of adults diagnosed with lung cancer at ages ≥30 years from 2007-2018 within an integrated healthcare system, overall and sex-specific prevalence of never smoking were estimated according to sociodemographic and clinical characteristics. Adjusted prevalence ratio (aPR) and 95% confidence interval (CI) were also estimated using modified Poisson regression to identify patient characteristics associated with never smoking, overall and by sex. Similar analyses were conducted to explore whether prevalence and association patterns differed between non-Hispanic White and Asian/Pacific Islander patients. Among 17,939 patients with lung cancer, 2,780 (15.5%) never smoked and 8,698 (48.5%) had adenocarcinoma. Overall prevalence of never smoking was higher among females than males (21.2% vs. 9.2%, aPR 2.13, 95% CI: 1.98-2.29); Asian/Pacific Islander (aPR 2.85, 95% CI: 2.65-3.07) and Hispanic (aPR 1.72, 95% CI: 1.51-1.95) than non-Hispanic White patients; patients who primarily spoke Spanish (aPR 1.60, 95% CI: 1.32-1.94), any Asian language (aPR 1.20, 95% CI: 1.10-1.30), or other languages (aPR 1.84, 95% CI: 1.27-2.65) than English; patients living in the least vs. most deprived neighborhoods (aPR 1.36, 95% CI: 1.24-1.50); and patients with adenocarcinoma (aPR 2.57, 95% CI: 2.18-3.03), other non-small cell lung cancer (NSCLC) (aPR 2.00, 95% CI: 1.63-2.45), or carcinoid (aPR 3.60, 95% CI: 2.96-4.37) than squamous cell carcinoma tumors. Patterns of never smoking associated with sociodemographic, but not clinical factors, differed by sex. The higher prevalence of never smoking associated with Asian/Pacific Islander race/ethnicity was more evident among females (aPR 3.30, 95% CI: 2.95-3.47) than males (aPR 2.25, 95% CI: 1.92-2.63), whereas the higher prevalence of never smoking associated with living in the least deprived neighborhoods was more evident among males (aPR 1.93, 95% CI: 1.56-2.38) than females (aPR 1.18, 95% CI: 1.06-1.31). Associations between primary language and never-smoking status were found only among females. Overall and sex-specific prevalence and association patterns differed between Asian/Pacific Islander and non-Hispanic white patients. Our findings suggest that patterns of never-smoking status associated with sociodemographic and clinical characteristics are different across sex and race/ethnicity among patients with lung cancer. Such data are critical to increasing awareness and expediting diagnosis of this disease.
Authors: Banks, Kian C; Sumner, Eric T; Alabaster, Amy; Hsu, Diana S; Quesenberry, Charles P; Sakoda, Lori C; Velotta, Jeffrey B
Transl Cancer Res. 2022 Oct;11(10):3522-3534.
Adiposity and cancer survival: a systematic review and meta-analysis
The increasing availability of clinical imaging tests (especially CT and MRI) that directly quantify adipose tissue has led to a rapid increase in studies examining the relationship of visceral, subcutaneous, and overall adiposity to cancer survival. To summarize this emerging body of literature, we conducted a systematic review and meta-analysis of imaging-measured as well as anthropometric proxies for adipose tissue distribution and cancer survival across a wide range of cancer types. Using keywords related to adiposity, cancer, and survival, we conducted a systematic search of the literature in PubMed and MEDLINE, Embase, and Web of Science Core Collection databases from database inception to 30 June 2021. We used a random-effect method to calculate pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) within each cancer type and tested for heterogeneity using Cochran’s Q test and the I2 test. We included 203 records for this review, of which 128 records were utilized for quantitative analysis among 10 cancer types: breast, colorectal, gastroesophageal, head and neck, hepatocellular carcinoma, lung, ovarian, pancreatic, prostate, and renal cancer. We found that imaging-measured visceral, subcutaneous, and total adiposity were not significantly associated with increased risk of overall mortality, death from primary cancer, or cancer progression among patients diagnosed with these 10 cancer types; however, we found significant or high heterogeneity for many cancer types. For example, heterogeneity was similarly high when the pooled HRs (95% CI) for overall mortality associated with visceral adiposity were essentially null as in 1.03 (0.55, 1.92; I2 = 58%) for breast, 0.99 (0.81, 1.21; I2 = 71%) for colorectal, versus when they demonstrated a potential increased risk 1.17 (0.85, 1.60; I2 = 78%) for hepatocellular carcinoma and 1.62 (0.90, 2.95; I2 = 84%) for renal cancer. Greater adiposity at diagnosis (directly measured by imaging) is not associated with worse survival among cancer survivors. However, heterogeneity and other potential limitations were noted across studies, suggesting differences in study design and adiposity measurement approaches, making interpretation of meta-analyses challenging. Future work to standardize imaging measurements and data analyses will strengthen research on the role of adiposity in cancer survival.
Authors: Cheng, En; Kirley, Jocelyn; Cespedes Feliciano, Elizabeth M; Caan, Bette J
Cancer Causes Control. 2022 Oct;33(10):1219-1246. Epub 2022-08-15.
Adherence to the American Cancer Society Guidelines on nutrition and physical activity for cancer prevention and obesity-related cancer risk and mortality in Black and Latina Women’s Health Initiative participants
Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women’s Health Initiative (WHI). Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking. Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR]highvs.low : 0.72; 95% CI, 0.55-0.94) and Latina (CSHRhighvs.low : 0.58, 95% CI, 0.36-0.93) women; but not conditional all-cause mortality (Black hazard ratio [HR]highvs.low : 0.86; 95% CI, 0.53-1.39; Latina HRhighvs.low : 0.81; 95% CI, 0.32-2.06). Higher adherence was associated with lower incidence of less common ORC (Ptrend = .025), but conditional mortality events were limited. Adherence and ORC-specific deaths were not associated and there was no evidence of effect modification. Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality. Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women’s Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers.
Authors: Pichardo, Margaret S; Cespedes Feliciano, Elizabeth M; Irwin, Melinda L; et al.
Cancer. 2022 10;128(20):3630-3640. Epub 2022-08-23.
Optimism, lifestyle, and longevity in a racially diverse cohort of women
Research has suggested optimism is associated with healthy aging and exceptional longevity, but most studies were conducted among non-Hispanic White populations. We examined associations of optimism to longevity across racial and ethnic groups and assessed healthy lifestyle as a possible mediating pathway. Participants from the Women’s Health Initiative (N = 159,255) completed a validated measure of optimism and provided other demographic and health data at baseline. We evaluated associations of optimism with increments in lifespan using accelerated failure time models, and with likelihood of exceptional longevity (survival to age ≥90) using Poisson regression models. Causal mediation analysis explored whether lifestyle-related factors mediated optimism-lifespan associations. After covariate adjustment, the highest versus lowest optimism quartile was associated with 5.4% (95% confidence interval [CI] = 4.5, 6.4%) longer lifespan. Within racial and ethnic subgroups, these estimates were 5.1% (95%CI = 4.0, 6.1%) in non-Hispanic White, 7.6% (95%CI = 3.6, 11.7%) in Black, 5.4% (95%CI = -0.1, 11.2%) in Hispanic/Latina, and 1.5% (95% CI = -5.0, 8.5) in Asian women. A high proportion (53%) of the women achieved exceptional longevity. Participants in the highest versus lowest optimism quartile had greater likelihood of achieving exceptional longevity (e.g., full sample risk ratio = 1.1, 95%CI = 1.1, 1.1). Lifestyle mediated 24% of the optimism-lifespan association in the full sample, 25% in non-Hispanic White, 10% in Black, 24% in Hispanic/Latina, and 43% in Asian women. Higher optimism was associated with longer lifespan and a greater likelihood of achieving exceptional longevity overall and across racial and ethnic groups. The contribution of lifestyle to these associations was modest. Optimism may promote health and longevity in diverse racial and ethnic groups. Future research should investigate these associations in less long-lived populations.
Authors: Koga, Hayami K; Trudel-Fitzgerald, Claudia; Lee, Lewina O; James, Peter; Kroenke, Candyce; Garcia, Lorena; Shadyab, Aladdin H; Salmoirago-Blotcher, Elena; Manson, JoAnn E; Grodstein, Francine; Kubzansky, Laura D
J Am Geriatr Soc. 2022 10;70(10):2793-2804. Epub 2022-06-08.
T1 signal intensity ratio of the pancreas as an imaging biomarker for the staging of chronic pancreatitis
Our purpose was to validate the T1 SIR (T1 score) as an imaging biomarker for the staging of CP in a large, multi-institutional, prospective study. The prospective study population included 820 participants enrolled in the PROCEED study from nine clinical centers between June 2017 and December 2021. A radiologist at each institution used a standardized method to measure the T1 signal intensity of the pancreas and the reference organs (spleen, paraspinal muscle, liver), which was used to derive respective T1 scores. Participants were stratified according to the seven mechanistic stages of chronic pancreatitis (MSCP 0-6) based on their clinical history, MRCP, and CT findings. The mean pancreas-to-spleen T1 score was 1.30 in participants with chronic abdominal pain, 1.22 in those with acute or recurrent acute pancreatitis, and 1.03 in definite CP. After adjusting for covariates, we observed a linear, progressive decline in the pancreas-to-spleen T1 score with increasing MSCP from 0 to 6. The mean pancreas-to-spleen T1 scores were 1.34 (MSCP 0), 1.27 (MSCP 1), 1.21 (MSCP 2), 1.16 (MSCP 3), 1.18 (MSCP 4), 1.12 (MSCP 5), and 1.05 (MSCP 6) (p < 0.0001). The pancreas-to-liver and pancreas-to-muscle T1 scores showed less linear trends and wider confidence intervals. The T1 score calculated by SIR of the pancreas-to-spleen shows a negative linear correlation with the progression of chronic pancreatitis. It holds promise as a practical imaging biomarker in evaluating disease severity in clinical research and practice.
Authors: Tirkes, Temel; Van Den Eeden, Stephen K; Consortium for the Study of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (CPDPC),; et al.
Abdom Radiol (NY). 2022 Oct;47(10):3507-3519. Epub 2022-07-20.
GA White Paper: Challenges and Gaps in Innovation for the Performance of Colonoscopy for Screening and Surveillance of Colorectal Cancer
In 2018, the American Gastroenterological Association’s Center for GI Innovation and Technology convened a consensus conference, entitled “Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes.” The conference participants, which included more than 60 experts in colorectal cancer, considered recent improvements in colorectal cancer screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation. This white paper originates from that conference. It aims to summarize current patient- and physician-centered gaps and challenges in colonoscopy, diagnostic and therapeutic challenges affecting colonoscopy uptake, and the potential use of emerging technologies and quality metrics to improve patient outcomes.
Authors: Komanduri, Srinadh; Lieberman, David; Muthusamy, V Raman; et al.
Clin Gastroenterol Hepatol. 2022 Oct;20(10):2198-2209.e3. Epub 2022-06-07.
ASSOCIATION OF CHRONIC PANCREATITIS PAIN FEATURES WITH PHYSICAL, MENTAL AND SOCIAL HEALTH
Pain is a cardinal symptom of chronic pancreatitis (CP). Using PROMIS measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them to controls. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities. We analyzed baseline data in 488 CP patients and 254 controls enrolled in PROCEED, an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile which captures seven symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database. Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes: 2.54-7.03), and higher prevalence of clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, ORs: 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes: 4.08-10.37), and clinically significant depression, anxiety, sleep disturbance and physical disability (ORs: 2.80-5.38). Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP. gov number-NCT03099850.
Authors: Yadav, Dhiraj; Van Den Eeden, Stephen K; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC),; et al.
Clin Gastroenterol Hepatol. 2022 Sep 30.
Association of sleep duration and insomnia with metabolic syndrome and its components in the Women’s Health Initiative
Epidemiological evidence suggests that inadequate sleep duration and insomnia may be associated with increased risk of metabolic syndrome (MetS). However, longitudinal data with repeated measures of sleep duration and insomnia and of MetS are limited. We examined the association of sleep duration and insomnia with MetS and its components using longitudinal data from the Women’s Health Initiative (WHI). The study included postmenopausal women (ages 50-79 years) diabetes-free at enrollment in the WHI, with baseline data on sleep duration (n = 5,159), insomnia (n = 5,063), MetS, and its components. Repeated measures of self-reported sleep duration and insomnia were available from years 1 or 3 of follow-up and of the MetS components from years 3, 6 and 9. Associations were assessed using logistic regression and generalized estimating equations models, and odds ratios and 95% confidence intervals (CI) adjusted for major risk factors were calculated. In cross-sectional analysis, baseline sleep duration ≥ 9 h was positively associated with MetS (OR = 1.51; 95%CI 1.12-2.04), while sleep duration of 8- < 9 h was associated with waist circumference > 88 cm and triglycerides ≥ 150 mg/dL (OR = 1.18; 95%CI 1.01-1.40 and OR = 1.23; 95%CI 1.05-1.46, respectively). Insomnia had a borderline positive association with MetS (OR = 1.14; 95%CI 0.99-1.31), and significant positive associations with waist circumference > 88 cm and glucose ≥ 100 mg/dL (OR = 1.18; 95%CI 1.03-1.34 and OR = 1.17; 95%CI 1.02-1.35, respectively). In the longitudinal analysis, change from restful sleep to insomnia over time was associated with increased odds of developing MetS (OR = 1.40; 95%CI 1.01-1.94), and of a triglyceride level ≥ 150 mg/dL (OR = 1.48; 95%CI 1.08-2.03). Among postmenopausal women in the WHI, sleep duration and insomnia were associated with current and future risk of MetS and some of its components.
Authors: Peila, Rita; Allison, Matthew; Rohan, Thomas E; et al.
BMC Endocr Disord. 2022 Sep 14;22(1):228. Epub 2022-09-14.
eQTL set-based association analysis identifies novel susceptibility loci for Barrett’s esophagus and esophageal adenocarcinoma
Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach. This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis.
Authors: Wang, Xiaoyu; Risch, Harvey A; Dai, James Y; et al.
Cancer Epidemiol Biomarkers Prev. 2022 Sep 02;31(9):1735-1745.
Novel, Emerging Risk Factors for Colorectal Cancer Remain Understudied
Authors: Burnett-Hartman, Andrea N; Murphy, Caitlin C; Lee, Jeffrey K
Gastroenterology. 2022 09;163(3):574-576. Epub 2022-07-07.
CMV Colitis Masquerading as MALT Lymphoma in an Immunocompetent Patient
Authors: Lam, Angela Y; Lee, Jeffrey K
ACG Case Rep J. 2022 Sep;9(9):e00851. Epub 2022-09-01.
Electronic cigarette use and risk of COVID-19 among young adults without a history of cigarette smoking
It is unknown whether use of e-cigarettes increases susceptibility to COVID-19. In a large clinical sample of young adults, we evaluated whether current or ever e-cigarette use was associated with polymerase chain reaction (PCR)-confirmed COVID-19. To address the confounding of combustible smoking, the sample was restricted to never smokers. This retrospective cohort study analyzed data from the electronic health records of 74,853 young adults (aged 18-35 years), without a history of cigarette smoking, who were screened for e-cigarette use (current, former, never) in the Kaiser Permanente Northern California (KPNC) healthcare system from 3/5/2020 (baseline) to 11/30/2020 (pre-vaccine). COVID-19 risk was estimated in time-to-event analyses using multivariable Cox proportional hazard regression models, adjusted for socio-demographics and medical comorbidities. E-cigarette status in the cohort was: 1.6% current, 1.2% former, and 97.2% never. During follow-up, 1965 (2.6%) patients acquired COVID-19. We did not find evidence that current (vs never) e-cigarette use was associated with risk of COVID-19 (aHR = 1.12 95%CI:0.77-1.62). However, we did find suggestive evidence that former (versus never) e-cigarette use may be associated with greater risk of COVID-19 (aHR = 1.39 95%CI:0.98-1.96). While e-cigarette use is associated with health risks for young adults, results from this study suggest that current use of e-cigarettes may not increase susceptibility for COVID-19 among young adults who have never smoked cigarettes.
Authors: Young-Wolff, Kelly C; Slama, Natalie E; Alexeeff, Stacey E; Prochaska, Judith J; Fogelberg, Renee; Sakoda, Lori C
Prev Med. 2022 09;162:107151. Epub 2022-07-06.
Age-stratified prevalence and predictors of neoplasia among US adults undergoing screening colonoscopy in a national endoscopy registry
Several U.S. organizations now recommend starting average-risk colorectal cancer screening at age 45 years, but the prevalence of colonic neoplasia in individuals younger than 50 years has not been well characterized. We used a national endoscopic registry to calculate age-stratified prevalence and predictors of colorectal neoplasia. Outpatient screening colonoscopies performed during 2010-2020 in the GI Quality Improvement Consortium registry were analyzed. We measured the prevalence of advanced neoplasia and adenomas by age, sex, and race/ethnicity, as well as the prevalence ratio of neoplasia compared with the reference group of 50- to 54-year-olds. Multivariable logistic regression models were used to identify predictors of neoplasia. We identified 3,928,727 screening colonoscopies, of which 129,736 (3.3%) were performed on average-risk individuals younger than 50 years. The prevalence of advanced neoplasia was 6.2% for 50- to 54-year-olds and 5.0% (prevalence ratio, 0.81; 95% confidence interval, 0.78-0.83) for average-risk 45- to 49-year-olds. Men had higher prevalence of neoplasia than women for all age groups. White individuals had higher prevalence of advanced neoplasia than persons of other racial/ethnic groups in most age groups, which was partially driven by serrated lesions. On multivariable regression, White individuals had higher odds of advanced neoplasia than Black, Hispanic, and Asian individuals in both younger and older age groups. In a large U.S. endoscopy registry, the prevalence of advanced neoplasia in 45- to 49-year-olds was substantial and supports beginning screening at age 45 years. White individuals had higher risk of advanced neoplasia than Black, Hispanic, and Asian individuals across the age spectrum. These findings may inform adenoma detection benchmarks and risk-based screening strategies.
Authors: Liang, Peter S; Williams, J Lucas; Dominitz, Jason A; Corley, Douglas A; Zauber, Ann G
Gastroenterology. 2022 09;163(3):742-753.e4. Epub 2022-05-26.
Impact of the COVID-19 pandemic on fecal immunochemical testing, colonoscopy services, and colorectal neoplasia detection in a large United States community-based population
The COVID-19 pandemic has affected clinical services globally, including colorectal cancer (CRC) screening and diagnostic testing. We investigated the pandemic’s impact on fecal immunochemical test (FIT) screening, colonoscopy utilization, and colorectal neoplasia detection across 21 medical centers in a large integrated health care organization. We performed a retrospective cohort study in Kaiser Permanente Northern California patients ages 18 to 89 years in 2019 and 2020 and measured changes in the numbers of mailed, completed, and positive FITs; colonoscopies; and cases of colorectal neoplasia detected by colonoscopy in 2020 vs 2019. FIT kit mailings ceased in mid-March through April 2020 but then rebounded and there was an 8.7% increase in kits mailed compared with 2019. With the later mailing of FIT kits, there were 9.0% fewer FITs completed and 10.1% fewer positive tests in 2020 vs 2019. Colonoscopy volumes declined 79.4% in April 2020 compared with April 2019 but recovered to near pre-pandemic volumes in September through December, resulting in a 26.9% decline in total colonoscopies performed in 2020. The number of patients diagnosed by colonoscopy with CRC and advanced adenoma declined by 8.7% and 26.9%, respectively, in 2020 vs 2019. The pandemic led to fewer FIT screenings and colonoscopies in 2020 vs 2019; however, after the lifting of shelter-in-place orders, FIT screenings exceeded, and colonoscopy volumes nearly reached numbers from those same months in 2019. Overall, there was an 8.7% reduction in CRC cases diagnosed by colonoscopy in 2020. These data may help inform the development of strategies for CRC screening and diagnostic testing during future national emergencies.
Authors: Lee, Jeffrey K; Li, Dan; Corley, Douglas A; Levin, Theodore R; et al.
Gastroenterology. 2022 09;163(3):723-731.e6. Epub 2022-05-14.
Ovarian Cystadenomas: Growth Rate and Reliability of Imaging Measurements
To evaluate the growth rate of benign ovarian cystadenomas and the degree of variability in ultrasound measurements. Two independent retrospective cohorts of women found to have benign cystadenomas at surgery were identified. To assess growth rate, ultrasounds on women in a community-based health system were reviewed and the growth rate was determined based on the maximum reported size dimension using a mixed effect model. To assess measurement variability, two radiologists independently measured presurgical adnexal imaging findings for women in a tertiary care referral setting. Interobserver, intra-observer, and intermodality (cine clip versus still images) variability in measurements was determined using correlation coefficients (CC) and Bland-Altman analysis, with the proportion of measurements varying by more than 1 cm calculated. For growth rate assessment, 405 women with 1412 ultrasound examinations were identified. The median growth rate was 0.65 cm/year with mucinous cystadenomas growing faster at 0.83 cm/year compared to 0.51 cm/year for serous cystadenomas (median test P < .0001). To evaluate measurement variability, 75 women were identified with 176 ultrasound studies. The within-subject standard deviations for ultrasound measurements were 0.74 cm for cine clip images and 0.41 cm for static images, with 11% of measurements overall differing by more than 1 cm. Cystadenomas grow on average 0.65 cm/year, which is similar in magnitude to the inherent error observed in measurement on ultrasound, suggesting that repeat ultrasound at intervals of longer than a year will often be needed to accurately assess growth if a cyst represents a benign cystadenoma.
Authors: Suh-Burgmann, Elizabeth; Nakhaei, Masoud; Gupta, Sonia; Brook, Alexander; Hecht, Jonathan; Hung, Yun-Yi; Levine, Deborah
J Ultrasound Med. 2022 Sep;41(9):2157-2167. Epub 2021-11-30.
High Prevalence of Osteopathy in Chronic Pancreatitis: A Cross-sectional Analysis from the PROCEED Study
Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP. We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy. The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs 26.4%; P = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [CI], 1.15-1.45), female sex (OR, 3.08; 95% CI, 1.75-5.43), white race (OR, 2.68; 95% CI, 1.20-6.01), and underweight body mass index category (OR, 7.40; 95% CI, 1.56-34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and other patient and disease-related features of CP. In the largest study of patients with CP who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP. gov number, NCT03099850.
Authors: Hart, Phil A; Van Den Eden, Stephen K; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC),; et al.
Clin Gastroenterol Hepatol. 2022 09;20(9):2005-2013. Epub 2021-09-24.
Results and lessons from dual extraction of DNA and RNA from formalin-fixed paraffin-embedded breast tumor tissues for a large Cancer epidemiologic study
The use of archived formalin-fixed paraffin-embedded (FFPE) tumor tissues has become a common practice in clinical and epidemiologic genetic research. Simultaneous extraction of DNA and RNA from FFPE tissues is appealing but can be practically challenging. Here we report our results and lessons learned from processing FFPE breast tumor tissues for a large epidemiologic study. Qiagen AllPrep DNA/RNA FFPE kit was adapted for dual extraction using tissue punches or sections from breast tumor tissues. The yield was quantified using Qubit and fragmentation analysis by Agilent Bioanalyzer. A subset of the DNA samples were used for genome-wide DNA methylation assays and RNA samples for sequencing. The QC metrices and performance of the assays were analyzed with pre-analytical variables. A total of 1859 FFPE breast tumor tissues were processed. We found it critical to adjust proteinase K digestion time based on tissue volume to achieve balanced yields of DNA and RNA. Tissue punches taken from tumor-enriched regions provided the most reliable output. A median of 1475 ng DNA and 1786 ng RNA per sample was generated. The median DNA integrity number (DIN) was 3.8 and median DV200 for RNA was 33.2. Of 1294 DNA samples used in DNA methylation assays, 97% passed quality check by qPCR and 92% generated data deemed high quality. Of the 130 RNA samples with DV200 ≥ 20% used in RNA-sequencing, all but 5 generated usable transcriptomic data with a mapping rate ≥ 60%. Dual DNA/RNA purification using Qiagen AllPrep FFPE extraction protocol is feasible for clinical and epidemiologic studies. We recommend tissue punches as a reliable source material and fine tuning of proteinase K digestion time based on tissue volume. Our protocol and recommendations may be adapted by future studies for successful extraction of archived tumor tissues.
Authors: Ondracek, Rochelle Payne; Palmer, Julie R; Ambrosone, Christine B; et al.
BMC Genomics. 2022 Aug 25;23(1):614. Epub 2022-08-25.
Genome-Wide Interaction Analysis of Genetic Variants with Menopausal Hormone Therapy for Colorectal Cancer Risk
The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2- or 3-degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2-degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10-4). Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.
Authors: Tian, Yu; Sakoda, Lori C; Chang-Claude, Jenny; et al.
J Natl Cancer Inst. 2022 08 08;114(8):1135-1148.
Evaluating and Improving Cancer Screening Process Quality in a Multilevel Context: The PROSPR II Consortium Design and Research Agenda
Cancer screening is a complex process involving multiple steps and levels of influence (e.g., patient, provider, facility, health care system, community, or neighborhood). We describe the design, methods, and research agenda of the Population-based Research to Optimize the Screening Process (PROSPR II) consortium. PROSPR II Research Centers (PRC), and the Coordinating Center aim to identify opportunities to improve screening processes and reduce disparities through investigation of factors affecting cervical, colorectal, and lung cancer screening in U.S. community health care settings. We collected multilevel, longitudinal cervical, colorectal, and lung cancer screening process data from clinical and administrative sources on >9 million racially and ethnically diverse individuals across 10 heterogeneous health care systems with cohorts beginning January 1, 2010. To facilitate comparisons across organ types and highlight data breadth, we calculated frequencies of multilevel characteristics and volumes of screening and diagnostic tests/procedures and abnormalities. Variations in patient, provider, and facility characteristics reflected the PROSPR II health care systems and differing target populations. PRCs identified incident diagnoses of invasive cancers, in situ cancers, and precancers (invasive: 372 cervical, 24,131 colorectal, 11,205 lung; in situ: 911 colorectal, 32 lung; precancers: 13,838 cervical, 554,499 colorectal). PROSPR II’s research agenda aims to advance: (i) conceptualization and measurement of the cancer screening process, its multilevel factors, and quality; (ii) knowledge of cancer disparities; and (iii) evaluation of the COVID-19 pandemic’s initial impacts on cancer screening. We invite researchers to collaborate with PROSPR II investigators. PROSPR II is a valuable data resource for cancer screening researchers.
Authors: Beaber, Elisabeth F; Corley, Douglas A; Doria-Rose, V Paul; et al.
Cancer Epidemiol Biomarkers Prev. 2022 Aug 02;31(8):1521-1531.
Estimating Cancer Screening Sensitivity and Specificity Using Healthcare Utilization Data: Defining the Accuracy Assessment Interval
The effectiveness and efficiency of cancer screening in real-world settings depend on many factors, including test sensitivity and specificity. Outside of select experimental studies, not everyone receives a gold standard test that can serve as a comparator in estimating screening test accuracy. Thus, many studies of screening test accuracy use the passage of time to infer whether or not cancer was present at the time of the screening test, particularly for patients with a negative screening test. We define the accuracy assessment interval as the period of time after a screening test that is used to estimate the test’s accuracy. We describe how the length of this interval may bias sensitivity and specificity estimates. We call for future research to quantify bias and uncertainty in accuracy estimates and to provide guidance on setting accuracy assessment interval lengths for different cancers and screening modalities.
Authors: Chubak, Jessica; Burnett-Hartman, Andrea N; Barlow, William E; Corley, Douglas A; Croswell, Jennifer M; Neslund-Dudas, Christine; Vachani, Anil; Silver, Michelle I; Tiro, Jasmin A; Kamineni, Aruna
Cancer Epidemiol Biomarkers Prev. 2022 Aug 02;31(8):1517-1520.
Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
Authors: Byun, Jinyoung; Spitz, Margaret; Amos, Christopher I; et al.
Nat Genet. 2022 Aug;54(8):1167-1177. Epub 2022-08-01.
Anti-Müllerian hormone levels and breast cancer risk in the study of women’s health across the nation
The relation of premenopausal anti-Müllerian hormone (AMH) levels with breast cancer risk has been evaluated in a few studies, but primarily in non-Hispanic White women. We evaluated the association of AMH levels with breast cancer risk in Study of Women’s Health Across the Nation (SWAN), a multi-ethnic cohort of women. At enrollment, participants had an intact uterus and ≥ 1 ovary, and ≥ 1 menstrual period in the last 3 months. AMH at first measurement was assessed in 1,529 pre- or perimenopausal women using a high-sensitivity ELISA assay; values were natural log transformed. Breast cancer diagnoses were assessed at enrollment and subsequent follow-up visits through 2018 (median 6.1 years). In total, 84 women reported an incident breast cancer diagnosis. In multivariable Cox regression models adjusting for age, race and ethnicity, body mass index, and other factors, higher AMH levels were associated with a non-significant increased breast cancer risk. Compared to women in the 1st quartile, the hazard ratio (95% confidence interval) for women in the 4th quartile was 1.77 (0.87-3.60). Our results did not suggest a significant association between AMH and breast cancer risk; however, estimates were consistent with prior studies that reported positive associations.
Authors: Grimes, Nydjie P; Bertone-Johnson, Elizabeth R; Whitcomb, Brian W; Sievert, Lynnette L; Crawford, Sybil L; Gold, Ellen B; Avis, Nancy E; Greendale, Gail A; Santoro, Nanette; Habel, Laurel A; Reeves, Katherine W
Cancer Causes Control. 2022 Aug;33(8):1039-1046. Epub 2022-06-29.
Current and future colorectal cancer screening strategies
Despite strong evidence of effectiveness, colorectal cancer (CRC) screening remains underused. Currently, there are several options for CRC screening, each with its own performance characteristics and considerations for practice. This Review aims to cover current CRC screening guidelines and highlight future blood-based and imaging-based options for screening. In current practice, the leading non-invasive option is the faecal immunochemical test (FIT) based on its high specificity, good sensitivity, low cost and ease of use in mailed outreach programmes. There are currently five blood-based CRC screening tests in varying stages of evaluation, including one that is currently sold in the USA as a laboratory-developed test. There are ongoing studies on the diagnostic accuracy and longitudinal performance of blood tests and they have the potential to disrupt the CRC screening landscape. Imaging-based options, including the colon capsule, MR colonography and the CT capsule, are also being tested in active studies. As the world attempts to recover from the COVID-19 pandemic and adapts to the start of CRC screening among people at average risk starting at age 45 years, non-invasive options will become increasingly important.
Authors: Shaukat, Aasma; Levin, Theodore R
Nat Rev Gastroenterol Hepatol. 2022 08;19(8):521-531. Epub 2022-05-03.
Facilitating Adherence to Annual Screening for Lung Cancer: Are Program-Level Interventions Enough?
Authors: Sakoda, Lori C; Gould, Michael K
Chest. 2022 07;162(1):8-10.
The association of abdominal adiposity with premature discontinuation of postoperative chemotherapy in colon cancer
Patients with colon cancer who prematurely discontinue postoperative chemotherapy may have an increased risk of disease recurrence and death. This study tested the hypothesis that the quantity and distribution of abdominal adipose tissue predict premature chemotherapy discontinuation. This cohort study included 533 patients with stage II-III colon cancer who initiated a planned regimen of 24-weeks of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposures were body mass index (BMI) and computed tomography-derived abdominal adiposity measures (e.g., visceral, subcutaneous, and intramuscular adipose tissue). The primary endpoint was premature chemotherapy discontinuation, defined as receiving <6 cycles of FOLFOX. Generalized linear models quantified the relative risk (RR) of premature chemotherapy discontinuation adjusted for age, sex, cancer stage, height, and muscle area, using two-sided statistical tests. Forty-two patients [7.9% (95% CI: 5.7, 10.5)] prematurely discontinued chemotherapy. Visceral adipose tissue [RR: 3.27 (95% CI: 1.26, 8.49)] and intramuscular adipose tissue [RR: 2.79 (95% CI: 1.09, 7.12)] were statistically significantly associated with an increased risk of premature chemotherapy discontinuation. BMI [RR: 2.07 (95% CI: 0.75, 5.73)] and subcutaneous adipose tissue [RR: 2.32 (95% CI: 0.91, 5.94)] were not statistically significantly associated with premature chemotherapy discontinuation. Among patients with stage II-III colon cancer who initiate postoperative chemotherapy, excess visceral and intramuscular adiposity may be risk factors for the premature discontinuation of chemotherapy.
Authors: Brown, Justin C; Meyerhardt, Jeffrey A; Cespedes Feliciano, Elizabeth M; Cheng, En; Caan, Bette J
Clin Nutr. 2022 Jul;41(7):1600-1604. Epub 2022-05-27.
Telehealth for Preoperative Evaluation of Patients With Breast Cancer During the COVID-19 Pandemic
Introduction The COVID-19 pandemic drove rapid, widespread adoption of telehealth (TH). We evaluated surgical telehealth utilization and outcomes for newly diagnosed breast cancer patients during the initial pandemic period. Methods We identified patients with breast cancer diagnosed March 17, 2020 through May 17, 2020 who underwent surgery as the initial treatment. Clinicodemographic characteristics were collected. Initial consultation types (office, telephone, or video) were categorized. Outcomes included time to consultation, surgeon touchpoints, time to surgery, surgery types, and reexcision rates. Continuous variables were compared using Mann-Whitney tests or t-tests, and categorical variables were compared using χ2 or Fisher’s exact tests. Results Of 158 patients, 56% had initial telehealth consultations (21% telephone, 35% video) and 42% did not have a preoperative physical examination. Age, race/ethnicity, and stage distributions were similar between initial visit types. Median time to consultation was lower in the initial telehealth group than the office group (6 days vs 9 days, p = 0.01). Other outcomes (surgeon touchpoints, time to surgery, surgery type, reconstruction) were similar between visit types. We observed higher reexcision rates in patients with initial telehealth visits (20% telehealth vs 4% office, p = 0.01), but evaluation was limited by small numbers. The reexcision rate was 13% for patients with telehealth visits and no preoperative physical exam. Discussion During the initial pandemic period, the majority of new breast cancer patients had an initial telehealth surgical consultation. Office and telehealth consultation visits had comparable numbers of postconsultation surgeon touchpoints and most outcomes. Our findings suggest that telehealth consultations may be feasible for preoperative breast cancer consultations.
Authors: Tang, Annie; Arasu, Vignesh A; Liu, Raymond; Habel, Laurel A; Kushi, Lawrence H; Chang, Sharon B; et al.
Perm J. 2022 06 29;26(2):54-63. Epub 2022-06-15.
Risk of severe clinical outcomes among persons with SARS-CoV-2 infection with differing levels of vaccination during widespread Omicron (B.1.1.529) and Delta (B.1.617.2) variant circulation in Northern California: A retrospective cohort study
The incidence of and risk factors for severe clinical outcomes with the Omicron (B.1.1.529) SARS-CoV-2 variant have not been well-defined. We conducted a retrospective cohort study to assess risks of severe clinical outcomes within 21 days after SARS-CoV-2 diagnosis in a large, diverse, integrated health system. Among 118,078 persons with incident SARS-CoV-2 infection, 48,101 (41%) were during the Omicron period and 69,977 (59%) during the Delta (B.1.617.2) period. Cumulative incidence of any hospitalization (2.4% versus 7.8%; adjusted hazard ratio [aHR] 0.55; 95% confidence interval [CI] (0.51-0.59), with low-flow oxygen support (1.6% versus 6.4%; aHR 0.46; CI 0.43-0.50), with high-flow oxygen support (0.6% versus 2.8%; aHR 0.47; CI 0.41-0.54), with invasive mechanical ventilation (0.1% versus 0.7%; aHR 0.43; CI 0.33-0.56), and death (0.2% versus 0.7%; aHR 0.54; CI 0.42-0.70) were lower in the Omicron than the Delta period. The risk of hospitalization was higher among unvaccinated persons (aHR 8.34; CI 7.25-9.60) and those who completed a primary COVID-19 vaccination series (aHR 1.72; CI 1.49-1.97) compared with those who completed a primary vaccination series and an additional dose. The strongest risk factors for all severe clinical outcomes were older age, higher body mass index and select comorbidities. Persons with SARS-CoV-2 infection were significantly less likely to develop severe clinical outcomes during the Omicron period compared with the Delta period. COVID-19 primary vaccination and additional doses were associated with reduced risk of severe clinical outcomes among those with SARS-CoV-2 infection. National Cancer Institute and The Permanente Medical Group.
Authors: Skarbinski, Jacek; Wood, Mariah S; Chervo, Tyler C; Schapiro, Jeffrey M; Elkin, Eric P; Valice, Emily; Amsden, Laura B; Hsiao, Crystal; Quesenberry, Charles; Corley, Douglas A; Kushi, Lawrence H
Lancet Reg Health Am. 2022 Jun 16:100297.
Association of Physician Adenoma Detection Rates With Postcolonoscopy Colorectal Cancer
Although colonoscopy is frequently performed in the United States, there is limited evidence to support threshold values for physician adenoma detection rate as a quality metric. To evaluate the association between physician adenoma detection rate values and risks of postcolonoscopy colorectal cancer and related deaths. Retrospective cohort study in 3 large integrated health care systems (Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente Washington) with 43 endoscopy centers, 383 eligible physicians, and 735 396 patients aged 50 to 75 years who received a colonoscopy that did not detect cancer (negative colonoscopy) between January 2011 and June 2017, with patient follow-up through December 2017. The adenoma detection rate of each patient’s physician based on screening examinations in the calendar year prior to the patient’s negative colonoscopy. Adenoma detection rate was defined as a continuous variable in statistical analyses and was also dichotomized as at or above vs below the median for descriptive analyses. The primary outcome (postcolonoscopy colorectal cancer) was tumor registry-verified colorectal adenocarcinoma diagnosed at least 6 months after any negative colonoscopy (all indications). The secondary outcomes included death from postcolonoscopy colorectal cancer. Among 735 396 patients who had 852 624 negative colonoscopies, 440 352 (51.6%) were performed on female patients, median patient age was 61.4 years (IQR, 55.5-67.2 years), median follow-up per patient was 3.25 years (IQR, 1.56-5.01 years), and there were 619 postcolonoscopy colorectal cancers and 36 related deaths during more than 2.4 million person-years of follow-up. The patients of physicians with higher adenoma detection rates had significantly lower risks for postcolonoscopy colorectal cancer (hazard ratio [HR], 0.97 per 1% absolute adenoma detection rate increase [95% CI, 0.96-0.98]) and death from postcolonoscopy colorectal cancer (HR, 0.95 per 1% absolute adenoma detection rate increase [95% CI, 0.92-0.99]) across a broad range of adenoma detection rate values, with no interaction by sex (P value for interaction = .18). Compared with adenoma detection rates below the median of 28.3%, detection rates at or above the median were significantly associated with a lower risk of postcolonoscopy colorectal cancer (1.79 vs 3.10 cases per 10 000 person-years; absolute difference in 7-year risk, -12.2 per 10 000 negative colonoscopies [95% CI, -10.3 to -13.4]; HR, 0.61 [95% CI, 0.52-0.73]) and related deaths (0.05 vs 0.22 cases per 10 000 person-years; absolute difference in 7-year risk, -1.2 per 10 000 negative colonoscopies [95%, CI, -0.80 to -1.69]; HR, 0.26 [95% CI, 0.11-0.65]). Within 3 large community-based settings, colonoscopies by physicians with higher adenoma detection rates were significantly associated with lower risks of postcolonoscopy colorectal cancer across a broad range of adenoma detection rate values. These findings may help inform recommended targets for colonoscopy quality measures.
Authors: Schottinger, Joanne E; Lee, Jeffrey K; Fireman, Bruce H; Quesenberry, Charles P; Corley, Douglas A; et al.
JAMA. 2022 06 07;327(21):2114-2122.
Diabetes Incidence Among Hispanic/Latino Adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
To examine diabetes incidence in a diverse cohort of U.S. Hispanic/Latinos. The Hispanic Community Health Study/Study of Latinos is a prospective cohort study with participants aged 18-74 years from four U.S. metropolitan areas. Participants were assessed for diabetes at the baseline examination (2008-2011), annually via telephone interview, and at a second examination (2014-2017). A total of 11,619 participants returned for the second examination. The overall age-adjusted diabetes incidence rate was 22.1 cases/1,000 person-years. The incidence was high among those with Puerto Rican and Mexican backgrounds as well as those aged ≥45 years and with a BMI ≥30 kg/m2. Significant differences in diabetes awareness, treatment, and health insurance coverage, but not glycemic control, were observed across Hispanic/Latino background groups, age groups, and BMI categories. Differences in diabetes incidence by Hispanic/Latino background, age, and BMI suggest the susceptibility of these factors.
Authors: Cordero, Christina; Espinoza Giacinto, Rebeca A; Avilés-Santa, Larissa; et al.
Diabetes Care. 2022 06 02;45(6):1482-1485.
Identification of Drug-Cancer Associations: A Nationwide Screening Study
The main tool in drug safety monitoring, spontaneous reporting of adverse effects, is unlikely to detect delayed adverse drug effects including cancer. Hypothesis-free screening studies based on administrative data could improve ongoing drug safety monitoring. Using Danish health registries, we conducted a series of case-control studies by identifying individuals with incident cancer in Denmark from 2001 to 2018, matching each case with 10 population controls on age, sex, and calendar time. ORs were estimated using conditional logistic regression accounting for matching factors, educational level, and selected comorbidities. A total of 13,577 drug-cancer associations were examined for individual drugs and 8,996 for drug classes. We reviewed 274 drug-cancer pairs where an association with high use and a cumulative dose-response pattern was present. We classified 65 associations as not readily attributable to bias of which 20 were established as carcinogens by the International Agency for Research on Cancer and the remaining 45 associations may warrant further study. The screening program identified drugs with known carcinogenic effects and highlighted a number of drugs that were not established as carcinogens and warrant further study. The effect estimates in this study should be interpreted cautiously and will need confirmation targeted epidemiologic and translational studies. This study provides a screening tool for drug carcinogenicity aimed at hypothesis generation and explorative purposes. As such, the study may help to identify drugs with unknown carcinogenic effects and, ultimately, improve drug safety as part of the ongoing safety monitoring of drugs.
Authors: Kristensen, Kasper Bruun; Friis, Søren; Lund, Lars Christian; Hallas, Jesper; Cardwell, Chris R; Andreassen, Bettina K; Habel, Laurel A; Pottegård, Anton
Cancer Res Commun. 2022 Jun;2(6):552-560. Epub 2022-06-29.
Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies
Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies. In the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation’s largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders). Several studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes. In this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases.
Authors: Figueiredo, Jane C; Kushi, Lawrence H; Corley, Douglas A; Skarbinski, Jacek; et al.
Open Forum Infect Dis. 2022 Jun;9(6):ofac171. Epub 2022-04-27.
Risk of heart failure with preserved versus reduced ejection fraction in women with breast cancer
While clinical heart failure (HF) is recognized as an adverse effect from breast cancer (BC) treatment, sparse data exist on specific HF phenotypes in affected BC survivors. We examined risk of HF by left ventricular ejection fraction (LVEF) status in women with a history of BC. 14,804 women diagnosed with all stages of invasive BC from 2005 to 2013 and with no history of HF were matched 1:5 to 74,034 women without BC on birth year, race, and ethnicity. LVEF values were extracted from echocardiography studies within 30 days before through 90 days after the HF clinical encounter. HF was stratified into HF with preserved ejection fraction (HFpEF, LVEF ≥ 45%) and HF with reduced ejection fraction (HFrEF, LVEF < 45%). Cumulative incidence rates (CIRs) were estimated with competing risk of overall death. Hazard ratios (HR) were calculated by multivariable Cox proportional hazards regression. Mean time to HF diagnosis was 5.31 years (range 0.03-13.03) in cases and 5.25 years (range 0.01-12.94) in controls. 10-year CIRs were 1.2% and 0.9% for overall HF, 0.8% and 0.7% for HFpEF, and 0.4% and 0.2% for HFrEF in cases and controls, respectively. In fully adjusted models, an overall significant increased risk of HF in cases versus controls was observed (HR: 1.31, 95% CI 1.14, 1.51). The increased risk was seen for both HFrEF (HR: 1.59, 95% CI 1.22, 2.08) and HFpEF (HR: 1.22; 95% CI 1.03, 1.45). BC survivors experienced higher risk of HF compared with women without BC, and the risk persisted across LVEF phenotypes. Systematic cardio-oncology surveillance should be considered to mitigate this risk in BC patients.
Authors: Kwan, Marilyn L; Cheng, Richard K; Iribarren, Carlos; Shen, Hanjie; Laurent, Cecile A; Roh, Janise M; Hershman, Dawn L; Kushi, Lawrence H; Greenlee, Heather; Rana, Jamal S
Breast Cancer Res Treat. 2022 Jun;193(3):669-675. Epub 2022-04-16.
Trajectories of objectively measured physical function among older breast cancer survivors in comparison with cancer-free controls
Aging associated with progressive declines in physical function is well-known; however, it is unclear how breast cancer diagnosis affects the trajectories of physical function over a long period of time. The current study examined the trajectories in objective measures of physical function over 20 years for women with breast cancer and matched controls. 2712 community-dwelling women (452 breast cancer cases and 1:5 matched cancer-free controls) aged 65 years or older at baseline (1986-1988) within the Study of Osteoporotic Fractures were followed for 20 years. Objective physical function was assessed up to 9 times, including hand grip strength, timed chair stand, gait speed and quadriceps strength. Linear mixed models were used to model physical function changes in terms of secular time trend, group (cases or controls), period (pre-and post-diagnosis status), and their interaction terms. We observed all measures of physical function declined over time. While no differences in trends between cases and controls during the pre-diagnosis period were observed, after cancer diagnosis, grip strength and gait speed declined significantly faster in cases than controls. Quadriceps strength significantly decreased ~ 7 pounds shortly after breast cancer diagnosis, and then improved over time. Our study revealed that older breast cancer survivors relative to older women without cancer had significantly worse declines in grip strength and gait speed. Breast cancer survivors also had a sharp, short-term drop followed by gradual improvement over time in quadriceps strength. These findings suggest exercise training targeting muscle strength and mobility would be beneficial among older breast cancer survivors.
Authors: Luo, Juhua; Carter, Stephen J; Feliciano, Elizabeth M Cespedes; Hendryx, Michael
Breast Cancer Res Treat. 2022 Jun;193(2):467-476. Epub 2022-03-26.
“You have to be sure that the patient has the full picture”: Adaptation of the Best Case/Worst Case communication tool for geriatric oncology.
BACKGROUND: Shared decision making (SDM) is especially important for older adults with cancer given the risks of over- and undertreatment, uncertainty regarding benefits/harms worsened by research underrepresentation, and individual preferences. We aimed to adapt the Best Case/Worst Case (BC/WC) communication tool, which improves SDM in geriatric surgery, to geriatric oncology. n METHODS: We conducted focus groups with 40 stakeholders (fourteen older adults with lung cancer, twelve caregivers, fourteen medical oncologists) to elicit perspectives on using the BC/WC tool for geriatric oncology and to identify components needing refinement. During each focus group, participants viewed a BC/WC demonstration video and answered questions modified from the Decision Aid Acceptability Scale. We analyzed transcripts using deductive and inductive thematic analyses. n DISCUSSION: Participants believed that the BC/WC tool could help patients understand their cancer care choices, explore tradeoffs and picture potential outcomes, and deliberate about decisions based on their goals, preferences, and values. Oncologists also reported the tool could guide conversations to address points that may frequently be skipped (e.g., alternative options, treatment goals). Participant preferences varied widely regarding discussion of the worst-case scenario and desire for statistical information. n CONCLUSION: The BC/WC tool is a promising strategy that may improve SDM in geriatric oncology and patient understanding of alternative options and treatment goals. Based on participant input, adaptations will include framing cancer care as a series of decisions, eliciting patient preferences and asking permission before offering the worst-case scenario, and selection of the two most relevant options to present if multiple exist.
Authors: Wong, Melisa L;Nicosia, Francesca M;Smith, Alexander K;Walter, Louise C;Lam, Vivian;Cohen, Harvey Jay;Loh, Kah Poh;Mohile, Supriya G;Ursem, Carling J;Schwarze, Margaret L
J Geriatr Oncol. 2022 Jun;13(5):606-613. doi: 10.1016/j.jgo.2022.01.014. Epub 2022 Feb 2.
Predicting obstructive sleep apnea severity in children referred for polysomnography: use of the Pediatric Sleep Questionnaire and Subscales
This study evaluated the role of the Pediatric Sleep Questionnaire (PSQ) and associated subscales in predicting the severity of obstructive sleep apnea (OSA) in children referred for attended polysomnography (PSG). This is a retrospective study of children (0-18 years) who completed PSQs the night of their initial diagnostic PSG (2019-2020). We excluded children with previous PSG, positive airway pressure titrations, or underlying genetic or craniofacial syndromes. Area under the receiver operating characteristic curve (AUC [95%CIs]) were estimated for prediction of varying severities of obstructive apnea-hypopnea index (oAHI > 2, 5, 10, and 25/h) by the PSQ’s sleep-related breathing disorders (SRBD) scale and subscales. Of 477 children, median (IQR) age at PSG was 5.7 (4.3); 60% of children were male, 21% were obese, and 4% had oAHI > 25/h. SRBD score did not improve discrimination of OSA cases at any oAHI threshold, with AUC CI that crossed 50% at all severities. Snoring subscale scores were predictive at oAHI > 2/h (AUC = 64.5% [59.5-69.5%]), oAHI > 5/h (AUC = 64.3% [59.6-69.0%]), and oAHI > 10 (AUC = 67.2% [62.0-72.4%]) thresholds, but were not predictive at oAHI > 25/h. The addition of demographic data (age and gender) improved the classification of the SRBD scale. When utilized in children referred for attended PSG due to concerns for an underlying sleep disorder, the PSQ snoring subscale was more predictive of OSA at varying thresholds than the SRBD scale. While the original intent of the PSQ was not for the purpose of predicting severity in children referred for PSG, future directions include augmenting the questionnaire with additional clinical variables.
Authors: Bseikri, Mustafa; Zhang, Jie; Kirley, Jocelyn; Lee, Catherine; Castillo, Adrienne; Feliciano, Elizabeth M Cespedes
Sleep Breath. 2022 May 28.
Reduced Implementation and Completion of Average-Risk Annual Fecal Immunochemical Test Colorectal Cancer Screening in Black Patients Aged 45-49 Years
Authors: Coronado, Gloria D; Dickerson, John F; Burnett-Hartman, Andrea N; Carethers, John M; Lee, Jeff; Mcburnie, Mary Ann
Clin Gastroenterol Hepatol. 2022 May 27.
Risk of Cardiovascular Disease in Women With and Without Breast Cancer: The Pathways Heart Study
To examine cardiovascular disease (CVD) and mortality risk in women with breast cancer (BC) by cancer therapy received relative to women without BC. The study population comprised Kaiser Permanente Northern California members. Cases with invasive BC diagnosed from 2005 to 2013 were matched 1:5 to controls without BC on birth year and race/ethnicity. Cancer treatment, CVD outcomes, and covariate data were from electronic health records. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of CVD incidence and mortality by receipt of chemotherapy treatment combinations, radiation therapy, and endocrine therapy. A total of 13,642 women with BC were matched to 68,202 controls without BC. Over a 7-year average follow-up (range < 1-14 years), women who received anthracyclines and/or trastuzumab had high risk of heart failure/cardiomyopathy relative to controls, with the highest risk seen in women who received both anthracyclines and trastuzumab (HR, 3.68; 95% CI, 1.79 to 7.59). High risk of heart failure and/or cardiomyopathy was also observed in women with BC with a history of radiation therapy (HR, 1.38; 95% CI, 1.13 to 1.69) and aromatase inhibitor use (HR, 1.31; 95% CI, 1.07 to 1.60), relative to their controls. Elevated risks for stroke, arrhythmia, cardiac arrest, venous thromboembolic disease, CVD-related death, and death from any cause were also observed in women with BC on the basis of cancer treatment received. Women with BC had increased incidence of CVD events, CVD-related mortality, and all-cause mortality compared with women without BC, and risks varied according to the history of cancer treatment received. Studies are needed to determine how women who received BC treatment should be cared for to improve cardiovascular outcomes.
Authors: Greenlee, Heather; Rana, Jamal S; Cheng, Richard; Rillamas-Sun, Eileen; Neugebauer, Romain; Kwan, Marilyn L; Kwan, Marilyn L; et al.
J Clin Oncol. 2022 05 20;40(15):1647-1658. Epub 2022-04-06.
Risk of Cardiometabolic Risk Factors in Women With and Without a History of Breast Cancer: The Pathways Heart Study
The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC. Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:5 to noncancer controls on birth year, race, and ethnicity. Cumulative incidence rates of hypertension, diabetes, and dyslipidemia were estimated with competing risk of overall death. Subdistribution hazard ratios (sHRs) were estimated by Fine and Gray regression, adjusted for cardiovascular disease-related risk factors, and stratified by treatment and body mass index (BMI). A total of 14,942 BC cases and 74,702 matched controls were identified with mean age 61.2 years and 65% non-Hispanic White. Compared with controls, BC cases had higher cumulative incidence rates of hypertension (10.9% v 8.9%) and diabetes (2.1% v 1.7%) after 2 years, with higher diabetes incidence persisting after 10 years (9.3% v 8.8%). In multivariable models, cases had higher risk of diabetes (sHR, 1.16; 95% CI, 1.07 to 1.26) versus controls. Cases treated with chemotherapy (sHR, 1.23; 95% CI, 1.11 to 1.38), left-sided radiation (sHR, 1.29; 95% CI, 1.13 to 1.48), or endocrine therapy (sHR, 1.23; 95% CI, 1.12 to 1.34) continued to have higher diabetes risk. Hypertension risk was higher for cases receiving left-sided radiation (sHR, 1.11; 95% CI, 1.02 to 1.21) or endocrine therapy (sHR, 1.10; 95% CI, 1.03 to 1.16). Normal-weight (BMI < 24.9 kg/m2) cases had higher risks overall and within treatment subgroups versus controls. BC survivors at KPNC experienced elevated risks of diabetes and hypertension compared with women without BC depending on treatments received and BMI. Future studies should examine strategies for cardiometabolic risk factor prevention in BC survivors.
Authors: Kwan, Marilyn L; Iribarren, Carlos; Neugebauer, Romain; Rana, Jamal S; Nguyen-Huynh, Mai; Kushi, Lawrence H; Greenlee, Heather; et al.
J Clin Oncol. 2022 05 20;40(15):1635-1646. Epub 2022-01-13.
Fertility Preservation and Financial Hardship among Adolescent and Young Adult Women with Cancer
Financial hardship among adolescents and young adults (AYA) with cancer who receive gonadotoxic treatments may be exacerbated by the use of fertility services. This study examined whether AYA women with cancer who used fertility preservation had increased financial hardship. AYA women with cancer in North Carolina and California completed a survey in 2018-2019. Cancer-related financial hardship was compared between women who cryopreserved oocytes or embryos for fertility preservation after cancer diagnosis (n = 65) and women who received gonadotoxic treatment and reported discussing fertility with their provider, but did not use fertility preservation (n = 491). Multivariable log-binomial regression was used to estimate prevalence ratios and 95% confidence intervals (CI). Women were a median age of 33 years at diagnosis and 7 years from diagnosis at the time of survey. Women who used fertility preservation were primarily ages 25 to 34 years at diagnosis (65%), non-Hispanic White (72%), and had at least a Bachelor’s degree (85%). In adjusted analysis, use of fertility preservation was associated with 1.50 times the prevalence of material financial hardship (95% CI: 1.08-2.09). The magnitude of hardship was also substantially higher among women who used fertility preservation: 12% reported debt of ≥$25,000 versus 5% in the referent group. This study provides new evidence that cryopreserving oocytes or embryos after cancer diagnosis for future family building is associated with increased financial vulnerability. More legislation that mandates insurance coverage to mitigate hardships stemming from iatrogenic infertility could improve access to fertility preservation for young women with cancer.
Authors: Meernik, Clare; Mersereau, Jennifer E; Baggett, Christopher D; Engel, Stephanie M; Moy, Lisa M; Cannizzaro, Nancy T; Peavey, Mary; Kushi, Lawrence H; Chao, Chun R; Nichols, Hazel B
Cancer Epidemiol Biomarkers Prev. 2022 05 04;31(5):1043-1051.
Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region
Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. The study identifies multifaceted evidence of a possible functional effect for rs1318920.
Authors: Jordahl, Kristina M; Scacheri, Peter C; Peters, Ulrike; et al.
Cancer Epidemiol Biomarkers Prev. 2022 05 04;31(5):1077-1089.
Effect of Lifestyle Coaching or Enhanced Pharmacotherapy on Blood Pressure Control Among Black Adults With Persistent Uncontrolled Hypertension: A Cluster Randomized Clinical Trial
Greater difficulty in controlling blood pressure (BP) and adverse lifestyle practices such as higher salt intake or less physical activity may account for some of the differences between BP control rates in Black vs White adults, thereby exposing Black adults to a higher risk of vascular events. To determine whether a lifestyle coaching intervention or an enhanced pharmacotherapy protocol is more effective than usual care in improving BP control rates in Black adults treated within an integrated health care delivery system. Shake, Rattle & Roll, a cluster randomized clinical trial, was conducted from June 5, 2013, to June 11, 2018, in a large integrated health care delivery system. Enrollment was completed during a 12-month period and interventions were implemented for 12 months. Follow-up lasted 48 months after enrollment. Panels of Black adult members of the health care delivery system with BP of at least 140/90 mm Hg from 98 adult primary care physicians were randomly assigned at the primary care physician level to usual care (UC group [n = 1129]), enhanced pharmacotherapy monitoring (EP group [n = 346]) of current BP management protocol, or diet and lifestyle coaching consisting of photographs, stories, and recipes, for example, that are appropriate for Black adults (LC group [n = 286]) focused on the Dietary Approaches to Stop Hypertension (DASH) diet. Data were analyzed from June 1, 2016, to March 25, 2022. The UC group received care per customary protocol. The EP group was contacted by a research nurse and/or a clinical pharmacist to discuss barriers to hypertension control, and drug therapy emphasized the use of thiazide diuretic intensification and addition of spironolactone as needed. The LC group received as many as 16 telephone sessions with a lifestyle coach and an emphasis on implementing reduction of sodium intake and the DASH diet. Intention-to-treat analysis of BP control rates at end of the 12-month intervention. Among the 1761 participants, the mean (SD) age was 61 (13) years, and 1214 (68.9%) were women. At the end of the 12-month intervention period, there was no significant difference in BP control rate among study groups (UC, 61.8% [95% CI, 58.8%-64.9%]; EP, 64.5% [95% CI, 59.0%-69.4%]; LC, 67.8% [95% CI, 62.1%-73.2%]; LC vs EP, P = .07). However, greater BP control was present in the LC group vs UC at 24 months (UC, 61.2% [95% CI, 57.3%-64.7%]; EP, 67.6% [95% CI, 61.9%-72.8%]; LC, 72.4% [95% CI, 66.9%-78.1%]; LC vs UC, P = .001), and 48 months (UC, 64.5% [95% CI, 61.6%-67.2%]; EP, 66.5% [95% CI, 61.3%-71.3%]; LC, 73.1% [95% CI, 67.6%-77.9%]; LC vs UC, P = .006) after enrollment. The contribution of BP medication adherence to explain group differences was inconclusive. In this cluster randomized clinical trial including Black adults with persistent uncontrolled hypertension, a 12-month LC intervention was more effective at controlling BP than UC at 24 and 48 months after enrollment. Further research is needed to explore the potential implementation of this intervention into clinical practice. ClinicalTrials.gov Identifier: NCT01892592.
Authors: Nguyen-Huynh, Mai N; Young, Joseph D; Ovbiagele, Bruce; Alexander, Janet G; Alexeeff, Stacey; Lee, Catherine; Blick, Noelle; Caan, Bette J; Go, Alan S; Sidney, Stephen
JAMA Netw Open. 2022 May 02;5(5):e2212397. Epub 2022-05-02.
Psychological predictors of delayed active treatment following active surveillance for low-risk prostate cancer: The Patient REported outcomes for Prostate cARE prospective cohort study
In a prospective, comparative effectiveness study, we assessed clinical and psychological factors associated with switching from active surveillance (AS) to active treatment (AT) among low-risk prostate cancer (PCa) patients. Using ultra-rapid case identification, we conducted pretreatment telephone interviews (N = 1139) with low-risk patients (PSA ≤ 10, Gleason≤6) and follow-up interviews 6-10 months post-diagnosis (N = 1057). Among men remaining on AS for at least 12 months (N = 601), we compared those who continued on AS (N = 515) versus men who underwent delayed AT (N = 86) between 13 and 24 months, using Cox proportional hazards models. Delayed AT was predicted by time dependent PSA levels (≥10 vs. <10; HR = 5.6, 95% CI 2.4-13.1) and Gleason scores (≥7 vs. ≤6; adjusted HR = 20.2, 95% CI 12.2-33.4). Further, delayed AT was more likely among men whose urologist initially recommended AT (HR = 2.13, 95% CI 1.07-4.22), for whom tumour removal was very important (HR = 2.18, 95% CI 1.35-3.52), and who reported greater worry about not detecting disease progression early (HR = 1.67, 1.05-2.65). In exploratory analyses, 31% (27/86) switched to AT without evidence of progression, while 4.7% (24/515) remained on AS with evidence of progression. After adjusting for clinical evidence of disease progression over the first year post-diagnosis, we found that urologists' initial treatment recommendation and patients' early treatment preferences and concerns about AS each independently predicted undergoing delayed AT during the second year post-diagnosis. These findings, along with almost one-half undergoing delayed AT without evidence of progression, suggest the need for greater decision support to remain on AS when it is clinically indicated.
Authors: Taylor, Kathryn L; Luta, George; Zotou, Vasiliki; Lobo, Tania; Hoffman, Richard M; Davis, Kimberly M; Potosky, Arnold L; Li, Tengfei; Aaronson, David; Van Den Eeden, Stephen K
BJUI Compass. 2022 May;3(3):226-237. Epub 2021-12-14.
American Cancer Society nutrition and physical activity guideline for cancer survivors
The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors’ ability to adhere to recommendations. Approaches to meet survivors’ needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.
Authors: Rock, Cheryl L; Caan, Bette J; Neuhouser, Marian L; McCullough, Marjorie L; et al.
CA Cancer J Clin. 2022 05;72(3):230-262. Epub 2022-03-16.
Association between residential green cover and direct healthcare costs in Northern California: An individual level analysis of 5 million persons
Prior studies have shown higher green cover levels are associated with beneficial health outcomes. We sought to determine if residential green cover was also associated with direct healthcare costs. We linked residential Normalized Difference Vegetation Index (NDVI) satellite data for 5,189,303 members of Kaiser Permanente Northern California (KPNC) to direct individual healthcare costs for 2003-2015. Using generalized linear regression to adjust for confounding, we examined the association between direct healthcare costs and green cover within250, 500, and 1000 meters (m) of an individual’s residence. Costs were determined from an internal cost accounting system that captures administrative and patient care costs for each clinical encounter. Sensitivity analyses included adjustments for comorbidity and an alternative measure of green cover, tree canopy. We observed a significant inverse association between higher levels of residential green cover and lower direct healthcare costs. The relative rate of total cost for the highest compared to the lowest decile of NDVI was 0.92 (95% CI 0.90-0.93) for the 500 m buffer. The association was robust to adjustment from a broad array of confounders, found at each buffer size, and largely driven by hospitalization, and emergency department visits. Individuals in the top decile of residential green cover had adjusted healthcare costs of $374.04 (95% CI $307.31-$439.41) per person per year less than individuals living in the bottom or least green decile. Sensitivity analyses including tree canopy cover as the green space measure yielded similar findings. Analyses that included adjustment for comorbidity were consistent with the hypothesis that green cover reduces healthcare costs by improving health status. Green cover was associated with lower direct healthcare costs, raising the possibility that residential greening can have a significant healthcare cost impact across the population.
Authors: Van Den Eeden, Stephen K; H E M Browning, Matthew; Becker, Douglas A; Shan, Jun; Alexeeff, Stacey E; Thomas Ray, G; Quesenberry, Charles P; Kuo, Ming
Environ Int. 2022 05;163:107174. Epub 2022-03-17.
Comparison of Electronic Frailty Metrics for Prediction of Adverse Outcomes of Abdominal Surgery
Electronic frailty metrics have been developed for automated frailty assessment and include the Hospital Frailty Risk Score (HFRS), the Electronic Frailty Index (eFI), the 5-Factor Modified Frailty Index (mFI-5), and the Risk Analysis Index (RAI). Despite substantial differences in their construction, these 4 electronic frailty metrics have not been rigorously compared within a surgical population. To characterize the associations between 4 electronic frailty metrics and to measure their predictive value for adverse surgical outcomes. This retrospective cohort study used electronic health record data from patients who underwent abdominal surgery from January 1, 2010, to December 31, 2020, at 20 medical centers within Kaiser Permanente Northern California (KPNC). Participants included adults older than 50 years who underwent abdominal surgical procedures at KPNC from 2010 to 2020 that were sampled for reporting to the National Surgical Quality Improvement Program. Pearson correlation coefficients between electronic frailty metrics and area under the receiver operating characteristic curve (AUROC) of univariate models and multivariate preoperative risk models for 30-day mortality, readmission, and morbidity, which was defined as a composite of mortality and major postoperative complications. Within the cohort of 37 186 patients, mean (SD) age, 67.9 (female, 19 127 [51.4%]), correlations between pairs of metrics ranged from 0.19 (95% CI, 0.18- 0.20) for mFI-5 and RAI 0.69 (95% CI, 0.68-0.70). Only 1085 of 37 186 (2.9%) were classified as frail based on all 4 metrics. In univariate models for morbidity, HFRS demonstrated higher predictive discrimination (AUROC, 0.71; 95% CI, 0.70-0.72) than eFI (AUROC, 0.64; 95% CI, 0.63-0.65), mFI-5 (AUROC, 0.58; 95% CI, 0.57-0.59), and RAI (AUROC, 0.57; 95% CI, 0.57-0.58). The predictive discrimination of multivariate models with age, sex, comorbidity burden, and procedure characteristics for all 3 adverse surgical outcomes improved by including HFRS into the models. In this cohort study, the 4 electronic frailty metrics demonstrated heterogeneous correlation and classified distinct groups of surgical patients as frail. However, HFRS demonstrated the highest predictive value for adverse surgical outcomes.
Authors: Le, Sidney T; Liu, Vincent X; Kipnis, Patricia; Zhang, Jie; Peng, Peter D; Cespedes Feliciano, Elizabeth M
JAMA Surg. 2022 05 01;157(5):e220172. Epub 2022-05-11.
Declining Colectomy Rates for Nonmalignant Colorectal Polyps in a Large, Ethnically Diverse, Community-based Population
Despite studies showing improved safety, efficacy, and cost-effectiveness of endoscopic resection for nonmalignant colorectal polyps, colectomy rates for nonmalignant colorectal polyps have been increasing in the United States and Europe. Given this alarming trend, we aimed to investigate whether colectomy rates for nonmalignant colorectal polyps are increasing or declining in a large, integrated, community-based healthcare system with access to advanced endoscopic resection procedures. We identified all individuals aged 50-85 years who underwent a colonoscopy between 2008 and 2018 and were diagnosed with a nonmalignant colorectal polyp(s) at the Kaiser Permanente Northern California integrated healthcare system. Among these individuals, we identified those who underwent a colectomy for nonmalignant colorectal polyps within 12 months after the colonoscopy. We calculated annual colectomy rates for nonmalignant colorectal polyps and stratified rates by age, sex, and race and ethnicity. Changes in rates over time were tested by the Cochran-Armitage test for a linear trend. Among 229,730 patients who were diagnosed with nonmalignant colorectal polyps between 2008 and 2018, 1,611 patients underwent a colectomy. Colectomy rates for nonmalignant colorectal polyps decreased significantly from 125 per 10,000 patients with nonmalignant polyps in 2008 to 12 per 10,000 patients with nonmalignant polyps in 2018 (P < 0.001 for trend). When stratified by age, sex, and race and ethnicity, colectomy rates for nonmalignant colorectal polyps also significantly declined from 2008 to 2018. In a large, ethnically diverse, community-based population in the United States, we found that colectomy rates for nonmalignant colorectal polyps declined significantly over the past decade likely because of the establishment of advanced endoscopy centers, improved care coordination, and an organized colorectal cancer screening program.
Authors: Alam, Asim; Corley, Douglas A; Lee, Jeffrey K; Lee, Jeffrey K; et al.
Clin Transl Gastroenterol. 2022 05 01;13(5):e00477. Epub 2022-05-01.
Post-diagnostic beta blocker use and breast cancer-specific mortality: a population-based cohort study
Beta blockers (BB) have been associated with improved, worsened, or unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of BBs and death from breast cancer in a large, representative sample of New Zealand (NZ) women with breast cancer. Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. The median follow-up time was 4.51 years. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic BB use. Of the 14,976 women included in analyses, 21% used a BB after diagnosis. BB use (vs non-use) was associated with a small and nonstatistically significant increased risk of BCD (adjusted hazard ratio: 1.11; 95% CI 0.95-1.29). A statistically significant increased risk confined to short-term use (0-3 months) was seen (HR = 1.40; 1.14-1.73), and this risk steadily decreased with increasing duration of use and became a statistically significant protective effect at 3 + years of use (HR = 0.55; 0.34-0.88). Our findings suggest that any increased risk associated with BB use may be driven by risk in the initial few months of use. Long-term BB use may be associated with a reduction in BCD.
Authors: Scott, Oliver William; Tin Tin, Sandar; Elwood, J Mark; Cavadino, Alana; Habel, Laurel A; Kuper-Hommel, Marion; Campbell, Ian; Lawrenson, Ross
Breast Cancer Res Treat. 2022 May;193(1):225-235. Epub 2022-03-14.
Quantifying cancer risk from exposures to medical imaging in the Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study: research methods and cohort profile
The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods. The RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages. The fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine. The RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.
Authors: Kwan, Marilyn L; Kushi, Lawrence H; Smith-Bindman, Rebecca; et al.
Cancer Causes Control. 2022 May;33(5):711-726. Epub 2022-02-02.
Genetic associations and architecture of asthma-chronic obstructive pulmonary disease overlap
Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone. What is the genetic architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma? We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10-6) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2). We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10-8) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent. We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.
Authors: John, Catherine; Iribarren, Carlos; Tesfaigzi, Yohannes; Tobin, Martin D; et al.
Chest. 2022 05;161(5):1155-1166. Epub 2022-01-31.
American Society for Gastrointestinal Endoscopy guideline on screening for pancreatic cancer in individuals with genetic susceptibility: methodology and review of evidence
Authors: Calderwood, Audrey H; Naveed, Mariam; Qumseya, Bashar J; et al.
Gastrointest Endosc. 2022 05;95(5):827-854.e3. Epub 2022-02-16.
Genetic variants associated with circulating C-reactive protein levels and colorectal cancer survival: Sex- and lifestyle factors- specific associations
Elevated blood levels of C-reactive protein (CRP) have been linked to colorectal cancer (CRC) survival. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC-specific mortality. Our study included 16 142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium. We identified 618 common single nucleotide polymorphisms (SNPs) associated with CRP levels from the NHGRI-EBI GWAS Catalog. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between SNPs and CRC-specific mortality adjusting for age, sex, genotyping platform/study and principal components. We investigated their interactions with sex and lifestyle factors using likelihood ratio tests. Of 5472 (33.9%) deaths accrued over up to 10 years of follow-up, 3547 (64.8%) were due to CRC. No variants were associated with CRC-specific mortality after multiple comparison correction. We observed strong evidence of interaction between variant rs1933736 at FRK gene and sex in relation to CRC-specific mortality (corrected Pinteraction = .0004); women had higher CRC-specific mortality associated with the minor allele (HR = 1.11, 95% CI = 1.04-1.19) whereas an inverse association was observed for men (HR = 0.88, 95% CI = 0.82-0.94). There was no evidence of interactions between CRP-associated SNPs and alcohol, obesity or smoking. Our study observed a significant interaction between sex and a CRP-associated variant in relation to CRC-specific mortality. Future replication of this association and functional annotation of the variant are needed.
Authors: Huang, Yuhan; Schoen, Robert E; Newcomb, Polly A; et al.
Int J Cancer. 2022 05 01;150(9):1447-1454. Epub 2022-01-13.
Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p < 0.05. TWAS further identified two novel genes (SHOX2 and CRISPLD2) whose genetically predicted expression was significantly associated with MD phenotypes. Our findings provided novel insight into the genetic background of MD phenotypes, and further demonstrated their shared genetic basis with breast cancer.
Authors: Chen, Hongjie; Habel, Laurel A; Lindström, Sara; et al.
Breast Cancer Res. 2022 Apr 12;24(1):27. Epub 2022-04-12.
Risk Stratification for Early-Onset Colorectal Cancer Using a Combination of Genetic and Environmental Risk Scores: An International Multi-Center Study
The incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants. Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores. Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.
Authors: Archambault, Alexi N; Sakoda, Lori C; Lee, Jeffrey K; Corley, Douglas A; Hayes, Richard B; et al.
J Natl Cancer Inst. 2022 04 11;114(4):528-539.
Role of dietary patterns and acculturation in cancer risk and mortality among postmenopausal Hispanic women: results from the Women’s Health Initiative (WHI)
To investigate the association between dietary patterns and total and obesity-related cancers risk. Additionally, to examine if acculturation modifies this relationship. Dietary intake of postmenopausal Hispanic women (N=5,482) enrolled in the Women’s Health Initiative was estimated from a Food Frequency Questionnaire and used to calculate dietary pattern scores; Healthy Eating Index-2015 (HEI-2015), Mexican Diet (MexD) score, alternate Mediterranean Diet Score (aMED), and the energy adjusted-Dietary Inflammatory Index (E-DII™). Associations were evaluated using Cox proportional hazards regression models. 631 cancers and 396 obesity-related cancers were diagnosed over a mean-follow up of 12 years. Across dietary scores, there were no significant associations with cancer risk or mortality. Trend analysis suggest a potentially lower risk for total cancer related to the highest MexD score (HR 0.68, 95% CI 0.45-1.04, P-trend=0.03), and lower risk for obesity-related cancer mortality related to the highest score category for MexD (HR 0.65, 95% CI 0.37-1.16, P-trend=0.02), and aMED (HR 0.87, 95% CI 0.45-1.67, P-trend=0.04). Further analysis suggests less acculturated women with higher MexD scores had 56% lower risk for any cancer (HR 0.44, 95% CI 0.22-0.88, P-trend=0.03) and 83% lower risk for cancer mortality (HR 0.17, 95% CI 0.04-0.76, P-trend=0.01) compared to more acculturated Hispanic women. Dietary patterns were not associated with cancer risk and mortality in postmenopausal Hispanic women. Less-acculturated, Spanish-preferred speakers, who reported consuming a more traditional Mexican diet may experience a lower risk for cancer and cancer mortality.
Authors: Lopez-Pentecost, Melissa; Kroenke, Candyce H; Thomson, Cynthia A; et al.
Z Gesundh Wiss. 2022 Apr;30(4):811-822. Epub 2020-07-14.
Joint associations between neighborhood walkability, greenness, and particulate air pollution on cardiovascular mortality among adults with a history of stroke or acute myocardial infarction
Fine particulate matter (PM2.5) is a known risk factor for cardiovascular disease (CVD). Neighborhood walkability and greenness may also be associated with CVD, but there is limited evidence on their joint or interacting effects with PM2.5. Cox proportional hazard models were used to estimate the risk of CVD mortality among adults with a history of acute myocardial infarction and/or stroke living in Northern California. We assessed the independent and joint effects of walkability, greenness (Normalized Differentiated Vegetation Index [NDVI]), and PM2.5 at residential addresses, controlling for age, sex, race/ethnicity, comorbidities, BMI, smoking, revascularization, medications, and socioeconomic status. Greenness had a nonlinear association with CVD mortality (P = 0.038), with notably protective effects (HR = 0.87 [95% confidence interval {CI} = 0.78, 0.97]) at higher greenness levels (NDVI ≥ 0.3) and moderate attenuation after adjusting for PM2.5 (HR = 0.92 [95% CI = 0.82, 1.03]) per 0.1 increase in NDVI. Walkability had no independent effect on CVD mortality. PM2.5 had a strong independent effect in models adjusted for greenness and walkability (HR = 1.20 [95% CI = 1.08, 1.33)) per 10 μg/m3 increase in PM2.5. There was an interaction between walkability and PM2.5 (P = 0.037), where PM2.5 had slightly stronger associations in more walkable than less walkable neighborhoods (HR = 1.23 [95% CI = 1.06, 1.42] vs. 1.17 [95% CI = 1.04, 1.32]) per 10 μg/m3 increase in PM2.5. Greenness had no interaction with PM2.5 (P = 0.768) nor walkability (P = 0.385). High greenness may be protective of CVD mortality among adults with CVD history. PM2.5 associated CVD mortality risk varies slightly by level of neighborhood walkability, though these small differences may not be clinically meaningful.
Authors: Liao NS; Van Den Eeden SK; Sidney S; Deosaransingh K; Schwartz J; Uong SP; Alexeeff SE
Environ Epidemiol. 2022 Apr;6(2):e200. Epub 2022-02-18.
Eosinophilic esophagitis: New molecules, better life?
Eosinophilic esophagitis (EoE) is an antigen-mediated chronic T helper type 2 (Th2)-associated inflammatory disorder that has emerged in the last three decades as an increasingly common cause of esophageal symptoms. Despite rising incidence and prevalence, there are currently no approved therapies for EoE in the United States and only one oral topical corticosteroid approved in Europe and Canada. Current management relies on labor- and endoscopy-intensive dietary elimination, proton-pump inhibitors (PPIs) with only moderate efficacy, and use of inhaled or nebulized topical corticosteroids designed for asthma and limited by accessibility. Fortunately, progress in elucidating the underlying pathophysiology of EoE has led to the development of new therapies derived from molecular targets necessary for disease pathogenesis. We summarize established and emerging medical therapies for EoE, with a focus on new treatments with specific molecular targets that are likely to change EoE management paradigms in the next decade.
Authors: Lam, Angela Y; Ma, Christopher; Lee, Jeffrey K; Bredenoord, Albert J
Curr Opin Pharmacol. 2022 04;63:102183. Epub 2022-02-15.
Too Good to Be True? Evaluation of Colonoscopy Sensitivity Assumptions Used in Policy Models
Models can help guide colorectal cancer screening policy. Although models are carefully calibrated and validated, there is less scrutiny of assumptions about test performance. We examined the validity of the CRC-SPIN model and colonoscopy sensitivity assumptions. Standard sensitivity assumptions, consistent with published decision analyses, assume sensitivity equal to 0.75 for diminutive adenomas (<6 mm), 0.85 for small adenomas (6-10 mm), 0.95 for large adenomas (≥10 mm), and 0.95 for preclinical cancer. We also selected adenoma sensitivity that resulted in more accurate predictions. Targets were drawn from the Wheat Bran Fiber study. We examined how well the model predicted outcomes measured over a three-year follow-up period, including the number of adenomas detected, the size of the largest adenoma detected, and incident colorectal cancer. Using standard sensitivity assumptions, the model predicted adenoma prevalence that was too low (42.5% versus 48.9% observed, with 95% confidence interval 45.3%-50.7%) and detection of too few large adenomas (5.1% versus 14.% observed, with 95% confidence interval 11.8%-17.4%). Predictions were close to targets when we set sensitivities to 0.20 for diminutive adenomas, 0.60 for small adenomas, 0.80 for 10- to 20-mm adenomas, and 0.98 for adenomas 20 mm and larger. Colonoscopy may be less accurate than currently assumed, especially for diminutive adenomas. Alternatively, the CRC-SPIN model may not accurately simulate onset and progression of adenomas in higher-risk populations. Misspecification of either colonoscopy sensitivity or disease progression in high-risk populations may affect the predicted effectiveness of colorectal cancer screening. When possible, decision analyses used to inform policy should address these uncertainties.See related commentary by Etzioni and Lange, p. 702.
Authors: Rutter, Carolyn M; Nascimento de Lima, Pedro; Lee, Jeffrey K; Ozik, Jonathan
Cancer Epidemiol Biomarkers Prev. 2022 04 01;31(4):775-782.
Trends and Projections in National U.S. Healthcare Spending for Gastrointestinal Malignancies (1996-2030)
The management of gastrointestinal (GI) cancers is associated with high health care spending. We estimated trends in United States (US) health care spending for patients with GI cancers between 1996 and 2016 and developed projections to 2030. We used economic data, adjusted for inflation, developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. Corresponding US age-adjusted prevalence of GI cancers was estimated from the Global Burden of Diseases Study. Prevalence-adjusted temporal trends in the US health care spending in patients with GI cancers, stratified by cancer site, age, and setting of care, were estimated using joinpoint regression, expressed as annual percentage change (APC) with 95% confidence intervals (CIs). Autoregressive integrated moving average models were used to project spending to 2030. In 2016, total spending for GI cancers was primarily attributable to colorectal ($10.50 billion; 95% CI, $9.35-$11.70 billion) and pancreatic cancer ($2.55 billion; 95% CI, $2.23-$2.82 billion), and primarily for inpatient care (64.5%). Despite increased total spending, more recent per-patient spending for pancreatic (APC 2008-2016, -1.4%; 95% CI, -2.2% to -0.7%), gallbladder/biliary tract (APC 2010-2016, -4.3%; 95% CI, -4.8% to -3.8%), and gastric cancer (APC 2011-2016, -4.4%; 95% CI, -5.8% to -2.9%) decreased. Increasing price and intensity of care provision was the largest driver of higher expenditures. By 2030, it is projected more than $21 billion annually will be spent on GI cancer management. Total spending for GI cancers in the US is substantial and projected to increase. Expenditures are primarily driven by inpatient care for colorectal cancer, although per-capita spending trends differ by GI cancer type.
Authors: Stukalin, Igor; Ahmed, Newaz Shubidito; Fundytus, Adam M; Qian, Alexander S; Coward, Stephanie; Kaplan, Gilaad G; Hilsden, Robert J; Burak, Kelly W; Lee, Jeffrey K; Singh, Siddharth; Ma, Christopher
Gastroenterology. 2022 04;162(4):1098-1110.e2. Epub 2021-12-16.
MRI based validation of abdominal adipose tissue measurements from DXA in postmenopausal women
Visceral adipose tissue (VAT) is a hypothesized driver of chronic disease. Dual-energy X-ray absorptiometry (DXA) potentially offers a lower cost and more available alternative compared to gold-standard magnetic resonance imaging (MRI) for quantification of abdominal fat sub-compartments, VAT and subcutaneous adipose tissue (SAT). We sought to validate VAT and SAT area (cm2) from historical DXA scans against MRI. Participants (n = 69) from the Women’s Health Initiative (WHI) completed a 3 T MRI scan and a whole body DXA scan (Hologic QDR2000 or QDR4500; 2004-2005). A subset of 43 participants were scanned on both DXA devices. DXA-derived VAT and SAT at the 4th lumbar vertebrae (5 cm wide) were analyzed using APEX software (v4.0, Hologic, Inc., Marlborough, MA). MRI VAT and SAT areas for the corresponding DXA region of interest were quantified using sliceOmatic software (v5.0, Tomovision, Magog, Canada). Pearson correlations between MRI and DXA-derived VAT and SAT were computed, and a Bland-Altman analysis was performed. Participants were primarily non-Hispanic white (86%) with a mean age of 70.51 ± 5.79 years and a mean BMI of 27.33 ± 5.40 kg/m2. Correlations between MRI and DXA measured VAT and SAT were 0.90 and 0.92, respectively (p ≤ 0.001). Bland-Altman plots showed that DXA-VAT slightly overestimated VAT on the QDR4500 (-3.31 cm2); this bias was greater in the smaller subset measured on the older DXA model (QDR2000; -30.71 cm2). The overestimation of DXA-SAT was large (-85.16 to -118.66 cm2), but differences were relatively uniform for the QDR4500. New software applied to historic Hologic DXA scans provide estimates of VAT and SAT that are well-correlated with criterion MRI among postmenopausal women.
Authors: Bea, Jennifer W; LeBoff, Meryl S; Odegaard, Andrew O; et al.
J Clin Densitom. 2022 Apr-Jun;25(2):189-197. Epub 2021-07-29.
Associations between infant growth and pubertal onset timing in a multiethnic prospective cohort of girls
Early puberty increases risk of adverse health conditions throughout the life course. US girls are experiencing earlier puberty without clear reasons. Studies suggest early life factors, such as infant growth, may influence pubertal timing. We assessed the associations between infant growth and onset of breast development (thelarche), pubic hair development (pubarche), and menarche in girls. A prospective cohort of girls born at a Kaiser Permanente Northern California medical facility in 2005-11 was used. Weight-for-age z-scores were calculated at birth and 24 months. Difference in z-scores greater than 0.67 represent rapid “catch-up” growth, less than -0.67 represent delayed “catch-down” growth, and between -0.67 and 0.67 represent “normal” growth. Pubertal onset was measured using clinician-assessed sexual maturity ratings (SMRs) and defined as the age at transition from SMR 1 to SMR 2 + for both thelarche and pubarche. SMR data was collected through June 2020. Menarche was analyzed as a secondary outcome. Weibull and modified Poisson regression models were used. Models were adjusted for potential confounders. There were 15,196 girls included in the study. Approximately 30.2% experienced catch-up growth, 25.8% experienced catch-down growth, and 44% had normal growth. Girls with catch-up growth had increased risk of earlier thelarche (hazard ratio = 1.26, 95% confidence interval (CI): 1.18, 1.35), pubarche (1.38, 95% CI: 1.28, 1.48), and menarche (< 12y, relative risk = 1.52, 95% CI: 1.36, 1.69) compared to those with normal growth, after adjusting for covariates. These associations were partially mediated by childhood body mass index. Catch-down growth was associated with later pubertal onset. Girls who experience infant catch-up growth have higher risk of earlier pubertal development compared to girls with normal growth and the associations are partially explained by childhood obesity. This information may help clinicians to monitor girls who are at high risk of developing earlier.
Authors: Aghaee, Sara; Quesenberry, Charles P; Deardorff, Julianna; Kushi, Lawrence H; Greenspan, Louise C; Ferrara, Assiamira; Kubo, Ai
BMC Pediatr. 2022 Mar 31;22(1):171. Epub 2022-03-31.
The evolving landscape of sex-based differences in lung cancer: a distinct disease in women.
In stark contrast to a few decades ago when lung cancer was predominantly a disease of men who smoke, incidence rates of lung cancer in women are now comparable to or higher than those in men and are rising alarmingly in many parts of the world. Women face a unique set of risk factors for lung cancer compared to men. These include exogenous exposures including radon, prior radiation, and fumes from indoor cooking materials such as coal, in addition to endogenous exposures such as oestrogen and distinct genetic polymorphisms. Current screening guidelines only address tobacco use and likely underrepresent lung cancer risk in women. Women were also not well represented in some of the landmark prospective studies that led to the development of current screening guidelines. Women diagnosed with lung cancer have a clear mortality benefit compared to men even when other clinical and demographic characteristics are accounted for. However, there may be sex-based differences in outcomes and side effects of systemic therapy, particularly with chemotherapy and immunotherapy. Ongoing research is needed to better investigate these differences to address the rapidly changing demographics of lung cancer worldwide.
Authors: Ragavan, Meera;Patel, Manali I
Eur Respir Rev. 2022 Mar 31;31(163):pii: 210100. doi: 10.1183/16000617.0100-2021. Epub 2022 Jan 12.
UACA locus is associated with breast cancer chemoresistance and survival.
Few germline genetic variants have been robustly linked with breast cancer outcomes. We conducted trans-ethnic meta genome-wide association study (GWAS) of overall survival (OS) in 3973 breast cancer patients from the Pathways Study, one of the largest prospective breast cancer survivor cohorts. A locus spanning the UACA gene, a key regulator of tumor suppressor Par-4, was associated with OS in patients taking Par-4 dependent chemotherapies, including anthracyclines and anti-HER2 therapy, at a genome-wide significance level ([Formula: see text]). This association was confirmed in meta-analysis across four independent prospective breast cancer cohorts (combined hazard ratio = 1.84, [Formula: see text]). Transcriptome-wide association study revealed higher UACA gene expression was significantly associated with worse OS ([Formula: see text]). Our study identified the UACA locus as a genetic predictor of patient outcome following treatment with anthracyclines and/or anti-HER2 therapy, which may have clinical utility in formulating appropriate treatment strategies for breast cancer patients based on their genetic makeup.
Authors: Zhu, Qianqian; Schultz, Emily; Long, Jirong; Roh, Janise M; Valice, Emily; Laurent, Cecile A; Radimer, Kelly H; Yan, Li; Ergas, Isaac J; Davis, Warren; Ranatunga, Dilrini; Gandhi, Shipra; Kwan, Marilyn L; Bao, Ping-Ping; Zheng, Wei; Shu, Xiao-Ou; Ambrosone, Christine; Yao, Song; Kushi, Lawrence H
NPJ Breast Cancer. 2022 Mar 23;8(1):39. doi: 10.1038/s41523-022-00401-5.
Long-Term Survival and Causes of Death After Diagnoses of Common Cancers in 3 Cohorts of US Health Professionals
Few studies investigated long-term overall survival and causes of death among men and women diagnosed with most commonly occurring cancers. We estimated long-term (≥30-year) overall and cause-specific cumulative mortality for men diagnosed with prostate (n = 6873), lung and bronchus (n = 1290), colon and rectum (n = 1418), bladder (n = 1321), and melanoma (n = 2654) cancer in the Health Professionals Follow-up Study between 1986 and 2012 and women with breast (n = 18 280), lung and bronchus (n = 3963), colon and rectum (n = 3461), uterine corpus (n = 1641), and thyroid (n = 1103) cancer in the Nurses’ Health Study between 1976 and 2012 and Nurses’ Health Study II between 1989 and 2013. We reported overall and cause-specific cumulative mortality of 30 years among men and 35 years among women. Among male cancer survivors, the 30-year cumulative cancer-specific mortality was 15.4% (95% confidence interval [CI] = 14.4% to 16.4%) for prostate, 83.5% (95% CI = 81.2% to 85.5%) for lung and bronchus, 37.0% (95% CI = 34.4% to 39.5%) for colon and rectum, 22.5% (95% CI = 20.0% to 25.0%) for urinary bladder, and 8.0% (95% CI = 6.9% to 9.1%) for melanoma. Among female cancer survivors, the 35-year cumulative cancer-specific mortality rate was 20.6% (95% CI = 19.7% to 21.6%) for breast, 83.5% (95% CI = 81.6% to 85.2%) for lung and bronchus, 39.6% (95% CI = 37.5% to 41.6%) for colon and rectum, 16.6% (95% CI = 14.7% to 18.6%) for uterine corpus, and 3.2% (95% CI = 2.1% to 4.3%) for thyroid. Except for lung cancer, most patients with common cancer were more likely to die from causes other than primary cancers. We observed 2 basic trends for cumulative cancer-specific mortality. The first is a sustained but nevertheless excess risk: Prostate or breast cancer-specific cumulative mortality continued to increase after diagnosis from 5 to 30 years or longer. The second is greatly diminished risk of index cancer-specific mortality following diagnosis 10 years or longer previously. For example, colorectal cancer-specific mortality increased by less than 4 percentage points between 10 and 30 or 35 years after diagnosis, and this finding also applied to lung, bladder, melanoma, uterine corpus, and thyroid cancer. Except for lung cancer, patients diagnosed with common cancers were more likely to die from causes other than primary cancers. Patients with lung, colorectal, bladder, melanoma, uterine corpus, or thyroid cancer surviving longer than 10 years after diagnosis are unlikely to die from that disease.
Authors: Cheng, En; Lee, Dong Hoon; Tamimi, Rulla M; Hankinson, Susan E; Willett, Walter C; Giovannucci, Edward L; Eliassen, A Heather; Stampfer, Meir J; Mucci, Lorelei A; Fuchs, Charles S; Spiegelman, Donna
JNCI Cancer Spectr. 2022 Mar 02;6(2).
Diet- and Lifestyle-Based Prediction Models to Estimate Cancer Recurrence and Death in Patients With Stage III Colon Cancer (CALGB 89803/Alliance)
Current tools in predicting survival outcomes for patients with colon cancer predominantly rely on clinical and pathologic characteristics, but increasing evidence suggests that diet and lifestyle habits are associated with patient outcomes and should be considered to enhance model accuracy. Using an adjuvant chemotherapy trial for stage III colon cancer (CALGB 89803), we developed prediction models of disease-free survival (DFS) and overall survival by additionally incorporating self-reported nine diet and lifestyle factors. Both models were assessed by multivariable Cox proportional hazards regression and externally validated using another trial for stage III colon cancer (CALGB/SWOG 80702), and visual nomograms of prediction models were constructed accordingly. We also proposed three hypothetical scenarios for patients with (1) good-risk, (2) average-risk, and (3) poor-risk clinical and pathologic features, and estimated their predictive survival by considering clinical and pathologic features with or without adding self-reported diet and lifestyle factors. Among 1,024 patients (median age 60.0 years, 43.8% female), we observed 394 DFS events and 311 deaths after median follow-up of 7.3 years. Adding self-reported diet and lifestyle factors to clinical and pathologic characteristics meaningfully improved performance of prediction models (c-index from 0.64 [95% CI, 0.62 to 0.67] to 0.69 [95% CI, 0.67 to 0.72] for DFS, and from 0.67 [95% CI, 0.64 to 0.70] to 0.71 [95% CI, 0.69 to 0.75] for overall survival). External validation also indicated good performance of discrimination and calibration. Adding most self-reported favorable diet and lifestyle exposures to multivariate modeling improved 5-year DFS of all patients and by 6.3% for good-risk, 21.4% for average-risk, and 42.6% for poor-risk clinical and pathologic features. Diet and lifestyle factors further inform current recurrence and survival prediction models for patients with stage III colon cancer.
Authors: Cheng, En; Fuchs, Charles S; et al.
J Clin Oncol. 2022 03 01;40(7):740-751. Epub 2022-01-07.
Lifestyle and Cardiovascular Risk Factors Associated With Heart Failure Subtypes in Postmenopausal Breast Cancer Survivors
Breast cancer (BC) survivors experience an increased burden of long-term comorbidities, including heart failure (HF). However, there is limited understanding of the risk for the development of HF subtypes, such as HF with preserved ejection fraction (HFpEF), in BC survivors. This study sought to estimate the incidence of HFpEF and HF with reduced ejection fraction (HFrEF) in postmenopausal BC survivors and to identify lifestyle and cardiovascular risk factors associated with HF subtypes. Within the Women’s Health Initiative, participants with an adjudicated diagnosis of invasive BC were followed to determine the incidence of hospitalized HF, for which adjudication procedures determined left ventricular ejection fraction. We calculated cumulative incidences of HF, HFpEF, and HFrEF. We estimated HRs for risk factors in relation to HF, HFpEF, and HFrEF using Cox proportional hazards survival models. In 2,272 BC survivors (28.6% Black and 64.9% White), the cumulative incidences of hospitalized HFpEF and HFrEF were 6.68% and 3.96%, respectively, over a median of 7.2 years (IQR: 3.6-12.3 years). For HFpEF, prior myocardial infarction (HR: 2.83; 95% CI: 1.28-6.28), greater waist circumference (HR: 1.99; 95% CI: 1.14-3.49), and smoking history (HR: 1.65; 95% CI: 1.01-2.67) were the strongest risk factors in multivariable models. With the exception of waist circumference, similar patterns were observed for HFrEF, although none were significant. In relation to those without HF, the risk of overall mortality in BC survivors with hospitalized HFpEF was 5.65 (95% CI: 4.11-7.76), and in those with hospitalized HFrEF, it was 3.77 (95% CI: 2.51-5.66). In this population of older, racially diverse BC survivors, the incidence of HFpEF, as defined by HF hospitalizations, was higher than HFrEF. HF was also associated with an increased mortality risk. Risk factors for HF were largely similar to the general population with the exception of prior myocardial infarction for HFpEF. Notably, both waist circumference and smoking represent potentially modifiable factors.
Authors: Reding, Kerryn W; Caan, Bette; Anderson, Garnet; et al.
JACC CardioOncol. 2022 Mar;4(1):53-65. Epub 2022-03-15.
Social Isolation and Incident Heart Failure Hospitalization in Older Women: Women’s Health Initiative Study Findings
Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potential mediator and age and race and ethnicity as effect modifiers. Methods and Results This study included 44 174 postmenopausal women of diverse race and ethnicity from the WHI (Women’s Health Initiative) study who underwent annual assessment for HF adjudication from baseline enrollment (1993-1998) through 2018. We conducted a mediation analysis to examine depressive symptoms as a potential mediator and further examined effect modification by age and race and ethnicity. Incident HF requiring hospitalization was the main outcome. Social isolation was a composite variable based on marital/partner status, religious ties, and community ties. Depressive symptoms were assessed using CES-D (Center for Epidemiology Studies-Depression). Over a median follow-up of 15.0 years, we analyzed data from 36 457 women, and 2364 (6.5%) incident HF cases occurred; 2510 (6.9%) participants were socially isolated. In multivariable analyses adjusted for sociodemographic, behavioral, clinical, and general health/functioning; socially isolated women had a higher risk of incident HF than nonisolated women (HR, 1.23; 95% CI, 1.08-1.41). Adding depressive symptoms in the model did not change this association (HR, 1.22; 95% CI, 1.07-1.40). Neither race and ethnicity nor age moderated the association between social isolation and incident HF. Conclusions Socially isolated older women are at increased risk for developing HF, independent of traditional HF risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000611.
Authors: Cené, Crystal W; Kroenke, Candyce H; et al.
J Am Heart Assoc. 2022 03;11(5):e022907. Epub 2022-02-22.
Accounting for EGFR mutations in epidemiological analyses of non-small cell lung cancers: Examples based on the International Lung Cancer Consortium data
Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches. Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74-0.77) in the training and 0.77 (95% CI, 0.74-0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.
Authors: Schmid, Sabine; Brennan, Paul; Liu, Geoffrey; et al.
Cancer Epidemiol Biomarkers Prev. 2022 Mar 01;31(3):679-687.
Factors influencing genetic counseling and testing for hereditary breast and ovarian cancer syndrome in a large US health care system
Investigate whether disparities and other factors influence referral to genetic counseling and testing for hereditary breast and ovarian cancer syndrome (HBOC) in a large health care system. Examination of clinical, demographic, and socioeconomic factors from electronic health records associated with genetic referral and testing within 12 months after a new cancer diagnosed between August 1, 2013 and December 31, 2018. For patients meeting institutional criteria for HBOC testing, 60.6% were referred for genetic counseling, 88% of whom underwent germline testing; at least one pathogenic variant was found in 15.3%. Referral rates for patients with breast (69%) or ovarian cancer (65.7%) were much higher than for metastatic prostate (11.1%, p < 0.0001) or pancreatic cancer (22.3%, p < 0.0001); referral criteria were implemented more recently for the latter two cancers. Younger age, family history, and chemotherapy were associated with referral. Higher Elixhauser comorbidity score and prior cancer were associated with non-referral. No other factors were associated with genetic referral for all eligible cancers combined, although differences were seen in specific cancers. Race was a significant factor only for breast cancer, with fewer Asians than Whites referred. Health disparities in referral to genetics for HBOC cancers are mitigated in a comprehensive integrated health care system.
Authors: Powell, C Bethan; Laurent, Cecile; Garcia, Christine; Hoodfar, Elizabeth; Karlea, Audrey; Kobelka, Christine; Lee, Jaimie; Roh, Janise; Kushi, Lawrence H
Clin Genet. 2022 03;101(3):324-334. Epub 2021-12-27.
Correlates of physical activity among older breast cancer survivors: Findings from the Women’s Health Initiative LILAC study
Physical activity can attenuate cancer-related declines in physical functioning, improve emotional well-being, and prolong survival among older (≥65 years) breast cancer survivors. However, factors associated with physical activity among older breast cancer survivors are not well-understood. Participants were enrolled in the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study. Descriptive statistics, multiple linear regression, and relative risk [RR] regression were used to assess the association of demographic, clinical, physical and psychosocial variables with the total duration of and participation in physical activity among postmenopausal breast cancer survivors. Age-specific correlates (65-74 years vs. 75-84 years vs. ≥85 years) of physical activity were also examined. The majority of participants (n = 3710, mean age = 78.8 ± 5.9) were white (90.7%) and had in situ/localized breast cancer (78.9%). Women who had higher education (RR = 1.47 for graduate/professional school versus high school or less, 95% CI: 1.32, 1.63), higher self-rated health (RR = 1.04 for 10 point increase, 95% CI:1.02, 1.07), higher physical functioning (RR = 1.03 for 5 point increase, 95% CI: 1.02, 1.04), and higher social support (RR = 1.41 for social support all of the time versus none of the time, 95% CI: 1.01, 1.96), were more likely to engage in any physical activity. Similar results were observed for duration of physical activity. Among women aged <75, radiation therapy, but not chemotherapy, was associated with longer duration of total physical activity (adjusted difference = 19.7 min/week, 95% CI: 6.1, 33.3), but was not associated with duration among older women. The association between pain and duration of moderate/strenuous activity also differed with age: among women aged <75, those with moderate pain averaged fewer minutes of moderate/strenuous physical activity than those with no pain (adjusted difference:-14.4 min/week, 95% CI:-28.5, -0.1). However, among women aged ≥85, those with moderate pain averaged more minutes of moderate/strenuous physical activity per week than those with no pain (adjusted difference:16.6 min/week; 95% CI:2.9, 30.3). Multiple factors were associated with physical activity among older breast cancer survivors in the WHI. Future physical activity interventions should focus on age-related (e.g., comorbidities) and treatment-related factors (e.g., radiation) as well as certain subgroups, such as women with higher symptom burden.
Authors: Krok-Schoen, Jessica L; Bea, Jennifer W; Paskett, Electra D; et al.
J Geriatr Oncol. 2022 03;13(2):143-151. Epub 2021-12-07.
Impact of the Affordable Care Act on Colorectal Cancer Incidence and Mortality
The Patient Protection and Affordable Care Act eliminated cost sharing for preventive services, including colorectal cancer screening for individuals aged 50-75 years with private health insurance. This study examines the impact of the Affordable Care Act’s removal of cost sharing for colorectal cancer screening on colorectal cancer incidence and mortality. Trends in colorectal cancer incidence and colorectal cancer‒related mortality were modeled among 2,113,283 Kaiser Permanente Northern California members aged ≥50 years between 2003 and 2016 using an interrupted time-series design. As a sensitivity analysis, a controlled analysis utilized a comparison group of members covered with pre‒Affordable Care Act zero cost sharing for colorectal cancer screening. Analyses were performed in 2019 and 2020. The colorectal cancer incidence dropped by 17% around the time the Affordable Care Act was enacted (change in level incidence rate ratio; 95% CI=0.77, 0.90, 2-sided p-value <0.0001), followed by a 3% further decrease per year (95% CI=0.93, 1.00, p=0.05). A similar pattern was observed for colorectal cancer‒related mortality. The controlled results indicated that the elimination of cost sharing for screening due to the Affordable Care Act was associated with greater improvements in colorectal cancer outcomes among members previously covered by health plans with out-of-pocket costs for screening than among those with health plans with zero cost sharing for screening before the Affordable Care Act. The elimination of cost sharing for colorectal cancer screening due to the Affordable Care Act was associated with a decrease in age-, race/ethnicity-, and sex-adjusted colorectal cancer incidence and colorectal cancer‒related mortality, implying that policies that remove barriers to screening, particularly financial burden from cost sharing, can result in improved colorectal cancer outcomes.
Authors: Lee, Catherine; Kushi, Lawrence H; Reed, Mary E; Eldridge, Elizabeth H; Lee, Jeffrey K; Zhang, Jie; Spiegelman, Donna
Am J Prev Med. 2022 03;62(3):387-394. Epub 2021-11-08.
The Kaiser Permanente Research Bank Cancer Cohort: a collaborative resource to improve cancer care and survivorship
The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and surveys linked to electronic health records (EHR) from approximately 400,000 adult KP members. Within the KPRB, we developed a Cancer Cohort to address issues related to cancer survival, and to understand how genetic, lifestyle and environmental factors impact cancer treatment, treatment sequelae, and prognosis. We describe the Cancer Cohort design and implementation, describe cohort characteristics after 5 years of enrollment, and discuss future directions. Cancer cases are identified using rapid case ascertainment algorithms, linkage to regional or central tumor registries, and direct outreach to KP members with a history of cancer. Enrollment is primarily through email invitation. Participants complete a consent form, survey, and donate a blood or saliva sample. All cancer types are included. As of December 31, 2020, the cohort included 65,225 cases (56% female, 44% male) verified in tumor registries. The largest group was diagnosed between 60 and 69 years of age (31%) and are non-Hispanic White (83%); however, 10,076 (16%) were diagnosed at ages 18-49 years, 4208 (7%) are Hispanic, 3393 (5%) are Asian, and 2389 (4%) are Black. The median survival time is 14 years. Biospecimens are available on 98% of the cohort. The KPRB Cancer Cohort is designed to improve our understanding of treatment efficacy and factors that contribute to long-term cancer survival. The cohort’s diversity – with respect to age, race/ethnicity and geographic location – will facilitate research on factors that contribute to cancer survival disparities.
Authors: Feigelson, Heather Spencer; Van Den Eeden, Stephen K; McGlynn, Elizabeth A; et al.
BMC Cancer. 2022 Feb 25;22(1):209. Epub 2022-02-25.
Association between Improved Colorectal Screening and Racial Disparities
Authors: Doubeni, Chyke A; Corley, Douglas A; Zhao, Wei; Lau, YanKwan; Jensen, Christopher D; Levin, Theodore R
N Engl J Med. 2022 02 24;386(8):796-798.
Cardiometabolic risk factors, physical activity, and postmenopausal breast cancer mortality: results from the Women’s Health Initiative
Higher physical activity levels are associated with lower breast cancer-specific mortality. In addition, the metabolic syndrome is associated with higher breast cancer-specific mortality. Whether the physical activity association with breast cancer mortality is modified by number of metabolic syndrome components (cardiometabolic risk factors) in postmenopausal women with early-stage breast cancer remains unknown. Cardiovascular risk factors included high waist circumference, hypertension, high cholesterol, and diabetes. Breast cancers were verified by medical record review. Mortality finding were enhanced by serial National Death Index queries. Cox proportional hazards regression models were used to estimate associations between baseline physical activity and subsequent breast cancer-specific and overall mortality following breast cancer diagnosis in Women’s Health Initiative participants. These associations were examined after stratifying by cardiometabolic risk factor group. Among 161,308 Women’s Health Initiative (WHI) participants, 8543 breast cancers occurred after 9.5 years (median) follow-up in women, additionally with information on cardiometabolic risk factors and physical activity at entry. In multi-variable analyses, as measured from cancer diagnosis, higher physical activity levels were associated with lower all-cause mortality risk (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.78-0.95, trend P < 0.001) but not with breast cancer-specific mortality (HR 0.85, 95% CI 0.70 to 1.04, trend P = 0.09). The physical activity and all-cause mortality association was not significantly modified by cardiometabolic risk factor number. Among women with early-stage breast cancer, although higher antecedent physical activity was associated with lower risk of all-cause mortality, the association did not differ by cardiometabolic risk factor number.
Authors: Dieli-Conwright, Christina M; Pan, Kathy; Mortimer, Joanne; et al.
BMC Womens Health. 2022 02 05;22(1):32. Epub 2022-02-05.
Effect of Exercise on Sarcopenia among Cancer Survivors: A Systematic Review
Sarcopenia is related to adverse health outcomes in cancer survivors. Previous reviews reported exercise improved muscle mass or function in cancer survivors, but thus far a systematic review examining the effect of exercise on sarcopenia in this population has not been conducted. Therefore, we systematically searched PubMed, CENTRAL (Cochrane Central Register of Controlled Trials) and ClinicalTrials.gov for publications and ongoing trials (through November 2021) that reported exercise interventions and diagnosed sarcopenia among cancer survivors. Seven exercise trials were eligible for this review. Six of seven studies showed exercise increased skeletal muscle post intervention (1.6% to 5.4% increase within intervention groups compared to baseline, p ≤ 0.07; 2.1% to 12.8% greater increase for intervention than control groups, p ≤ 0.02) and in the three studies that reported sarcopenia reversal, an improvement (18.2% to 42.9% decrease in sarcopenia in exercise groups, 5.2% increase to 16.7% decrease in sarcopenia in control groups, p = 0.04) was observed. Existing research indicates the potential for exercise to improve health outcomes for cancer survivors through building muscle and attenuating sarcopenia. More high-quality, long-term, large randomized controlled trials examining effects of different exercise types and doses to improve sarcopenia should be conducted to further explore this important topic.
Authors: Cao, Anlan; Ferrucci, Leah M; Caan, Bette J; Irwin, Melinda L
Cancers (Basel). 2022 Feb 03;14(3). Epub 2022-02-03.
Ambient UVR and Environmental Arsenic Exposure in Relation to Cutaneous Melanoma in Iowa
Intermittent sun exposure is the major environmental risk factor for cutaneous melanoma (CM). Cumulative sun exposure and other environmental agents, such as environmental arsenic exposure, have not shown consistent associations. Ambient ultraviolet radiation (UVR) was used to measure individual total sun exposure as this is thought to be less prone to misclassification and recall bias. Data were analyzed from 1096 CM cases and 1033 controls in the Iowa Study of Skin Cancer and Its Causes, a population-based, case-control study. Self-reported residential histories were linked to satellite-derived ambient UVR, spatially derived environmental soil arsenic concentration, and drinking water arsenic concentrations. In men and women, ambient UVR during childhood and adolescence was not associated with CM but was positively associated during adulthood. Lifetime ambient UVR was positively associated with CM in men (OR for highest vs. lowest quartile: 6.09, 95% confidence interval (CI) 2.21-16.8), but this association was not as strong among women (OR for highest vs. lowest quartile: 2.15, 95% CI 0.84-5.54). No association was detected for environmental soil or drinking water arsenic concentrations and CM. Our findings suggest that lifetime and adulthood sun exposures may be important risk factors for CM.
Authors: Langston ME; Brown HE; Lynch CF; Roe DJ; Dennis LK
Int J Environ Res Public Health. 2022 02 03;19(3). Epub 2022-02-03.
POST-ENDOSCOPY ESOPHAGEAL NEOPLASIA IN BARRETT’S ESOPHAGUS: CONSENSUS STATEMENTS FROM AN INTERNATIONAL EXPERT PANEL
Authors: Wani, Sachin; Yadlapati, Rena; Singh, Siddharth; Sawas, Tarek; Katzka, David A; Post-Endoscopy Esophageal Neoplasia Expert Consensus Panel,
Gastroenterology. 2022 02;162(2):366-372. Epub 2021-10-14.
Evaluation of Social Isolation, Loneliness, and Cardiovascular Disease Among Older Women in the US
Social isolation and loneliness are increasing public health concerns and have been associated with increased risk of cardiovascular disease (CVD) among older adults. To examine the associations of social isolation and loneliness with incident CVD in a large cohort of postmenopausal women and whether social support moderated these associations. This prospective cohort study, conducted from March 2011 through March 2019, included community-living US women aged 65 to 99 years from the Women’s Health Initiative Extension Study II who had no history of myocardial infarction, stroke, or coronary heart disease. Social isolation and loneliness were ascertained using validated questionnaires. The main outcome was major CVD, which was physician adjudicated using medical records and included coronary heart disease, stroke, and death from CVD. Continuous scores of social isolation and loneliness were analyzed. Hazard ratios (HRs) and 95% CIs for CVD were calculated for women with high social isolation and loneliness scores (midpoint of the upper half of the distribution) vs those with low scores (midpoint of the lower half of the distribution) using multivariable Cox proportional hazards regression models adjusting for age, race and ethnicity, educational level, and depression and then adding relevant health behavior and health status variables. Questionnaire-assessed social support was tested as a potential effect modifier. Among 57 825 women (mean [SD] age, 79.0 [6.1] years; 89.1% White), 1599 major CVD events occurred over 186 762 person-years. The HR for the association of high vs low social isolation scores with CVD was 1.18 (95% CI, 1.13-1.23), and the HR for the association of high vs low loneliness scores with CVD was 1.14 (95% CI, 1.10-1.18). The HRs after additional adjustment for health behaviors and health status were 1.08 (95% CI, 1.03-1.12; 8.0% higher risk) for social isolation and 1.05 (95% CI, 1.01-1.09; 5.0% higher risk) for loneliness. Women with both high social isolation and high loneliness scores had a 13.0% to 27.0% higher risk of incident CVD than did women with low social isolation and low loneliness scores. Social support was not a significant effect modifier of the associations (social isolation × social support: r, -0.18; P = .86; loneliness × social support: r, 0.78; P = .48). In this cohort study, social isolation and loneliness were independently associated with modestly higher risk of CVD among postmenopausal women in the US, and women with both social isolation and loneliness had greater CVD risk than did those with either exposure alone. The findings suggest that these prevalent psychosocial processes merit increased attention for prevention of CVD in older women, particularly in the era of COVID-19.
Authors: Golaszewski, Natalie M; Saquib, Nazmus; Bellettiere, John; et al.
JAMA Netw Open. 2022 02 01;5(2):e2146461. Epub 2022-02-01.
Care in the time of COVID-19: impact on the diagnosis and treatment of breast cancer in a large, integrated health care system
To delineate operational changes in Kaiser Permanente Northern California breast care and evaluate the impact of these changes during the initial COVID-19 Shelter-in-Place period (SiP, 3/17/20-5/17/20). By extracting data from institutional databases and reviewing electronic medical charts, we compared clinical and treatment characteristics of breast cancer patients diagnosed 3/17/20-5/17/20 to those diagnosed 3/17/19-5/17/2019. Outcomes included time from biopsy to consultation and treatment. Comparisons were made using Chi-square or Wilcoxon rank-sum tests. Fewer new breast cancers were diagnosed in 2020 during the SiP period than during a similar period in 2019 (n = 247 vs n = 703). A higher percentage presented with symptomatic disease in 2020 than 2019 (78% vs 37%, p < 0.001). Higher percentages of 2020 patients presented with grade 3 (37% vs 25%, p = 0.004) and triple-negative tumors (16% vs 10%, p = 0.04). A smaller percentage underwent surgery first in 2020 (71% vs 83%, p < 0.001) and a larger percentage had neoadjuvant chemotherapy (16% vs 11%, p < 0.001). Telehealth utilization increased from 0.8% in 2019 to 70.0% in 2020. Times to surgery and neoadjuvant chemotherapy were shorter in 2020 than 2019 (19 vs 26 days, p < 0.001, and 23 vs 28 days, p = 0.03, respectively). During SiP, fewer breast cancers were diagnosed than during a similar period in 2019, and a higher proportion presented with symptomatic disease. Early-stage breast cancer diagnoses decreased, while metastatic cancer diagnoses remained similar. Telehealth increased significantly, and times to treatment were shorter in 2020 than 2019. Our system continued to provide timely breast cancer treatment despite significant pandemic-driven disruption.
Authors: Tang, Annie; Arasu, Vignesh A; Liu, Raymond; Habel, Laurel A; Kushi, Lawrence H; Permanente Medical Group Breast Research Collaborative,; et al.
Breast Cancer Res Treat. 2022 Feb;191(3):665-675. Epub 2022-01-06.
Positive predictive value and sensitivity of ICD-9-CM codes for identifying pediatric leukemia
To facilitate community-based epidemiologic studies of pediatric leukemia, we validated use of ICD-9-CM diagnosis codes to identify pediatric leukemia cases in electronic medical records of six U.S. integrated health plans from 1996-2015 and evaluated the additional contributions of procedure codes for diagnosis/treatment. Subjects (N = 408) were children and adolescents born in the health systems and enrolled for at least 120 days after the date of the first leukemia ICD-9-CM code or tumor registry diagnosis. The gold standard was the health system tumor registry and/or medical record review. We calculated positive predictive value (PPV) and sensitivity by number of ICD-9-CM codes received in the 120-day period following and including the first code. We evaluated whether adding chemotherapy and/or bone marrow biopsy/aspiration procedure codes improved PPV and/or sensitivity. Requiring receipt of one or more codes resulted in 99% sensitivity (95% confidence interval [CI]: 98-100%) but poor PPV (70%; 95% CI: 66-75%). Receipt of two or more codes improved PPV to 90% (95% CI: 86-93%) with 96% sensitivity (95% CI: 93-98%). Requiring at least four codes maximized PPV (95%; 95% CI: 92-98%) without sacrificing sensitivity (93%; 95% CI: 89-95%). Across health plans, PPV for four codes ranged from 84-100% and sensitivity ranged from 83-95%. Including at least one code for a bone marrow procedure or chemotherapy treatment had minimal impact on PPV or sensitivity. The use of diagnosis codes from the electronic health record has high PPV and sensitivity for identifying leukemia in children and adolescents if more than one code is required.
Authors: Weinmann, Sheila; Francisco, Melanie C; Kwan, Marilyn L; Bowles, Erin J A; Rahm, Alanna Kulchak; Greenlee, Robert T; Stout, Natasha K; Pole, Jason D; Kushi, Lawrence H; Smith-Bindman, Rebecca; Miglioretti, Diana L
Pediatr Blood Cancer. 2022 02;69(2):e29383. Epub 2021-11-13.
Scaling of computed tomography body composition to height: relevance of height-normalized indices in patients with colorectal cancer
Body weight scales to height with a power of ≈2 (weight/height2 ), forming the basis of body mass index (BMI). The corresponding scaling of body composition measured by abdominal computed tomography (CT) to height has not been established. The objective of this analysis was to quantify the scaling of body composition measured by a single-slice axial abdominal CT image (skeletal muscle, and visceral, subcutaneous, and total adipose tissue) to height in patients with colorectal cancer (CRC). This cross-sectional study included non-Hispanic white males and females, aged 18-80 years, who were diagnosed with stage I-III CRC at an integrated health care system in North America between January 2006 and December 2011. Body composition was measured by a single-slice axial CT image of the third lumbar vertebra and analysed with a semi-automated threshold segmentation procedure. Allometric regression models were used to quantify height scaling powers (β ± standard error) for each body composition measure, adjusted for age, for males and females. An interaction test was used to determine if height scaling powers were statistically significantly different between males and females. Among 2036 subjects, the mean (standard deviation) age was 64 ± 11 years, 1008 (49.5%) were female, and the mean (standard deviation) BMI was 27.9 ± 5.4 kg/m2 . Powers for skeletal muscle area were 1.06 ± 0.12 for males and 0.80 ± 0.12 for females (P = 0.049). Powers for visceral adipose tissue area were 1.81 ± 0.64 for males and 0.57 ± 0.79 for females (P = 0.16). Powers for subcutaneous adipose tissue area were 2.04 ± 0.42 for males and 0.81 ± 0.45 for females (P = 0.056). Powers for total abdominal adipose tissue area were 1.80 ± 0.46 for males and 0.76 ± 0.50 for females (P = 0.20). Body composition measured by single-slice axial abdominal CT, particularly muscle area, scales to height with age-adjusted powers that are different than 2 and are distinct between males and females. These observations may have implications for the development of height-adjusted body composition indices in patients with cancer.
Authors: Brown, Justin C; Heymsfield, Steven B; Caan, Bette J
J Cachexia Sarcopenia Muscle. 2022 02;13(1):203-209. Epub 2021-11-06.
Interpersonal violence and painful bladder symptoms in community-dwelling midlife to older women
Women are more likely to present with genitourinary complaints immediately after exposure to interpersonal violence, but little is known about the long-term effects of violence on women’s urologic health, including their susceptibility to bladder pain and infections. To determine whether lifetime interpersonal violence exposure and current posttraumatic stress disorder (PTSD) symptoms are associated with the prevalence or severity of painful bladder symptoms and a greater lifetime history of antibiotic-treated urinary tract infections in community-dwelling midlife and older women. We examined the cross-sectional data from a multiethnic cohort of community-dwelling women aged 40 to 80 years enrolled in a northern California integrated healthcare system. Women completed structured self-report questionnaires about their past exposure to physical and verbal/emotional intimate partner violence and sexual assault. The symptoms of PTSD were assessed using the PTSD checklist for the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Civilian version. Additional structured self-report measures assessed the current bladder pain, other lower urinary tract symptoms, and the history of antibiotic-treated urinary tract infections. Multivariable logistic regression models examined self-reported interpersonal violence exposure history and current PTSD symptoms in relation to current bladder pain and antibiotic-treated urinary tract infection history. Among 1974 women (39% non-Latina White, 21% Black, 20% Latina, and 19% Asian), 22% reported lifetime interpersonal violence exposure, 22% reported bladder pain, and 60% reported a history of ever having an antibiotic-treated urinary tract infection. Lifetime experiences of sexual assault (odds ratio, 1.39; [95% confidence interval, 1.02-1.88]) and current PTSD symptoms (odds ratio, 1.96; [95% confidence interval, 1.45-2.65]) were associated with current bladder pain. A lifetime experience of physical intimate partner violence was associated with having a urinary tract infection at any time in life previously (odds ratio, 1.38; [95% confidence interval, 1.00-1.86]), as was emotional intimate partner violence (odds ratio, 1.88; [95% confidence interval, 1.43-2.48]), sexual assault (odds ratio, 1.44; [95% confidence interval, 1.09-1.91]), and current PTSD symptoms (odds ratio, 1.54; [95% confidence interval, 1.16-2.03]). In this ethnically diverse, community-based cohort, lifetime interpersonal violence exposures and current PTSD symptoms were independently associated with current bladder pain and the lifetime history of antibiotic-treated urinary tract infections in midlife to older women. The findings suggest that interpersonal violence and PTSD symptoms may be underrecognized markers of risk for urologic pain and infections in women, highlighting a need for trauma-informed care of these issues.
Authors: Raphael, Eva; Van Den Eeden, Stephen K; Gibson, Carolyn J; Tonner, Chris; Thom, David H; Subak, Leslee; Huang, Alison J
Am J Obstet Gynecol. 2022 02;226(2):230.e1-230.e10. Epub 2021-09-20.
The association of bowel function, participation in life activities, and quality of life in rectal cancer survivors
To evaluate whether limited participation in life activities is associated with quality of life (QOL) in rectal cancer survivors, and if so, whether this association is independent of bowel function difficulties. We surveyed rectal cancer survivors from four healthcare systems about their QOL, bowel function, and participation in life activities. Additional demographic and clinical variables were extracted from the electronic health record. We examined independent associations between bowel function, participation in life activities, and QOL, controlling for potential confounders. We also identified factors, including ostomy status, that correlate with participation in life activities. Of the 527 respondents, 52% were male, 80% were non-Hispanic white, and the mean age was 63. In fully adjusted models for all rectal cancer survivors, participation in life activities was positively associated with QOL, while bowel function was not. Bowel function retained an independent association with QOL for those who previously had an ostomy and were therefore more likely to have a low rectal anastomosis. Lower participation in life activities was correlated with lower self-reported physical and cognitive function, younger age, financial difficulty, and being non-Hispanic white. Rectal cancer survivors’ participation in life activities was strongly associated with QOL, even when controlling for numerous confounders, including bowel function. Identifying ways to improve participation in life activities may be critical to developing rehabilitative and other supportive interventions that optimize QOL among rectal cancer survivors.
Authors: Bulkley, Joanna E; McMullen, Carmit K; Rawlings, Andreea M; Krouse, Robert S; Francisco, Melanie C; Sterrett, Andrew T; Burnett-Hartman, Andrea N; Pawloski, Pamala A; Corley, Douglas A; Colwell, Janice C; Feigelson, Heather Spencer
Qual Life Res. 2022 Feb;31(2):487-495. Epub 2021-07-12.
TP53 Gain-of-Function and Non-Gain-of-Function Mutations Are Differentially Associated With Sidedness-Dependent Prognosis in Metastatic Colorectal Cancer
To examine the association of gain-of-function (GOF) and non-gain-of-function (non-GOF) TP53 mutations with prognosis of metastatic right-sided (RCC) versus left-sided colorectal cancer (LCC). This cohort study included patients with metastatic colorectal cancer (CRC) who had next-generation sequencing performed from November 2017 to January 2021. We defined R175H, R248W, R248Q, R249S, R273H, R273L, and R282W as GOF and all other mutp53 as non-GOF. We used Cox regression modeling to examine the association between GOF and non-GOF mutp53 and overall survival (OS), adjusting for age, sex, ethnicity, performance status, Charlson comorbidity index and receipt of chemotherapy. Of total 1,043 patients, 735 had tumors with mutp53 and 308 had wild-type p53 (wtp53). GOF was associated with worse OS than non-GOF mutp53 only in LCC (hazard ratio [HR] = 1.66 [95% CI, 1.20 to 2.29]), but not in RCC (HR = 0.79 [95% CI, 0.49 to 1.26]). Importantly, RCC was associated with worse OS than LCC only in the subset of patients whose CRC carried non-GOF (HR = 1.76 [95% CI, 1.30 to 2.39]), but not GOF mutp53 (HR = 0.92 [95% CI, 0.55 to 1.53]) or wtp53 (HR = 0.88 [95% CI, 0.60 to 1.28]). These associations were largely unchanged after also adjusting for RAS, BRAF, and PIK3CA mutations, and microsatellite instability-high. Poorer survival of patients with metastatic RCC versus LCC appeared to be restricted to the subset with non-GOF mutp53, whereas GOF versus non-GOF mutp53 was associated with poorer survival only among patients with LCC. This approach of collectively classifying mutp53 into GOF and non-GOF provides new insight for prognostic stratification and for understanding the mechanism of sidedness-dependent prognosis. If confirmed, future CRC clinical trials may benefit from incorporating this approach.
Authors: Pan, Minggui; Solorzano, Aleyda V; Habel, Laurel A; et al.
J Clin Oncol. 2022 01 10;40(2):171-179. Epub 2021-11-29.
Greater Body Fatness Is Associated With Higher Protein Expression of LEPR in Breast Tumor Tissues: A Cross-Sectional Analysis in the Women’s Circle of Health Study
The mechanisms underlying the association of overall and central body fatness with poorer breast cancer outcomes remain unclear; altered gene and/or protein expression of the adipokines and their receptors in breast tumors might play a role. In a sample of Black and White women with primary invasive breast cancer, we investigated associations of body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), fat mass index (FMI), and percent body fat with protein expression (log-transformed, n = 722) and gene expression (log2-transformed, n = 148) of leptin (LEP), leptin receptor (LEPR), adiponectin (ADIPOQ), and adiponectin receptors 1 and 2 (ADIPOR1, ADIPOR2). Multivariable linear models, adjusting for race, menopausal status, and estrogen receptor status, were used to assess these associations, with Bonferroni correction for multiple comparisons. In multivariable models, we found that increasing BMI (β = 0.0529, 95% CI: 0.0151, 0.0906) and FMI (β = 0.0832, 95% CI: 0.0268, 0.1397) were associated with higher LEP gene expression, corresponding to 34.5% and 38.3% increases in LEP gene expression for a standard deviation (SD) increase in BMI and FMI, respectively. Increasing BMI (β = 0.0028, 95% CI: 0.0011, 0.0045), waist circumference (β = 0.0013, 95% CI: 0.0005, 0.0022), hip circumference (β = 0.0015, 95% CI: 0.0007, 0.0024), and FMI (β = 0.0041, 95% CI: 0.0015, 0.0067) were associated with higher LEPR protein expression. These associations equate to 16.8%, 17.6%, 17.7%, 17.2% increases in LEPR protein expression for a 1-SD increase in BMI, waist circumference, hip circumference, and FMI, respectively. Further, these associations were stronger among White and postmenopausal women and ER+ cases; formal tests of interaction yielded evidence of effect modification by race. No associations of body fatness with LEP protein expression, LEPR gene expression, or protein or gene expression of ADIPOQ, ADIPOR1, and ADIPOR2 were found. These findings support an association of increased body fatness – beyond overall body size measured using BMI – with higher LEP gene expression and higher LEPR protein expression in breast tumor tissues. Clarifying the impact of adiposity-related adipokine and adipokine receptor expression in breast tumors on long-term breast cancer outcomes is a critical next step.
Authors: Llanos, Adana A M; Cespedes Feliciano, Elizabeth M; Demissie, Kitaw; et al.
Front Endocrinol (Lausanne). 2022;13:879164. Epub 2022-06-29.
Advancing Diversity, Equity, and Inclusion in Scientific Publishing
Authors: Doubeni, Chyke A; Corley, Douglas A; Peek, Richard M
Gastroenterology. 2022 01;162(1):59-62.e1. Epub 2021-11-03.
Endoscopic Surveillance and Dysplasia Management in IBD: Plus Ça Change, Plus C’est la Même Chose
Authors: Velayos, Fernando S; Lee, Jeffrey K
Dig Dis Sci. 2022 01;67(1):81-84. Epub 2021-10-27.
The Friends of Cancer Research Real World Data (RWD) Collaboration Pilot 2.0: Methodological Recommendations from Oncology Case Studies
The purpose of this study was to evaluate the potential collective opportunities and challenges of transforming real-world data (RWD) to real-world evidence for clinical effectiveness by focusing on aligning analytic definitions of oncology end points. Patients treated with a qualifying therapy for advanced non-small cell lung cancer in the frontline setting meeting broad eligibility criteria were included to reflect the real-world population. Although a trend toward improved outcomes in patients receiving PD-(L)1 therapy over standard chemotherapy was observed in RWD analyses, the magnitude and consistency of treatment effect was more heterogeneous than previously observed in controlled clinical trials. The study design and analysis process highlighted the identification of pertinent methodological issues and potential innovative approaches that could inform the development of high-quality RWD studies.
Authors: Rivera, Donna R; Kushi, Lawrence; Sakoda, Lori C; Allen, Jeff D; et al.
Clin Pharmacol Ther. 2022 01;111(1):283-292. Epub 2021-11-11.
Rising Early-Onset Colorectal Cancer Incidence is Not an Artifact of Increased Screening Colonoscopy Use in a Large, Diverse Healthcare System
Authors: Lee, Jeffrey K; Merchant, Sophie A; Jensen, Christopher D; Murphy, Caitlin C; Udaltsova, Natalia; Corley, Douglas A
Gastroenterology. 2022 01;162(1):325-327.e3. Epub 2021-09-20.
Program components and results from an organized colorectal cancer screening program using annual fecal immunochemical testing
Programmatic colorectal cancer (CRC) screening increases uptake, but the design and resources utilized for such models are not well known. We characterized program components and participation at each step in a large program that used mailed fecal immunochemical testing (FIT) with opportunistic colonoscopy. Mixed-methods with site visits and retrospective cohort analysis of 51-75-year-old adults during 2017 in the Kaiser Permanente Northern California integrated health system. Among 1,023,415 screening-eligible individuals, 405,963 (40%) were up to date with screening at baseline, and 507,401 of the 617,452 not up-to-date were mailed a FIT kit. Of the entire cohort (n = 1,023,415), 206,481 (20%) completed FIT within 28 days of mailing, another 61,644 (6%) after a robocall at week 4, and 40,438 others (4%) after a mailed reminder letter at week 6. There were over 800,000 medical record screening alerts generated and about 295,000 FIT kits distributed during patient office visits. About 100,000 FIT kits were ordered during direct-to-patient calls by medical assistants and 111,377 people (11%) completed FIT outside of the automated outreach period. Another 13,560 (1.3%) completed a colonoscopy, sigmoidoscopy, or fecal occult blood test unrelated to FIT. Cumulatively, 839,463 (82%) of those eligible were up to date with screening at the end of the year and 12,091 of 14,450 patients (83.7%) with positive FIT had diagnostic colonoscopy. The >82% screening participation achieved in this program resulted from a combination of prior endoscopy (40%), large initial response to mailed FIT kits (20%), followed by smaller responses to automated reminders (10%) and personal contact (12%).
Authors: Selby, Kevin; Jensen, Christopher D; Levin, Theodore R; Lee, Jeffrey K; Schottinger, Joanne E; Zhao, Wei K; Corley, Douglas A; Doubeni, Chyke A
Clin Gastroenterol Hepatol. 2022 01;20(1):145-152. Epub 2020-09-30.
Changes in older adults’ life space during lung cancer treatment: A mixed methods cohort study.
BACKGROUND: Maintenance of function during cancer treatment is important to older adults. Characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment remain unknown. n METHODS: This mixed methods cohort study recruited adults age ≥65 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. LSA scores range from 0 to 120 (greater mobility); LSA <60 is considered restricted. We used mixed-effects models to examine pretreatment LSA, change from 0 to 1 month, and change from 1 to 6 months. A subgroup participated in semistructured interviews pretreatment and at 2 and 6 months to understand the patient experience of life-space change. For each interview participant, we created joint displays of longitudinal LSA scores juxtaposed with illustrative quotes. n RESULTS: Among 93 patients, median age was 73 (range 65-94). Mean pretreatment LSA score was 67.1. On average, LSA declined 10.1 points from pretreatment to 1 month and remained stable at 6 months. Pretreatment LSA score was associated with several demographic, clinical, geriatric assessment, and symptom characteristics. LSA decline at 1 month was greater among patients with high anxiety (slope = -12.6 vs. -2.3, p = 0.048). Pretreatment body mass index <21 kg/m n CONCLUSION: Older adults with NSCLC have low pretreatment life space with many developing restricted life space during treatment. Incorporating life-space assessments into clinical cancer care may help older adults concretely visualize how treatment might impact their daily function to allow for informed decision making and identify early changes in mobility to implement supportive interventions.
Authors: Wong, Melisa L;Walter, Louise C;et al.
J Am Geriatr Soc. 2022 Jan;70(1):136-149. doi: 10.1111/jgs.17474. Epub 2021 Oct 5.
Neighborhood and Individual Socioeconomic Disadvantage and Survival Among Patients With Nonmetastatic Common Cancers
Disadvantaged neighborhood-level and individual-level socioeconomic status (SES) have each been associated with suboptimal cancer care and inferior outcomes. However, independent or synergistic associations between neighborhood and individual socioeconomic disadvantage have not been fully examined, and prior studies using simplistic neighborhood SES measures may not comprehensively assess multiple aspects of neighborhood SES. To investigate the associations of neighborhood SES (using a validated comprehensive composite measure) and individual SES with survival among patients with nonmetastatic common cancers. This prospective, population-based cohort study was derived from the Surveillance, Epidemiology, and End Results-Medicare database from January 1, 2008, through December 31, 2011, with follow-up ending on December 31, 2017. Participants included older patients (≥65 years) with breast, prostate, lung, or colorectal cancer. Neighborhood SES was measured using the area deprivation index (ADI; quintiles), a validated comprehensive composite measure of neighborhood SES. Individual SES was assessed by Medicare-Medicaid dual eligibility (yes vs no), a reliable indicator for patient-level low income. The primary outcome was overall mortality, and the secondary outcome was cancer-specific mortality. Hazard ratios (HRs) for the associations of ADI and dual eligibility with overall and cancer-specific mortality were estimated via Cox proportional hazards regression. Statistical analyses were conducted from January 23 to April 15, 2021. A total of 96 978 patients were analyzed, including 25 968 with breast, 35 150 with prostate, 16 684 with lung, and 19 176 with colorectal cancer. Median age at diagnosis was 76 years (IQR, 71-81 years) for breast cancer, 73 years (IQR, 70-77 years) for prostate cancer, 76 years (IQR, 71-81 years) for lung cancer, and 78 years (IQR, 72-84 years) for colorectal cancer. Among lung and colorectal cancer patients, 8412 (50.4%) and 10 486 (54.7%), respectively, were female. The proportion of non-Hispanic White individuals among breast cancer patients was 83.7% (n = 21 725); prostate cancer, 76.8% (n = 27 001); lung cancer, 83.5% (n = 13 926); and colorectal cancer, 81.1% (n = 15 557). Neighborhood-level and individual-level SES were independently associated with overall mortality, and no interactions were detected. Compared with the most affluent neighborhoods (ADI quintile 1), living in the most disadvantaged neighborhoods (ADI quintile 5) was associated with higher risk of overall mortality (breast: HR, 1.34; 95% CI, 1.26-1.43; prostate: HR, 1.51; 95% CI, 1.42-1.62; lung: HR, 1.21; 95% CI, 1.14-1.28; and colorectal: HR, 1.24; 95% CI, 1.17-1.32). Individual socioeconomic disadvantage (dual eligibility) was associated with higher risk of overall mortality (breast: HR, 1.22; 95% CI, 1.15-1.29; prostate: HR, 1.29; 95% CI, 1.21-1.38; lung: HR, 1.14; 95% CI, 1.09-1.20; and colorectal: HR, 1.23; 95% CI, 1.17-1.29). A similar pattern was observed for cancer-specific mortality. In this cohort study, neighborhood-level deprivation was associated with worse survival among patients with nonmetastatic breast, prostate, lung, and colorectal cancer, even after accounting for individual SES. These findings suggest that, in order to improve cancer outcomes and reduce health disparities, policies for ongoing investments in low-resource neighborhoods and low-income households are needed.
Authors: Cheng, En; Soulos, Pamela R; Irwin, Melinda L; Cespedes Feliciano, Elizabeth M; Presley, Carolyn J; Fuchs, Charles S; Meyerhardt, Jeffrey A; Gross, Cary P
JAMA Netw Open. 2021 12 01;4(12):e2139593. Epub 2021-12-01.
Dietary Advanced Glycation End-Products (AGEs) and Mortality After Breast Cancer in the Women’s Health Initiative (WHI)
Advanced glycation end-products (AGE) are formed through nonenzymatic glycation of free amino groups in proteins or lipid. They are associated with inflammation and oxidative stress, and their accumulation in the body is implicated in chronic disease morbidity and mortality. We examined the association between postdiagnosis dietary Nε-carboxymethyl-lysine (CML)-AGE intake and mortality among women diagnosed with breast cancer. Postmenopausal women aged 50 to 79 years were enrolled in the Women’s Health Initiative (WHI) between 1993 and 1998 and followed up until death or censoring through March 2018. We included 2,023 women diagnosed with first primary invasive breast cancer during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis. Cox proportional hazards (PH) regression models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) of association between tertiles of postdiagnosis CML-AGE intake and mortality risk from all causes, breast cancer, and cardiovascular disease. After a median 15.1 years of follow-up, 630 deaths from all causes were reported (193 were breast cancer-related, and 129 were cardiovascular disease-related). Postdiagnosis CML-AGE intake was associated with all-cause (HRT3vsT1, 1.37; 95% CI, 1.09-1.74), breast cancer (HRT3vsT1, 1.49; 95% CI, 0.98-2.24), and cardiovascular disease (HRT3vsT1, 1.91; 95% CI, 1.09-3.32) mortality. Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer. Our findings suggest that dietary AGEs may contribute to the risk of mortality after breast cancer diagnosis. Further prospective studies examining dietary AGEs in breast cancer outcomes and intervention studies targeting dietary AGE reduction are needed to confirm our findings.
Authors: Omofuma, Omonefe O; Caan, Bette J; Steck, Susan E; et al.
Cancer Epidemiol Biomarkers Prev. 2021 12;30(12):2217-2226. Epub 2021-09-28.
Abdominal adipose tissue radiodensity is associated with survival after colorectal cancer
Adipose tissue radiodensity may have prognostic importance for colorectal cancer (CRC) survival. Lower radiodensity is indicative of larger adipocytes, while higher radiodensity may represent adipocyte atrophy, inflammation, or edema. We investigated associations of adipose tissue radiodensity and longitudinal changes in adipose tissue radiodensity with mortality among patients with nonmetastatic CRC. In 3023 patients with stage I-III CRC, radiodensities of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were quantified from diagnostic computed tomography (CT) images. There were 1775 patients with follow-up images available. Cox proportional hazards models and restricted cubic splines were used to examine associations of at-diagnosis values and of longitudinal changes in VAT and SAT radiodensities with risks of death after adjusting for potential confounders, including body size and comorbidities. VAT and SAT radiodensities were linearly associated with all-cause mortality: the HRs for death per SD increase were 1.21 (95% CI, 1.11-1.32) for VAT radiodensity and 1.18 (95% CI, 1.11-1.26) for SAT radiodensity. Changes in adipose tissue radiodensity had curvilinear associations with risks of death. The HR for an increase in VAT radiodensity of at least 1 SD was 1.53 (95% CI, 1.23-1.90), while the HR for a decrease of at least 1 SD was nonsignificant at 1.11 (95% CI, 0.84-1.47) compared with maintaining radiodensity within 1 SD of baseline. Similarly, increases (HR, 1.88; 95% CI, 1.48-2.40) but not decreases (HR, 1.20; 95% CI, 0.94-1.54) in SAT radiodensity significantly increased the risk of death compared with no change in radiodensity. In patients with nonmetastatic CRC, adipose tissue radiodensity is a novel risk factor for total mortality that is independent of BMI and changes in body weight.
Authors: Feliciano, Elizabeth M Cespedes; Winkels, Renate M; Meyerhardt, Jeffrey A; Prado, Carla M; Afman, Lydia A; Caan, Bette J
Am J Clin Nutr. 2021 12 01;114(6):1917-1924.
Adherence to Lung Cancer Screening: What Exactly Are We Talking About?
Authors: Sakoda, Lori C; Henderson, Louise M; Rivera, M Patricia
Ann Am Thorac Soc. 2021 12;18(12):1951-1952.
The learning health system: the tools are here, why aren’t we moving forward? Embedding researchers and delivery science for accelerating health care change
Authors: Corley, Douglas A; Kilbourne, Amy
Gastroenterology. 2021 12;161(6):1747-1750. Epub 2021-08-09.
Characterizing the Spectrum of Bladder Health and Lower Urinary Tract Symptoms (LUTS) among Women: Results from the CARDIA Study
To operationalize a new definition for bladder health, we examined the distribution of lower urinary tract symptoms (LUTS) and impact, along with associated factors, among women in the Coronary Artery Risk Development in Young Adults (CARDIA) study. We performed cluster analyses using validated LUTS symptom burden and impact scales collected between 2005-2006 and 2010-2011. We performed multinomial logistic regression analyses to evaluate cardiovascular factors (metabolic syndrome, cardiovascular health behaviors, and inflammation) between clusters after adjusting for covariates (demographic, obstetric/gynecologic, co-morbidities). Among CARDIA women (median age 51, range 42-59) with complete LUTS data (n = 1302), we identified and compared 4 cluster groups: women who reported no or very mild symptoms and no impact on well-being (bladder health, 44%, n = 569), versus women with LUTS and negative impact on well-being ranging from mild (31%, n = 407), moderate (20%, n = 259), to severe (5%, n = 67). With each 1-point lower BMI (kg/m2), odds of membership in mild (OR 0.97, CI 0.95-0.99), moderate (OR 0.95, CI 0.93-0.98), and severe (OR 0.90, CI 0.88-0.94) LUTS cluster groups versus the bladder health group were lower. Compared to women with metabolic syndrome, women without metabolic syndrome had lower odds of membership in mild (OR 0.67, CI 0.45-0.99), moderate (OR 0.51, CI 0.33-0.79), and severe (OR 0.48, CI 0.24-0.94) LUTS cluster groups versus the bladder health group. Two out of 5 midlife women met our definition of bladder health. Bladder health and cardiovascular health among women may share common factors, including lower BMI and the absence of metabolic syndrome.
Authors: Markland, Alayne D; Shan, Liang; Brady, Sonya S; Schreiner, Pamela J; Sidney, Stephen; Van Den Eeden, Stephen K; Lewis, Cora E
Urology. 2021 12;158:88-94. Epub 2021-06-02.
Comparing Different Interventions’ Effects on Latinas’ Screening Mammography Attainment and Participant-Driven Information Diffusion
Evaluation of multiple community-based approaches to improve Latinas’ breast cancer (BC) screening utilization has resulted in inconsistent findings. Factors contributing to this variation include heterogeneity in approaches (e.g., types of conceptual frameworks) and study quality (e.g., lack of measurement of spillover effects). This pilot study sought to clarify which approach may be most effective by evaluating the relative efficacy of two conceptual approaches using an area-level design with 145 Latinas nonadherent to U.S. Preventive Services Taskforce (USPSTF) BC screening guidelines. Each study arm included identical intervention format and duration (e.g., three group-based sessions, logistic assistance (LA) via five monthly calls and referral to free/low-cost screening programs). However, study content differed. While educate+LA addressed participants’ BC prevention and screening behavior, empower+LA addressed participants’ and their social networks’ BC screening. After adjusting for age, insurance status, and baseline mammography intention, when compared with educate+LA participants, empower+LA participants were more likely to report obtaining mammograms, engaging more individuals about BC, initiating BC conversations in public settings, and discussing mammography specifically. Our study has important implications regarding the utility of evaluating behavioral interventions overall in terms of behavioral and spillover network effects.
Authors: Molina, Yamilé; Kroenke, Candyce H; et al.
Health Educ Behav. 2021 12;48(6):818-830. Epub 2021-05-27.
Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study
Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes’ coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.
Authors: Nounu, Aayah; Slattery, Martha L; Relton, Caroline L; et al.
Nutrients. 2021 11 21;13(11). Epub 2021-11-21.
Description of Major Osteoporotic Fractures in Women with Invasive Breast Cancer Who Received Endocrine Therapy
Authors: Lo, Joan C; Laurent, Cecile A; Roh, Janise M; Lee, Jean; Chandra, Malini; Yao, Song; Kwan, Marilyn L
JAMA Netw Open. 2021 11 01;4(11):e2133861. Epub 2021-11-01.
Plasma metabolomic profiles associated with chronic distress in women
Several forms of chronic distress including anxiety and depression are associated with adverse cardiometabolic outcomes. Metabolic alterations may underlie these associations. Whether these forms of distress are associated with metabolic alterations even after accounting for comorbid conditions and other factors remains unclear. Using an agnostic approach, this study examines a broad range of metabolites in relation to chronic distress among women. For this cross-sectional study of chronic distress and 577 plasma metabolites, data are from different substudies within the Women’s Health Initiative (WHI) and Nurses’ Health Studies (NHSI, NHSII). Chronic distress was characterized by depressive symptoms and other depression indicators in the WHI and NHSII substudies, and by combined indicators of anxiety and depressive symptoms in the NHSI substudy. We used a two-phase discovery-validation framework, with WHI (N = 1317) and NHSII (N = 218) substudies in the discovery phase (identifying metabolites associated with distress) and NHSI (N = 558) substudy in the validation phase. A differential network analysis provided a systems-level assessment of metabolomic alterations under chronic distress. Analyses adjusted for potential confounders and mediators (demographics, comorbidities, medications, lifestyle factors). In the discovery phase, 46 metabolites were significantly associated with depression measures. In validation, six of these metabolites demonstrated significant associations with chronic distress after adjustment for potential confounders. Among women with high distress, we found lower gamma-aminobutyric acid (GABA), threonine, biliverdin, and serotonin and higher C16:0 ceramide and 3-methylxanthine. Our findings suggest chronic distress is associated with metabolomic alterations and provide specific targets for future study of biological pathways in chronic diseases.
Authors: Shutta, Katherine H; Tinker, Lesley F; Kubzansky, Laura D; et al.
Psychoneuroendocrinology. 2021 11;133:105420. Epub 2021-09-20.
Systematic review with meta-analysis: the prevalence of post-colonoscopy colorectal cancers using the World Endoscopy Organization nomenclature
Post-colonoscopy colorectal cancers (PCCRCs) have been proposed as a performance metric for colonoscopy quality assurance programs. Previously, there was no standardised terminology or reporting methods. In 2018, the World Endoscopy Organization (WEO) advised standardised definitions and prevalence calculation methodology. To assess PCCRC burden using WEO standardised methods, to explore causes of heterogeneity, and to review changes in prevalence over time METHODS: We updated a prior systematic review by searching Ovid MEDLINE and EMBASE databases from 1 January 2013 to 31 January 2021 to identify population-based studies (or multicentre studies representative of the local population) reporting PCCRC prevalence (PROSPERO [CRD42020183796]). Two authors independently determined study eligibility, assessed quality, and extracted data. We estimated the PCCRC 3-year prevalence using WEO-recommended methodologies and investigated between-study sources of heterogeneity. We examined changes in prevalence over time. Fifteen studies reporting on 25 872 PCCRC cases met eligibility criteria. Pooled PCCRC 3 year prevalence was 8.2% (95% CI = 6.9%-9.4%, I2 = 98.2%) across four European studies using WEO precise methodology. Proximal PCCRC prevalence was greater than distal (9.7% [95% CI = 7.0%-12.4%] vs 5.4% [95% CI = 2.9%-7.8%], I2 = 99.2%). Seven studies reporting PCCRC rates over time showed no consistent trend: four showed a decrease, one an increase and two were unchanged. Between-study heterogeneity was high. Pooled 3-year PCCRC prevalence was 8.2% (95% CI = 6.9%-9.4%). Despite WEO standardised methodology to define and calculate PCCRC rates, there was significant heterogeneity among studies. Comparing rates between populations remains challenging and additional studies are needed to better understand the global PCCRC burden to inform quality assurance programs.
Authors: Kang, James H-E; Evans, Nicole; Singh, Siddharth; Samadder, Niloy J; Lee, Jeffrey K
Aliment Pharmacol Ther. 2021 11;54(10):1232-1242. Epub 2021-09-29.
Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies
Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs. The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.
Authors: Julián-Serrano, Sachelly; Van Den Eeden, Stephen K; Stolzenberg-Solomon, Rachael Z; et al.
Am J Clin Nutr. 2021 10 04;114(4):1408-1417.
Implementation of Intraoperative Ultrasound Localization for Breast-Conserving Surgery in a Large, Integrated Health Care System is Feasible and Effective
Intraoperative ultrasound (IUS) localization for breast cancer is a noninvasive localization technique. In 2015, an IUS program for breast-conserving surgery (BCS) was initiated in a large, integrated health care system. This study evaluated the clinical results of IUS implementation. The study identified breast cancer patients with BCS from 1 January to 31 October 2015 and from 1 January to 31 October 2019. Clinicopathologic characteristics were collected, and localization types were categorized. Clinical outcomes were analyzed, including localization use, surgeon adoption of IUS, day-of-surgery intervals, and re-excision rates. Multivariate logistic regression analysis was performed to evaluate predictors of re-excision. The number of BCS procedures increased 23%, from 1815 procedures in 2015 to 2226 procedures in 2019. The IUS rate increased from 4% of lumpectomies (n = 79) in 2015 to 28% of lumpectomies (n = 632) in 2019 (p < 0.001). Surgeons using IUS increased from 6% (5 of 88 surgeons) in 2015 to 70% (42 of 60 surgeons) in 2019. In 2019, 76% of IUS surgeons performed at least 25% of lumpectomies with IUS. The mean time from admission to incision was shorter with IUS or seed localization than with wire localization (202 min with IUS, 201 with seed localization, 262 with wire localization in 2019; p < 0.001). The IUS re-excision rates were lower than for other localization techniques (13.6%, vs 19.6% for seed localization and 24.7% for wire localization in 2019; p = 0.006), and IUS predicted lower re-excision rates in a multivariable model (odds ratio [OR], 0.59). In a high-volume integrated health system, IUS was adopted for BCS by a majority of surgeons. The use of IUS decreased the time from admission to incision compared with wire localization, and decreased re-excision rates compared with other localization techniques.
Authors: Chakedis, Jeffery M; Arasu, Vignesh A; Permanente Medical Group Breast Research Collaborative,; et al.
Ann Surg Oncol. 2021 Oct;28(10):5648-5656. Epub 2021-08-26.
Smoking Behavior and Prognosis After Colorectal Cancer Diagnosis: A Pooled Analysis of 11 Studies
Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies, but current evidence on smoking in association with survival after CRC diagnosis is limited. We pooled data from 12 345 patients with stage I-IV CRC from 11 epidemiologic studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of prediagnostic smoking behavior with overall, CRC-specific, and non-CRC-specific survival. Among 12 345 patients with CRC, 4379 (35.5%) died (2515 from CRC) over a median follow-up time of 7.5 years. Smoking was strongly associated with worse survival in stage I-III patients, whereas no association was observed among stage IV patients. Among stage I-III patients, clear dose-response relationships with all survival outcomes were seen for current smokers. For example, current smokers with 40 or more pack-years had statistically significantly worse overall, CRC-specific, and non-CRC-specific survival compared with never smokers (hazard ratio [HR] =1.94, 95% confidence interval [CI] =1.68 to 2.25; HR = 1.41, 95% CI = 1.12 to 1.78; and HR = 2.67, 95% CI = 2.19 to 3.26, respectively). Similar associations with all survival outcomes were observed for former smokers who had quit for less than 10 years, but only a weak association with non-CRC-specific survival was seen among former smokers who had quit for more than 10 years. This large consortium of CRC patient studies provides compelling evidence that smoking is strongly associated with worse survival of stage I-III CRC patients in a clear dose-response manner. The detrimental effect of smoking was primarily related to noncolorectal cancer events, but current heavy smoking also showed an association with CRC-specific survival.
Authors: Alwers, Elizabeth; Sakoda, Lori C; Brenner, Hermann; et al.
JNCI Cancer Spectr. 2021 10;5(5). Epub 2021-08-31.
AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review
The purpose of this Clinical Practice Update Expert Review is to provide clinicians with guidance on the diagnosis and management of atrophic gastritis, a common preneoplastic condition of the stomach, with a primary focus on atrophic gastritis due to chronic Helicobacter pylori infection-the most common etiology-or due to autoimmunity. To date, clinical guidance for best practices related to the diagnosis and management of atrophic gastritis remains very limited in the United States, which leads to poor recognition of this preneoplastic condition and suboptimal risk stratification. In addition, there is heterogeneity in the definitions of atrophic gastritis, autoimmune gastritis, pernicious anemia, and gastric neoplasia in the literature, which has led to confusion in clinical practice and research. Accordingly, the primary objective of this Clinical Practice Update is to provide clinicians with a framework for the diagnosis and management of atrophic gastritis. By focusing on atrophic gastritis, this Clinical Practice Update is intended to complement the 2020 American Gastroenterological Association Institute guidelines on the management of gastric intestinal metaplasia. These recent guidelines did not specifically discuss the diagnosis and management of atrophic gastritis. Providers should recognize, however, that a diagnosis of intestinal metaplasia on gastric histopathology implies the diagnosis of atrophic gastritis because intestinal metaplasia occurs in underlying atrophic mucosa, although this is often not distinctly noted on histopathologic reports. Nevertheless, atrophic gastritis represents an important stage with distinct histopathologic alterations in the multistep cascade of gastric cancer pathogenesis. The Best Practice Advice statements presented herein were developed from a combination of available evidence from published literature and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out. These statements are meant to provide practical advice to clinicians practicing in the United States. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Atrophic gastritis is defined as the loss of gastric glands, with or without metaplasia, in the setting of chronic inflammation mainly due to Helicobacter pylori infection or autoimmunity. Regardless of the etiology, the diagnosis of atrophic gastritis should be confirmed by histopathology. BEST PRACTICE ADVICE 2: Providers should be aware that the presence of intestinal metaplasia on gastric histology almost invariably implies the diagnosis of atrophic gastritis. There should be a coordinated effort between gastroenterologists and pathologists to improve the consistency of documenting the extent and severity of atrophic gastritis, particularly if marked atrophy is present. BEST PRACTICE ADVICE 3: Providers should recognize typical endoscopic features of atrophic gastritis, which include pale appearance of gastric mucosa, increased visibility of vasculature due to thinning of the gastric mucosa, and loss of gastric folds, and, if with concomitant intestinal metaplasia, light blue crests and white opaque fields. Because these mucosal changes are often subtle, techniques to optimize evaluation of the gastric mucosa should be performed. BEST PRACTICE ADVICE 4: When endoscopic features of atrophic gastritis are present, providers should assess the extent endoscopically. Providers should obtain biopsies from the suspected atrophic/metaplastic areas for histopathological confirmation and risk stratification; at a minimum, biopsies from the body and antrum/incisura should be obtained and placed in separately labeled jars. Targeted biopsies should additionally be obtained from any other mucosal abnormalities. BEST PRACTICE ADVICE 5: In patients with histology compatible with autoimmune gastritis, providers should consider checking antiparietal cell antibodies and anti-intrinsic factor antibodies to assist with the diagnosis. Providers should also evaluate for anemia due to vitamin B-12 and iron deficiencies. BEST PRACTICE ADVICE 6: All individuals with atrophic gastritis should be assessed for H pylori infection. If positive, treatment of H pylori should be administered and successful eradication should be confirmed using nonserological testing modalities. BEST PRACTICE ADVICE 7: The optimal endoscopic surveillance interval for patients with atrophic gastritis is not well-defined and should be decided based on individual risk assessment and shared decision making. A surveillance endoscopy every 3 years should be considered in individuals with advanced atrophic gastritis, defined based on anatomic extent and histologic grade. BEST PRACTICE ADVICE 8: The optimal surveillance interval for individuals with autoimmune gastritis is unclear. Interval endoscopic surveillance should be considered based on individualized assessment and shared decision making. BEST PRACTICE ADVICE 9: Providers should recognize pernicious anemia as a late-stage manifestation of autoimmune gastritis that is characterized by vitamin B-12 deficiency and macrocytic anemia. Patients with a new diagnosis of pernicious anemia who have not had a recent endoscopy should undergo endoscopy with topographical biopsies to confirm corpus-predominant atrophic gastritis for risk stratification and to rule out prevalent gastric neoplasia, including neuroendocrine tumors. BEST PRACTICE ADVICE 10: Individuals with autoimmune gastritis should be screened for type 1 gastric neuroendocrine tumors with upper endoscopy. Small neuroendocrine tumors should be removed endoscopically, followed by surveillance endoscopy every 1-2 years, depending on the burden of neuroendocrine tumors. BEST PRACTICE ADVICE 11: Providers should evaluate for iron and vitamin B-12 deficiencies in patients with atrophic gastritis irrespective of etiology, especially if corpus-predominant. Likewise, in patients with unexplained iron or vitamin B-12 deficiency, atrophic gastritis should be considered in the differential diagnosis and appropriate diagnostic evaluation pursued. BEST PRACTICE ADVICE 12: In patients with autoimmune gastritis, providers should recognize that concomitant autoimmune disorders, particularly autoimmune thyroid disease, are common. Screening for autoimmune thyroid disease should be performed.
Authors: Shah, Shailja C; Piazuelo, M Blanca; Kuipers, Ernst J; Li, Dan
Gastroenterology. 2021 10;161(4):1325-1332.e7. Epub 2021-08-26.
Cancer screening in the U.S. through the COVID-19 pandemic, recovery, and beyond
COVID-19 has proved enormously disruptive to the provision of cancer screening, which does not just represent an initial test but an entire process, including risk detection, diagnostic follow-up, and treatment. Successful delivery of services at all points in the process has been negatively affected by the pandemic. There is a void in empirical high-quality evidence to support a specific strategy for administering cancer screening during a pandemic and its resolution phase, but several pragmatic considerations can help guide prioritization efforts. Targeting guideline-eligible people who have never been screened, or those who are significantly out of date with screening, has the potential to maximize benefits now and into the future. Disruptions to care due to the pandemic could represent an unparalleled opportunity to reassess early detection programs towards an explicit, thoughtful, and just prioritization of populations historically experiencing cancer disparities. By focusing screening services on populations that have the most to gain, and by careful and deliberate planning for the period following the pandemic, we can positively affect cancer outcomes for all.
Authors: Croswell, Jennifer M; Corley, Douglas A; Lafata, Jennifer Elston; Haas, Jennifer S; Inadomi, John M; Kamineni, Aruna; Ritzwoller, Debra P; Vachani, Anil; Zheng, Yingye; National Cancer Institute Population-based Research to Optimize the Screening Process (PROSPR) II Consortium,
Prev Med. 2021 10;151:106595. Epub 2021-06-30.
Ultrasound characteristics of early stage high-grade serous ovarian cancer
Survival from ovarian cancer is strongly dependent on the stage at diagnosis. Therefore, when confronted with a woman with an isolated adnexal mass, clinicians worry about missing the opportunity to detect cancer at an early stage. High-grade serous ovarian cancers account for 80% of ovarian cancer deaths, largely because of their tendency to be diagnosed at a late stage. Among adnexal masses, large size and the presence of solid areas on ultrasound examination have been found to be associated with cancer, but it is unclear whether these characteristics identify early-stage cases. This study aimed to evaluate the ultrasound findings associated with clinically detected early-stage high-grade serous ovarian cancer. This was a retrospective cohort study of women diagnosed with stage I or II high-grade serous ovarian or fallopian tube cancer measuring at least 1 cm at pathology from 2007 to 2017. Preoperative ultrasound examinations were independently reviewed by 3 radiologists. Adnexal masses were scored for size and volume; overall appearance; presence, thickness, and vascularity of septations; morphology and vascularity of other solid components; and degree of ascites. Characteristics were compared between masses of <5 cm and larger masses and between stage I and stage II cases. Interobserver variability was assessed. Among 111 women identified, 4 had bilateral ovarian involvement, for a total of 115 adnexal masses characterized by ultrasound examination. The mean age at diagnosis was 61.8 years (range, 42-91 years). The median mass size was 9.6 cm (range, 2.2-23.6 cm) with 87% of cases having a mass size of ≥5 cm. A mixed cystic and solid appearance was most common (77.4%), but a completely solid appearance was more frequently seen for tumors of <5 cm compared with larger tumors (26.7% vs 13.0%). Solid components other than septations were seen in 97.4% of cases. The characteristics of stage I and II cases were similar other than ascites, which was more commonly seen in stage II cases (18.0% vs 3.1%, respectively). Interobserver concordance was high for size and volume measurements (correlation coefficients, 0.96-0.99), with moderate agreement observed across the other ultrasound characteristics (Fleiss kappa, 0.45-0.58). In this community-based cohort, early-stage high-grade serous cancers rarely presented as masses of <5 cm or masses without solid components other than septations. Our findings provide additional support for the observation of small masses without solid areas on ultrasound examination.
Authors: Suh-Burgmann, Elizabeth; Brasic, Natasha; Jha, Priyanka; Hung, Yun-Yi; Goldstein, Ruth B
Am J Obstet Gynecol. 2021 10;225(4):409.e1-409.e8. Epub 2021-05-13.
Hydrochlorothiazide and risk of melanoma subtypes
Hydrochlorothiazide (HCTZ), a common diuretic known to be photosensitizing and previously associated with non-melanoma skin cancer, was recently reported to be associated with two melanoma subtypes, nodular and lentigo, among residents of Denmark. Our goal was to examine whether Danish findings could be replicated in a US cohort, using a similar study design and analysis. Among non-Hispanic White enrollees of Kaiser Permanente Northern California, we conducted an analysis of 9176 melanoma cases and 264 781 controls, matched on age, sex and time in health plan. We examined use of HCTZ prior to cancer diagnosis (cases) or comparable date for controls, categorized as never use, ever use and high use (≥50 000 mg). Electronic health records provided data on prescriptions, cancer diagnoses, and covariates. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for education, income and number of dermatology, internal medicine and urgent care visits. We observed a small increase in risk of melanoma, all types combined, associated with high use (≥50 000 mg) of HCTZ (OR = 1.11, 95% CI 1.00-1.23) and no evidence of a dose-response. Risk was more elevated for lentigo subtype (OR = 1.57, 95% CI 1.01-2.42). The somewhat elevated risk for nodular subtype was not statistically significant (OR = 1.22, 95% CI 0.78-1.90). There was very little association of high use with the superficial spreading subtype (OR = 1.05, 95% CI 0.80-1.37). Our findings support a recent report of an association between high use of HCTZ and increased risk of the lentigo subtype of melanoma.
Authors: Habel, Laurel A; Achacoso, Ninah; Fireman, Bruce; Pedersen, Sidsel Arnspang; Pottegård, Anton
Pharmacoepidemiol Drug Saf. 2021 10;30(10):1396-1401. Epub 2021-05-26.
Financial Toxicity of Cancer Care: An Analysis of Financial Burden in Three Distinct Health Care Systems.
PURPOSE: The financial toxicity of cancer care is a source of significant distress for patients with cancer. The purpose of this study is to understand factors associated with financial toxicity in three distinct care systems. n METHODS: We conducted a cross-sectional survey of patients in three care systems, Stanford Cancer Institute (SCI), VA Palo Alto Health Care System (VAPAHCS), and Santa Clara Valley Medical Center (SCVMC), from October 2017 to May 2019. We assessed demographic factors, employment status, and out-of-pocket costs (OOPCs) and administered the validated COmprehensive Score for financial Toxicity tool. We calculated descriptive statistics and conducted linear regression models to analyze factors associated with financial toxicity. n RESULTS: Four hundred forty-four of 578 patients (77%) completed the entire COmprehensive Score for financial Toxicity tool and were included in the analysis. Most respondents at SCI were White, with annual household income (AHI) > $50,000 USD and Medicare insurance. At the VAPAHCS, most were White, with AHI ≤ $50,000 USD and insured by the Veterans Administration. At SCVMC, most were Asian and/or Pacific Islander, with AHI ≤ $25,000 USD and Medicaid insurance. Low AHI ( n CONCLUSION: Low AHI, high OOPCs, and employment changes contribute to financial toxicity; however, there are variations based on site of care. Future studies should tailor financial toxicity interventions within care delivery systems.
Authors: Parikh, Divya A;Ragavan, Meera;Dutta, Ritika;Garnet Edwards, Jeffrey;Dickerson, James;Maitra, Debeshi;Aggarwal, Sangeeta;Lee, Fa-Chyi;Patel, Manali I
JCO Oncol Pract. 2021 Oct;17(10):e1450-e1459. doi: 10.1200/OP.20.00890. Epub 2021 Apr 7.
Modeling risks of cardiovascular and cancer mortality following a diagnosis of loco-regional breast cancer
Many women with breast cancer also have a high likelihood of cardiovascular mortality, and while there are several cardiovascular risk prediction models, none have been validated in a cohort of breast cancer patients. We first compared the performance of commonly-used cardiovascular models, and then derived a new model where breast cancer and cardiovascular mortality were modeled simultaneously, to account for the competing risk endpoints and commonality of risk factors between the two events. We included 20,462 women diagnosed with stage I-III breast cancer between 2000 and 2010 in Kaiser Permanente Northern California (KPNC) with follow-up through April 30, 2015, and examined the performance of the Framingham, CORE and SCOREOP cardiovascular risk models by area under the receiver operating characteristic curve (AUC), and observed-to -expected (O/E) ratio. We developed a multi-state model based on cause-specific hazards (CSH) to jointly model the causes of mortality. The extended models including breast cancer characteristics (grade, tumor size, nodal involvement) with CVD risk factors had better discrimination at 5-years with AUCs of 0.85 (95% CI 0.83, 0.86) for cardiovascular death and 0.80 (95% CI 0.78, 0.87) for breast cancer death compared with the existing cardiovascular models evaluated at 5 years AUCs ranging 0.71-0.78. Five-year calibration for breast and cardiovascular mortality from our multi-state model was also excellent (O/E = 1.01, 95% CI 0.91-1.11). A model incorporating cardiovascular risk factors, breast cancer characteristics, and competing events, outperformed traditional models of cardiovascular disease by simultaneously estimating cancer and cardiovascular mortality risks.
Authors: Leoce, Nicole M; Jin, Zhezhen; Kehm, Rebecca D; Roh, Janise M; Laurent, Cecile A; Kushi, Lawrence H; Terry, Mary Beth
Breast Cancer Res. 2021 09 27;23(1):91. Epub 2021-09-27.
Plant-Based Dietary Patterns and Breast Cancer Recurrence and Survival in the Pathways Study
Plant-based diets are recommended for cancer survivors, but their relationship with breast cancer outcomes has not been examined. We evaluated whether long-term concordance with plant-based diets reduced the risk of recurrence and mortality among a prospective cohort of 3646 women diagnosed with breast cancer from 2005 to 2013. Participants completed food frequency questionnaires at diagnosis and 6-, 25-, and 72-month follow-up, from which we derived plant-based diet indices, including overall (PDI), healthful (hPDI), and unhealthful (uPDI). We observed 461 recurrences and 653 deaths over a median follow-up of 9.51 years. Using multivariable-adjusted Cox proportional hazards models, we estimated hazard ratios (HR) and 95% confidence intervals for breast cancer recurrence and all-cause, breast-cancer-specific, and non-breast-cancer mortality. Increased concordance with hPDI was associated with a reduced hazard of all-cause (HR 0.93, 95% CI: 0.83-1.05) and non-breast-cancer mortality (HR 0.83, 95% CI: 0.71-0.98), whereas increased concordance with uPDI was associated with increased hazards (HR 1.07, 95% CI: 0.96-1.2 and HR 1.20, 95% CI: 1.02-1.41, respectively). No associations with recurrence or breast-cancer-specific mortality were observed. In conclusion, healthful vs. unhealthful plant-based dietary patterns had differing associations with mortality. To enhance overall survival, dietary recommendations for breast cancer patients should emphasize healthful plant foods.
Authors: Anyene, Ijeamaka C; Ergas, Isaac J; Kwan, Marilyn L; Roh, Janise M; Ambrosone, Christine B; Kushi, Lawrence H; Cespedes Feliciano, Elizabeth M
Nutrients. 2021 Sep 25;13(10). Epub 2021-09-25.
Development and Validation of a Simulation Model-Based Clinical Decision Tool: Identifying Patients Where 21-Gene Recurrence Score Testing May Change Decisions
There is a need for industry-independent decision tools that integrate clinicopathologic features, comorbidities, and genomic information for women with node-negative, invasive, hormone receptor-positive, human epidermal growth factor receptor-2-negative (early-stage) breast cancer. We adapted an extant Cancer Intervention and Surveillance Modeling Network simulation model to estimate the 10-year risk of distant recurrence, breast cancer-specific mortality, other-cause mortality, and life-years gained with chemoendocrine versus endocrine therapy. We simulated outcomes for 1,512 unique patient subgroups based on all possible combinations of age, tumor size, grade, and comorbidity level; simulations were performed with and without 21-gene recurrence scores (RSs). Model inputs were derived from clinical trials, large US cohort studies, registry, and claims data. External validation was performed by comparing results to observed rates in two independent sources. We highlight results for one scenario where treatment choice may be uncertain. Chemoendocrine versus endocrine therapy in a 65-69-year-old woman with a small (≤ 2 cm), intermediate-grade tumor, and mild comorbidities provides a 1.3% absolute reduction in 10-year distant recurrence risk, with 0.23 life-years gained. With these tumor features, a woman like this will have a 28% probability of having an RS 16-20, 18% RS 21-25, and 11% RS 26+. If testing is done, and her RS is 16-20, chemoendocrine therapy reduces 10-year distant recurrence risk to 1%, with 0.20 life-years gained, a similar result as without testing. The absolute benefits would increase to 4.8%-5.5% if the RS was 26+. The model closely reproduced observed rates in both independent data sets. Our validated clinical decision tool is flexible, readily adaptable to include new therapies, and can support discussions about genomic testing and early breast cancer treatment.
Authors: Jayasekera, Jinani; Sparano, Joseph A; O'Neill, Suzanne; Chandler, Young; Isaacs, Claudine; Kurian, Allison W; Kushi, Lawrence; Schechter, Clyde B; Mandelblatt, Jeanne
J Clin Oncol. 2021 09 10;39(26):2893-2902. Epub 2021-07-12.
ASO Visual Abstract: Implementation of Intraoperative Ultrasound Localization for Breast-Conserving Surgery in a Large, Integrated Health Care System is Feasible and Effective
Authors: Chakedis, Jeffery M; Arasu, Vignesh A; Permanente Medical Group Breast Research Collaborative,; et al.
Ann Surg Oncol. 2021 Sep 01.
Simplifying ADR reporting – a worthy goal, but the devil is in the details
Authors: Lam, Angela Y; Lee, Jeffrey K; Levin, Theodore R
Clin Gastroenterol Hepatol. 2021 09;19(9):1793-1795. Epub 2021-04-24.
Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment
Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP < 0.15). Evidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy. We found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.
Authors: Morra, Anna; Campa, Daniele; Schmidt, Marjanka K; et al.
Breast Cancer Res. 2021 08 18;23(1):86. Epub 2021-08-18.
Risk stratification for colorectal cancer in individuals with subtypes of serrated polyps
The longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood. This community-based, case-control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006-2016. Nested within this population, we identified 695 cases of CRC and 3475 CRC-free controls (matched 5:1 to cases for age, sex and year of colonoscopy). Two expert pathologists reviewed the tissue slides of all SPs identified on the first colonoscopy and reclassified them to sessile serrated lesions (SSLs), hyperplastic polyps (HPs) and traditional serrated adenomas. SPs with borderline characteristics of SSLs but insufficient to make a definitive diagnosis were categorised as unspecified SPs. The association with development of CRC was assessed using multivariable logistic regression. Compared with individuals with no polyp, the adjusted ORs (aORs) for SSL alone or with synchronous adenoma were 2.9 (95% CI: 1.8 to 4.8) and 4.4 (95% CI: 2.7 to 7.2), respectively. The aORs for SSL with dysplasia, large proximal SSL,and small proximal SSL were 10.3 (95% CI: 2.1 to 50.3), 12.8 (95% CI: 3.5 to 46.9) and 1.9 (95% CI: 0.8 to 4.7), respectively. Proximal unspecified SP also conferred an increased risk (aOR: 5.8, 95% CI: 2.2 to 15.2). Women with SSL were associated with higher risk (aOR: 4.4; 95% CI: 2.3 to 8.2) than men (aOR: 1.7; 95% CI: 0.8 to 3.8). Increased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs.
Authors: Li, Dan; Doherty, Amanda R; Raju, Menaka; Liu, Liyan; Lei, Nan Ye; Amsden, Laura B; Lee, Jeffrey K; Levin, Theodore R; Corley, Douglas A; Herrinton, Lisa J
Gut. 2021 Aug 11.
Patient, Family, and Clinician Perspectives on End-of-Life Care Quality Domains and Candidate Indicators for Adolescents and Young Adults With Cancer
End-of-life care quality indicators specific to adolescents and young adults (AYAs) aged 12 to 39 years with cancer have not been developed. To identify priority domains for end-of-life care from the perspectives of AYAs, family caregivers, and clinicians, and to propose candidate quality indicators reflecting priorities. This qualitative study was conducted from December 6, 2018, to January 5, 2021, with no additional follow-up. In-depth interviews were conducted with patients, family caregivers, and clinicians and included a content analysis of resulting transcripts. A multidisciplinary advisory group translated priorities into proposed quality indicators. Interviews were conducted at the Dana-Farber Cancer Institute, Kaiser Permanente Northern California, Kaiser Permanente Southern California, and an AYA cancer support community (lacunaloft.org). Participants included 23 AYAs, 28 caregivers, and 29 clinicians. Stage IV or recurrent cancer. Care priorities. Interviews were conducted with 23 patients (mean [SD] age, 29.3 [7.3] years; 12 men [52%]; 18 White participants [78%]), 28 family caregivers (23 women [82%]; 14 White participants [50%]), and 29 clinicians (20 women [69%]; 13 White participants [45%]). Caregivers included 22 parents (79%), 5 spouses or partners (18%), and 1 other family member (4%); the 29 clinicians included 15 physicians (52%), 6 nurses or nurse practitioners (21%), and 8 social workers or psychologists (28%). Interviews identified 7 end-of-life priority domains: attention to physical symptoms, attention to quality of life, psychosocial and spiritual care, communication and decision-making, relationships with clinicians, care and treatment, and independence. Themes were consistent across the AYA age range and participant type. Although some domains were represented in quality indicators developed for adults, unique domains were identified, as well as AYA-specific manifestations of existing domains. For example, quality of life included global quality of life; attainment of life goals, legacy, and meaning; support of personal relationships; and normalcy. Within communication and decision-making, domains included communication early in the disease course, addressing prognosis and what to expect at the end of life, and opportunity for AYAs to hold desired roles in decision-making. Care and treatment domains relevant to cancer therapy, use of life-prolonging measures, and location of death emphasized the need for preference sensitivity rather than a standard path. This finding differs from existing adult indicators that propose that late-life chemotherapy, intensive measures, and hospital death should be rare. The findings of this qualitative study suggest that AYAs with cancer have priorities for care at the end of life that are not fully encompassed in existing indicators for adults. Use of new indicators for this young population may better reflect patient- and family-centered experiences of quality care.
Authors: Mack, Jennifer W; Kushi, Larry; Altschuler, Andrea; et al.
JAMA Netw Open. 2021 08 02;4(8):e2121888. Epub 2021-08-02.
Association Between Smoking and Molecular Subtypes of Colorectal Cancer
Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking. A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutation, KRAS mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction. Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (P trend < .001). The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and BRAF. Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio = 1.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio = 1.35, 95% confidence interval = 1.22 to 1.49; P difference = 2.1 x 10-6). The association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P difference < .001). Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heavier smokers had particularly higher risk of CRC subtypes that were CIMP positive and MSI high in combination, suggesting that smoking may be involved in the development of colorectal tumors via the serrated pathway.
Authors: Wang, Xiaoliang; Sakoda, Lori C; Peters, Ulrike; et al.
JNCI Cancer Spectr. 2021 08;5(4). Epub 2021-06-14.
Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women’s Health Initiative (WHI) randomised trial
In the Women’s Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components. In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score. HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01). While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk. ClinicalTrials.gov (NCT00000611).
Authors: Pan, Kathy; Caan, Bette; Kroenke, Candyce; Chlebowski, Rowan T; et al.
Br J Cancer. 2021 08;125(3):372-379. Epub 2021-05-18.
ASGE guideline on the management of cholangitis
Cholangitis is a GI emergency requiring prompt recognition and treatment. The purpose of this document from the American Society for Gastrointestinal Endoscopy’s (ASGE) Standards of Practice Committee is to provide an evidence-based approach for management of cholangitis. This document addresses the modality of drainage (endoscopic vs percutaneous), timing of intervention (<48 hours vs >48 hours), and extent of initial intervention (comprehensive therapy vs decompression alone). Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to formulate recommendations on these topics. The ASGE suggests endoscopic rather than percutaneous drainage and biliary decompression within 48 hours. Additionally, the panel suggests that sphincterotomy and stone removal be combined with drainage rather than decompression alone, unless patients are too unstable to tolerate more extensive endoscopic treatment.
Authors: Buxbaum, James L; Lee, Jeffrey K; Wani, Sachin; et al.
Gastrointest Endosc. 2021 08;94(2):207-221.e14. Epub 2021-05-20.
ASGE guideline on the role of endoscopy in the management of malignant hilar obstruction
This clinical guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the management of patients with malignant hilar obstruction (MHO). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses primary drainage modality (percutaneous transhepatic biliary drainage [PTBD] vs endoscopic biliary drainage [EBD]), drainage strategy (unilateral vs bilateral), and stent selection (plastic stent [PS] vs self-expandable metal stent [SEMS]). Regarding drainage modality, in patients with MHO undergoing drainage before potential resection or transplantation, the panel suggests against routine use of PTBD as first-line therapy compared with EBD. In patients with unresectable MHO undergoing palliative drainage, the panel suggests PTBD or EBD. The final decision should be based on patient preferences, disease characteristics, and local expertise. Regarding drainage strategy, in patients with unresectable MHO undergoing palliative stent placement, the panel suggests placement of bilateral stents compared with a unilateral stent in the absence of liver atrophy. Finally, regarding type of stent, in patients with unresectable MHO undergoing palliative stent placement, the panel suggests placing SEMSs or PSs. However, in patients who have a short life expectancy and who place high value on avoiding repeated interventions, the panel suggests using SEMSs compared with PSs. If optimal drainage strategy has not been established, the panel suggests placing PSs. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.
Authors: Qumseya, Bashar J; Lee, Jeffrey K; Wani, Sachin; et al.
Gastrointest Endosc. 2021 08;94(2):222-234.e22. Epub 2021-05-20.
Defining the clinician’s role in mitigating financial toxicity: an exploratory study.
BACKGROUND: Financial toxicity describes the financial burden imposed onto patients by a cancer diagnosis and is a growing concern. Many clinicians do not currently address financial toxicity despite patients’ desire for them to do so. Current literature explores physicians’ perspectives but does not clearly define an actionable role clinicians can take to address financial toxicity. We sought to fill this gap by first assessing clinicians’ perspective on their role in alleviating financial toxicity at our institution. We subsequently aimed to identify current barriers to mitigating financial toxicity and to garner feedback on clinician-oriented interventions to address this growing problem. n METHODS: We developed an 18-item electronic, anonymous survey through Redcap. We invited all oncology clinicians including attending physicians, advance practice providers, and trainees at our institution to participate. n RESULTS: A total of 72 clinicians (30%) completed the survey. The majority agreed that clinicians have a role in addressing cost. The top three barriers to discussing cost with patients were knowledge of out of pocket costs, time, and awareness of resources. Less than half of respondents used an existing comparative cost tool to incorporate cost consciousness into treatment decisions. The most desired intervention was an institutional resource guide. In open-ended comments, the most common barrier described was transparency of out of pocket costs, and the most common solution proposed was a multi-disciplinary approach to addressing financial concerns patient face. n DISCUSSION: Improving price transparency, incorporating existing resources into clinical practice, and streamlining multi-disciplinary support may help overcome barriers to addressing financial toxicity.
Authors: Ragavan, Meera;Parikh, Divya;Patel, Manali
Support Care Cancer. 2021 Aug;29(8):4835-4845. doi: 10.1007/s00520-021-05984-6. Epub 2021 Feb 5.
Engagement in perinatal depression treatment: a qualitative study of barriers across and within racial/ethnic groups
To better understand previously observed racial/ethnic disparities in perinatal depression treatment rates we examined care engagement factors across and within race/ethnicity. Obstetric patients and women’s health clinician experts from a large healthcare system participated in this qualitative study. We conducted focus groups with 30 pregnant or postpartum women of Asian, Black, Latina, and White race/ethnicity with positive depression screens. Nine clinician experts in perinatal depression (obstetric, mental health, and primary care providers) were interviewed. A semi-structured format elicited treatment barriers, cultural factors, and helpful strategies. Discussion transcripts were coded using a general inductive approach with themes mapped to the Capability-Opportunity-Motivation-Behavior (COM-B) theoretical framework. Treatment barriers included social stigma, difficulties recognizing one’s own depression, low understanding of treatment options, and lack of time for treatment. Distinct factors emerged for non-White women including culturally specific messages discouraging treatment, low social support, trauma history, and difficulty taking time off from work for treatment. Clinician factors included knowledge and skill handling perinatal depression, cultural competencies, and language barriers. Participants recommended better integration of mental health treatment with obstetric care, greater treatment convenience (e.g., telemedicine), and programmatic attention to cultural factors and social determinants of health. Women from diverse backgrounds with perinatal depression encounter individual-level, social, and clinician-related barriers to treatment engagement, necessitating care strategies that reduce stigma, offer convenience, and attend to cultural and economic factors. Our findings suggest the importance of intervention and policy approaches effecting change at multiple levels to increase perinatal depression treatment engagement.
Authors: Iturralde, Esti; Hsiao, Crystal A; Nkemere, Linda; Kubo, Ai; Sterling, Stacy A; Flanagan, Tracy; Avalos, Lyndsay A
BMC Pregnancy Childbirth. 2021 Jul 16;21(1):512. Epub 2021-07-16.
Particulate Matter and Cardiovascular Risk in Adults with Chronic Obstructive Pulmonary Disease
Rationale: People with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease and may be more susceptible to air pollution exposure. However, no study has examined the association between long-term fine particulate matter exposure (≤2.5 μm in aerodynamic diameter) and risk of cardiovascular events in this potentially vulnerable population. Objectives: To estimate the association between long-term fine particulate matter and risk of cardiovascular events among adults with COPD. Methods: This retrospective cohort study included 169,714 adults with COPD who were members of the Kaiser Permanente Northern California health plan during 2007-2016. Electronic health record data were linked to 1 km modeled particulate matter ≤2.5 μm in aerodynamic diameter exposure estimates. We fit Cox proportional hazard models, adjusting for age, sex, race/ethnicity, calendar year, smoking, body mass index, comorbidities, medications, and socioeconomic status. In low exposure analyses, we examined effects below the current regulation limit (12 μg/m3). Measurements and Main Results: Among adults with COPD, a 10-μg/m3 increase in 1-year mean fine particulate matter exposure was associated with an elevated risk of cardiovascular mortality (hazard ratio, 1.10; 95% confidence interval [CI], 1.01-1.20). Effects were stronger in low exposure analyses (hazard ratio, 1.88; 95% CI, 1.56-2.27). Fine particulate matter exposure was not associated with acute myocardial infarction or stroke in overall analyses. Conclusions: Long-term fine particulate matter exposure was associated with an increased risk of cardiovascular mortality among adults with COPD. Current regulations may not sufficiently protect those with COPD.
Authors: Alexeeff, Stacey E; Deosaransingh, Kamala; Liao, Noelle S; Van Den Eeden, Stephen K; Schwartz, Joel; Sidney, Stephen
Am J Respir Crit Care Med. 2021 07 15;204(2):159-167.
Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women
Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
Authors: Adedokun, Babatunde; Kushi, Lawrence H; Huo, Dezheng; et al.
Nat Commun. 2021 07 07;12(1):4198. Epub 2021-07-07.
Efficacy of paired tumor and germline testing in evaluation of patients with Lynch-like syndrome in a large integrated healthcare setting
Patients with mismatch repair (MMR) deficient colorectal cancer (CRC) without detectable germline pathogenic variants (PVs) or likely pathogenic variants (LPVs) in MMR genes are often labeled as Lynch-like syndrome (LLS). We sought to evaluate the efficacy of paired tumor and germline testing in risk stratification of patients with LLS in a large, community-based, integrated healthcare setting. Through the universal screening program for Lynch syndrome at Kaiser Permanente Northern California, we identified all patients with MMR deficient colorectal tumors without detectable germline PVs or LPVs between April 2011 and October 2018. These patients were categorized as LLS and were offered paired tumor and germline testing. Risk stratification and patient management were assessed upon completion of all testing. Of the 50 patients with LLS who underwent paired tumor and germline testing, 62% (n = 31) were categorized as sporadic, 6% (n = 3) had Lynch syndrome, and 32% (n = 16) remained inconclusive. Among the sporadic cases, 65% (n = 20) had a PV (n = 18) or LPV (n = 2) in combination with loss of heterozygosity while 35% (n = 11) had two somatic PVs/LPVs involving the same MMR gene. Our findings showed paired tumor and germline testing resolved the etiology in the majority of patients and is a valuable strategy in risk stratification and management of patients with LLS. Further studies are needed to assess the optimal application of paired testing in different practice settings, particularly with evolving technology and decreasing cost of molecular sequencing.
Authors: Carwana, Holly; Hoodfar, Elizabeth; Bergoffen, JoAnn; Li, Dan
Fam Cancer. 2021 07;20(3):223-230. Epub 2020-11-20.
Childhood Socioeconomic Status and Menarche: A Prospective Study
The relationship between socioeconomic status (SES) and menarche has implications for understanding social level influences on early life development and adult disease, including breast cancer, but remains ill defined. We report here results from the Breast Cancer and the Environment Research Program, which permitted a longitudinal study of age at menarche in relationship to childhood SES in a diverse cohort of 1,069 girls across three urban areas of the United States. We assessed the association of SES index quintiles with age at pubertal onset with breast budding and subsequent tempo to the age at menarche between 2004 and 2015 using multiple-event Cox regression models to estimate hazard ratios and 95% confidence intervals. In an unadjusted model, lower SES was predictive of both earlier pubertal onset and tempo and thus earlier age at menarche in trends across quintiles. After adjusting for the potentially mediating effects of body mass index, SES trends remained significant for both outcomes. After adjusting for both body mass index and race/ethnicity, the association with SES remained substantial for pubertal onset but was much diminished and nonsignificant for tempo and thus age at menarche. These results suggest that a lower SES environment and social adversity affect the age at menarche primarily by hastening pubertal onset rather than by shortening tempo.
Authors: Hiatt, Robert A; Stewart, Susan L; Deardorff, Julianna; Danial, Elizabeth; Abdiwahab, Ekland; Pinney, Susan M; Teitelbaum, Susan L; Windham, Gayle C; Wolff, Mary S; Kushi, Lawrence H; Biro, Frank M
J Adolesc Health. 2021 07;69(1):33-40.
Sarcopenia in the Older Adult With Cancer
Authors: Williams, Grant R; Dunne, Richard F; Giri, Smith; Shachar, Shlomit S; Caan, Bette J
J Clin Oncol. 2021 07 01;39(19):2068-2078. Epub 2021-05-27.
Genetically predicted circulating C-reactive protein concentration and colorectal cancer survival: A Mendelian randomization consortium study
A positive association between circulating C-reactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically predicted CRP concentrations and colorectal cancer-specific survival. We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic-risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Because of the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically predicted CRP concentrations and colorectal cancer-specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components. Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to colorectal cancer. Genetically predicted CRP concentration was not associated with colorectal cancer-specific survival (HD, -1.15; 95% CI, -2.76 to 0.47 per 100,000 person-years; P = 0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location. Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on colorectal cancer-specific survival. Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.
Authors: Hua, Xinwei; Schoen, Robert E; Newcomb, Polly A; et al.
Cancer Epidemiol Biomarkers Prev. 2021 07;30(7):1349-1358. Epub 2021-05-10.
Sugary truth of early-onset colorectal neoplasia – not so sweet after all
Authors: Lee, Jeffrey K; Burnett-Hartman, Andrea; Murphy, Caitlin C
Gastroenterology. 2021 07;161(1):27-29. Epub 2021-04-24.
Leukemia Risk in a Cohort of 3.9 Million Children With and Without Down Syndrome
To assess leukemia risks among children with Down syndrome in a large, contemporary cohort. Retrospective cohort study including 3 905 399 children born 1996-2016 in 7 US healthcare systems or Ontario, Canada, and followed from birth to cancer diagnosis, death, age 15 years, disenrollment, or December 30, 2016. Down syndrome was identified using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes. Cancer diagnoses were identified through linkages to tumor registries. Incidence and hazard ratios (HRs) of leukemia were estimated for children with Down syndrome and other children adjusting for health system, child’s age at diagnosis, birth year, and sex. Leukemia was diagnosed in 124 of 4401 children with Down syndrome and 1941 of 3 900 998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1405/100 000 (95% CI 1076-1806) at age 4 years and unchanged at age 14 years. The cumulative incidence of acute lymphoid leukemia in children with Down syndrome was 1059/100 000 (95% CI 755-1451) at age 4 and 1714/100 000 (95% CI 1264-2276) at age 14 years. Children with Down syndrome had a greater risk of AML before age 5 years than other children (HR 399, 95% CI 281-566). Largest HRs were for megakaryoblastic leukemia before age 5 years (HR 1500, 95% CI 555-4070). Children with Down syndrome had a greater risk of acute lymphoid leukemia than other children regardless of age (<5 years: HR 28, 95% CI 20-40, ≥5 years HR 21, 95% CI 12-38). Down syndrome remains a strong risk factor for childhood leukemia, and associations with AML are stronger than previously reported.
Authors: Marlow, Emily C; Kwan, Marilyn L; Miglioretti, Diana L; et al.
J Pediatr. 2021 Jul;234:172-180.e3. Epub 2021-03-06.
Mediation analysis of racial disparities in triple-negative breast cancer incidence among postmenopausal women
Triple-negative breast cancer (TNBC) is disproportionately higher in Black women relative to White women. The objective of this study was to examine to what extent the association between race/ethnicity and risk of TNBC is mediated by potentially modifiable factors. A total of 128,623 Black and White women aged 50-79 years from the Women’s Health Initiative were followed for a mean of 15.8 years. 643 incident TNBC cases (92 Black women and 551 White women) were confirmed by medical record review. Mediation analyses were conducted using an approach under a counterfactual framework. Black women had approximately twofold higher risk of TNBC compared with white women (HR = 1.93, 95% CI 1.52-2.45). We observed that 48% of the racial disparity was mediated by metabolic dysfunction defined by having 3 or more cardiometabolic risk factors including elevated waist circumference, having history of diabetes, high cholesterol and hypertension. The racial disparity was not significantly mediated by other factors studied, including socioeconomic, lifestyle or reproductive factors. Our study observed that approximately half of the racial disparity between postmenopausal Black and White women in TNBC incidence was driven by metabolic dysfunction.
Authors: Luo, Juhua; Kroenke, Candyce H; Wactawski-Wende, Jean; et al.
Breast Cancer Res Treat. 2021 Jul;188(1):283-293. Epub 2021-03-07.
Genetic architectures of proximal and distal colorectal cancer are partly distinct
An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
Authors: Huyghe, Jeroen R; Sakoda, Lori C; Caan, Bette J; Peters, Ulrike; et al.
Gut. 2021 07;70(7):1325-1334. Epub 2021-02-25.
Validation of the Updated Hepatocellular Carcinoma Early Detection Screening Algorithm in a Community-based Cohort of Patients With Cirrhosis of Multiple Etiologies
The Hepatocellular carcinoma (HCC) Early detection Screening (HES) algorithm has been proposed to improve the performance of the serum alpha-fetoprotein (AFP) test in surveillance for HCC. The HES algorithm incorporates data on age, level of alanine aminotransferase, platelet count, and rate of AFP change to increase likelihood of earlier detection and thereby reduce HCC-related mortality. We updated the HES algorithm to include etiology of cirrhosis and validated it in a community-based cohort. We collected data from the Veterans Health Administration, from 2010 through 2015, on etiologies for HCC, including hepatitis C, hepatitis B, alcoholic liver disease, and non-alcoholic fatty liver disease. We used these data to update the HES algorithm and tested its accuracy using data from patients with cirrhosis in the Kaiser Permanente Northern California healthcare system (validation cohort). Among the 7432 patients with cirrhosis in the validation cohort, 1102 were diagnosed with HCC during a median follow-up time of 3.21 years; 709 patients had early-stage HCC. The HES algorithm identified patients who would receive a diagnosis of early-stage HCC within the next 6 months with 51.20% sensitivity and 90.00% specificity, compared with 46.02% sensitivity for the AFP test alone (5.18% absolute improvement; P = .0015). In HCC screening, a positive result from HES or AFP test leads to follow-up evaluation with more sensitive imaging methods. The number of early-stage HCC cases detected per 1000 imaging analyses were 136.46 with the HES algorithm vs 118.01 with the AFP test alone (P < .0005). The HES algorithm identified 56.00% of patients with HCC in the 6 months before their diagnosis despite no detection of nodules by surveillance ultrasound; the AFP test identified only 50.00% of these patients. We validated the HES algorithm using data from a diverse community-based cohort of patients with cirrhosis. The algorithm offers a modest but useful advantage over the AFP test alone in detection of early-stage HCC with virtually no added cost.
Authors: Tayob, Nabihah; Corley, Douglas A; Christie, Israel; Almers, Lucy; Rahal, Ahmed K; Richardson, Peter; White, Donna L; Davila, Jessica; Kanwal, Fasiha; El-Serag, Hashem B
Clin Gastroenterol Hepatol. 2021 07;19(7):1443-1450.e6. Epub 2020-08-05.
Immunotherapy in Older Adults With Cancer.
Authors: Presley, Carolyn J;Gomes, Fabio;Burd, Christin E;Kanesvaran, Ravindran;Wong, Melisa L
J Clin Oncol. 2021 Jul 01;39(19):2115-2127. doi: 10.1200/JCO.21.00138. Epub 2021 May 27.
Does the Hispanic Mortality Advantage Vary by Marital Status Among Postmenopausal Women in the Women’s Health Initiative?
Literature assessing the effect of marital status on mortality has underrepresented, or altogether omitted Hispanics and the potential moderating effect of Hispanic ethnicity on these relationships. Given cultural and network dynamics, marital advantages in older Hispanic women may be greater than other groups given their family-focused, collectivist orientation. The purpose of this study was to understand whether older Hispanic women exhibited a more pronounced marital advantage as compared with non-Hispanic Whites. We used longitudinal data from the Women’s Health Initiative (WHI) Observational Study and Clinical Trials (N = 161,808) collected initially from 1993 to 1998 and followed until 2018. Our sample excluded those respondents indicating “other” as their race-ethnicity and those missing marital status and race-ethnicity variables (N = 158,814). We used Cox-proportional hazards models to assess the association between race-ethnicity, marital status, and the interactive effect of race-ethnicity and marital status on survival. After controlling for socioeconomic status (SES) and health controls, we found a Hispanic survival advantage when compared with non-Hispanic Whites and all other racial-ethnic groups with the exception of Asian/Pacific Islander women (all significant HRs < 0.78, all ps ≤ 0.001). Hispanics had a higher rate of divorce when compared with non-Hispanic Whites. The interactive effect of race-ethnicity and marital status was not significant. U.S. Hispanic, postmenopausal women exhibit a mortality advantage over and above marital status despite their high rates of divorce. Implications and potential explanations are discussed. NCT00000611.
Authors: Flores, Melissa; Kroenke, Candyce H; Thomson, Cynthia A; et al.
Ann Behav Med. 2021 06 28;55(7):612-620.
Two-Sample Mendelian Randomization Analysis of Associations Between Periodontal Disease and Risk of Cancer
Observational studies indicate that periodontal disease may increase the risk of colorectal, lung, and pancreatic cancers. Using a 2-sample Mendelian randomization (MR) analysis, we assessed whether a genetic predisposition index for periodontal disease was associated with colorectal, lung, or pancreatic cancer risks. Our primary instrument included single nucleotide polymorphisms with strong genome-wide association study evidence for associations with chronic, aggressive, and/or severe periodontal disease (rs729876, rs1537415, rs2738058, rs12461706, rs16870060, rs2521634, rs3826782, and rs7762544). We used summary-level genetic data for colorectal cancer (n = 58 131 cases; Genetics and Epidemiology of Colorectal Cancer Consortium, Colon Cancer Family Registry, and Colorectal Transdisciplinary Study), lung cancer (n = 18 082 cases; International Lung Cancer Consortium), and pancreatic cancer (n = 9254 cases; Pancreatic Cancer Consortia). Four MR approaches were employed for this analysis: random-effects inverse-variance weighted (primary analyses), Mendelian Randomization-Pleiotropy RESidual Sum and Outlier, simple median, and weighted median. We conducted secondary analyses to determine if associations varied by cancer subtype (colorectal cancer location, lung cancer histology), sex (colorectal and pancreatic cancers), or smoking history (lung and pancreatic cancer). All statistical tests were 2-sided. The genetic predisposition index for chronic or aggressive periodontitis was statistically significantly associated with a 3% increased risk of colorectal cancer (per unit increase in genetic index of periodontal disease; P = .03), 3% increased risk of colon cancer (P = .02), 4% increased risk of proximal colon cancer (P = .01), and 3% increased risk of colorectal cancer among females (P = .04); however, it was not statistically significantly associated with the risk of lung cancer or pancreatic cancer, overall or within most subgroups. Genetic predisposition to periodontitis may be associated with colorectal cancer risk. Further research should determine whether increased periodontitis prevention and increased cancer surveillance of patients with periodontitis is warranted.
Authors: Corlin, Laura; Sakoda, Lori C; Michaud, Dominique S; et al.
JNCI Cancer Spectr. 2021 06;5(3). Epub 2021-04-19.
A prognostic information system for real-time personalized care: Lessons for embedded researchers
Embedded researchers could play a central role in developing tools to personalize care using electronic medical records (EMRs). However, few studies have described the steps involved in developing such tools, or evaluated the key factors in success and failure. This case study describes how we used an EMR-derived data warehouse to develop a prototype informatics tool to help oncologists counsel patients with pancreatic cancer about their prognosis. The tool generated real-time prognostic information based on tumor type and stage, age, comorbidity status and lab tests. Our multidisciplinary team included embedded researchers, application developers, user experience experts, and an oncologist leader.This prototype succeeded in establishing proof of principle, but did not reach adoption into actual practice. In pilot testing, oncologists succeeded in generating prognostic information in real time. A few found it helpful in patient encounters, but all identified critical areas for further development before implementation. Generalizable lessons included the need to (1) include a wide range of potential use cases and stakeholders when selecting use cases for such tools; (2) develop talking points for clinicians to explain results from predictive tools to patients; (3) develop ways to reduce lag time between events and data availability; and (4) keep the options presented in the user interface very simple. This case demonstrates that embedded researchers can lead collaborations using EMR-derived data to create systems for real-time personalized patient counseling, and highlights challenges that such teams can anticipate.
Authors: Lieu, Tracy A; Neugebauer, Romain; Van Den Eeden, Stephen K; Baer, David M; et al.
Healthc (Amst). 2021 Jun;8 Suppl 1:100486. Epub 2021-06-23.
Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer
Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P = .04). In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.
Authors: Archambault, Alexi N; Sakoda, Lori C; Hayes, Richard B; et al.
JNCI Cancer Spectr. 2021 06;5(3). Epub 2021-05-20.
Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study
The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
Authors: Tsilidis, Konstantinos K; Sakoda, Lori C; Gunter, Marc J; et al.
Am J Clin Nutr. 2021 06 01;113(6):1490-1502.
Weight stability masks changes in body composition in colorectal cancer: a retrospective cohort study
There is an emerging viewpoint that change in body weight is not sufficiently sensitive to promptly identify clinically meaningful change in body composition, such as skeletal muscle depletion. We aimed to determine whether body weight stability is associated with skeletal muscle depletion and whether skeletal muscle depletion is prognostic of death independently of change in body weight. This retrospective cohort included 1921 patients with stage I-III colorectal cancer. Computed tomography (CT)-based skeletal muscle characteristics and body weight were measured at diagnosis and after a mean 15.0-mo follow-up. Body weight stability was defined as weight change less than ±5% during follow-up. Sarcopenia and myosteatosis were defined using established thresholds for patients with cancer. Multivariable-adjusted logistic and flexible parametric proportional hazards survival models were used to quantify statistical associations. At follow-up, 1026 (53.3%) patients were weight stable. Among patients with weight stability, incident sarcopenia and myosteatosis occurred in 8.5% (95% CI: 6.3%, 10.6%) and 13.5% (95% CI: 11.1%, 15.9%), respectively. Men were more likely to be weight stable than were women (56.7% compared with 49.9%; P = 0.04). Weight-stable men were less likely to develop incident sarcopenia (5.4% compared with 15.4%; P = 0.003) and myosteatosis (9.3% compared with 20.8%; P = 0.001) than weight-stable women. Among all patients, the development of incident sarcopenia (HR: 1.40; 95% CI: 1.02, 1.91) and of myosteatosis (HR: 1.41; 95% CI: 1.05, 1.90) were associated with a higher risk of death, independently of change in body weight. Patient sex did not modify the relation between skeletal muscle depletion and death. Body weight stability masks clinically meaningful skeletal muscle depletion. Body composition quantified using clinically acquired CT images may provide a vital sign to identify patients at increased risk of death. These data may inform the design of future cachexia trials.
Authors: Brown, Justin C; Caan, Bette J; Cespedes Feliciano, Elizabeth M; Xiao, Jingjie; Weltzien, Erin; Prado, Carla M; Kroenke, Candyce H; Castillo, Adrienne; Kwan, Marilyn L; Meyerhardt, Jeffrey A
Am J Clin Nutr. 2021 06 01;113(6):1482-1489.
Initiation and adherence to adjuvant endocrine therapy among urban, insured American Indian/Alaska Native breast cancer survivors
It has been shown that racial/ethnic disparities exist with regard to initiation of and adherence to adjuvant endocrine therapy (AET). However, the relationship among American Indian/Alaska Native (AIAN) individuals is poorly understood, particularly among those who reside in urban areas. We evaluated whether AET initiation and adherence were lower among AIAN individuals than those of other races/ethnicities who were enrolled in the Kaiser Permanente of Northern California (KPNC) health system. We identified 23,680 patients from the period 1997 to 2014 who were eligible for AET (first primary, stage I-III, hormone receptor-positive breast cancer) and used KPNC pharmacy records to identify AET prescriptions and refill dates. We assessed AET initiation (≥1 filled prescription within 1 year of diagnosis) and AET adherence (proportion of days covered ≥80%) every year up to 5 years after AET initiation. At the end of the 5-year follow-up period, 83% of patients were AET initiators, and 58% were AET adherent. Compared with other races/ethnicities, AIAN women had the second-lowest rate of AET initiation (non-Hispanic Black [NHB], 78.0%; AIAN, 78.6%; Hispanic, 83.0%; non-Hispanic White [NHW], 82.5%; Asian/Pacific Islander [API], 84.7%), the lowest rate of AET adherence after 1 year and 5 years of follow-up (70.3% and 50.8%, respectively), and the greatest annual decline in AET adherence during the 4- to 5-year period of follow-up (a 13.8% decrease in AET adherence [from 64.6% to 50.8%]) after initiation of AET. In adjusted multivariable models, AIAN, Hispanic, and NHB women were less likely than NHW women to be AET adherent. At the end of the 5-year period, total underutilization (combining initiation and adherence) in AET-eligible patients was greatest among AIAN (70.6%) patients, followed by NHB (69.6%), Hispanic (63.2%), NHW (58.7%), and API (52.3%) patients, underscoring the AET treatment gap. Our results suggest that AET initiation and adherence are particularly low for insured AIAN women.
Authors: Emerson, Marc A; Achacoso, Ninah S; Benefield, Halei C; Troester, Melissa A; Habel, Laurel A
Cancer. 2021 06 01;127(11):1847-1856. Epub 2021-02-23.
Smoking modifies pancreatic cancer risk loci on 2q21.3
Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10-8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, P interaction = 3.08 × 10-9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r 2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. SIGNIFICANCE: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.
Authors: Mocci, Evelina; Van Den Eeden, Stephen K; Stolzenberg-Solomon, Rachael; et al.
Cancer Res. 2021 06 01;81(11):3134-3143. Epub 2021-02-11.
Girls’ Pubertal Timing and Tempo and Mental Health: A Longitudinal Examination in an Ethnically Diverse Sample
Earlier timing and faster tempo of puberty have been linked to adolescents’ poor mental health. Previous research rarely adjusted for childhood mental health, did not use physical examination to assess puberty, and excluded Latinas and Asian Americans. This study addressed these limitations. We followed 822 girls, recruited at ages 6-8, for 8 years. Breast and pubic hair development and anxiety and depressive symptoms were assessed prospectively and repeatedly. Structural equation models tested whether pubertal timing and tempo were associated with adolescent mental health symptoms and whether associations varied by ethnicity. Models were adjusted for childhood mental health symptoms, body mass index, and family income. Earlier breast development was associated with higher depressive symptoms among whites (β = -.19; p < .01) and higher anxiety symptoms among Latinas (β = -.26; p < .05), but lower depressive symptoms among Asians (β = .24, p < .05). Later pubic hair development (b = .24; p < .05) and faster pubic hair tempo (β = .26; p < .01) were associated with higher anxiety symptoms among Latinas. Faster pubic hair tempo was associated with lower depressive symptoms among Asians (β = -.34; p < .05). Tempo of breast development showed no associations. Findings confirmed that earlier breast development was associated with higher mental health symptoms for Latina and white girls but was protective among Asians. Results for pubic hair and pubertal tempo were inconsistent, requiring future examination. While targeted interventions to prevent mental health problems among early-maturing girls are critical, there is variability among who might benefit most.
Authors: Deardorff, Julianna; Greenspan, Louise C; Hiatt, Robert A; Hiatt, Robert A; et al.
J Adolesc Health. 2021 06;68(6):1197-1203. Epub 2021-02-23.
Editors in Chief, Gastroenterology
Authors: Stange, Eduard F; von Bünau, Rudolf; Erhardt, Andreas
Gastroenterology. 2021 06;160(7):2632. Epub 2020-12-30.
The effect of using fecal testing after a negative sigmoidoscopy on the risk of death from colorectal cancer
To examine whether receiving a fecal occult blood test after a negative sigmoidoscopy reduced mortality from colorectal cancer. We used a nested case-control design with incidence-density matching in historical cohorts of 1,877,740 50-90-year-old persons during 2006-2012, in an integrated health-system setting. We selected 1758 average risk patients who died from colorectal cancer and 3503 matched colorectal cancer-free persons. Colorectal cancer-specific death was ascertained from cancer and mortality registries. Screening histories were determined from electronic and chart-audit clinical data in the 5- to 10-year period prior to the reference date. We evaluated receipt of subsequent fecal occult blood test within five years of the reference date among patients with negative sigmoidoscopy two to six years before the reference date. Of the 5261 patients, 831 patients (204 colorectal cancer deaths/627 controls) had either negative sigmoidoscopy only (n = 592) or negative sigmoidoscopy with subsequent screening fecal occult blood test (n = 239). Fifty-six (27.5%) of the 204 patients dying of colorectal cancer and 183 (29.2%) of the 627 colorectal cancer-free patients received fecal occult blood test following a negative sigmoidoscopy. Conditional regressions found no significant association between fecal occult blood test receipt and colorectal cancer death risk, overall (adjusted odds ratio = 0.93, confidence interval: 0.65-1.33), or for right (odds ratio = 1.02, confidence interval: 0.65-1.60) or left-colon/rectum (odds ratio = 0.77, confidence interval: 0.39-1.52) cancers. Similar results were obtained in sensitivity analyses with alternative exposure ascertainment windows or timing of fecal occult blood test. Our results suggest that receipt of at least one fecal occult blood test during the several years after a negative sigmoidoscopy did not substantially reduce mortality from colorectal cancer.
Authors: Doubeni CA; Corley DA; Lee JK; Levin TR; Weiss NS; et al.
J Med Screen. 2021 06;28(2):140-147. Epub 2020-05-21.
Particulate Air Pollution and Risk of Cardiovascular Events Among Adults With a History of Stroke or Acute Myocardial Infarction
Background Previous studies have found associations between fine particulate matter <2.5 µm in diameter (PM2.5) and increased risk of cardiovascular disease (CVD) among populations with no CVD history. Less is understood about susceptibility of adults with a history of CVD and subsequent PM2.5-related CVD events and whether current regulation levels for PM2.5 are protective for this population. Methods and Results This retrospective cohort study included 96 582 Kaiser Permanente Northern California adults with a history of stroke or acute myocardial infarction. Outcome, covariate, and address data obtained from electronic health records were linked to time-varying 1-year mean PM2.5 exposure estimates based on residential locations. Cox proportional hazard models estimated risks of stroke, acute myocardial infarction, and cardiovascular mortality associated with PM2.5 exposure, adjusting for multiple covariates. Secondary analyses estimated risks below federal and state regulation levels (12 µg/m3 for 1-year mean PM2.5). A 10-µg/m3 increase in 1-year mean PM2.5 exposure was associated with an increase in risk of cardiovascular mortality (hazard ratio [HR], 1.20; 95% CI, 1.11-1.30), but no increase in risk of stroke or acute myocardial infarction. Analyses of <12 µg/m3 showed increased risk for CVD mortality (HR, 2.31; 95% CI, 1.96-2.71), stroke (HR, 1.41; 95% CI, 1.09-1.83]), and acute myocardial infarction (HR, 1.51; 95% CI, 1.21-1.89) per 10-µg/m3 increase in 1-year mean PM2.5. Conclusions Adults with a history of CVD are susceptible to the effects of PM2.5 exposure, particularly on CVD mortality. Increased risks observed at exposure levels <12 µg/m3 highlight that current PM2.5 regulation levels may not be protective for this susceptible population.
Authors: Liao, Noelle S; Sidney, Stephen; Deosaransingh, Kamala; Van Den Eeden, Stephen K; Schwartz, Joel; Alexeeff, Stacey E
J Am Heart Assoc. 2021 05 18;10(10):e019758. Epub 2021-05-04.
Metabolic syndrome risk components and mortality after triple-negative breast cancer diagnosis in postmenopausal women in the Women’s Health Initiative
Triple-negative breast cancer (TNBC) has a high recurrence risk and poor clinical outcomes. Associations between metabolic syndrome (MetS) risk components and mortality in postmenopausal women with TNBC were examined in the Women’s Health Initiative. Five hundred forty-four postmenopausal women were diagnosed with nonmetastatic TNBC. Baseline risk components included a high waist circumference (≥88 cm), high blood pressure, hypercholesterolemia, and diabetes. Groups were categorized by the number of MetS risk components: none, 1 or 2, or 3 or 4. Hazard ratios (HRs) and 95% confidence intervals (CIs) across groups were computed with multivariable adjusted Cox models. Outcomes included breast cancer-specific mortality and breast cancer overall mortality (breast cancer followed by death from any cause). Variables in the multivariable model included age at TNBC diagnosis; race/ethnicity; income; education; clinical/observational trial status; history of oral contraceptive, hormone, and/or statin use; cancer stage; and chemotherapy and/or radiation treatment status. Of the 544 participants with TNBC, 33% had no MetS risk components (n = 178), 59% had 1 or 2 risk components (n = 323), and 8% had 3 or 4 risk components (n = 43). After a median follow-up from diagnosis of 8.3 years, multivariable results showed that women with 3 or 4 risk components had a nonsignificantly higher risk of breast cancer mortality (HR, 2.05; 95% CI, 0.94-4.47 trend P = .114) and a significantly higher risk of overall mortality (HR, 2.13; 95% CI, 1.22-3.71; trend P = .006) versus women with 0 risk components. Postmenopausal women with TNBC and 3 or 4 MetS risk components have a nonsignificantly higher breast cancer mortality risk and a significantly higher overall mortality risk, likely because of negative influences of metabolic risk factors on several causes of death.
Authors: Yuan, Yuan; Kroenke, Candyce H; Nelson, Rebecca A; et al.
Cancer. 2021 05 15;127(10):1658-1667. Epub 2021-01-21.
An Intervention to Tag Findings Suspicious for Lung Cancer on Chest Computed Tomography Has Good Sensitivity and Number Needed to Diagnose
In 2015, Kaiser Permanente Northern California implemented an intervention to improve follow-up for pulmonary findings on diagnostic chest computed tomography (CT). The intervention includes tagging CT reports with the prefix “#PUL” followed by a character (0-6 or X) to track specific findings. #PUL5, indicating “suspicious for malignancy,” triggers automatic referral for multidisciplinary care review. Among patients who obtained an index chest CT exam from August 2015 to July 2017 without an exam in the previous 2 years, we computed the frequency of lung cancer diagnosis within 120 days of CT in relation to each #PUL tag. For #PUL5, we computed sensitivity, specificity, positive and negative predictive values, and number needed to diagnose. We also performed a chart review to assess why some patients diagnosed with lung cancer were not tagged #PUL5. Of the 39,409 patients with a tagged CT report, 1105 (2.8%) had a new primary lung cancer diagnosis within 120 days. Among the 2255 patients tagged #PUL5, 821 were diagnosed with lung cancer, with a sensitivity of 74% (95% confidence interval, 72%-77%). The positive predictive value was 36% (35%-38%), number needed to diagnosis was 2.7 (2.6-2.9), and specificity and negative predictive values were > 95%. Chart review identified opportunities to improve system defaults and clarify concepts. The intervention performed well but needed improvement. Automating CT reports was simple and generalizable, and enabled reduction of care gaps and system improvement.
Authors: Dusendang, Jennifer R; Sakoda, Lori C; Urbania, Thomas H; Ely, Sora; Osinski, Todd; Patel, Ashish; Herrinton, Lisa J
Perm J. 2021 05 12;25. Epub 2021-05-12.
Prescription medications for sleep disturbances among midlife women during 2 years of follow-up: a SWAN retrospective cohort study
To examine the effects of prescription sleep medications on patient-reported sleep disturbances. Retrospective cohort. Longitudinal cohort of community-dwelling women in the USA. Racially and ethnically diverse middle-aged women who reported a sleep disturbance. New users of prescription sleep medications propensity score matched to women not starting sleep medications. Self-reported sleep disturbance during the previous 2 weeks-difficulty initiating sleep, waking frequently and early morning awakening-using a 5-point Likert scale, ranging from no difficulty on any night (rating 1) to difficulty on 5 or more nights a week (rating 5). Sleep disturbances were compared at 1 year (primary outcome) and 2 years of follow-up. 238 women who started sleep medications were matched with 447 non-users. Participants had a mean age of 49.5 years and approximately half were white. At baseline, sleep disturbance ratings were similar: medication users had a mean score for difficulty initiating sleep of 2.7 (95% CI 2.5 to 2.9), waking frequently 3.8 (95% CI 3.6 to 3.9) and early morning awakening 2.8 (95% CI 2.6 to 3.0); non-users ratings were 2.6 (95% CI 2.5 to 2.7), 3.7 (95% CI 3.6 to 3.9) and 2.7 (95% CI 2.6 to 2.8), respectively. After 1 year, ratings for medication users were 2.6 (95% CI 2.4 to 2.8) for initiating sleep, 3.6 (95% CI 3.4 to 3.8) for waking frequently and 2.8 (95% CI 2.6 to 3.0) for early morning awakening; for non-users, the mean ratings were 2.3 (95% CI 2.2 to 2.5), 3.5 (95% CI 3.3 to 3.6) and 2.5 (95% CI 2.3 to 2.6), respectively. None of the 1 year changes were statistically significant nor were they different between medication users and non-users. Two-year follow-up results were consistent, without statistically significant reductions in sleep disturbance in medication users compared with non-users. These analyses suggest that women who initiated sleep medications rated their sleep disturbances similar after 1 and 2 years. The effectiveness of long-term sleep medication use should be re-examined.
Authors: Solomon, Daniel H; Ruppert, Kristine; Habel, Laurel A; Finkelstein, Joel S; Lian, Pam; Joffe, Hadine; Kravitz, Howard M
BMJ Open. 2021 05 11;11(5):e045074. Epub 2021-05-11.
Alignment of dietary patterns with the Dietary Guidelines for Americans 2015-2020 and risk of all-cause and cause-specific mortality in the Women’s Health Initiative Observational Study
Poor diet quality is a leading risk factor for death in the United States. We examined the association between Healthy Eating Index-2015 (HEI-2015) scores and death from all causes, cardiovascular disease (CVD), cancer, Alzheimer disease, and dementia not otherwise specified (NOS) among postmenopausal women in the Women’s Health Initiative Observational Study (1993-2017). This analysis included 59,388 participants who completed a food frequency questionnaire and were free of cancer, CVD, and diabetes at enrollment. Stratified Cox proportional hazards models were fit using person-years from enrollment as the underlying time metric. We estimated multivariable adjusted hazard ratios and 95% confidence intervals for risk of death associated with HEI-2015 quintiles, with higher scores reflecting more optimal diet quality. Over a median of 18.2 years, 9,679 total deaths 3,303 cancer deaths, 2,362 CVD deaths, and 488 deaths from Alzheimer disease and dementia NOS occurred. Compared with those with lower scores, women with higher HEI-2015 scores had an 18% lower risk of all-cause death and 21% lower risk of cancer death. HEI-2015 scores were not associated with death due to CVD, Alzheimer disease, and dementia NOS. Consuming a diet aligned with 2015-2020 US dietary guidelines may have beneficial impacts for preventing overall causes of death and death from cancer.
Authors: George, Stephanie M; Cespedes Feliciano, Elizabeth M; Caan, Bette J; Neuhouser, Marian L; et al.
Am J Epidemiol. 2021 05 04;190(5):886-892.
Ten-year Thyroid Cancer Incidence in an Integrated Healthcare Delivery System
The incidence of papillary thyroid cancer (PTC) has increased in recent decades, but data from community-based settings are limited. This study characterizes PTC trends in a large, integrated healthcare system over 10 years. The annual incidence of PTC (2006-2015) was examined among Kaiser Permanente Northern California adults aged 21 to 84 years using Cancer Registry data, including tumor size and stage. Incidence estimates were age-adjusted using the 2010 US Census. Of 2990 individuals newly diagnosed with PTC (76.8% female, 52.7% non-Hispanic White), 38.5% and 61.5% were aged < 45 and < 55 years, respectively. At diagnosis, 60.9% had PTC tumors ≤ 2 cm, 9.2% had tumors > 4 cm, and 66.1% had Stage I disease. The annual age-adjusted incidence of PTC increased from 9.4 (95% confidence interval [CI] = 8.1-10.7) to 14.5 (95% CI = 13.1-16.0) per 100,000 person-years and was higher for female patients than for male patients. Incidence tended to be higher in Asian/Pacific Islanders and lower in Black individuals. Increasing incidence was notable for Stage I disease (especially 2006-2012) and evident across a range of tumor sizes (3.0-4.6 for ≤ 1 cm, 2.5-3.5 for 1-2 cm, and 2.4-4.7 for 2-4 cm) but was modest for large tumors (0.9-1.5 for > 4 cm) per 100,000 person-years. Increasing PTC incidence over 10 years was most evident for tumors ≤ 4 cm and Stage I disease. Although these findings may be attributable to greater PTC detection, the increase across a range of tumor sizes suggests that PTC burden might also have increased.
Authors: Kim, Stephanie J; Durr, Megan L; Darbinian, Jeanne A; Sakoda, Lori C; Meltzer, Charles J; Arzumanyan, Hasmik; Wang, Kevin H; Lin, Jonathan K; Gurushanthaiah, Deepak; Lo, Joan C
Perm J. 2021 05;25.
COVID-19: Guidance for What Clinicians and Scientists Should Do and When
Authors: Corley, Douglas A; Peek, Richard M
Gastroenterology. 2021 05;160(6):1922-1923.
Validation of Tools for Predicting Incident Adenocarcinoma of the Esophagus or Esophagogastric Junction
Guidelines suggest screening of individuals who are at increased risk of esophageal adenocarcinoma (EAC). Tools for identifying patients at risk of Barrett’s esophagus have been validated. Here, we aimed to compare and validate the tools for the primary outcomes of interest: EAC and esophagogastric junction adenocarcinoma (EGJAC). Retrospective longitudinal analysis of the Kaiser Permanente Northern California Multiphasic Health Checkup Cohort, a community-based cohort including 206,974 patients enrolled between 1964 and 1973 followed through 2016. Baseline questionnaires and anthropometrics classified predictor variables for each tool and were linked to cancer registry outcomes. Analyses used logistic regression, Cox proportional hazards regression, and Kaplan-Meier survival curves. We identified 168 incident EAC cases and 151 EGJAC cases at a mean of 32 years after enrollment (mean follow-up among controls 26 years). Gastroesophageal reflux disease (GERD) symptoms predicted incident EAC (hazard ratio 2.66; 95% confidence interval 1.01, 7.00), but not EGJAC. The Nord-Trøndelag Health Study tool, Kunzmann tool, and Michigan Barrett’s Esophagus pREdiction Tool were more accurate than GERD for predicting EAC, with individuals in the fourth quartile of Kunzmann having 17-fold the risk of those in the 1st quartile (hazard ratio = 16.7, 95% confidence interval = 4.72, 58.8). Each tool also predicted incident EGJAC with smaller magnitudes of effect. The study independently validated 4 tools for predicting incident EAC and EGJAC in a large community-based population. The Kunzmann tool appears best calibrated; all appear preferable to using GERD alone for risk stratification. Future studies should determine how best to implement such tools into clinical practice.
Authors: Rubenstein, Joel H; Raghunathan, Trivellore; Doan, Cecilia; Schneider, Jennifer; Zhao, Wei; Metko, Valbona; Nofz, Kimberly; Khodadost, Maryam; Corley, Douglas A
Am J Gastroenterol. 2021 05 01;116(5):949-957.
“I Had to Make Them Feel at Ease”: Narrative Accounts of How Women With Breast Cancer Navigate Social Support
Social scientific studies of social support predominantly focus on the positive associations between social support and emotional well-being. The negative aspects of social support have received much less attention. We conducted semi-structured interviews of women with breast cancer (n = 47) to examine the emotional strain associated with social support and how recipients navigate it in ways that protect themselves and their relationships. Based on our analysis of narratives of women’s lived experiences of breast cancer, we found that social support can be perceived negatively and associated with experiences of emotional strain. Interviewees engaged in strategies of avoidance, information control, and cognitive reframing to minimize emotional strain. We applied the concept of emotion work to understand the complexity of emotional strain in this context. The findings highlight the difficulties of social support from a recipient’s perspective and emphasize the importance of perception and agency in navigating this experience.
Authors: Wright, Jaime D; Kroenke, Candyce H; Kwan, Marilyn L; Kushi, Lawrence H
Qual Health Res. 2021 05;31(6):1056-1068. Epub 2021-02-28.
The Adolescent and Young Adult (AYA) Horizon Study: An AYA cancer survivorship cohort
In the United States, >45,000 adolescent and young adult (AYA) women are diagnosed with cancer annually. Reproductive issues are critically important to AYA cancer survivors, but insufficient information is available to address their concerns. The AYA Horizon Study was initiated to contribute high-quality, contemporary evidence on reproductive outcomes for female cancer survivors in the United States. The study cohort includes women diagnosed with lymphoma, breast, melanoma, thyroid, or gynecologic cancer (the five most common cancers among women ages 15-39 years) at three study sites: the state of North Carolina and the Kaiser Permanente health systems in Northern and Southern California. Detailed information on cancer treatment, fertility procedures, and pregnancy (e.g., miscarriage, live birth) and birth (e.g., birth weight, gestational length) outcomes are leveraged from state cancer registries, health system databases and administrative insurance claims, national data on assisted reproductive technology procedures, vital records, and survey data. We identified a cohort of 11,072 female AYA cancer survivors that includes >1,200 African American women, >1,400 Asian women, >1,600 Medicaid enrollees, and >2,500 Hispanic women using existing data sources. Active response to the survey component was low overall (N = 1,679), and notably lower among minority groups compared with non-Hispanic white women. Passive data collection through linkage reduces participant burden and prevents systematic cohort attrition or potential selection biases that can occur with active participation requirements. The AYA Horizon study will inform survivorship planning as fertility and parenthood gain increasing recognition as key aspects of high-quality cancer care.
Authors: Nichols, Hazel B; Kwan, Marilyn L; Kushi, Lawrence H; et al.
Cancer Epidemiol Biomarkers Prev. 2021 05;30(5):857-866. Epub 2021-02-22.
Germline variation in the insulin-like growth factor pathway and risk of Barrett’s esophagus and esophageal adenocarcinoma
Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
Authors: Dighe, Shruti G; Corley, Douglas A; Buas, Matthew F; et al.
Carcinogenesis. 2021 04 17;42(3):369-377.
A large-scale association study detects novel rare variants, risk genes, functional elements, and polygenic architecture of prostate cancer susceptibility
To identify rare variants associated with prostate cancer susceptibility and better characterize the mechanisms and cumulative disease risk associated with common risk variants, we conducted an integrated study of prostate cancer genetic etiology in two cohorts using custom genotyping microarrays, large imputation reference panels, and functional annotation approaches. Specifically, 11,984 men (6,196 prostate cancer cases and 5,788 controls) of European ancestry from Northern California Kaiser Permanente were genotyped and meta-analyzed with 196,269 men of European ancestry (7,917 prostate cancer cases and 188,352 controls) from the UK Biobank. Three novel loci, including two rare variants (European ancestry minor allele frequency < 0.01, at 3p21.31 and 8p12), were significant genome wide in a meta-analysis. Gene-based rare variant tests implicated a known prostate cancer gene (HOXB13), as well as a novel candidate gene (ILDR1), which encodes a receptor highly expressed in prostate tissue and is related to the B7/CD28 family of T-cell immune checkpoint markers. Haplotypic patterns of long-range linkage disequilibrium were observed for rare genetic variants at HOXB13 and other loci, reflecting their evolutionary history. In addition, a polygenic risk score (PRS) of 188 prostate cancer variants was strongly associated with risk (90th vs. 40th-60th percentile OR = 2.62, P = 2.55 × 10-191). Many of the 188 variants exhibited functional signatures of gene expression regulation or transcription factor binding, including a 6-fold difference in log-probability of androgen receptor binding at the variant rs2680708 (17q22). Rare variant and PRS associations, with concomitant functional interpretation of risk mechanisms, can help clarify the full genetic architecture of prostate cancer and other complex traits. SIGNIFICANCE: This study maps the biological relationships between diverse risk factors for prostate cancer, integrating different functional datasets to interpret and model genome-wide data from over 200,000 men with and without prostate cancer.See related commentary by Lachance, p. 1637.
Authors: Emami, Nima C; Presti, Joseph; Habel, Laurel A; Sakoda, Lori C; Schaefer, Catherine; Van Den Eeden, Stephen K; Witte, John S; et al.
Cancer Res. 2021 04 01;81(7):1695-1703. Epub 2020-12-08.
Diet Quality and Breast Cancer Recurrence and Survival: The Pathways Study
Prior research suggests a relationship between overall diet quality and breast cancer survival, although few studies have reported on this topic. We evaluated whether 4 dietary quality indices consistent with healthy eating recommendations around the time of breast cancer diagnosis were associated with risk of recurrence, cause-specific, and all-cause mortality. A total of 3660 women diagnosed with invasive breast cancer were included. Diet was assessed an average of 2.3 (range = 0.7-18.7) months after diagnosis, from which 4 dietary quality indices were derived: the American Cancer Society guidelines (ACS), the alternate Mediterranean Diet Index (aMED), the Dietary Approaches to Stop Hypertension (DASH), and the 2015 Healthy Eating Index (HEI). Over 40 888 person-years of follow-up, 461 breast cancer recurrences, and 655 deaths were ascertained. Cox models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs). Adjusted comparisons between extreme quintiles showed all 4 dietary quality indices to be inversely associated with all-cause mortality, suggesting a 21%-27% lower risk (ACS HR = 0.73, 95% CI = 0.56 to 0.95; aMED HR = 0.79, 95% CI = 0.61 to 1.03; DASH HR = 0.76, 95% CI = 0.58 to 1.00; HEI HR = 0.77, 95% CI = 0.60 to 1.01). Similar patterns were noted for non-breast cancer mortality (ACS HR = 0.69, 95% CI = 0.48 to 0.98; aMED HR = 0.73, 95% CI = 0.50 to 1.05; DASH HR = 0.55, 95% CI = 0.38 to 0.79; HEI HR = 0.67, 95% CI = 0.48 to 0.94). None of the dietary quality indices were associated with recurrence or breast cancer-specific mortality. Food intake patterns concordant with dietary quality indices consistent with recommendations for healthy eating may be beneficial for women with breast cancer.
Authors: Ergas, Isaac J; Cespedes Feliciano, Elizabeth M; Bradshaw, Patrick T; Roh, Janise M; Kwan, Marilyn L; Cadenhead, Jen; Santiago-Torres, Margarita; Troeschel, Alyssa N; Laraia, Barbara; Madsen, Kristine; Kushi, Lawrence H
JNCI Cancer Spectr. 2021 04;5(2). Epub 2021-03-02.
Patterns and Factors Associated With Adherence to Lung Cancer Screening in Diverse Practice Settings
For lung cancer screening to confer mortality benefit, adherence to annual screening with low-dose computed tomography scans is essential. Although the National Lung Screening Trial had an adherence rate of 95%, current data are limited on screening adherence across diverse practice settings in the United States. To evaluate patterns and factors associated with adherence to annual screening for lung cancer after negative results of a baseline examination, particularly in centralized vs decentralized screening programs. This observational cohort study was conducted at 5 academic and community-based sites in North Carolina and California among 2283 individuals screened for lung cancer between July 1, 2014, and March 31, 2018, who met US Preventive Services Task Force eligibility criteria, had negative results of a baseline screening examination (American College of Radiology Lung Imaging Reporting and Data System category 1 or 2), and were eligible to return for a screening examination in 12 months. To identify factors associated with adherence, the association of adherence with selected baseline demographic and clinical characteristics, including type of screening program, was estimated using multivariable logistic regression. Screening program type was classified as centralized if individuals were referred through a lung cancer screening clinic or program and as decentralized if individuals had a direct clinician referral for the baseline low-dose computed tomography scan. Adherence to annual lung cancer screening, defined as a second low-dose computed tomography scan within 11 to 15 months after baseline screening. Among the 2283 eligible individuals (1294 men [56.7%]; mean [SD] age, 64.9 [5.8] years; 1160 [50.8%] aged ≥65 years) who had negative screening results at baseline, overall adherence was 40.2% (n = 917), with higher adherence among those who underwent screening through centralized (46.0% [478 of 1039]) vs decentralized (35.3% [439 of 1244]) programs. The independent factor most strongly associated with adherence was type of screening program, with a 2.8-fold increased likelihood of adherence associated with centralized screening (adjusted odds ratio [aOR], 2.78; 95% CI, 1.99-3.88). Another associated factor was age (65-69 vs 55-59 years: aOR, 1.38; 95% CI, 1.07-1.77; 70-74 vs 55-59 years: aOR, 1.47; 95% CI, 1.10-1.96). After negative results of a baseline examination, adherence to annual lung cancer screening was suboptimal, although adherence was higher among individuals who were screened through a centralized program. These results support the value of centralized screening programs and the need to further implement strategies that improve adherence to annual screening for lung cancer.
Authors: Sakoda, Lori C; Quesenberry, Charles P; Henderson, Louise M; et al.
JAMA Netw Open. 2021 04 01;4(4):e218559. Epub 2021-04-01.
Clustering of Social and Physical Pain Variables and Their Association With Mortality in Two Population-Based Cohorts
Social pain and physical pain are related bidirectionally, but how these variables cluster in the population is unknown. This study included 2833 women from the Study of Women’s Health Across the Nation (SWAN), a community-based cohort of middle-aged women, and 3972 women from the Pathways Study, a population-based cohort of women diagnosed with American Joint Committee on Cancer stages I-IV breast cancer diagnosed between 2005 and 2013. Women provided data on measures related to social pain (social network size, social support, loneliness, social well-being) and physical pain (sensitivity to pain, bodily pain) at study baseline. Analyzing each cohort separately, we used latent class analysis to evaluate social-physical pain clusters, logistic regression to evaluate predictors of categorization into clusters, and Cox proportional hazards models to evaluate associations of clusters with all-cause mortality. We also performed a meta-analysis to combine cohort mortality associations. Each cluster analysis produced a “low social-physical pain” cluster (SWAN, 48.6%; Pathways, 35.2%) characterized by low social and pain symptoms, a “high social-physical pain” cluster (SWAN, 17.9%; Pathways, 17.9%) characterized by high symptoms, and a “low social/high physical pain” cluster of women with high pain and compromised social functioning but otherwise low social symptoms (SWAN, 33.5%; Pathways, 46.9%). In meta-analysis, categorization into the high social-physical pain cluster was associated with elevated mortality (adjusted hazard ratio = 1.34, 95% confidence interval = 1.05-1.71, Q statistic = 0.782), compared with those in the low social-physical pain cluster. In two cohorts of women, latent class analysis produced similar sets of social-physical pain clusters, with the same proportion having both high social and pain symptoms; women in this cluster had elevated mortality.
Authors: Kroenke, Candyce H; Alexeeff, Stacey; Kushi, Lawrence H; Kwan, Marilyn L; Matthews, Karen A
Psychosom Med. 2021 04 01;83(3):228-238.
Predictive Value of DXA Appendicular Lean Mass for Incident Fractures, Falls, and Mortality, Independent of Prior Falls, FRAX, and BMD: Findings from the Women’s Health Initiative (WHI)
In the Women’s Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX® ) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height2 ) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height2 (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height2 was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83-0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98-1.14). There were no associations between ALM/height2 and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height2 , depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height2 and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Authors: Harvey, Nicholas C; Cespedes Feliciano, Elizabeth M; McCloskey, Eugene; et al.
J Bone Miner Res. 2021 04;36(4):654-661. Epub 2021-01-28.
Multicenter Comparison of 17-Gene Genomic Prostate Score as a Predictor of Outcomes in Black and White Men with Clinically Localized Prostate Cancer
Adoption of prognostic molecular assays for prostate cancer requires evidence of robust performance in different racial groups. Retrospective analysis was conducted to assess the performance of the Oncotype DX® Genomic Prostate Score® test in African American and Caucasian American men with surgically treated prostate cancer. We compared the assay results (scale 0-100) and the 4 gene group scores in biopsy specimens from 201 African American and 1,144 Caucasian American men with clinically localized prostate cancer in 6 cohorts. Adverse pathology was defined as high grade (primary Gleason pattern 4 or any pattern 5) and/or nonorgan-confined disease (≥pT3). Binary logistic regression models were used for adverse pathology. Biochemical recurrence was defined as 2 successive prostate specific antigen levels >0.2 ng/ml or initiation of salvage therapy after radical prostatectomy. Cox proportional hazards models evaluated the association of the assay result or racial group with time to biochemical recurrence. Each cohort had different clinical risk distributions and percentages of African Americans, although median and interquartile ranges of the assay results and gene group scores were similar between both racial groups. In a multivariable model with the assay and pathological/clinical features including race, the assay was significantly associated with adverse pathology (p ≤0.004) and biochemical recurrence (p <0.001). Race was not a significant predictor of either end point. The assay is similarly predictive of outcomes in African American and Caucasian American patients, and improves risk stratification in men with newly diagnosed prostate cancer from both racial groups.
Authors: Cullen, Jennifer; Lynch, Julie A; Klein, Eric A; Van Den Eeden, Stephen K; Carroll, Peter R; Mohler, James L; Knezevic, Dejan; Farrington, Thomas A; Lu, Ruixiao
J Urol. 2021 Apr;205(4):1047-1054. Epub 2020-12-01.
Heterogeneity in colorectal cancer incidence among people recommended 3-yearly surveillance post-polypectomy: a validation study
Colonoscopy surveillance is recommended for patients at increased risk of colorectal cancer (CRC) following adenoma removal. Low-, intermediate-, and high-risk groups are defined by baseline adenoma characteristics. We previously examined intermediate-risk patients from hospital data and identified a higher-risk subgroup who benefited from surveillance and a lower-risk subgroup who may not require surveillance. This study explored whether these findings apply in individuals undergoing CRC screening. This retrospective study used data from the UK Flexible Sigmoidoscopy Screening Trial (UKFSST), English CRC screening pilot (ECP), and US Kaiser Permanente CRC prevention program (KPCP). Screening participants (50 - 74 years) classified as intermediate-risk at baseline colonoscopy were included. CRC data were available through 2006 (KPCP) or 2014 (UKFSST, ECP). Lower- and higher-risk subgroups were defined using our previously identified baseline risk factors: higher-risk participants had incomplete colonoscopies, poor bowel preparation, adenomas ≥ 20 mm or with high-grade dysplasia, or proximal polyps. We compared CRC incidence in these subgroups and in the presence vs. absence of surveillance using Cox regression. Of 2291 intermediate-risk participants, 45 % were classified as higher risk. Median follow-up was 11.8 years. CRC incidence was higher in the higher-risk than lower-risk subgroup (hazard ratio [HR] 2.08, 95 % confidence interval [CI] 1.07 - 4.06). Surveillance reduced CRC incidence in higher-risk participants (HR 0.35, 95 %CI 0.14 - 0.86) but not statistically significantly so in lower-risk participants (HR 0.41, 95 %CI 0.12 - 1.38). As previously demonstrated for hospital patients, screening participants classified as intermediate risk comprised two risk subgroups. Surveillance clearly benefited the higher-risk subgroup.
Authors: Robbins, Emma C; Levin, Theodore; Cross, Amanda J; et al.
Endoscopy. 2021 Apr;53(4):402-410. Epub 2020-08-19.
Lubrication Practices and Receptive Anal Sex: Implications for STI Transmission and Prevention
Implications of lubricant use in men having sex with men (MSM) are poorly characterized, particularly associations with sexual behavior and rectal sexually transmitted infection (STI) risk. We sought to clarify covariates associated with lubrication type including differing sexual preferences and rectal STI prevalence. Primary English-speaking individuals ≥18 years old visiting San Francisco City Clinic (SFCC) between April and May of 2018 who endorsed lubricant use during receptive anal sex within the last 3 months were studied. Associations between lubrication type used and collected covariates were assessed using Kruskal-Wallis analysis of variance for continuous variables and Chi-squared test for categorical variables. We used logistic regression to examine the association between lubrication type and rectal STI test result. Rectal STI test positivity. From all enrolled participants, 179 completed the survey and endorsed use of a lubricant during receptive anal sex within the last 3 months. Silicone lubricant users had the most sexual partners in the last 3 months (13 [mean] ± 30 [SD], P= .0003) and were most likely to have a history of gonorrhea. Oil-based lubricant users had the most partners with whom they had receptive anal sex in the last 3 months (7 ± 6, P= .03). Water-based lubricant users most commonly used a condom in their last sexual encounter and had the fewest sexual partners in the last 3 months (4 ± 4, P= .0003). Spit/saliva lubricant use was associated with positive rectal STI result. Silicone and oil-based lubricant users were more likely to report condomless receptive anal sex and to have a history of gonorrhea while spit/saliva lubricant use associated with positive rectal STI acquisition. A Lee, TW Gaither, ME Langston, et al. Lubrication Practices and Receptive Anal Sex: Implications for STI Transmission and Prevention. J Sex Med 2021;XX:XXX-XXX.
Authors: Lee A; Gaither TW; Langston ME; Cohen SE; Breyer BN
Sex Med. 2021 Mar 28;9(3):100341. Epub 2021-03-28.
mHealth Mindfulness Intervention for Women with Moderate-to-Moderately-Severe Antenatal Depressive Symptoms: a Pilot Study Within an Integrated Health Care System
Traditional mindfulness-based interventions have been shown to reduce depression symptoms in pregnant women, although in-person classes may pose significant accessibility barriers, particularly during the COVID-19 pandemic. Mobile technology offers greater convenience, but little is known regarding the efficacy of self-paced, mobile-delivered (mHealth) mindfulness interventions in this population. This study tested the feasibility and acceptability of offering such an intervention for pregnant women with moderate-to-moderately-severe depression symptoms. We conducted a single-arm trial within Kaiser Permanente Northern California (KPNC). Participants were identified through KPNC’s universal perinatal depression screening program. Eligible participants included English-speaking pregnant women (<28 weeks of gestation) with moderate-to-moderately-severe depressive symptoms without a regular (<3 times/week) mindfulness/meditation practice. Participants were asked to follow a self-paced, 6-week mindfulness meditation program using a mobile app, Headspace™, 10-20 min/day. Outcome measures included feasibility, acceptability, and patient-reported outcomes (e.g., depression symptoms). Of the 27 women enrolled, 20 (74%) completed the study. Over half (55%) of participants used the app ≥50% of the days during the 6-week intervention. Responses to the semi-structured interviews indicated that women appreciated the convenience of the intervention and the ability to engage without having to attend classes or arrange childcare. We observed significant improvements in pre-postintervention scores for depression symptoms, perceived stress, sleep disturbance, and mindfulness. Our study demonstrates the feasibility and acceptability of an mHealth mindfulness intervention for women with moderate-to-moderately-severe antenatal depression symptoms. The preliminary data further suggest that an efficacy trial is warranted.
Authors: Kubo, Ai; Aghaee, Sara; Kurtovich, Elaine M; Nkemere, Linda; Quesenberry, Charles P; McGinnis, MegAnn K; Avalos, Lyndsay A
Mindfulness (N Y). 2021 Mar 11:1-11.
Response to Li and Hopper
Authors: Thomas, Minta; Sakoda, Lori C; Lee, Jeffrey K; Corley, Douglas A; Hsu, Li; et al.
Am J Hum Genet. 2021 03 04;108(3):527-529.
Association of Cannabis Retailer Proximity and Density With Cannabis Use Among Pregnant Women in Northern California After Legalization of Cannabis for Recreational Use
Authors: Young-Wolff, Kelly C; Adams, Sara R; Padon, Alisa; Silver, Lynn D; Alexeeff, Stacey E; Van Den Eeden, Stephen K; Avalos, Lyndsay A
JAMA Netw Open. 2021 03 01;4(3):e210694. Epub 2021-03-01.
Validated training tools are needed for assessing competency in colorectal endoscopic mucosal resection
Authors: Kidambi, Trilokesh D; Lee, Jeffrey K
Gastrointest Endosc. 2021 03;93(3):776-777.
Paradigm-Shifting Research in Gastroenterology, Hepatology, and Nutrition: A Top 20 List of Articles Published in 2020
Authors: Corley, Douglas A; Peek, Richard M; Simpson, Brook A
Gastroenterology. 2021 03;160(4):979-981. Epub 2021-01-14.
An update on the epidemiology, molecular characterization, diagnosis, and screening strategies for early-onset colorectal cancer
Rising trends in the incidence and mortality of early-onset colorectal cancer (CRC) in those who are younger than 50 years have been well established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC, as well as on identifying strategies for early detection and prevention. In this review, we provide a contemporary update on early-onset CRC with a particular focus on epidemiology, molecular characterization, red flag signs and symptoms, and screening for early-onset CRC.
Authors: Burnett-Hartman, Andrea N; Lee, Jeffrey K; Demb, Joshua; Gupta, Samir
Gastroenterology. 2021 03;160(4):1041-1049. Epub 2021-01-05.
Disparities in Preventable Mortality from Colorectal Cancer: are they the result of structural racism?
Authors: Doubeni, Chyke A; Selby, Kevin; Levin, Theodore R
Gastroenterology. 2021 03;160(4):1022-1025. Epub 2021-01-05.
A combined proteomics and Mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer
Evidence for aspirin’s chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively). MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin’s reduction of metastasis. Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
Authors: Nounu, Aayah; Sakoda, Lori C; Relton, Caroline L; et al.
Cancer Epidemiol Biomarkers Prev. 2021 03;30(3):564-575. Epub 2020-12-14.
Cancer Screening during COVID-19: A Perspective from NCI’s PROSPR consortium
Authors: National Cancer Institute’s PROSPR Consortium,; Corley, Douglas A; Haas, Jennifer S; et al.
Gastroenterology. 2021 03;160(4):999-1002. Epub 2020-10-21.
Identifying novel susceptibility genes for colorectal cancer risk from a transcriptome-wide association study of 125,478 subjects
Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.
Authors: Guo, Xingyi; Sakoda, Lori C; Zheng, Wei; et al.
Gastroenterology. 2021 03;160(4):1164-1178.e6. Epub 2020-10-12.
Natural language processing for the accurate identification of colorectal cancer mismatch repair status in Lynch syndrome screening
Lynch syndrome (LS) is the most common type of hereditary colorectal cancer (CRC) syndrome caused by pathogenic variants in mismatch repair (MMR) genes.1 Current multisociety guidelines recommend screening all CRC tumors for LS.2,3 The most widely adopted screening method is MMR immunohistochemistry (IHC) followed by germline analysis if indicated.2,3 However, the text-based nature of pathology and IHC reports used for LS screening results impedes creation of an efficient tracking system for identifying affected patients and screening outcomes.4 In this study, we developed and validated a natural language processing (NLP) tool for extracting MMR IHC results in LS screening in a large, diverse, multicenter, community-based setting.5.
Authors: Li D; Udaltsova N; Layefsky E; Doan C; Corley DA
Clin Gastroenterol Hepatol. 2021 03;19(3):610-612.e1. Epub 2020-02-07.
Expanding Beyond Maximum Grade: Chemotherapy Toxicity over Time by Age and Performance Status in Advanced Non-Small Cell Lung Cancer in CALGB 9730 (Alliance A151729).
BACKGROUND: Prior comparisons of chemotherapy adverse events (AEs) by age and performance status (PS) are limited by the traditional maximum grade approach, which ignores low-grade AEs and longitudinal changes. n MATERIALS AND METHODS: To compare fatigue and neuropathy longitudinally by age (<65, ≥65 years) and PS (0-1, 2), we analyzed data from a large phase III trial of carboplatin and paclitaxel versus paclitaxel for advanced non-small cell lung cancer (CALGB 9730, n = 529). We performed multivariable (a) linear mixed models to estimate mean AE grade over time, (b) linear regression to estimate area under the curve (AUC), and (c) proportional hazards models to estimate the hazard ratio of developing grade ≥2 AE, as well as traditional maximum grade analyses. n RESULTS: Older patients had on average a 0.17-point (95% confidence interval [CI], 0.00-0.34; p = .049) higher mean fatigue grade longitudinally compared with younger patients. PS 2 was associated with earlier development of grade ≥2 fatigue (hazard ratio [HR], 1.56; 95% CI, 1.07-2.27; p = .02). For neuropathy, older age was associated with earlier development of grade ≥2 neuropathy (HR, 1.41; 95% CI, 1.00-1.97; p = .049). Patients with PS 2 had a 1.30 point lower neuropathy AUC (95% CI, -2.36 to -0.25; p = .02) compared with PS 0-1. In contrast, maximum grade analyses only detected a higher percentage of older adults with grade ≥3 fatigue and neuropathy at some point during treatment. n CONCLUSION: Our comparison of complementary but distinct aspects of chemotherapy toxicity identified important longitudinal differences in fatigue and neuropathy by age and PS that are missed by the traditional maximum grade approach. Clinical trial identification number: NCT00003117 (CALGB 9730) IMPLICATIONS FOR PRACTICE: The traditional maximum grade approach ignores persistent low-grade adverse events (AEs) and changes over time. This toxicity over time analysis of fatigue and neuropathy during chemotherapy for advanced non-small cell lung cancer demonstrates how to use longitudinal methods to comprehensively characterize AEs over time by age and performance status (PS). We identified important longitudinal differences in fatigue and neuropathy that are missed by the maximum grade approach. This new information about how older adults and patients with PS 2 experience these toxicities longitudinally may be used clinically to improve discussions about treatment options and what to expect to inform shared decision making and symptom management.
Authors: Wong, Melisa L;Wang, Xiaofei;et al.
Oncologist. 2021 Mar;26(3):e435-e444. doi: 10.1002/onco.13527. Epub 2020 Oct 1.
Cardiometabolic risk factors and survival after cancer in the Women’s Health Initiative
Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer. This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women’s Health Initiative (WHI). Cardiovascular risk factors included waist circumference, hypertension, high cholesterol, and type 2 diabetes. Obesity-related cancers included breast cancer, colorectal cancer, endometrial cancer, kidney cancer, pancreatic cancer, ovarian cancer, stomach cancer, liver cancer, and non-Hodgkin lymphoma. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for important predictors of survival. After a median follow-up of 10.0 years from the date of the cancer diagnosis, there were 3607 total deaths, with 1546 (43%) due to cancer. Most participants (62.9%) had 1 or 2 cardiometabolic risk factors, and 8.1% had 3 or 4. In adjusted models, women with 3 to 4 risk factors (vs none) had a higher risk of all-cause mortality (HR, 1.99; 95% CI, 1.73-2.30), death due to cardiovascular disease (CVD) (HR, 4.01; 95% CI, 2.88-5.57), cancer-specific mortality (HR, 1.37; 95% CI, 1.1-1.72), and other-cause mortality (HR, 2.14; 95% CI, 1.70-2.69). A higher waist circumference was associated with greater all-cause mortality (HR, 1.17; 95% CI, 1.06-1.30) and cancer-specific mortality (HR, 1.22; 95% CI, 1.04-1.42). Among postmenopausal women diagnosed with cancer in the WHI, cardiometabolic risk factors before the cancer diagnosis were associated with greater all-cause, CVD, cancer-specific, and other-cause mortality. These results raise hypotheses regarding potential clinical intervention strategies targeting cardiometabolic abnormalities that require future prospective studies for confirmation. This study uses information from the Women’s Health Initiative (WHI) to find out whether cardiac risk factors are related to a greater risk of dying among older women with cancer. The WHI is the largest study of medical problems faced by older women in this country. The results show that women who have 3 or 4 risk factors are more likely to die of any cause, heart disease, or cancer in comparison with women with no risk factors. It is concluded that interventions to help to lower the burden of cardiac risk factors can have an important impact on survivorship among women with cancer.
Authors: Simon, Michael S; Caan, Bette J; Beebe-Dimmer, Jennifer L; et al.
Cancer. 2021 02 15;127(4):598-608. Epub 2020-11-05.
Cross-cancer evaluation of polygenic risk scores for 16 cancer types in two large cohorts
Even distinct cancer types share biological hallmarks. Here, we investigate polygenic risk score (PRS)-specific pleiotropy across 16 cancers in European ancestry individuals from the Genetic Epidemiology Research on Adult Health and Aging cohort (16,012 cases, 50,552 controls) and UK Biobank (48,969 cases, 359,802 controls). Within cohorts, each PRS is evaluated in multivariable logistic regression models against all other cancer types. Results are then meta-analyzed across cohorts. Ten positive and one inverse cross-cancer associations are found after multiple testing correction. Two pairs show bidirectional associations; the melanoma PRS is positively associated with oral cavity/pharyngeal cancer and vice versa, whereas the lung cancer PRS is positively associated with oral cavity/pharyngeal cancer, and the oral cavity/pharyngeal cancer PRS is inversely associated with lung cancer. Overall, we validate known, and uncover previously unreported, patterns of pleiotropy that have the potential to inform investigations of risk prediction, shared etiology, and precision cancer prevention strategies.
Authors: Graff, Rebecca E; Alexeeff, Stacey E; Corley, Douglas A; Kushi, Lawrence H; Van Den Eeden, Stephen K; Habel, Laurel A; Sakoda, Lori C; et al.
Nat Commun. 2021 02 12;12(1):970. Epub 2021-02-12.
Why Do Epidemiologic Studies Find an Inverse Association Between Intraprostatic Inflammation and Prostate Cancer: A Possible Role for Colliding Bias?
Inflammation is an emerging risk factor for prostate cancer based largely on evidence from animal models and histopathologic observations. However, findings from patho-epidemiologic studies of intraprostatic inflammation and prostate cancer have been less supportive, with inverse associations observed in many studies of intraprostatic inflammation and prostate cancer diagnosis. Here, we propose collider stratification bias as a potential methodologic explanation for these inverse findings and provide strategies for conducting future etiologic studies of intraprostatic inflammation and prostate cancer.
Authors: Langston ME; Sfanos KS; Khan S; Nguyen TQ; De Marzo AM; Platz EA; Sutcliffe S
Cancer Epidemiol Biomarkers Prev. 2021 Feb;30(2):255-259.
Association of Major Dietary Protein Sources With All-Cause and Cause-Specific Mortality: Prospective Cohort Study
Background Dietary recommendations regarding protein intake have been focused on the amount of protein. However, such recommendations without considering specific protein sources may be simplistic and insufficient. Methods and Results We included 102 521 postmenopausal women enrolled in the Women’s Health Initiative between 1993 and 1998, and followed them through February 2017. During 1 876 205 person-years of follow-up, 25 976 deaths occurred. Comparing the highest with the lowest quintile, plant protein intake was inversely associated with all-cause mortality (hazard ratio [HR], 0.91 [0.86, 0.96]), cardiovascular disease mortality (HR, 0.88 [0.79, 0.97]), and dementia mortality (HR, 0.79 [0.67, 0.94]). Among major protein sources, comparing the highest with the lowest quintile of consumption, processed red meat (HR, 1.06 [1.01, 1.10]) or eggs (HR, 1.14 [1.10, 1.19]) was associated with higher risk of all-cause mortality. Unprocessed red meat (HR, 1.12 [1.02, 1.23]), eggs (HR, 1.24 [1.14, 1.34]), or dairy products (HR, 1.11 [1.02, 1.22]) was associated with higher risk of cardiovascular disease mortality. Egg consumption was associated with higher risk of cancer mortality (HR, 1.10 [1.02, 1.19]). Processed red meat consumption was associated with higher risk of dementia mortality (HR, 1.20 [1.05, 1.32]), while consumption of poultry (HR, 0.85 [0.75, 0.97]) or eggs (HR, 0.86 [0.75, 0.98]) was associated with lower risk of dementia mortality. In substitution analysis, substituting of animal protein with plant protein was associated with a lower risk of all-cause mortality, cardiovascular disease mortality, and dementia mortality, and substitution of total red meat, eggs, or dairy products with nuts was associated with a lower risk of all-cause mortality. Conclusions Different dietary protein sources have varying associations with all-cause mortality, cardiovascular disease mortality, and dementia mortality. Our findings support the need for consideration of protein sources in future dietary guidelines.
Authors: Sun, Yangbo; Liu, Buyun; Snetselaar, Linda G; Wallace, Robert B; Shadyab, Aladdin H; Kroenke, Candyce H; Haring, Bernhard; Howard, Barbara V; Shikany, James M; Valdiviezo, Carolina; Bao, Wei
J Am Heart Assoc. 2021 02;10(5):e015553. Epub 2021-02-24.
When Should We Let Colorectal Cancer Screening Get Personal?
Although screening reduces colorectal cancer (CRC) incidence and related mortality, national CRC screening rates remain suboptimal. Identifying strategies to improve screening rates remains an area of intense focus, and previous literature supports an association between the perceived risk of CRC and a likelihood or intent to complete screening. However, risk estimation alone through the validated National Cancer Institute Colorectal Cancer Risk Assessment Tool does not improve screening uptake compared with general education. Future studies should couple risk estimation with patient navigation and decision support aids to build upon our existing armamentarium of effective interventions.
Authors: Lam, Angela Y; Lee, Jeffrey K
Am J Gastroenterol. 2021 02 01;116(2):278-279.
Racial/ethnic disparities in survival after breast cancer diagnosis by estrogen and progesterone receptor status: A pooled analysis
Limited studies have investigated racial/ethnic survival disparities for breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status in a multiethnic population. Using multivariable Cox proportional hazards models, we assessed associations of race/ethnicity with ER/PR-specific breast cancer mortality in 10,366 California women diagnosed with breast cancer from 1993 to 2009. We evaluated joint associations of race/ethnicity, health care, sociodemographic, and lifestyle factors with mortality. Among women with ER/PR+ breast cancer, breast cancer-specific mortality was similar among Hispanic and Asian American women, but higher among African American women [HR, 1.31; 95% confidence interval (CI), 1.05-1.63] compared with non-Hispanic White (NHW) women. Breast cancer-specific mortality was modified by surgery type, hospital type, education, neighborhood socioeconomic status (SES), smoking history, and alcohol consumption. Among African American women, breast cancer-specific mortality was higher among those treated at nonaccredited hospitals (HR, 1.57; 95% CI, 1.21-2.04) and those from lower SES neighborhoods (HR, 1.48; 95% CI, 1.16-1.88) compared with NHW women without these characteristics. Breast cancer-specific mortality was higher among African American women with at least some college education (HR, 1.42; 95% CI, 1.11-1.82) compared with NHW women with similar education. For ER-/PR- disease, breast cancer-specific mortality did not differ by race/ethnicity and associations of race/ethnicity with breast cancer-specific mortality varied only by neighborhood SES among African American women. Racial/ethnic survival disparities are more striking for ER/PR+ than ER-/PR- breast cancer. Social determinants and lifestyle factors may explain some of the survival disparities for ER/PR+ breast cancer. Addressing these factors may help reduce the higher mortality of African American women with ER/PR+ breast cancer.
Authors: John, Esther M; Kwan, Marilyn L; Wu, Anna H; et al.
Cancer Epidemiol Biomarkers Prev. 2021 02;30(2):351-363. Epub 2020-12-18.
Authors Response
Authors: Beasley, Jeannette M; Rillamas-Sun, Eileen; Tinker, Lesley F; Wylie-Rosett, Judith; Mossavar-Rahmani, Yasmin; Datta, Mridul; Caan, Bette J; LaCroix, Andrea Z
J Acad Nutr Diet. 2021 02;121(2):210-212. Epub 2020-11-13.
ASGE guideline on the role of endoscopy in the management of benign and malignant gastroduodenal obstruction
This American Society for Gastrointestinal Endoscopy guideline provides evidence-based recommendations for the endoscopic management of gastric outlet obstruction (GOO). We applied the Grading of Recommendations, Assessment, Development and Evaluation methodology to address key clinical questions. These include the comparison of (1) surgical gastrojejunostomy to the placement of self-expandable metallic stents (SEMS) for malignant GOO, (2) covered versus uncovered SEMS for malignant GOO, and (3) endoscopic and surgical interventions for the management of benign GOO. Recommendations provided in this document were founded on the certainty of the evidence, balance of benefits and harms, considerations of patient and caregiver preferences, resource utilization, and cost-effectiveness.
Authors: ASGE Standards of Practice Committee,; Pawa, Swati; (ASGE Standards of Practice Committee Chair, 2017-2020),; et al.
Gastrointest Endosc. 2021 02;93(2):309-322.e4. Epub 2020-11-07.
Influence of Telemedicine-First Intervention on Patient Visit Choice, Post-Visit Care, and Patient Satisfaction in Gastroenterology
Authors: Munroe, Craig A; Lin, Teresa Y; Rouillard, Smita; Fox, Jeffrey; Lee, Jeffrey K; Corley, Douglas A
Gastroenterology. 2021 02;160(3):929-931.e2. Epub 2020-10-16.
Urban-Rural Disparities and Temporal Trends in Peptic Ulcer Disease Epidemiology, Treatment, and Outcomes in the United States
The incidence of peptic ulcer disease (PUD) has been decreasing over time with Helicobacter pylori eradication and use of acid-suppressing therapies. However, PUD remains a common cause of hospitalization in the United States. We aimed to evaluate contemporary national trends in the incidence, treatment patterns, and outcomes for PUD-related hospitalizations and compare care delivery by hospital rurality. Data from the National Inpatient Sample were used to estimate weighted annual rates of PUD-related hospitalizations. Temporal trends were evaluated by joinpoint regression and expressed as annual percent change with 95% confidence intervals (CIs). We determined the proportion of hospitalizations requiring endoscopic and surgical interventions, stratified by clinical presentation and rurality. Multivariable logistic regression was used to assess independent predictors of in-hospital mortality and postoperative morbidity. There was a 25.8% reduction (P < 0.001) in PUD-related hospitalizations from 2005 to 2014, although the rate of decline decreased from -7.2% per year (95% CI: 13.2% to -0.7%) before 2008 to -2.1% per year (95% CI: 3.0% to -1.1%) after 2008. In-hospital mortality was 2.4% (95% CI: 2.4%-2.5%). Upper endoscopy (84.3% vs 78.4%, P < 0.001) and endoscopic hemostasis (26.1% vs 16.8%, P < 0.001) were more likely to be performed in urban hospitals, whereas surgery was performed less frequently (9.7% vs 10.5%, P < 0.001). In multivariable logistic regression, patients managed in urban hospitals were at higher risk for postoperative morbidity (odds ratio 1.16 [95% CI: 1.04-1.29]), but not death (odds ratio 1.11 [95% CI: 1.00-1.23]). The rate of decline in hospitalization rates for PUD has stabilized over time, although there remains significant heterogeneity in treatment patterns by hospital rurality.
Authors: Guo, Howard; Ma, Christopher; Ma, Christopher; et al.
Am J Gastroenterol. 2021 02 01;116(2):296-305.
Analysis of Survival Among Adults With Early-Onset Colorectal Cancer in the National Cancer Database.
IMPORTANCE: While increased adherence to colorectal cancer (CRC) screening guidelines in the US has been associated with significant reductions in cancer incidence in US individuals aged 50 years and older, the incidence of CRC among those aged younger than 50 years has been steadily increasing. Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC. OBJECTIVE: To characterize the overall survival for individuals with early-onset CRC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the National Cancer Database. Included individuals were ages 0 to 90 years and diagnosed with primary CRC from January 1, 2004, through December 31, 2015. Individuals diagnosed at ages 51 through 55 years were selected as the reference group and defined as later-onset CRC for this study. Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at that age in our population, given that these individuals disproportionately presented with earlier stage. All statistical analyses were conducted from January 4, 2020, through December 26, 2020. EXPOSURES: Early-onset CRC was defined as age younger than 50 years at diagnosis. MAIN OUTCOMES AND MEASURES: Overall survival was assessed by Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: Among 769 871 individuals with CRC (377 890 [49.1%] women; 636 791 White individuals [82.7%]), 353 989 individuals (46.0%) died (median [range] follow-up: 2.9 [0-14.0] years), 102 168 individuals (13.3%) had early-onset CRC, and 78 812 individuals (10.2%) had later-onset CRC. Individuals with early-onset CRC, compared with those diagnosed with CRC at ages 51 through 55 years, had a lower 10-year survival rate (53.6% [95% CI, 53.2%-54.0%] vs 54.3% [95% CI, 53.8%-54.8%]; P < .001) in unadjusted analysis. However, after adjustment for other factors associated with mortality, most notably stage, individuals with early-onset CRC had a lower risk of death compared with individuals diagnosed from ages 51 through 55 years (adjusted hazard ratio [HR], 0.95 [95% CI, 0.93-0.96]; P < .001). In the model adjusted for stage, the HR for individuals with early-onset CRC was 0.89 (95% CI, 0.88-0.90; P < .001). The survival advantage was greatest for individuals diagnosed at ages 35 through 39 years (adjusted HR, 0.88 [95% CI, 0.84-0.92]; P < .001) and stages I (adjusted HR, 0.87 [95% CI, 0.81-0.93]; P < .001) and II (adjusted HR, 0.86 [95% CI, 0.82-0.90]; P < .001) and was absent among those diagnosed at ages 25 years or younger and stages III through IV. CONCLUSIONS AND RELEVANCE: These findings suggest that there is a survival benefit for individuals with early-onset CRC compared with those diagnosed with CRC at later ages. Further study is needed to understand the underlying heterogeneity of survival among individuals with early-onset CRC by age and stage.
Authors: Cheng, En; Blackburn, Holly N; Ng, Kimmie; Spiegelman, Donna; Irwin, Melinda L; Ma, Xiaomei; Gross, Cary P; Tabung, Fred K; Giovannucci, Edward L; Kunz, Pamela L; Llor, Xavier; Billingsley, Kevin; Meyerhardt, Jeffrey A; Ahuja, Nita; Fuchs, Charles S
JAMA Netw Open. 2021 Jun 1;4(6):e2112539. doi: 10.1001/jamanetworkopen.2021.12539.
Long-Term PM2.5 Exposure and Risks of Ischemic Heart Disease and Stroke Events: Review and Meta-Analysis
Background Fine particulate matter <2.5 µm in diameter (PM2.5) has known effects on cardiovascular morbidity and mortality. However, no study has quantified and compared the risks of incident myocardial infarction, incident stroke, ischemic heart disease (IHD) mortality, and cerebrovascular mortality in relation to long-term PM2.5 exposure. Methods and Results We sought to quantitatively summarize studies of long-term PM2.5 exposure and risk of IHD and stroke events by conducting a review and meta-analysis of studies published by December 31, 2019. The main outcomes were myocardial infarction, stroke, IHD mortality, and cerebrovascular mortality. Random effects meta-analyses were used to estimate the combined risk of each outcome among studies. We reviewed 69 studies and included 42 studies in the meta-analyses. In meta-analyses, we found that a 10-µg/m3 increase in long-term PM2.5 exposure was associated with an increased risk of 23% for IHD mortality (95% CI, 15%-31%), 24% for cerebrovascular mortality (95% CI, 13%-36%), 13% for incident stroke (95% CI, 11%-15%), and 8% for incident myocardial infarction (95% CI, -1% to 18%). There were an insufficient number of studies of recurrent stroke and recurrent myocardial infarction to conduct meta-analyses. Conclusions Long-term PM2.5 exposure is associated with increased risks of IHD mortality, cerebrovascular mortality, and incident stroke. The relationship with incident myocardial infarction is suggestive of increased risk but not conclusive. More research is needed to understand the relationship with recurrent events.
Authors: Alexeeff, Stacey E; Liao, Noelle S; Liu, Xi; Van Den Eeden, Stephen K; Sidney, Stephen
J Am Heart Assoc. 2021 01 05;10(1):e016890. Epub 2020-12-31.
Association of body mass index with colorectal cancer risk by genome-wide variants
Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.
Authors: Campbell PT; Slattery ML; Peters U; et al.
J Natl Cancer Inst. 2021 01 04;113(1):38-47.
Being Present 2.0: Online Mindfulness-Based Program for Metastatic Gastrointestinal Cancer Patients and Caregivers
A metastatic cancer diagnosis is associated with high levels of distress in patients and caregivers, which may be alleviated by mindfulness interventions. Research on scalable, tailored, online mindfulness training programs is needed. We sought to test the feasibility and acceptability of a remotely delivered 8-week mindfulness-based intervention, Being Present 2.0 (BP2.0). We performed a single-arm feasibility study of BP2.0 among patients with any metastatic gastrointestinal cancer receiving chemotherapy, with or without an informal caregiver. Participants were instructed to practice mindfulness using pre-recorded guided meditations 5 times per week using a study-specific website and to attend a weekly live, interactive virtual meeting facilitated by a trained instructor. The web-based platform enabled direct measurement of adherence. The study enrolled 46 of 74 (62%) patients contacted, together with 23 caregivers (69 participants total), from May to October 2018. Median patient age was 52 (range 20-70 years), 39% were male, 67% non-Hispanic white, 65% had colorectal cancer, and 78% lived outside of San Francisco. The top reasons cited for participation were to reduce stress/anxiety and learn how to meditate. Mean baseline National Comprehensive Cancer Network Distress Thermometer (NCCN DT) scores were 4.7 (patients) and 5.8 (caregivers). The study discontinuation rate was 20% (eight patients and six caregivers). Among the remaining 55 participants, 43 (78%) listened to at least one audio recording and/or attended at least one virtual meeting, although adherence data was incomplete. The retention rate was 71%, with 39 participants completing at least one follow-up assessment. In post-intervention qualitative interviews, 88% of respondents reported a positive experience. Compared to baseline, participants reported significantly reduced post-intervention NCCN DT scores (mean 3.1; P = .012). The BP2.0 online mindfulness-based program is feasible and acceptable for patients with metastatic gastrointestinal cancer and caregivers. These results will guide plans for a follow-up efficacy study. ClinicalTrials.gov Identifier: NCT03528863.
Authors: Dragomanovich, Hannah M; Kubo, Ai; Atreya, Chloe E; et al.
Glob Adv Health Med. 2021;10:21649561211044693. Epub 2021-11-03.
Long-term medical imaging use in children with central nervous system tumors
Children with central nervous system (CNS) tumors undergo frequent imaging for diagnosis and follow-up, but few studies have characterized longitudinal imaging patterns. We described medical imaging in children before and after malignant CNS tumor diagnosis. We conducted a retrospective cohort study of children aged 0-20 years diagnosed with CNS tumors between 1996-2016 at six U.S. integrated healthcare systems and Ontario, Canada. We collected computed topography (CT), magnetic resonance imaging (MRI), radiography, ultrasound, nuclear medicine examinations from 12 months before through 10 years after CNS diagnosis censoring six months before death or a subsequent cancer diagnosis, disenrollment from the health system, age 21 years, or December 31, 2016. We calculated imaging rates per child per month stratified by modality, country, diagnosis age, calendar year, time since diagnosis, and tumor grade. We observed 1,879 children with median four years follow-up post-diagnosis in the U.S. and seven years in Ontario, Canada. During the diagnosis period (±15 days of diagnosis), children averaged 1.10 CTs (95% confidence interval [CI] 1.09-1.13) and 2.14 MRIs (95%CI 2.12-2.16) in the U.S., and 1.67 CTs (95%CI 1.65-1.68) and 1.86 MRIs (95%CI 1.85-1.88) in Ontario. Within one year after diagnosis, 19% of children had ≥5 CTs and 45% had ≥5 MRIs. By nine years after diagnosis, children averaged one MRI and one radiograph per year with little use of other imaging modalities. MRI and CT are commonly used for CNS tumor diagnosis, whereas MRI is the primary modality used during surveillance of children with CNS tumors.
Authors: Bowles, Erin J A; Kwan, Marilyn L; Pole, Jason D; et al.
PLoS One. 2021;16(4):e0248643. Epub 2021-04-21.
The Role of Home-Based Exercise in Maintaining Skeletal Muscle During Preoperative Pancreatic Cancer Treatment
Loss of skeletal muscle and inferior muscle quality are associated with poor prognosis in patients undergoing preoperative treatment for pancreatic cancer, so maintaining skeletal muscle health before surgery may help accelerate patients’ functional recovery and improve their quality of life following surgery. While exercise helps maintain or increase skeletal muscle in individuals undergoing cancer treatment, its efficacy during pancreatic cancer treatment is unclear. Accordingly, in this study we compared changes in skeletal muscle quantity (skeletal muscle index [SMI]) and quality (skeletal muscle density [SMD]) during preoperative pancreatic cancer treatment in participants in a home-based exercise program (EP) and a historical cohort of patients who received the usual care (UC) with no formal exercise programming. Recommendations for the EP cohort included both aerobic and resistance exercise. We assessed changes in SMI and SMD using computed tomography scans administered at treatment planning (T0, prior to EP enrollment) and preoperative restaging (T1) for 33 EP and 64 UC patients and compared changes between groups. The UC patients had statistically significant SMI decreases from T0 to T1 (-1.4 ± 3.8 cm2/m2; p = .005), while the EP patients did not (0.2 ± 3.2 cm2/m2; p = .7). The SMI loss was significantly worse for the UC than for the EP patients (p = .03). Neither group demonstrated statistically significant changes in SMD from T0 to T1, nor did the groups differ in the amount of change in SMD. An adjusted linear regression model demonstrated that EP participation was significantly associated with better SMI maintenance (p = .02). These results suggest that participation in a home-based EP during preoperative treatment may help improve skeletal muscle health and clinical and quality of life outcomes for pancreatic cancer survivors.
Authors: Parker, Nathan H; Gorzelitz, Jessica; Ngo-Huang, An; Caan, Bette J; Prakash, Laura; Garg, Naveen; Petzel, Maria Q B; Schadler, Keri; Basen-Engquist, Karen; Katz, Matthew H G
Integr Cancer Ther. 2021 Jan-Dec;20:1534735420986615.
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
Authors: Conti, David V; Van Den Eeden, Stephen K; Haiman, Christopher A; et al.
Nat Genet. 2021 01;53(1):65-75. Epub 2021-01-04.
Re. “Association between low muscle mass and survival in incurable cancer patients: A systematic review”
Authors: Gonzalez, M Cristina; Caan, Bette; Prado, Carla M
Nutrition. 2021 01;81:111005. Epub 2020-08-31.
Sleep characteristics and risk of ovarian cancer among postmenopausal women
Several studies have assessed the relationship between sleep duration and ovarian cancer risk, but the results are conflicting. Importantly, no studies addressed the relationship between sleep disturbance or sleep quality and ovarian cancer incidence. Moreover, few studies have examined the relationships between sleep measures and subtypes of ovarian cancer. This study included 109,024 postmenopausal women ages 50-79 from the Women’s Health Initiative during 1993-1998 and followed through 2018. The Cox proportional hazards model was used to estimate adjusted HRs for the associations between sleep habits and the incidence of ovarian cancer and its subtypes. No association was observed between sleep duration, sleep quality, sleep disturbance, or insomnia and risk of overall ovarian cancer, serous/nonserous, or type I/type II ovarian cancer subtype. However, compared with women with average sleep quality, women with restful or very restful sleep quality had a significantly lower risk of invasive serous subtype [HR: 0.73, 95% confidence interval (CI): 0.60-0.90] while insomnia was associated with a higher risk of invasive serous subtype (HR: 1.36, 95% CI: 1.12-1.66). Associations with insomnia differed significantly by serous and nonserous subtypes, and type I and type II subtypes (P heterogeneity = 0.001 and P heterogeneity <0.001, respectively). This study provides no evidence on association between sleep habits and overall ovarian cancer risk among postmenopausal women. However, restful or very restful sleep quality was associated with a lower risk of invasive serous ovarian cancer, and insomnia was associated with a higher risk of invasive serous ovarian cancer. Associations with insomnia differed by subtypes. PREVENTION RELEVANCE: This study shows no association between sleep duration, sleep quality, or insomnia with the risk of overall ovarian cancer among postmenopausal women. However, restful sleep quality was associated with a lower risk of invasive serous ovarian cancer, and insomnia was associated with a higher risk of invasive serous ovarian cancer.
Authors: Liang, Xiaoyun; Harris, Holly R; Hendryx, Michael; Shadyab, Aladdin H; Hale, Lauren; Li, Yueyao; Crane, Tracy E; Cespedes Feliciano, Elizabeth M; Stefanick, Marcia L; Luo, Juhua
Cancer Prev Res (Phila). 2021 01;14(1):55-64. Epub 2020-09-11.
A descriptive pilot study of structural and functional social network ties among women in the women’s health initiative (WHI) study
Few studies examine the network structure and function of older women’s health discussion networks. We sought to assess the feasibility and acceptability of collecting social network data via telephone from 72 women from the Women’s Health Initiative study and to describe structural and functional characteristics. Women were socially connected and had dense networks. Women were emotionally close to network members, but their networks were not used to facilitate communication with health-care providers. One-third of network members was not influential on health-related decision-making. Collecting social network data via telephone is feasible and an acceptable, though un-preferred, mode of data collection.
Authors: Cené CW; Frerichs L; Evans JK; Kroenke CH; Dilworth-Anderson P; Corbie-Smith G; Snively B; Naughton MJ; Shumaker S
J Women Aging. 2021 Jan-Feb;33(1):1-29. Epub 2019-06-09.
Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study
Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models. In sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles. Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.
Authors: Bull, Caroline J; Sakoda, Lori C; Gunter, Marc J; et al.
BMC Med. 2020 12 17;18(1):396. Epub 2020-12-17.
Community Health Behaviors and Geographic Variation in Early-Onset Colorectal Cancer Survival Among Women
Despite overall reductions in colorectal cancer (CRC) morbidity and mortality, survival disparities by sex persist among young patients (age <50 years). Our study sought to quantify variance in early-onset CRC survival accounted for by individual/community-level characteristics among a population-based cohort of US women. Geographic hot spots-counties with high early-onset CRC mortality rates among women-were derived using 3 geospatial autocorrelation approaches with Centers for Disease Control and Prevention national mortality data. We identified women (age: 15-49 years) diagnosed with CRC from 1999 to 2016 in the National Institutes of Health/National Cancer Institute's Surveillance, Epidemiology, and End Results program. Patterns of community health behaviors by hot spot classification were assessed by Spearman correlation (ρ). Generalized R values were used to evaluate variance in survival attributed to individual/community-level features. Approximately 1 in every 16 contiguous US counties identified as hot spots (191 of 3,108), and 52.9% of hot spot counties (n = 101) were located in the South. Among 28,790 women with early-onset CRC, 13.7% of cases (n = 3,954) resided in hot spot counties. Physical inactivity and fertility were community health behaviors that modestly correlated with hot spot residence among women with early-onset CRC (ρ = 0.21 and ρ = -0.23, respectively; P < 0.01). Together, individual/community-level features accounted for distinct variance patterns in early-onset CRC survival among women (hot spot counties: 33.8%; non-hot spot counties: 34.1%). Individual/community-level features accounted for approximately one-third of variation in early-onset CRC survival among women and differed between hot spot vs non-hot spot counties. Understanding the impact of community health behaviors-particularly in regions with high early-onset CRC mortality rates-is critical for tailoring strategies to reduce early-onset CRC disparities.
Authors: Holowatyj AN; Langston ME; Han Y; Viskochil R; Perea J; Cao Y; Rogers CR; Lieu CH; Moore JX
Clin Transl Gastroenterol. 2020 Dec;11(12):e00266.
Development of a longitudinal two-biomarker algorithm for early detection of ovarian cancer in women with BRCA mutations
To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman’s baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.
Authors: Lentz, Scott E; Powell, C Bethan; Kushi, Lawrence H; Skates, Steven J; et al.
Gynecol Oncol. 2020 12;159(3):804-810. Epub 2020-10-01.
Genetic Variants in the Regulatory T cell-Related Pathway and Colorectal Cancer Prognosis
High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiation and function could be associated with colorectal cancer prognosis. In a prospective German cohort of 3,593 colorectal cancer patients, we assessed the association of 771 single-nucleotide polymorphisms (SNP) in 58 Treg-related genes with overall and colorectal cancer-specific survival using Cox regression models. Effect modification by microsatellite instability (MSI) status was also investigated because tumors with MSI show greater lymphocytic infiltration and have been associated with better prognosis. Replication of significant results was attempted in 2,047 colorectal cancer patients of the International Survival Analysis in Colorectal Cancer Consortium (ISACC). A significant association of the TGFBR3 SNP rs7524066 with more favorable colorectal cancer-specific survival [hazard ratio (HR) per minor allele: 0.83; 95% confidence interval (CI), 0.74-0.94; P value: 0.0033] was replicated in ISACC (HR: 0.82; 95% CI, 0.68-0.98; P value: 0.03). Suggestive evidence for association was found with two IL7 SNPs, rs16906568 and rs7845577. Thirteen SNPs with differential associations with overall survival according to MSI in the discovery analysis were not confirmed. Common genetic variation in the Treg pathway implicating genes such as TGFBR3 and IL7 was shown to be associated with prognosis of colorectal cancer patients. The implicated genes warrant further investigation.
Authors: Neumeyer, Sonja; Schoen, Robert E; Chang-Claude, Jenny; et al.
Cancer Epidemiol Biomarkers Prev. 2020 12;29(12):2719-2728. Epub 2020-10-02.
Sex-Specific Genetic Associations for Barrett’s Esophagus and Esophageal Adenocarcinoma
Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett’s esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored. Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits. We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, PBONF = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, PBONF = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals. The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.
Authors: Dong, Jing; Corley, Douglas A; Thrift, Aaron P; et al.
Gastroenterology. 2020 12;159(6):2065-2076.e1. Epub 2020-09-09.
Colorectal cancer screening in the COVID-19 era
Authors: Dekker, Evelien; Chiu, Han-Mo; Lansdorp-Vogelaar, Iris; WEO Colorectal Cancer Screening Committee,
Gastroenterology. 2020 Dec;159(6):1998-2003. Epub 2020-09-20.
Bariatric Surgery is Associated With Reduced Risk of Breast Cancer in Both Premenopausal and Postmenopausal Women
This retrospective cohort study examined whether bariatric surgery is associated with reduced risk of breast cancer among pre- and postmenopausal women. Obesity is associated with increased risk of breast cancer, but the impact of weight loss on breast cancer risk has been difficult to quantify. The cohort included obese (body mass index ≥35 kg/m) patients enrolled in an integrated health care delivery system between 2005 and 2012 (with follow-up through 2014). Female bariatric surgery patients (N = 17,998) were matched on body mass index, age, study site, and comorbidity index to 53,889 women with no bariatric surgery. Kaplan-Meier curves and Cox proportional hazards models were used to examine incident breast cancer up to 10 years after bariatric surgery. Pre- and postmenopausal women were examined separately, and further classified by estrogen receptor (ER) status. The analysis included 301 premenopausal and 399 postmenopausal breast cancer cases. In multivariable adjusted models, bariatric surgery was associated with a reduced risk of both premenopausal (HR = 0.72, 95% CI, 0.54-0.94) and postmenopausal (HR = 0.55, 95% CI, 0.42-0.72) breast cancer. Among premenopausal women, the effect of bariatric surgery was more pronounced among ER-negative cases (HR = 0.36, 95% CI, 0.16-0.79). Among postmenopausal women, the effect was more pronounced in ER-positive cases (HR = 0.52, 95% CI, 0.39-0.70). Bariatric surgery was associated with a reduced risk of breast cancer among severely obese women. These findings have significant public health relevance because the prevalence of obesity continues to rise, and few modifiable breast cancer risk factors have been identified, especially for premenopausal women.
Authors: Feigelson HS; Caan B; Weinmann S; Leonard AC; Powers JD; Yenumula PR; Arterburn DE; Koebnick C; Altaye M; Schauer DP
Ann Surg. 2020 12;272(6):1053-1059.
A Mobile Health Mindfulness Intervention for Women With Moderate to Moderately Severe Postpartum Depressive Symptoms: Feasibility Study
Approximately 20% of women suffer from postpartum depression (PPD). Due to barriers such as limited access to care, half of the women with PPD do not receive treatment. Therefore, it is critical to identify effective and scalable interventions. Traditional mindfulness programs have been effective in reducing depressive symptoms, however access remains a barrier. A self-paced mobile health (mHealth) mindfulness program may fit the lifestyle of busy mothers who are unable to attend in-person classes. However, little is known regarding the feasibility or efficacy of mHealth mindfulness interventions in postpartum women with depressive symptoms. This study aims to assess the feasibility, acceptability, and preliminary efficacy of an mHealth mindfulness intervention for postpartum women with moderate to moderately severe depressive symptoms. We conducted a single-arm feasibility trial of an mHealth mindfulness intervention within Kaiser Permanente Northern California (KPNC), a large integrated health care system. Participants were identified through clinician referral and electronic health records via KPNC’s universal perinatal depression screening program and recruited by the study team. Inclusion criteria included the following: English-speaking, up to 6 months postpartum with a Patient Health Questionnaire (PHQ-8) score of 10 to 19, and no regular mindfulness/meditation practice. Participants were asked to use a mindfulness app, Headspace, 10 to 20 min/day for 6 weeks. Baseline and postintervention surveys captured data on patient-reported outcomes (depression and stress symptoms, sleep quality, and mindfulness). Semistructured interviews captured acceptability. Retention and adherence were used to assess feasibility. Of the 115 women who were contacted and met the eligibility criteria or declined participation before eligibility assessment, 27 (23%) were enrolled. In addition, 70% (19/27) completed the study. The mean age of participants was 31 years (SD 5.2), 30% (8/27) were non-Hispanic White, and, on average, participants were 12.3 weeks postpartum (SD 5.7). Of the women who completed the study, 100% (19/19) used the Headspace app at least once, and nearly half (9/19, 47%) used the app on ≥50% of the days during the 6-week intervention period. Of the 16 participants who completed the postintervention interview, 69% (11/16) reported that they were very or extremely satisfied with the app. Interviews indicated that women appreciated the variety of meditations and felt that the program led to reduced anxiety and improved sleep. Significant improvements in pre- and postintervention scores were observed for depressive symptoms (PHQ-8: -3.8, P=.004), perceived stress (10-item Perceived Stress Scale: -6.0, P=.005), and sleep quality (Pittsburgh Sleep Quality Index: -2.1, P=.02, indicating less sleep disturbance). Improvements in mindfulness were also significant (Five Facet Mindfulness Questionnaire-Short Form: 10.9, P=.01). An mHealth mindfulness intervention for postpartum women with moderate to moderately severe depressive symptoms is feasible and acceptable. An efficacy trial is warranted.
Authors: Avalos, Lyndsay A; Aghaee, Sara; Kurtovich, Elaine; Quesenberry, Charles; Nkemere, Linda; McGinnis, MegAnn K; Kubo, Ai
JMIR Ment Health. 2020 Nov 12;7(11):e17405. Epub 2020-11-12.
Trends in Imaging for Suspected Pulmonary Embolism Across US Health Care Systems, 2004 to 2016
In response to calls to reduce unnecessary diagnostic testing with computed tomographic pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), there have been growing efforts to create and implement decision rules for PE testing. It is unclear if the use of advanced imaging tests for PE has diminished over time. To assess the use of advanced imaging tests, including chest computed tomography (CT) (ie, all chest CT except for CTPA), CTPA, and ventilation-perfusion (V/Q) scan, for PE from 2004 to 2016. Cohort study of adults by age group (18-64 years and ≥65 years) enrolled in 7 US integrated and mixed-model health care systems. Joinpoint regression analysis was used to identify years with statistically significant changes in imaging rates and to calculate average annual percentage change (growth) from 2004 to 2007, 2008 to 2011, and 2012 to 2016. Analyses were conducted between June 11, 2019, and March 18, 2020. Rates of chest CT, CTPA, and V/Q scan by year and age, as well as annual change in rates over time. Overall, 3.6 to 4.8 million enrollees were included each year of the study, for a total of 52 343 517 person-years of follow-up data. Adults aged 18 to 64 years accounted for 42 223
Authors: Wang, Ralph C; Miglioretti, Diana L; Marlow, Emily C; Kwan, Marilyn L; Theis, May K; Bowles, Erin J A; Greenlee, Robert T; Rahm, Alanna K; Stout, Natasha K; Weinmann, Sheila; Smith-Bindman, Rebecca
JAMA Netw Open. 2020 11 02;3(11):e2026930. Epub 2020-11-02.
Long-term follow-up of a racially and ethnically diverse population of men with localized prostate cancer who did not undergo initial active treatment
There is limited research on the racial/ethnic differences in long-term outcomes for men with untreated, localized prostate cancer. Men diagnosed with localized, Gleason ≤7 prostate cancer who were not treated within 1 year of diagnosis from 1997-2007 were identified. Cumulative incidence rates of the following events were calculated; treatment initiation, metastasis, death due to prostate cancer and all-cause mortality, accounting for competing risks. The Cox model of all-cause mortality and Fine-Gray sub distribution model to account for competing risks were used to test for racial/ethnic differences in outcomes adjusted for clinical factors. There were 3925 men in the study, 749 Hispanic, 2415 non-Hispanic white, 559 non-Hispanic African American, and 202 non-Hispanic Asian/Pacific Islander (API). Median follow-up was 9.3 years. At 19 years, overall cumulative incidence of treatment, metastasis, death due to prostate cancer, and all-cause mortality was 25.0%, 14.7%, 11.7%, and 67.8%, respectively. In adjusted models compared to non-Hispanic whites, African Americans had higher rates of treatment (HR = 1.39, 95% CI = 1.15-1.68); they had an increased risk of metastasis beyond 10 years after diagnosis (HR = 4.70, 95% CI = 2.30-9.61); API and Hispanic had lower rates of all-cause mortality (HR = 0.66, 95% CI = 0.52-0.84, and HR = 0.72, 95% CI = 0.62-0.85, respectively), and API had lower rates of prostate cancer mortality in the first 10 years after diagnosis (HR = 0.29, 95% CI = 0.09-0.90) and elevated risks beyond 10 years (HR = 5.41, 95% CI = 1.39-21.11). Significant risks of metastasis and prostate cancer mortality exist in untreated men beyond 10 years after diagnosis, but are not equally distributed among racial/ethnic groups.
Authors: Slezak, Jeff M; Van Den Eeden, Stephen K; Cannavale, Kimberly L; Chien, Gary W; Jacobsen, Steven J; Chao, Chun R
Cancer Med. 2020 11;9(22):8530-8539. Epub 2020-09-23.
Risk of Renal Cell Carcinoma Associated with Calcium Channel Blockers: A Nationwide Observational Study Focusing on Confounding by Indication
We examined whether the apparent association between renal cell carcinoma (RCC) and use of dihydropyridine calcium channel blockers (CCBs) was explained by confounding by indication since hypertension, the main indication for CCBs, is a risk factor for RCC. Using Danish health registries, we conducted a nested case-control study including 7315 RCC cases during 2000-2015. We matched each case with up to 20 controls on age and sex using risk-set sampling. We estimated odds ratios (ORs) for long-term CCB use associated with RCC using conditional logistic regression. We addressed confounding by indication by (1) adjusting for hypertension severity indicators; (2) evaluating dose-response patterns; (3) examining whether other first-line anti-hypertensives were associated with RCC; and (4) using an active comparator new user design by nesting the study in new users of CCBs or angiotensin-converting enzyme inhibitors (ACEIs). The adjusted OR for RCC associated with long-term CCB use compared to non-use was 1.76 (1.63-1.90). After we additionally adjusted for hypertension severity indicators, the OR remained elevated (OR 1.37; confidence interval [CI] 1.25, 1.49) with evidence of a dose-response pattern. Other anti-hypertensives were also associated with RCC, for example, ACEIs (OR 1.27; 95% CI = 1.16, 1.39) and thiazides (OR 1.22; 95% CI = 1.12, 1.34). In the active comparator new user design, the OR was 1.21 (95% CI = 0.95, 1.53) for use of CCBs compared with ACEIs. In this population, confounding by indication appeared to explain at least part of the association between RCC and dihydropyridine CCBs.
Authors: Kristensen, Kasper Bruun; Habel, Laurel A; Gagne, Joshua J; Friis, Søren; Andersen, Klaus Kaae; Hallas, Jesper; Pottegård, Anton
Epidemiology. 2020 11;31(6):860-871.
Primary Care Provider Beliefs and Recommendations About Colorectal Cancer Screening in Four Healthcare Systems
Primary care provider’s (PCP) perceptions of colorectal cancer screening test effectiveness and their recommendations for testing intervals influence patient screening uptake. Few large studies have examined providers’ perceptions and recommendations, including their alignment with evidence suggesting comparable test effectiveness and guideline recommendations for screening frequency. Providers (n = 1,281) within four healthcare systems completed a survey in 2017-2018 regarding their perceptions of test effectiveness and recommended intervals for colonoscopy and fecal immunochemical testing (FIT) for patients ages 40-49, 50-74, and ≥75 years. For patients 50-74 (screening eligible), 82.9% of providers rated colonoscopy as very effective versus 59.6% for FIT, and 26.3% rated colonoscopy as more effective than FIT. Also, for this age group, 77.9% recommended colonoscopy every 10 years and 92.4% recommended FIT annually. For patients ages 40-49 and ≥75, more than one-third of providers believed the tests were somewhat or very effective, although >80% did not routinely recommend screening by either test for these age groups. Provider screening test interval recommendations generally aligned with colorectal cancer guidelines; however, 25% of providers believed colonoscopy was more effective than FIT for mortality reduction, which differs from some modeling studies that suggest comparable effectiveness. The latter finding may have implications for health systems where FIT is the dominant screening strategy. Only one-third of providers reported believing these screening tests were effective in younger and older patients (i.e., <50 and ≥75 years). Evidence addressing these beliefs may be relevant if cancer screening recommendations are modified to include older and/or younger patients.
Authors: Ghai NR; Lee JK; Corley DA; et al.
Cancer Prev Res (Phila). 2020 11;13(11):947-958. Epub 2020-07-15.
Early Screening of African Americans (45-50 Years Old) in a Fecal Immunochemical Test-based Colorectal Cancer Screening Program
Some guidelines recommend starting colorectal cancer (CRC) screening before age 50 years for African Americans, but there are few data on screening uptake and yield in this population. We performed a prospective study of fecal immunochemical test (FIT) screening among African American members of the Kaiser Permanente Northern California health plan. We compared data from African American members screened when they were 45-50 years old (early screening group) in 2018 with data from previously unscreened African American, white, Hispanic, and Asian/Pacific Islander health plan members who were 51-56 years old. Screening outreach was performed with mailed FIT kits. Logistic regression models, adjusted for sex, were used to evaluate differences among groups in screening uptake, colonoscopy follow-up of abnormal test results, and test yield. Among 10,232 African Americans in the early screening group who were mailed a FIT, screening was completed by 33.1%. Among the 4% with positive test results, 85.3% completed a follow-up colonoscopy: 57.8% had any adenoma, 33.6% had an advanced adenoma (adenoma with advanced histology or polyp ≥10 mm), and 2.6% were diagnosed with CRC. African Americans in the early screening group were modestly more likely to have completed screening than previously unscreened African Americans, whites, and Hispanics 51-56 years old. The groups did not differ significantly in positive results from the FIT (range, 3.8%-4.6%) and more than 74% received a follow-up colonoscopy after a positive test result. The test yields for any adenoma (range, 56.7%-70.7%), advanced adenoma (range, 20.0%-33.6%), and CRC (range, 0%-7.1%) were similar. Proportions of African Americans who participated in early (aged 45-50 years) FIT screening and test yield were comparable to those of previously unscreened African Americans, whites, Hispanics, and Asian/Pacific Islanders who were 51-56 years old.
Authors: Levin TR; Jensen CD; Chawla NM; Sakoda LC; Lee JK; Zhao WK; Landau MA; Herm A; Eby E; Quesenberry CP; Corley DA
Gastroenterology. 2020 11;159(5):1695-1704.e1. Epub 2020-07-20.
Standardized reporting and management of suspicious findings on chest computed tomography is associated with improved lung cancer diagnosis in an observational study
Follow-up of chest CT scan findings suspicious for lung cancer may be delayed because of inadequate documentation. Standardized reporting and follow-up may reduce time to diagnosis and care for lung cancer. We implemented a reporting system that standardizes tagging of chest CT scan reports by classifying pulmonary findings. The system also automates referral of patients with findings suspicious for lung cancer to a multidisciplinary care team for rapid review and follow-up. The system was designed to reduce the time to diagnosis, particularly for early-stage lung cancer. We evaluated the effectiveness of this system, using a quasi-experimental stepped wedge cluster design, examining 99,148 patients who underwent diagnostic (nonscreening) chest CT imaging from 2015 to 2017 and who had not received a chest CT scan in the preceding 24 months. We evaluated the association of the intervention with the incidence of diagnosis and surgical treatment of early-stage (I, II) and late-stage (III, IV) lung cancer within 120 days of chest CT imaging. Forty percent of patients received the intervention. Among 2,856 patients (2.9%) who received diagnoses of lung cancer, 28% had early-stage disease. In multivariable analyses, the intervention was associated with 24% greater odds of early-stage diagnosis (OR, 1.24; 95% CI, 1.09-1.41) and no change in the odds of late-stage diagnosis (OR, 1.04; 95% CI, 0.95-1.14). The intervention was not associated with the rate of surgical treatment within 120 days. In this large quasi-experimental community-based observational study, implementation of a system that combines standardized tagging of chest CT scan reports with clinical navigation was effective for increasing the diagnosis of early-stage lung cancer.
Authors: Urbania TH; Dusendang JR; Herrinton LJ; Alexeeff S; Corley DA; Ely S; Patel A; Osinski T; Sakoda LC
Chest. 2020 11;158(5):2211-2220. Epub 2020-06-17.
Association Between Levels of Hormones and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus
Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones are associated with risk of EAC or Barrett’s esophagus (BE). We conducted a Mendelian randomization analysis using data from patients with EAC (n = 2488) or BE (n = 3247) and control participants (n = 2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single-nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs. Higher genetically predicted levels of follicle-stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01-1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per SD increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index. In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle-stimulating and luteinizing hormones and risk of BE and EAC.
Authors: Xie SH; Corley DA; Lagergren J; et al.
Clin Gastroenterol Hepatol. 2020 11;18(12):2701-2709.e3. Epub 2019-11-19.
Early life household intactness and timing of pubertal onset in girls: a prospective cohort study
Girls who experience early-life familial stress may have heightened risk of early puberty, which has adverse implications for adolescent and adult health. We assessed the association between household intactness and pubertal onset using a racially/ethnically diverse cohort of girls from Northern California. A prospective cohort study of 26,044 girls born in 2003-10. Girls living with both parents from birth up to 6 years were considered to come from “intact” households while others constituted “non-intact” households. Pubertal development was measured using pediatrician-assessed Tanner staging for breast and pubic hair. Pubertal onset was defined as the transition from Tanner Stage 1 to 2+ for breast (thelarche) and pubic hair (pubarche). Menarche data was collected from routine well-child questionnaires. Weibull regression models accommodating left, right, and interval censoring were used to determine risk of earlier thelarche and pubarche, and logistic regressions were used to assess the risk of early menarche (age < 12). Girls exposed to non-intact households before age 2 years were at increased risk for earlier thelarche and pubarche with significant effect modification by race/ethnicity, compared with girls from intact households. The associations were strongest among Black girls (adjusted hazard ratio [HR]: 1.60, 95% confidence interval [CI]: 1.29,1.98; HR: 1.42, 95%CI: 1.15,1.77 for thelarche and pubarche, respectively). There were no significant associations among Asian/Pacific Islanders. Girls who lived in non-intact households before age 2 years were also at increased risk for earlier menarche, but without race/ethnic interaction. Adjustment for prepubertal obesity did not change these associations. Associations between living in non-intact households after age 2 years and early puberty were weaker but still significant. Exposure to a non-intact household early in life may increase the risk of early puberty in girls. Future psychosocial interventions focused on improving family cohesiveness and efforts to reduce childhood stress among families that are non-intact may mitigate these negative associations, thereby preventing future adverse health effects of early puberty and health disparities.
Authors: Aghaee, Sara; Deardorff, Julianna; Greenspan, Louise C; Quesenberry, Charles P; Kushi, Lawrence H; Kubo, Ai
BMC Pediatr. 2020 10 28;20(1):464. Epub 2020-10-28.
Intake of dietary fruit, vegetables, and fiber and risk of colorectal cancer according to molecular subtypes: A pooled analysis of 9 studies
Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (P trend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. SIGNIFICANCE: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.
Authors: Hidaka, Akihisa; Sakoda, Lori C; Peters, Ulrike; et al.
Cancer Res. 2020 10 15;80(20):4578-4590. Epub 2020-08-14.
Identification of 31 loci for mammographic density phenotypes and their associations with breast cancer risk
Mammographic density (MD) phenotypes are strongly associated with breast cancer risk and highly heritable. In this GWAS meta-analysis of 24,192 women, we identify 31 MD loci at P < 5 × 10-8, tripling the number known to 46. Seventeen identified MD loci also are associated with breast cancer risk in an independent meta-analysis (P < 0.05). Mendelian randomization analyses show that genetic estimates of dense area (DA), nondense area (NDA), and percent density (PD) are all significantly associated with breast cancer risk (P < 0.05). Pathway analyses reveal distinct biological processes involving DA, NDA and PD loci. These findings provide additional insights into the genetic basis of MD phenotypes and their associations with breast cancer risk.
Authors: Sieh, Weiva; Alexeeff, Stacey E; Sakoda, Lori C; Risch, Neil; Habel, Laurel A; et al.
Nat Commun. 2020 10 09;11(1):5116. Epub 2020-10-09.
Breast Cancer Mortality Hot Spots Among Black Women With de Novo Metastatic Breast Cancer
Black women living in southern states have the highest breast cancer mortality rate in the United States. The prognosis of de novo metastatic breast cancer is poor. Given these mortality rates, we are the first to link nationally representative data on breast cancer mortality hot spots (counties with high breast cancer mortality rates) with cancer mortality data in the United States and investigate the association of geographic breast cancer mortality hot spots with de novo metastatic breast cancer mortality among Black women. We identified 7292 Black women diagnosed with de novo metastatic breast cancer in Surveillance, Epidemiology, and End Results (SEER). The county-level characteristics were obtained from 2014 County Health Rankings and linked to SEER. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for mortality between hot spot and non-hot spot counties. Among 7292 patients, 393 (5.4%) resided in breast cancer mortality hot spots. Women residing in hot spots had similar risks of breast cancer-specific mortality (aHR = 0.99, 95% CI = 0.85 to 1.15) and all-cause mortality (aHR = 0.97, 95% CI = 0.84 to 1.11) as women in non-hot spots after adjusting for individual and tumor-level factors and treatments. Additional adjustment for county-level characteristics did not impact mortality. Living in a breast cancer mortality hot spot was not associated with de novo metastatic breast cancer mortality among Black women. Future research should begin to examine variation in both individual and population-level determinants, as well as in molecular and genetic determinants that underlie the aggressive nature of de novo metastatic breast cancer.
Authors: Han Y; Langston M; Fuzzell L; Khan S; Lewis-Thames MW; Colditz GA; Moore JX
JNCI Cancer Spectr. 2021 Feb;5(1):pkaa086. Epub 2020-10-01.
Effects of cooking methods on total isothiocyanate yield from cruciferous vegetables
Cruciferous vegetables are primary sources of dietary isothiocyanates (ITCs), a group of phytochemicals showing promising cancer-chemopreventive activities in multiple cancer models. However, no study has thoroughly examined how cooking affects the yields of ITCs from cruciferous vegetables. In this study, a high-performance liquid chromatography (HPLC)-based cyclocondensation assay was performed to examine the ITC yields from four major cruciferous vegetables (broccoli, cabbage, cauliflower, and kale) under six cooking conditions (stir-frying, steaming, microwaving, boiling, stewing, and chip-baking for kale only) and measured the level of ITCs under the raw condition for a comprehensive list of cruciferous vegetables and ITC-containing condiments. A wide range of ITC yields was found across vegetables and condiments. Cooking significantly altered the ITC yields, showing an averagely four-fold increase by lightly cooking (stir-frying, steaming, and microwaving) and a 58% decrease by heavily cooking (boiling, stewing, and chip-baking). These findings will provide the evidence-based cooking guidance on cruciferous vegetable consumption and help better estimate dietary ITC exposure in epidemiologic studies.
Authors: Wang, Zinian; Kwan, Marilyn L; Pratt, Rachel; Roh, Janise M; Kushi, Lawrence H; Danforth, Kim N; Zhang, Yuesheng; Ambrosone, Christine B; Tang, Li
Food Sci Nutr. 2020 Oct;8(10):5673-5682. Epub 2020-09-09.
Addressing Disparities in Lung Cancer Screening Eligibility and Healthcare Access. An Official American Thoracic Society Statement
Background: There are well-documented disparities in lung cancer outcomes across populations. Lung cancer screening (LCS) has the potential to reduce lung cancer mortality, but for this benefit to be realized by all high-risk groups, there must be careful attention to ensuring equitable access to this lifesaving preventive health measure.Objectives: To outline current knowledge on disparities in eligibility criteria for, access to, and implementation of LCS, and to develop an official American Thoracic Society statement to propose strategies to optimize current screening guidelines and resource allocation for equitable LCS implementation and dissemination.Methods: A multidisciplinary panel with expertise in LCS, implementation science, primary care, pulmonology, health behavior, smoking cessation, epidemiology, and disparities research was convened. Participants reviewed available literature on historical disparities in cancer screening and emerging evidence of disparities in LCS.Results: Existing LCS guidelines do not consider racial, ethnic, socioeconomic, and sex-based differences in smoking behaviors or lung cancer risk. Multiple barriers, including access to screening and cost, further contribute to the inequities in implementation and dissemination of LCS.Conclusions: This statement identifies the impact of LCS eligibility criteria on vulnerable populations who are at increased risk of lung cancer but do not meet eligibility criteria for screening, as well as multiple barriers that contribute to disparities in LCS implementation. Strategies to improve the selection and dissemination of LCS in vulnerable groups are described.
Authors: Rivera, M Patricia; Sakoda, Lori C; Aldrich, Melinda C; et al.
Am J Respir Crit Care Med. 2020 10 01;202(7):e95-e112.
Streamlining genetic testing for women with ovarian cancer in a Northern California health care system
Referral to Genetics for pre-testing counseling may be inefficient for women with ovarian cancer. This study assesses feasibility of gynecologic oncologists directly offering genetic testing. A prospective pilot study was conducted at two gynecologic oncology hubs in an integrated healthcare system from May 1 to November 6, 2019. Gynecologic oncologists offered multigene panel testing to women with newly diagnosed ovarian cancer, followed by selective genetic counseling. Outcomes were compared between study participants and women from other hubs in the health system. Of ovarian cancer patients at study sites, 40 participated and all underwent genetic testing. Of 101 patients diagnosed at other sites, 85% were referred to genetics (p = .0061 compared to pilot participants) and 67% completed testing (p < .0001). The time from diagnosis to blood draw and notification of result was 18.5 and 34 days for the pilot group compared to 25.5 and 53 days at other sites. Panel testing detected 9 (22.5%) and 7 (10.3%, p = .08) pathogenic mutations in each group, respectively. Patients and providers were highly satisfied with the streamlined process. Genetic testing performed at the gynecologic oncology point of care for patients with ovarian cancer is feasible, increases uptake of testing, and improves time to results.
Authors: Powell, C Bethan; Kushi, Lawrence H; et al.
Gynecol Oncol. 2020 10;159(1):221-228. Epub 2020-08-07.
Association of Low Muscle Mass and Low Muscle Radiodensity With Morbidity and Mortality for Colon Cancer Surgery
Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an emerging area for improving preoperative risk stratification. To examine the associations of muscle characteristics with postoperative complications, length of hospital stay (LOS), readmission, and mortality in patients with colon cancer. This population-based retrospective cohort study was conducted among 1630 patients who received a diagnosis of stage I to III colon cancer from January 2006 to December 2011 at Kaiser Permanente Northern California, an integrated health care system. Preliminary data analysis started in 2017. Because major complication data were collected between 2018 and 2019, the final analysis using the current cohort was conducted between 2019 and 2020. Low skeletal muscle index (SMI) and/or low skeletal muscle radiodensity (SMD) levels were assessed using preoperative computerized tomography images. Length of stay, any complication (≥1 predefined complications) or major complications (Clavien-Dindo classification score ≥3), 30-day mortality and readmission up to 30 days postdischarge, and overall mortality. The mean (SD) age at diagnosis was 64.0 (11.3) years and 906 (55.6%) were women. Patients with low SMI or low SMD were more likely to remain hospitalized 7 days or longer after surgery (odds ratio [OR], 1.33; 95% CI, 1.05-1.68; OR, 1.39; 95% CI, 1.05-1.84, respectively) and had higher risks of overall mortality (hazard ratio, 1.40; 95% CI, 1.13-1.74; hazard ratio, 1.44; 95% CI, 1.12-1.85, respectively). Additionally, patients with low SMI were more likely to have 1 or more postsurgical complications (OR, 1.31; 95% CI, 1.04-1.65) and had higher risk of 30-day mortality (OR, 4.85; 95% CI, 1.23-19.15). Low SMD was associated with higher odds of having major complications (OR, 2.41; 95% CI, 1.44-4.04). Low SMI and low SMD were associated with longer LOS, higher risk of postsurgical complications, and short-term and long-term mortality. Research should evaluate whether targeting potentially modifiable factors preoperatively, such as preserving muscle mass, could reverse the observed negative associations with postoperative outcomes.
Authors: Xiao, Jingjie; Cespedes Feliciano, Elizabeth M; Meyerhardt, Jeffrey A; Kwan, Marilyn L; Alexeeff, Stacey E; Castillo, Adrienne L; Prado, Carla M; et al.
JAMA Surg. 2020 10 01;155(10):942-949.
Deep learning method for localization and segmentation of abdominal CT
Computed Tomography (CT) imaging is widely used for studying body composition, i.e., the proportion of muscle and fat tissues with applications in areas such as nutrition or chemotherapy dose design. In particular, axial CT slices from the 3rd lumbar (L3) vertebral location are commonly used for body composition analysis. However, selection of the third lumbar vertebral slice and the segmentation of muscle/fat in the slice is a tedious operation if performed manually. The objective of this study is to automatically find the middle axial slice at L3 level from a full or partial body CT scan volume and segment the skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) on that slice. The proposed algorithm includes an L3 axial slice localization network followed by a muscle-fat segmentation network. The localization network is a fully convolutional classifier trained on more than 12,000 images. The segmentation network is a convolutional neural network with an encoder-decoder architecture. Three datasets with CT images taken for patients with different types of cancers are used for training and validation of the networks. The mean slice error of 0.87±2.54 was achieved for L3 slice localization on 1748 CT scan volumes. The performance of five class tissue segmentation network evaluated on two datasets with 1327 and 1202 test samples. The mean Jaccard score of 97% was achieved for SM and VAT tissue segmentation on 1327 images. The mean Jaccard scores of 98% and 83% are corresponding to SAT and IMAT tissue segmentation on the same dataset. The localization and segmentation network performance indicates the potential for fully automated body composition analysis with high accuracy.
Authors: Dabiri, Setareh; Popuri, Karteek; Ma, Cydney; Chow, Vincent; Feliciano, Elizabeth M Cespedes; Caan, Bette J; Baracos, Vickie E; Beg, Mirza Faisal
Comput Med Imaging Graph. 2020 10;85:101776. Epub 2020-08-14.
Pathway Analysis of Renal Cell Carcinoma Genome-Wide Association Studies Identifies Novel Associations
Much of the heritable risk of renal cell carcinoma (RCC) associated with common genetic variation is unexplained. New analytic approaches have been developed to increase the discovery of risk variants in genome-wide association studies (GWAS), including multi-locus testing through pathway analysis. We conducted a pathway analysis using GWAS summary data from six previous scans (10,784 cases and 20,406 controls) and evaluated 3,678 pathways and gene sets drawn from the Molecular Signatures Database. To replicate findings, we analyzed GWAS summary data from the UK Biobank (903 cases and 451,361 controls) and the Genetic Epidemiology Research on Adult Health and Aging cohort (317 cases and 50,511 controls). We identified 14 pathways/gene sets associated with RCC in both the discovery (P < 1.36 × 10-5, the Bonferroni correction threshold) and replication (P < 0.05) sets, 10 of which include components of the PI3K/AKT pathway. In tests across 2,035 genes in these pathways, associations (Bonferroni corrected P < 2.46 × 10-5 in discovery and replication sets combined) were observed for CASP9, TIPIN, and CDKN2C. The strongest SNP signal was for rs12124078 (P Discovery = 2.6 × 10-5; P Replication = 1.5 × 10-4; P Combined = 6.9 × 10-8), a CASP9 expression quantitative trait locus. Our pathway analysis implicates genetic variation within the PI3K/AKT pathway as a source of RCC heritability and identifies several promising novel susceptibility genes, including CASP9, which warrant further investigation. Our findings illustrate the value of pathway analysis as a complementary approach to analyzing GWAS data.
Authors: Purdue, Mark P; Sakoda, Lori C; Yu, Kai; et al.
Cancer Epidemiol Biomarkers Prev. 2020 10;29(10):2065-2069. Epub 2020-07-30.
Evaluation of automated computed tomography segmentation to assess body composition and mortality associations in cancer patients
Body composition from computed tomography (CT) scans is associated with cancer outcomes including surgical complications, chemotoxicity, and survival. Most studies manually segment CT scans, but Automatic Body composition Analyser using Computed tomography image Segmentation (ABACS) software automatically segments muscle and adipose tissues to speed analysis. Here, we externally evaluate ABACS in an independent dataset. Among patients with non-metastatic colorectal (n = 3102) and breast (n = 2888) cancer diagnosed from 2005 to 2013 at Kaiser Permanente, expert raters annotated tissue areas at the third lumbar vertebra (L3). To compare ABACS segmentation results to manual analysis, we quantified the proportion of pixel-level image overlap using Jaccard scores and agreement between methods using intra-class correlation coefficients for continuous tissue areas. We examined performance overall and among subgroups defined by patient and imaging characteristics. To compare the strength of the mortality associations obtained from ABACS’s segmentations to manual analysis, we computed Cox proportional hazards ratios (HRs) and 95% confidence intervals (95% CI) by tertile of tissue area. Mean ± SD age was 63 ± 11 years for colorectal cancer patients and 56 ± 12 for breast cancer patients. There was strong agreement between manual and automatic segmentations overall and within subgroups of age, sex, body mass index, and cancer stage: average Jaccard scores and intra-class correlation coefficients exceeded 90% for all tissues. ABACS underestimated muscle and visceral and subcutaneous adipose tissue areas by 1-2% versus manual analysis: mean differences were small at -2.35, -1.97 and -2.38 cm2 , respectively. ABACS’s performance was lowest for the <2% of patients who were underweight or had anatomic abnormalities. ABACS and manual analysis produced similar associations with mortality; comparing the lowest to highest tertile of skeletal muscle from ABACS versus manual analysis, the HRs were 1.23 (95% CI: 1.00-1.52) versus 1.38 (95% CI: 1.11-1.70) for colorectal cancer patients and 1.30 (95% CI: 1.01-1.66) versus 1.29 (95% CI: 1.00-1.65) for breast cancer patients. In the first study to externally evaluate a commercially available software to assess body composition, automated segmentation of muscle and adipose tissues using ABACS was similar to manual analysis and associated with mortality after non-metastatic cancer. Automated methods will accelerate body composition research and, eventually, facilitate integration of body composition measures into clinical care.
Authors: Cespedes Feliciano EM; Liu V; Caan BJ; et al.
J Cachexia Sarcopenia Muscle. 2020 10;11(5):1258-1269. Epub 2020-04-20.
History of Early Childhood Infections and Acute Lymphoblastic Leukemia Risk Among Children in a U.S. Integrated Health Care System
Surrogate measures of infectious exposures have been consistently associated with lower childhood acute lymphoblastic leukemia (ALL) risk. However, recent reports have suggested that physician-diagnosed early-life infections increase ALL risk, thereby raising the possibility that stronger responses to infections might promote risk. We examined whether medically diagnosed infections were related to childhood ALL risk in an integrated health-care system in the United States. Cases of ALL (n = 435) diagnosed between 1994-2014 among children aged 0-14 years, along with matched controls (n = 2,170), were identified at Kaiser Permanente Northern California. Conditional logistic regression was used to estimate risk of ALL associated with history of infections during first year of life and across the lifetime (up to diagnosis). History of infection during first year of life was not associated with ALL risk (odds ratio (OR) = 0.85, 95% confidence interval (CI): 0.60, 1.21). However, infections with at least 1 medication prescribed (i.e., more “severe” infections) were inversely associated with risk (OR = 0.42, 95% CI: 0.20, 0.88). Similar associations were observed when the exposure window was expanded to include medication-prescribed infections throughout the subjects’ lifetime (OR = 0.52, 95% CI: 0.32, 0.85).
Authors: Morimoto LM; Kwan ML; Deosaransingh K; Munneke JR; Kang AY; Quesenberry C; Kogan S; de Smith AJ; Metayer C; Wiemels JL
Am J Epidemiol. 2020 10 01;189(10):1076-1085.
A Transcriptome-Wide Association Study (TWAS) Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer
Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
Authors: Zhong J; Van Den Eeden SK; Amundadottir LT; et al.
J Natl Cancer Inst. 2020 10 01;112(10):1003-1012.
Pilot pragmatic randomized trial of mHealth mindfulness-based intervention for advanced cancer patients and their informal caregivers
Assess the feasibility of conducting a cluster randomized trial (RCT) comparing technology-delivered mindfulness-based intervention (MBI) programs against a waitlist control arm targeting advanced cancer patients and their informal caregivers. Two-arm cluster RCT within Kaiser Permanente Northern California (KPNC). We recruited patients with metastatic solid malignancies or hematological cancers and their informal caregivers. Intervention-group participants chose to use either a commercially available mindfulness app (10-20 minutes/day) or a webinar-based mindfulness course for 6 weeks. The waitlist control group received usual care. We assessed feasibility measures and obtained participant-reported data on quality-of-life (primary outcome) and distress outcomes (secondary) pre- and post-intervention. 103 patients (median age 67 years; 70% female; 81% White) and 39 caregivers (median age 66 years; 79% female; 69% White) were enrolled. Nearly all participants chose the mindfulness app over the webinar-based program. Among the participants in the intervention arm who chose the mobile-app program and completed the postintervention (6-week) survey, 21 (68%) patients and 7 (47%) caregivers practiced mindfulness at least 50% of the days during the 6-week study period. Seventy-four percent of intervention participants were “very” or “extremely” satisfied with the mindfulness program. We observed improvements in anxiety, quality of life, and mindfulness among patients in the intervention arm compared to those in the control group. We demonstrated the feasibility of conducting a cluster RCT of mHealth MBI for advanced cancer patients and their caregivers. Such remote interventions can be helpful particularly during the COVID-19 pandemic. This article is protected by copyright. All rights reserved.
Authors: Kubo, Ai; Kurtovich, Elaine; McGinnis, MegAnn; Aghaee, Sara; Altschuler, Andrea; Quesenberry, Charles; Kolevska, Tatjana; Liu, Raymond; Greyz-Yusupov, Natalya; Avins, Andrew
Psychooncology. 2020 Sep 26.
A Comparative Analysis of Online Medical Record Utilization and Perception by Cancer Survivorship
Cancer survivors face many challenges including coordinating care across multiple providers and maintaining medical records from multiple institutions. Access and utilization of online medical records could help cancer survivors manage this complexity. Here, we examined how cancer survivors differ from those without a history of cancer with regards to utilization and perception of medical records. We conducted a cross-sectional study of 3491 respondents, from the Health Information National Trends survey 5, cycle 2. The association of medical record utilization and perceptions with cancer survivorship was assessed using survey-weighted logistic regression. Cancer survivors (n=593) were more likely to report that a provider maintains a computerized medical record [adjusted odds ratio (AOR)=2.05; 95% confidence (CI), 1.24-3.41] and were more likely to report confidence in medical record safeguards (AOR=1.44; 95% CI, 1.03-2.03). However, cancer survivors were no more likely to access online medical records than those without a history of cancer (AOR=1.13; 95% CI, 0.69-1.86). Cancer survivors were no more likely to report privacy concerns as a reason for not accessing online medical records, however, survivors were more likely to report a preference for speaking directly with a provider as a reason for not accessing online medical records (AOR=2.24; 95% CI, 0.99-5.05). Although cancer survivors are more likely to trust medical record safe guards and do not express increased concerns about online medical record privacy, a preference to speak directly with provider is a barrier of use.
Authors: Khan S; Lewis-Thames MW; Han Y; Fuzzell L; Langston ME; Moore JX
Med Care. 2020 Sep 10.
Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts
Deciphering the shared genetic basis of distinct cancers has the potential to elucidate carcinogenic mechanisms and inform broadly applicable risk assessment efforts. Here, we undertake genome-wide association studies (GWAS) and comprehensive evaluations of heritability and pleiotropy across 18 cancer types in two large, population-based cohorts: the UK Biobank (408,786 European ancestry individuals; 48,961 cancer cases) and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging cohorts (66,526 European ancestry individuals; 16,001 cancer cases). The GWAS detect 21 genome-wide significant associations independent of previously reported results. Investigations of pleiotropy identify 12 cancer pairs exhibiting either positive or negative genetic correlations; 25 pleiotropic loci; and 100 independent pleiotropic variants, many of which are regulatory elements and/or influence cross-tissue gene expression. Our findings demonstrate widespread pleiotropy and offer further insight into the complex genetic architecture of cross-cancer susceptibility.
Authors: Rashkin, Sara R; Alexeeff, Stacey E; Corley, Douglas A; Kushi, Lawrence H; Van Den Eeden, Stephen K; Habel, Laurel A; Sakoda, Lori C; Witte, John S; et al.
Nat Commun. 2020 09 04;11(1):4423. Epub 2020-09-04.
Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses
Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2). Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
Authors: Seyed Khoei, Nazlisadat; Schafmayer, Clemens; Freisling, Heinz; et al.
BMC Med. 2020 09 03;18(1):229. Epub 2020-09-03.
Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk
Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
Authors: Thomas, Minta; Sakoda, Lori C; Lee, Jeffrey K; Corley, Douglas A; Hsu, Li; et al.
Am J Hum Genet. 2020 09 03;107(3):432-444. Epub 2020-08-05.
Obesity and related conditions and risk of inflammatory breast cancer: a nested case-control study
Inflammatory breast cancer (IBC) is a rare, poorly understood and aggressive tumor. We extended prior findings linking high body mass index (BMI) to substantial increased IBC risk by examining BMI associations before and after adjustment for well-characterized comorbidities using medical record data for diabetes, insulin resistance, and disturbances of cholesterol metabolism in a general community healthcare setting. We identified 247 incident IBC cases diagnosed at Kaiser Permanente Northern California between 2005 and 2017 and 2470 controls matched 10:1 on birth year and geographic area and with ≥ 13 months of continuous enrollment prior to diagnosis/index date. We assessed exposures from 6 years up to one year prior to the diagnosis/index date, using logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Before adjustment for comorbidities, ORs (95% CIs) for BMI of 25-< 30, 30-< 35, and ≥ 35 compared to < 25 kg/m2 were 1.5 (0.9-2.3), 2.0 (1.2-3.1), and 2.5 (1.4-4.4), respectively. After adjustment for pre-diabetes/diabetes, HDL-C and triglyceride levels, and dyslipidemia, corresponding ORs were 1.3 (0.8-2.1), 1.6 (0.9-2.9), and 1.9 (1.0-3.5). The OR for HDL-C levels < 50 mg/dL compared to ≥ 65 mg/dL was 2.0 (1.2-3.3) in the adjusted model. In a separate model the OR for a triglyceride/HDL-C ratio ≥ 2.50 compared to < 1.62 was 1.7 (1.1-2.8) after adjustment for BMI, pre-diabetes/diabetes, and dyslipidemia. Results did not differ significantly by estrogen receptor status. Obesity and measures of insulin resistance independently increased IBC risk as did obesity and low HDL-C levels. These findings, if confirmed, have implications for IBC prevention.
Authors: Schairer C; Laurent CA; Moy LM; Gierach GL; Caporaso NE; Pfeiffer RM; Kushi LH
Breast Cancer Res Treat. 2020 Sep;183(2):467-478. Epub 2020-07-20.
The 17-Gene Genomic Prostate Score Test as a Predictor of Outcomes in Men with Unfavorable Intermediate Risk Prostate Cancer
To evaluate the association of the Genomic Prostate Score (GPS) assay result with biochemical recurrence (BCR), distant metastases (DM), and prostate-specific death (PCD) in unfavorable intermediate (UFI) risk prostate cancer patients. The GPS assay is used to help guide management decisions for newly diagnosed low and favorable intermediate (FI) risk disease. GPS results from 2 studies (Center for Prostate Disease Research [CPDR]; Kaiser Permanente Northern California [KPNC]) in men treated with radical prostatectomy were analyzed to determine associations of the GPS result with BCR, DM, and PCD in UFI risk disease. Analyses included 299 intermediate risk prostate patients, 175 of whom had UFI risk disease (KPNC = 103; CPDR = 72). The GPS result as a dichotomous value (≤40 vs >40) was a significant predictor of BCR in UFI patients in multivariate analyses (hazard ratio [HR] 6.0; 95% confidence interval [CI] 2.0-22.4; P = .0035; CPDR). The GPS result was a strong predictor of all 3 endpoints in multivariate analyses (BCR HR 7.1; 95% CI 5.7-8.8; P < .0001; DM HR 5.4; 95% CI 3.8-7.8; P < .0001; PCD HR 3.4; 95% CI 1.5-8.9; P = .006; KPNC). UFI patients with GPS >40 had outcomes consistent with high-risk disease, whereas UFI patients with GPS ≤40 had outcomes similar to FI risk patients (CPDR/KPNC). The GPS result was a strong independent predictor of BCR, DM, and PCD in intermediate risk prostate cancer. UFI patients with GPS >40 have a poor prognosis and may benefit from additional therapeutic options.
Authors: Cullen J; Kuo HC; Shan J; Lu R; Aboushwareb T; Van Den Eeden SK
Urology. 2020 09;143:103-111. Epub 2020-06-07.
Association of Prediagnostic Frailty, Change in Frailty Status, and Mortality After Cancer Diagnosis in the Women’s Health Initiative
Understanding changes in frailty in relation to cancer diagnosis can inform optimal selection of cancer treatments and survivorship care. To investigate associations of prediagnostic frailty and change in frailty status with mortality after a cancer diagnosis. This multicenter, prospective cohort study included 7257 community-dwelling, postmenopausal women in the United States who had frailty assessed at the Women’s Health Initiative (WHI) enrollment (1993-1998) and the 3-year visit who were subsequently diagnosed as having invasive cancer. The data were analyzed from January 7, 2019, to June, 8, 2020. Frailty scores were defined from validated questionnaire items conceptually aligned with the Fried frailty phenotype, including at least 3 of the following characteristics: self-reported unintentional weight loss, exhaustion, low physical activity, and muscle weakness or impaired walking. Physical function components of the frailty score were updated a median of 10 (range, 1-18) times. Using multivariable-adjusted Cox proportional hazards models, this study examined associations of prediagnostic frailty (at the 3-year visit, before cancer diagnosis) and prediagnostic changes in frailty (from enrollment to the 3-year visit) with mortality. Women were followed up beginning from cancer diagnosis for mortality outcomes through March 2018. In linear mixed-effects models with frailty scores as a function of time since cancer diagnosis, this study evaluated whether the time slope, ie, the rate of change in frailty score, increased after cancer diagnosis. This study included 7257 women in the WHI cohort who completed frailty assessments at enrollment and the 3-year WHI visit before cancer diagnosis and subsequently developed cancer. Cancer cases included 2644 breast cancers (36%), 822 lung cancers (11%), 691 colorectal cancers (10%), 445 endometrial cancers (6%), and 286 ovarian cancers (4%). At the 3-year visit, prior to cancer diagnosis, the mean (SD) age was 63 (7) years, and 1161 of 7257 (16%) of participating women met criteria for frailty; 2129 of 7257 (29%) were prefrail, and 3967 of 7257 (55%) were nonfrail. Over a median follow-up of 5.8 years after cancer diagnosis (range, 1 day to 19.9 years), 3056 women died. After multivariable adjustment, women who were frail (vs nonfrail) before cancer diagnosis had an increased risk of mortality after cancer diagnosis (hazard ratio [HR], 1.40; 95% CI, 1.26-1.55; P for trend <.001). Sustained frailty (21% [1537 of 7257] of women) or worsening frailty (22% [1578 of 7257]) vs being consistently nonfrail (45% [3266 of 7257]) before cancer diagnosis increased the risk of mortality after cancer diagnosis (HR, 1.25; 95% CI, 1.14-1.38 and 1.22; 95% CI, 1.11-1.34, respectively; P for trend <.001). In linear mixed-effects models, the rate of increase in physical frailty over time was statistically significantly higher after cancer diagnosis. Sustained and worsening frailty before cancer diagnosis was associated with an increased risk of mortality after cancer diagnosis in postmenopausal women. Furthermore, the rate of decline in physical function accelerated after cancer diagnosis. Frailty assessment could provide valuable information and perhaps prompt interventions to reduce and preempt worsening of physical frailty after cancer diagnosis.
Authors: Cespedes Feliciano, Elizabeth M; Hohensee, Chancellor; Rosko, Ashley E; Anderson, Garnet L; Paskett, Electra D; Zaslavsky, Oleg; Wallace, Robert B; Caan, Bette J
JAMA Netw Open. 2020 09 01;3(9):e2016747. Epub 2020-09-01.
Myocardial infarction accelerates breast cancer via innate immune reprogramming
Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity1 or surgery2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors3-5. While elevated risk and incidence of cardiovascular events in breast cancer is well established, whether such events impact cancer pathogenesis is not known. Here we show that myocardial infarction (MI) accelerates breast cancer outgrowth and cancer-specific mortality in mice and humans. In mouse models of breast cancer, MI epigenetically reprogrammed Ly6Chi monocytes in the bone marrow reservoir to an immunosuppressive phenotype that was maintained at the transcriptional level in monocytes in both the circulation and tumor. In parallel, MI increased circulating Ly6Chi monocyte levels and recruitment to tumors and depletion of these cells abrogated MI-induced tumor growth. Furthermore, patients with early-stage breast cancer who experienced cardiovascular events after cancer diagnosis had increased risk of recurrence and cancer-specific death. These preclinical and clinical results demonstrate that MI induces alterations in systemic homeostasis, triggering cross-disease communication that accelerates breast cancer.
Authors: Koelwyn GJ; Caan BJ; Moore KJ; et al.
Nat Med. 2020 09;26(9):1452-1458. Epub 2020-07-13.
Dietary Intakes of Women’s Health Initiative Long Life Study Participants Falls Short of the Dietary Reference Intakes
Understanding how nutrient intake in older women compares with recommendations is important. The Academy of Nutrition and Dietetics position statement summarizes the nutrient needs of older adults (aged ≥60 years) based on a systematic review. The objective of this study was to compare nutrient intake of Women’s Health Initiative Long Life Study participants to the Dietary Reference Intakes for nutrients reviewed in the Academy of Nutrition and Dietetics position statement. The study is a cross-sectional analysis. Participants (n=7,875) were mailed the General Nutrition Assessment Food Frequency Questionnaire during 2012-2013, of whom 77% (n=6,095) completed it, and 5,732 were included in the analytic sample after exclusion for implausible energy intakes. Mean intake of energy and protein, calcium, fiber, folate, potassium, sodium, vitamins B-12, D, E, and K were described overall and compared with recommendations. Demographic and lifestyle characteristics were summarized using descriptive statistics. The proportion of participants meeting recommendations was computed. Mean age of completers was 79±7 years and 53.5% were non-Hispanic white, 30% were non-Hispanic black, and 16.5% were Hispanic/Latina. Only one-third of women consumed ≥21 g/day fiber, whereas fewer met the Recommended Dietary Allowance for calcium (18.6%), vitamin E (16.9%), and vitamin D (1.7%). Just more than half (56%) of participants met the Recommended Dietary Allowance for protein of 0.8 g/kg body weight/day, and just less than half (47.0%) met potassium guidelines. These findings suggest older women within the Women’s Health Initiative were generally not achieving recommended intake for several key nutrients highlighted by the Academy of Nutrition and Dietetics position statement. These findings underscore the need to identify effective approaches for improving the nutrient density of dietary intake in older women.
Authors: Beasley JM; Rillamas-Sun E; Tinker LF; Wylie-Rosett J; Mossavar-Rahmani Y; Datta M; Caan BJ; LaCroix AZ
J Acad Nutr Diet. 2020 09;120(9):1530-1537. Epub 2020-07-14.
Telomere maintenance variants and survival after colorectal cancer: Smoking- and sex-specific associations
Telomeres play an important role in colorectal cancer prognosis. Variation in telomere maintenance genes may be associated with survival after colorectal cancer diagnosis, but evidence is limited. In addition, possible interactions between telomere maintenance genes and prognostic factors, such as smoking and sex, also remain to be investigated. We conducted gene-wide analyses of colorectal cancer prognosis in 4,896 invasive colorectal cancer cases from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO); 1,871 common variants within 13 telomere maintenance genes were included. Cox models were fit to estimate associations of these variants individually with overall and colorectal cancer-specific survival. Likelihood ratio tests were used to test for interaction by smoking and sex. P values were adjusted using Bonferroni correction. The association between minor allele of rs7200950 (ACD) with colorectal cancer-specific survival varied significantly by smoking pack-years (corrected P = 0.049), but no significant trend was observed. By sex, minor alleles for rs2975843 (TERF1), rs75676021 (POT1), and rs74429678 (POT1) were associated with decreased overall and/or colorectal cancer-specific survival in women but not in men. Our study reported a gene-wide statistically significant interaction with sex (TERF1, POT1). Although significant interaction by smoking pack-years (ACD) was observed, there was no evidence of a dose response. Validation of these findings in other large studies and further functional annotation on these SNPs are warranted. Our study found a gene-smoking and gene-sex interaction on survival after colorectal cancer diagnosis, providing new insights into the role of genetic polymorphisms in telomere maintenance on colorectal cancer prognosis.
Authors: Yin H; Sakoda LC; Newcomb PA; et al.
Cancer Epidemiol Biomarkers Prev. 2020 09;29(9):1817-1824. Epub 2020-06-25.
Sustained weight loss and risk of breast cancer in women ≥50 years: a pooled analysis of prospective data
Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk. Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up. Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2-4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5-<9 kg lost: HR = 0.75, 95% CI = 0.63 to 0.90; ≥9 kg lost: HR = 0.68, 95% CI = 0.50 to 0.93). Women who lost at least 9 kg and gained back some (but not all) of it were also at a lower risk of breast cancer. Other patterns of weight loss and gain over the two intervals had a similar risk of breast cancer to women with stable weight. These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.
Authors: Teras LR; Caan BJ; Smith-Warner SA; et al.
J Natl Cancer Inst. 2020 09 01;112(9):929-937.
Post-diagnosis dietary insulinemic potential and survival outcomes among colorectal cancer patients.
BACKGROUND: The empirical dietary index for hyperinsulinemia (EDIH) score is a validated food-based dietary score that assesses the ability of whole-food diets to predict plasma c-peptide concentrations. Although the EDIH has been extensively applied and found to be predictive of risk of developing major chronic diseases, its influence on cancer survival has not been evaluated. We applied the EDIH score in a large cohort of colorectal cancer patients to assess the insulinemic potential of their dietary patterns after diagnosis and determine its influence on survival outcomes. METHODS: We calculated EDIH scores to assess the insulinemic potential of post-diagnosis dietary patterns and examined survival outcomes in a sample of 1718 stage I-III colorectal cancer patients in the Nurses’ Health Study and Health Professionals Follow-up Study cohorts. Multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer-specific mortality and all-cause mortality. We also examined the influence of change in diet from pre- to post-diagnosis period, on mortality. RESULTS: During a median follow-up of 9.9 years, there were 1008 deaths, which included 272 colorectal cancer-specific deaths (27%). In the multivariable-adjusted analyses, colorectal cancer patients in the highest compared to lowest EDIH quintile, had a 66% greater risk of dying from colorectal cancer: HR, 1.66; 95% CI, 1.03, 2.69; and a 24% greater risk of all-cause death: HR, 1.24; 95%CI, 0.97, 1.58. Compared to patients who consumed low insulinemic diets from pre- to post-diagnosis period, patients who persistently consumed hyperinsulinemic diets were at higher risk of colorectal cancer death (HR,1.51; 95%CI, 0.98, 2.32) and all-cause death (HR, 1.31; 95%CI, 1.04, 2.64). CONCLUSION: Our findings suggest that a hyperinsulinemic dietary pattern after diagnosis of colorectal cancer is associated with poorer survival. Interventions with dietary patterns to reduce insulinemic activity and impact survivorship are warranted.
Authors: Tabung FK; Noonan A; Lee DH; Song M; Clinton SK; Spakowicz D; Wu K; Cheng E; Meyerhardt JA; Fuchs CS; Giovannucci EL
BMC Cancer. 2020 Aug 27;20(1):817. doi: 10.1186/s12885-020-07288-0.
Social Relationships and Risk of Type 2 Diabetes Among Postmenopausal Women
We examined whether social relationship variables (social support, social strain, social network size, and stressful life events) were associated with risk of developing type 2 diabetes among postmenopausal women. 139,924 postmenopausal women aged 50-79 years without prevalent diabetes at baseline were followed for a mean of 14 years. 19,240 women developed diabetes. Multivariable Cox proportional hazard models tested associations between social relationship variables and diabetes incidence after consideration of demographics, depressive symptoms, and lifestyle behaviors. We also examined moderating effects of obesity and race/ethnicity, and we tested whether social variable associations were mediated by lifestyle or depressive symptoms. Compared with the lowest quartile, women in the highest social support quartile had lower risk of diabetes after adjusting for demographic factors, health behaviors, and depressive symptoms (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.89-0.97). Social strain (HR = 1.09, 95% CI = 1.04-1.13) and stressful life events (HR = 1.10, 95% CI = 1.05-1.15) were associated with higher diabetes risks. The association between diabetes and social strain was stronger among African American women. Social relationship variables had direct relationships to diabetes, as well as indirect effects partially mediated by lifestyle and depressive symptoms. Social support, social strain, and stressful life events were associated with diabetes risk among postmenopausal women independently of demographic factors and health behaviors. In addition to healthy behaviors such as diet and physical activity, healthy social relationships among older women may be important in the prevention of diabetes.
Authors: Hendryx M; Nicholson W; Manson JE; Kroenke CH; Lee J; Weitlauf JC; Garcia L; Jonasson JM; Wactawski-Wende J; Luo J
J Gerontol B Psychol Sci Soc Sci. 2020 08 13;75(7):1597-1608.
Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location
Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided. Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors. We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.
Authors: Labadie, Julia D; Sakoda, Lori C; Newcomb, Polly A; et al.
2020 Aug;4(5):pkaa042. Epub 2020-05-19.
Urinary polycyclic aromatic hydrocarbons in relation to anthropometric measures and pubertal development in a cohort of Northern California girls
Polycyclic aromatic hydrocarbons (PAHs) are a class of ubiquitous, environmental chemicals that may have endocrine disrupting capabilities. We investigated whether childhood exposure to PAHs was associated with adiposity and pubertal timing in a longitudinal study of 404 girls enrolled in the Northern California site of the Breast Cancer and the Environment Research Program cohort. Baseline urinary samples from girls aged 6-8-years-old were assayed for 2-naphthol, fluorene metabolites, phenanthrene metabolites, 1-hydroxypyrene, and sum of PAH metabolites. Mixed-effects linear models were used to estimate how concentrations of PAH metabolites were related to changes in girl’s body mass index (BMI) and waist-to-height ratio from age 7 through 16 years old. Accelerated failure time models were used to estimate age of pubertal onset (Tanner stages 2 or higher for breast and pubic hair development). Higher adiposity measurements among high tertiles of baseline PAH metabolites were evident at age 7 years old and increased thereafter (i.e., BMI for all PAH metabolites, waist-to-height ratio for fluorene and phenanthrene metabolites) or leveled off (i.e., waist-to-height ratio for 2-naphthol, 1-hydroxypyrene, sum of PAHs). Among girls overweight/obese at baseline, median age of breast development onset for high tertiles was 9.1-9.4 years old compared with 10-10.2 years old for low tertiles for all PAH metabolites; in contrast, found no association or slightly later onset of breast development for girls with normal weight at baseline. These results suggest that exposure to specific PAHs during childhood may influence adiposity throughout adolescence and effect pubertal timing.
Authors: Dobraca, Dina; Laurent, Cecile A; Greenspan, Louise C; Hiatt, Robert A; Sjödin, Andreas; Kushi, Lawrence H; Windham, Gayle C
Environ Epidemiol. 2020 Aug;4(4):e0102. Epub 2020-07-06.
Postdiagnosis Physical Activity: Association With Long-Term Fatigue and Sleep Disturbance in Older Adult Breast Cancer Survivors
Physical activity is frequently proposed as an intervention to reduce fatigue and sleep disturbance in cancer survivors; however, the long-term effects of physical activity are often not reported, and older adults are typically excluded from these intervention studies. This article aimed to examine if postdiagnosis physical activity is associated with lower long-term fatigue and sleep disturbance in older adult breast cancer survivors. Data were analyzed of a prospective cohort of 440 breast cancer survivors aged 65 years or older from the Women’s Health Initiative study. Multiple linear and logistic regression models were used to examine associations of physical activity with fatigue and sleep disturbance. Higher postdiagnosis physical activity was associated with lower long-term fatigue but was not associated with lower sleep disturbance after adjusting for demographics, cancer characteristics, and baseline measures.
Authors: Vasbinder A; Reding KW; Wang D; Han CJ; Zaslavsky O; Langford D; Cespedes Feliciano EM; Barrington WE; Paskett ED
Clin J Oncol Nurs. 2020 08 01;24(4):381-391.
Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels
Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels. In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered. We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3, and CD300LG) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered (P=6.65×10-6 for the interaction test) and replicated at nominal significance level (P=0.013) in SMC5. In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.
Authors: Wang Z; Sitlani CM; CHARGE Gene-Lifestyle Interactions Working Group; et al.
Circ Genom Precis Med. 2020 08;13(4):e002772. Epub 2020-06-08.
Prediagnostic serum polychlorinated biphenyl concentrations and primary liver cancer: A case-control study nested within two prospective cohorts
Polychlorinated biphenyls (PCBs) were used in electrical equipment and a range of construction materials. Although banned in the United States and most of Europe in the 1970s, they are highly persistent in the environment and bioaccumulate. Whether PCBs are associated with liver cancer risk at general population levels is unknown. This study consisted of 136 incident liver cancer cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the Norwegian Janus cohort. Sera collected in the 1960s-1980s were measured for 37 PCB congeners and markers of hepatitis B (HBV) and C (HCV) infection. Odds ratios (OR) and 95% confidence intervals (CI) for tertiles of each lipid-adjusted PCB were estimated from conditional logistic regression. We also examined the molar sum of congeners in groups: total PCBs; low, medium, and high chlorination; and Wolff functional groups. Concentrations of individual congeners from the 1960s/1970s sera ranged from 1.3-123.0 and 1.4-116.0 ng/g lipid among MHC cases and controls, respectively, and from 1.9-258.0 and 1.9-271.0 ng/g lipid among Janus cases and controls, respectively. Among MHC participants with sera from the 1960s, collected an average of 27 years before diagnosis among cases, the top tertile of PCBs 151, 170, 172, 177, 178, 180, and 195 was significantly associated with elevated odds of liver cancer (OR range = 2.01-2.38); most of these congeners demonstrated exposure-response trends. For example, ORtertile 3vs1 = 2.38 (95% CI: 1.22-4.64, p-trend = 0.01) for PCB 180. As a group, Wolff group 1b congeners, which are biologically persistent and weak phenobarbital inducers, were associated with increased odds. In MHC participants, ever vs. never HBV or HCV infection modified the PCB-liver cancer associations. There was little evidence of an association between PCBs and odds of liver cancer among the Janus cohort. We observed associations between a number of PCB congeners and increased odds of liver cancer among MHC, but not Janus, participants with sera from the 1960s/1970s.
Authors: Niehoff NM; Zabor EC; Satagopan J; Widell A; O'Brien TR; Zhang M; Rothman N; Grimsrud TK; Van Den Eeden SK; Engel LS
Environ Res. 2020 08;187:109690. Epub 2020-05-20.
Social Support, Social Network Size, Social Strain, Stressful Life Events, and Coronary Heart Disease in Women With Type 2 Diabetes: A Cohort Study Based on the Women’s Health Initiative
We studied associations between social support, social network size, social strain, or stressful life events and risk of coronary heart disease (CHD) in postmenopausal women with type 2 diabetes. From the Women’s Health Initiative, 5,262 postmenopausal women with type 2 diabetes at baseline were included. Cox proportional hazards regression models adjusted for demographics, depressive symptoms, anthropometric variables, and lifestyle factors were used to examine associations between social factors and CHD. A total of 672 case subjects with CHD were observed during an average 12.79 (SD 6.29) years of follow-up. There was a significant linear trend toward higher risk of CHD as the number of stressful life events increased (P for trend = 0.01; hazard ratio [HR] [95% CI] for the third and fourth quartiles compared with first quartile: 1.27 [1.03-1.56] and 1.30 [1.04-1.64]). Being married or in an intimate relationship was related to decreased risk of CHD (HR 0.82 [95% CI 0.69-0.97]). Among postmenopausal women with type 2 diabetes, higher levels of stressful life events were associated with higher risk of CHD. Experience of stressful life events might be considered as a risk factor for CHD among women with type 2 diabetes.
Authors: Miao Jonasson J; Kroenke CH; Luo J; et al.
Diabetes Care. 2020 08;43(8):1759-1766. Epub 2020-06-04.
Lifestyle and Psychosocial Patterns and Diabetes Incidence Among Women with and Without Obesity: a Prospective Latent Class Analysis
We conducted latent class analyses to identify women with homogeneous combinations of lifestyle and behavioral variables and tested whether latent classes were prospectively associated with diabetes incidence for women with or without baseline obesity. A total of 64,710 postmenopausal women aged 50-79 years without prevalent diabetes at baseline (years 1993-1998) were followed until 2018 with a mean follow-up of 14.6 years (sd = 6.4). Lifestyle variables included smoking, diet quality, physical activity, and sleep quality. Psychosocial variables included social support, depression, and optimism. Multivariable Cox proportional hazards regression models tested associations between latent classes and diabetes incidence controlling for age, race/ethnicity, and education. During follow-up, 8076 (12.4%) women developed diabetes. For women without baseline obesity, five latent classes were identified. Compared with a lower risk referent, diabetes incidence was higher in classes characterized by high probability of multiple lifestyle and psychosocial risks (HR = 1.45; 95% CI 1.28, 1.64), poor diet and exercise (HR = 1.23; 95% CI 1.13, 1.33), and psychosocial risks alone (HR = 1.20; 95% CI 1.12, 1.29). For women with baseline obesity, four latent classes were identified. Compared with a lower risk referent, diabetes incidence was higher for women with obesity in classes characterized by high probability of multiple lifestyle and psychosocial risks (HR = 1.48; 95% CI 1.32, 1.66), poor diet and exercise (HR = 1.32; 95% CI 1.19, 1.47), and intermediate probabilities of multiple risks (HR = 1.17; 95% CI 1.05, 1.30). Diabetes prevention efforts that focus on diet and exercise may benefit from attention to how lifestyle behaviors interact with psychosocial variables to increase diabetes risks, and conversely, how psychological or social resources may be leveraged with lifestyle changes to reduce the risk for women with and without obesity.
Authors: Hendryx M; Dinh P; Chow A; Kroenke CH; Hingle M; Shadyab AH; Garcia L; Howard BV; Luo J
Prev Sci. 2020 08;21(6):850-860.
Cardiovascular Outcomes in Relation to Antihypertensive Medication Use in Women with and Without Cancer: Results from the Women’s Health Initiative
Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard clinical endpoints. Within a prospective study, we examined the risk of heart failure (HF) and coronary heart disease (CHD) events in relation to use of commonly used antihypertensive medications, including ACEis/ARBs, BBs, calcium channel blockers (CCB), and diuretics, comparing women with and without cancer. In a cohort of 56,997 Women’s Health Initiative study participants free of cardiovascular disease who received antihypertensive treatment, we used multivariable-adjusted Cox regression models to calculate the hazard ratios (HRs) of developing CHD, HF, and a composite outcome of cardiac events (combining CHD and HF) in relation to use of ACEis/ARBs, CCBs, or diuretics versus BBs, separately in women with and without cancer. Whereas there was no difference in risk of cardiac events comparing ACEi/ARB with BB use among cancer-free women (HR = 0.99 [0.88-1.12]), among cancer survivors ACEi/ARB users were at a 2.24-fold risk of total cardiac events (1.18-4.24); p-interaction = .06). When investigated in relation to CHD only, an increased risk was similarly observed in ACEi/ARB versus BB use for cancer survivors (HR = 1.87 [0.88-3.95]) but not in cancer-free women (HR = 0.91 [0.79-1.06]; p-interaction = .04). A similar pattern was also seen in relation to HF but did not reach statistical significance (p-interaction = .23). These results from this observational study suggest differing risks of cardiac events in relation to antihypertensive medications depending on history of cancer. Although these results require replication before becoming actionable in a clinical setting, they suggest the need for more rigorous examination of the effect of antihypertensive choice on long-term cardiac outcomes in cancer survivors. Although additional research is needed to replicate these findings, these data from a large, nationally representative sample of postmenopausal women indicate that beta blockers are favorable to angiotensin-converting enzyme inhibitors in reducing the risk of cardiac events among cancer survivors. This differs from the patterns observed in a noncancer cohort, which largely mirrors what is found in the randomized clinical trials in the general population.
Authors: Reding KW; Habel LA; Chlebowski RT; et al.
Oncologist. 2020 08;25(8):712-721. Epub 2020-04-06.
Increased Risk of Colorectal Cancer in Individuals With a History of Serrated Polyps
Serrated polyp (SPs) are precursors to 20% to 30% of cases of colorectal tumors, but patients’ long-term risk after removal of SPs is poorly understood. We investigated the risk of colorectal cancer (CRC) in individuals with a history of SPs. We performed a retrospective cohort study of Kaiser Permanente Northern California members who underwent colonoscopy from 2006 through 2016. Study participants were categorized based on the size and location of SPs. We used Cox proportional hazards modeling to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association of CRC diagnosed more than 1 year after colonoscopy, with polyp type vs no polyp after adjustment for year of colonoscopy, age, sex, race/ethnicity, and smoking history. The study included 233,393 individuals, of whom 445 developed incident CRC. At 10 years, the cumulative incidence rates of CRC for individuals with no polyp, proximal small SPs, proximal large SPs, and distal SPs were 4.7 (95% CI, 4.0-5.6), 14.8 (95% CI, 9.0-24.3), 30.2 (95% CI, 13.2-68.4), and 5.9 (95% CI, 3.6-9.5) per 1000 persons, respectively. In patients with SPs, risk of CRC was not increased until 3 years or more after the first colonoscopy (HR for small proximal SPs 2.6; 95% CI, 1.7-3.9 and HR for large proximal SPs 8.0; 95% CI, 3.6-16.1). The presence of synchronous adenomas increased the risk for CRC (HR for proximal SPs with synchronous adenomas 4.0; 95% CI, 3.0-5.5 and HR for distal SPs with synchronous adenomas 2.4; 95% CI, 1.7-3.4). In a retrospective analysis of a large cohort of individuals examined by colonoscopy, we found that risk of incident CRC increased in individuals with proximal SPs (large SPs in particular) 3 years or more after the colonoscopy. These findings support guidelines that recommend surveillance colonoscopy for individuals with SPs.
Authors: Li D; Liu L; Fevrier HB; Alexeeff SE; Doherty AR; Raju M; Amsden LB; Lee JK; Levin TR; Corley DA; Herrinton LJ
Gastroenterology. 2020 08;159(2):502-511.e2. Epub 2020-04-08.
Associations between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Liver Cancer Among Post-Menopausal Women
In almost all countries, incidence rates of liver cancer (LC) are 100%-200% higher in males than in females. However, this difference is predominantly driven by hepatocellular carcinoma (HCC), which accounts for 75% of LC cases. Intrahepatic cholangiocarcinoma (ICC) accounts for 12% of cases and has rates only 30% higher in males. Hormones are hypothesized to underlie observed sex differences. We investigated whether prediagnostic circulating hormone and sex hormone binding globulin (SHBG) levels were associated with LC risk, overall and by histology, by leveraging resources from five prospective cohorts. Seven sex steroid hormones and SHBG were quantitated using gas chromatography/tandem mass spectrometry and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 postmenopausal female LC cases (HCC, n = 83; ICC, n = 56) and 426 controls, matched on sex, cohort, age, race/ethnicity, and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between a one-unit increase in log2 hormone value (approximate doubling of circulating concentration) and LC were calculated using multivariable-adjusted conditional logistic regression. A doubling in the concentration of 4-androstenedione (4-dione) was associated with a 50% decreased LC risk (OR = 0.50; 95% CI = 0.30-0.82), whereas SHBG was associated with a 31% increased risk (OR = 1.31; 95% CI = 1.05-1.63). Examining histology, a doubling of estradiol was associated with a 40% increased risk of ICC (OR = 1.40; 95% CI = 1.05-1.89), but not HCC (OR = 1.12; 95% CI = 0.81-1.54). This study provides evidence that higher levels of 4-dione may be associated with lower, and SHBG with higher, LC risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease LC risk. Indeed, estradiol may be associated with an increased ICC risk.
Authors: Petrick JL; Van Den Eeden SK; McGlynn KA; et al.
Hepatology. 2020 08;72(2):535-547.
Clinical Utilization and Cost of Thrombophilia Testing in Patients with Venous Thromboembolism.
Introduction Testing for inherited and acquired thrombophilias adds to the cost of care of patients with venous thromboembolism (VTE), though results may not influence patient management. Methods This is a single-center, retrospective study conducted at Emory University Hospitals from January to December 2015 to (1) determine the pattern of thrombophilia testing in patients with VTE, (2) study the impact of results of thrombophilia testing on clinical decision-making, and (3) determine the direct costs of thrombophilia testing in patients with VTE. Results Of the 266 eligible patients, 189 (71%) underwent testing; 51 (26.9%) tested positive and the results impacted management in 32 (16.9%) of tested patients. Patient undergoing testing were more likely to be younger than 40 years (30.9 vs. 18.2%), have had prior pregnancy loss (9.0 vs. 0%), or known family history of hypercoagulability (24.9 vs. 10.4%), and were less likely to have had provoked VTE (37 vs. 79.2%). The most common thrombophilias tested were antiphospholipid syndrome (60.1%), factor V Leiden (59.7%), and prothrombin gene mutation (57.5%). Direct costs of thrombophilia testing were $2,364.32 per patient, $12,331.55 to diagnose 1 positive, and $19,653.41 per patient-management affected. Conclusion We noted significant variability in selection of patients and panel of tests, sparse utilization of test results in patient management, but high cost associated with thrombophilia testing in patients with VTE. With guidelines advocating selective use of thrombophilia testing and attention to potential impact of test results in patient management, we propose the need for measures at institutional levels to improve test-ordering practices.
Authors: Gaddh M; Cheng E; Elsebaie MAT; Bodo I
TH Open. 2020 Aug 9;4(3):e153-e162. doi: 10.1055/s-0040-1714334. eCollection 2020 Jul.
Geographic Variations of Potentially Curative Treatments for Hepatocellular Carcinoma in the United States: A SEER-Medicare Study.
BACKGROUND: Transplantation, surgical resection, radiofrequency ablation, and percutaneous ethanol injection are generally considered potentially curative treatments for patients with hepatocellular carcinoma (HCC). With the increasing incidence of HCC, it is critical to investigate geographic variations in curative treatments and their associations with survival among patients. METHODS: A total of 6,782 patients with HCC during 2004 to 2011 were identified in the SEER-Medicare linked database and placed in quartiles based on the proportions undergoing potentially curative treatments per hospital referral region (HRR). Hierarchical Cox proportional hazards models were used to examine the association between regional potentially curative treatment patterns and survival across quartiles. RESULTS: An average of 16.9% of patients with HCC underwent potentially curative treatments during 2004 to 2011, varying substantially from 0% to 34.5% across HRRs. Compared with patients residing in the lowest-quartile regions, those in the highest-quartile regions were more likely to be of other races (vs white or black), be infected with hepatitis B virus, and have more comorbidities. The 5-year survival was 4.7% in the lowest-quartile regions and 11.4% in the highest-quartile regions (P<.001). After controlling for confounders, patients in the highest-quartile regions had a lower risk of mortality (adjusted hazard ratio, 0.78; 95% CI, 0.72-0.85). CONCLUSIONS: Patients with HCC who resided in HRRs with higher proportions of potentially curative treatments had better survival. Given its proven survival benefits, prompt clinical and policy actions are needed to reduce variations in treatment utilization.
Authors: Cheng E; Hung P; Wang SY
J Natl Compr Canc Netw. 2020 Jun;18(6):729-736. doi: 10.6004/jnccn.2020.7529.
Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention-sponsored summit
Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.
Authors: Gupta S; Levin TR; Pignone M; et al.
CA Cancer J Clin. 2020 07;70(4):283-298. Epub 2020-06-25.
American Cancer Society guideline for diet and physical activity for cancer prevention
The American Cancer Society (ACS) publishes the Diet and Physical Activity Guideline to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. This guideline is developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and reflects the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS guideline focuses on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. This 2020 ACS guideline is consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes as well as for general health promotion, as defined by the 2015 to 2020 Dietary Guidelines for Americans and the 2018 Physical Activity Guidelines for Americans.
Authors: Rock CL; Kushi LH; Caan BJ; Doyle C; et al.
CA Cancer J Clin. 2020 07;70(4):245-271. Epub 2020-06-09.
Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments. To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci. We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by ABO, which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production. We identified 38 candidates of protein biomarkers for PDAC risk. This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.
Authors: Zhu J; Van Den Eeden SK; Wu L; et al.
Cancer Epidemiol Biomarkers Prev. 2020 07;29(7):1501-1508. Epub 2020-05-21.
Systemic Therapy of Extensive Stage Small Cell Lung Cancer in the Era of Immunotherapy.
In March 2019, the FDA approved the use of the anti-programmed death ligand 1 (PD-L1) antibody atezolizumab, as a first-line treatment option in combination with platinum-etoposide (PE) for patients with extensive stage small cell lung cancer (ED SCLC) based upon the results of the IMpower133 trial. More recently, the FDA approved the anti-PD-L1 antibody durvalumab in March 2020 , also in the frontline setting for SCLC based upon the results of the CASPIAN trial. Both these trials demonstrated a small, but significant overall survival (OS) benefit with the addition of a PD-L1 antibody to standard chemotherapy in the treatment of ED SCLC, thereby altering the treatment paradigm for this aggressive disease. Previously, the FDA had approved the anti-PD1 antibodies nivolumab and pembrolizumab as single-agent third-line treatment options based upon encouraging phase 1/2 data in patients with relapsed SCLC who had not received prior immunotherapy (IO). Despite these recent advances, the overall benefit of IO in SCLC remains somewhat disappointing in comparison with the results seen in non-small cell lung cancer (NSCLC). To date, no reliable biomarkers exist to predict responsiveness to IO in SCLC, and the utility of second- or third-line immunotherapy is questionable in patients who have received IO as part of first-line treatment. There has also been minimal success in identifying targetable mutations in SCLC. Novel approaches include combination approaches with IO, including PARP inhibitors and CDK inhibitors. Few ongoing trials, however, have enrolled patients who have received frontline immunotherapy given the only recent change in standard of care. Consequently, the results of current trials evaluating second- and third-line therapies need to be interpreted and translated into clinical practice with caution. The most significant challenge in SCLC remains the identification of molecular targets for which drugs can be developed that can improve survival over the current standard of care.
Authors: Ragavan, Meera;Das, Millie
Curr Treat Options Oncol. 2020 Jun 29;21(8):64. doi: 10.1007/s11864-020-00762-8..
Understanding sex disparities in lung cancer incidence: are women more at risk?
Authors: Ragavan, Meera V;Patel, Manali I
Lung Cancer Manag. 2020 Jun 22;9(3):LMT34. doi: 10.2217/lmt-2020-0013..
The Diet of Higher Insulinemic Potential Is Not Associated with Worse Survival in Patients with Stage III Colon Cancer (Alliance).
BACKGROUND: Hyperinsulinemia is considered to be important in the development of colon cancer, but few studies have investigated the associations of hyperinsulinemia with colon cancer survival via dietary scores. METHODS: Empirical dietary index for hyperinsulinemia (EDIH) was derived to assess the insulinemic potential of daily diets reflecting the long-term insulin exposure, with higher (more positive) scores indicating higher insulinemic diets. We prospectively estimated the HRs and 95% confidence intervals (CI) to investigate the association of EDIH with disease-free, recurrence-free, and overall survival among patients with stage III colon cancer (1999-2009) enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803). RESULTS: Of 1,024 patients (median follow-up: 7.3 years), 311 died, 350 had recurrences, and 394 had events for disease-free survival. Compared with patients in the lowest quintile of EDIH, the corresponding HRs of patients in the highest quintile for disease-free survival events, cancer recurrence, and overall mortality were 0.80 (95% CI, 0.56-1.15), 0.76 (95% CI, 0.51-1.11), and 0.77 (95% CI, 0.52-1.14). CONCLUSIONS: Higher EDIH was not associated with the risk of colon cancer recurrence or mortality in this population of patients with stage III colon cancer. IMPACT: EDIH, as a measure of dietary insulinemic potential, may be associated with colon cancer risk but not survival in patients with late-stage colon cancer.
Authors: Cheng E; Zhang S; Ou FS; Mullen B; Ng K; Saltz LB; Niedzwiecki D; Mayer RJ; Mowat RB; Whittom R; Hantel A; Benson A; Atienza D; Messino M; Kindler H; Giovannucci EL; Van Blarigan EL; Meyerhardt JA; Fuchs CS
Cancer Epidemiol Biomarkers Prev. 2020 Aug;29(8):1692-1695. doi: 10.1158/1055-9965.EPI-19-1454. Epub 2020 Jun 4.
Distinct trajectories of moderate to vigorous physical activity and sedentary behavior following a breast cancer diagnosis: the Pathways Study
To identify distinct trajectories of total moderate-to-vigorous physical activity (MVPA) and sedentary behavior following a breast cancer diagnosis and their correlates. The analysis examined 3000 female breast cancer survivors within Kaiser Permanente Northern California between 2006 and 2013. Self-reported time spent on total MVPA and sedentary behaviors were assessed at baseline (mean = 1.8 months post-diagnosis) and at 6 and 24 months follow up. Trajectory groups were identified using group-based trajectory modeling and K-means for longitudinal data analysis. Trajectory groups were named by baseline activity level (high, medium, or low) and direction of change (increaser, decreaser, or maintainer). Trajectory analyses identified three MVPA trajectories [high decreaser (7%), medium decreaser (35%), low maintainer (58%)] and four sedentary behavior trajectories [high maintainer (18%), high decreaser (27%), low increaser (24%), and low maintainer (31%)]. Women with higher education (ORs: 1.63-4.37), income (OR: 1.37), dispositional optimism (ORs: 1.60-1.86), and social support (OR: 1.33) were more likely to be high or medium decreasers of MVPA (all P < 0.05). High maintainers and high decreasers of sedentary behavior were more likely to have higher education (OR: 1.84) and social support (ORs: 1.42-1.86), but lower income (OR: 0.66; all P < 0.05). In the 24 months following breast cancer diagnosis, 42% of survivors decreased MVPA and 73% maintained or increased time on sedentary behavior. Socioeconomic status and stress coping at diagnosis predicted subsequent PA trajectory. It is important to prioritize exercise intervention and counseling during early stage of breast cancer survivorship, especially in survivors who are at high risk of becoming physically inactive post-diagnosis.
Authors: Shi Z; Rundle A; Genkinger JM; Cheung YK; Ergas IJ; Roh JM; Kushi LH; Kwan ML; Greenlee H
J Cancer Surviv. 2020 06;14(3):393-403. Epub 2020-03-04.
ANALYSES OF PREVENTIVE CARE MEASURES WITH INCOMPLETE HISTORICAL DATA IN ELECTRONIC MEDICAL RECORDS: AN EXAMPLE FROM COLORECTAL CANCER SCREENING
The calculation of quality of care measures based on electronic medical records (EMRs) may be inaccurate because of incomplete capture of past services. We evaluate the influence of different statistical approaches for calculating the proportion of patients who are up-to-date for a preventive service, using the example of colorectal cancer (CRC) screening. We propose an extension of traditional mixture models to account for the uncertainty in compliance, which is further complicated by the choice of various screening modalities with different recommended screening intervals. We conducted simulation studies to compare various statistical approaches and demonstrated that the proposed method can alleviate bias when individuals with complete prior medical history information were not representative of the targeted population. The method is motivated by and applied to data from the National Cancer Institute-funded consortium Population-Based Research Optimizing Screening through Personalized Regiments (PROSPR). Findings from the application are important for the evaluation of appropriate use of preventive care and provide a novel tool for dealing with similar analytical challenges with EMR data in broad settings.
Authors: Zheng, Yingye; Corley, Douglas A; Doubeni, Chyke; Halm, Ethan; Shortreed, Susan M; Barlow, William E; Zauber, Ann; Tosteson, Tor Devin; Chubak, Jessica
Ann Appl Stat. 2020 Jun;14(2):1030-1044. Epub 2020-06-29.
Hospital Characteristics and Breast Cancer Survival in the California Breast Cancer Survivorship Consortium
Racial/ethnic disparities in breast cancer survival are well documented, but the influence of health care institutions is unclear. We therefore examined the effect of hospital characteristics on survival. Harmonized data pooled from 5 case-control and prospective cohort studies within the California Breast Cancer Survivorship Consortium were linked to the California Cancer Registry and the California Neighborhoods Data System. The study included 9,701 patients with breast cancer who were diagnosed between 1993 and 2007. First reporting hospitals were classified by hospital type-National Cancer Institute (NCI) -designated cancer center, American College of Surgeons (ACS) Cancer Program, other-and hospital composition of the neighborhood socioeconomic status and race/ethnicity of patients with cancer. Multivariable Cox proportional hazards models adjusted for clinical and patient-level prognostic factors were used to examine the influence of hospital characteristics on survival. Fewer than one half of women received their initial care at an NCI-designated cancer center (5%) or ACS program (38%) hospital. Receipt of initial care in ACS program hospitals varied by race/ethnicity-highest among non-Latina White patients (45%), and lowest among African Americans (21%). African-American women had superior breast cancer survival when receiving initial care in ACS hospitals versus other hospitals (non-ACS program and non-NCI-designated cancer center; hazard ratio, 0.67; 95% CI, 0.55 to 0.83). Other hospital characteristics were not associated with survival. African American women may benefit significantly from breast cancer care in ACS program hospitals; however, most did not receive initial care at such facilities. Future research should identify the aspects of ACS program hospitals that are associated with higher survival and evaluate strategies by which to enhance access to and use of high-quality hospitals, particularly among African American women.
Authors: Shariff-Marco S; Kwan ML; Kurian AW; et al.
JCO Oncol Pract. 2020 06;16(6):e517-e528.
Association of Azithromycin Use With Cardiovascular Mortality
Azithromycin is one of the most commonly prescribed antibiotics in the US. It has been associated with an increased risk of cardiovascular death in some observational studies. To estimate the relative and absolute risks of cardiovascular and sudden cardiac death after an outpatient azithromycin prescription compared with amoxicillin, an antibiotic not known to increase cardiovascular events. This retrospective cohort study included 2 large, diverse, community-based integrated care delivery systems with comprehensive capture of encounters and prescriptions from January 1, 1998, to December 31, 2014. The cohort included patients aged 30 to 74 years who had at least 12 months of health-plan enrollment prior to antibiotic exposure. The exclusion criteria were absence of prescription benefits, prescription for more than 1 type of study antibiotic within 10 days, hospitalization or nursing home residence, and serious medical conditions. Risk of cardiovascular death associated with azithromycin vs amoxicillin exposure was calculated after controlling for confounding factors using a propensity score. Data were analyzed from December 1, 2016, to March 30, 2020. Outpatient prescription of azithromycin or amoxicillin. The primary outcomes were cardiovascular death and sudden cardiac death. An a priori subgroup analysis quantified the effects of azithromycin exposure among patients with increased baseline cardiovascular risk. The secondary outcomes were noncardiovascular death and all-cause mortality. The study included 7 824 681 antibiotic exposures, including 1 736 976 azithromycin exposures (22.2%) and 6 087 705 amoxicillin exposures (77.8%), among 2 929 008 unique individuals (mean [SD] age, 50.7 [12.3] years; 1 810 127 [61.8%] women). Azithromycin was associated with a significantly increased hazard of cardiovascular death (hazard ratio [HR], 1.82; 95% CI, 1.23-2.67) but not sudden cardiac death (HR, 1.59; 95% CI, 0.90-2.81) within 5 days of exposure. No increases in risk were found 6 to 10 days after exposure. Similar results were observed in patients within the top decile of cardiovascular risk (HR, 1.71; 95% CI, 1.06-2.76). Azithromycin was also associated with an increased risk of noncardiovascular death (HR, 2.17; 95% CI, 1.44-3.26) and all-cause mortality (HR, 2.00; 95% CI, 1.51-2.63) within 5 days of exposure. These findings suggest that outpatient azithromycin use was associated with an increased risk of cardiovascular death and noncardiovascular death. Causality cannot be established, particularly for noncardiovascular death, owing to the likelihood of residual confounding.
Authors: Zaroff JG; Cheetham TC; Palmetto N; Almers L; Quesenberry C; Schneider J; Gatto N; Corley DA
JAMA Netw Open. 2020 06 01;3(6):e208199. Epub 2020-06-01.
Childhood Adversity and Pubertal Development Among Puerto Rican Boys and Girls
Evidence stemming largely from retrospective studies suggests that childhood adversity (CA) is associated with earlier age at menarche, a marker of pubertal timing, among girls. Little is known about associations with pubertal tempo among boys or racial/ethnic minorities. We examined the association between CA and timing and tempo of pubertal development among boys and girls. The Boricua Youth Study is a longitudinal study of Puerto Rican youth residing in the San Juan metro area in Puerto Rico and the South Bronx, New York. CA was based on caretaker reports of parental loss and parental maladjustment and youth reports of child maltreatment and exposure to violence. Youth completed the Pubertal Development Scale (PDS) yearly for 3 years. In linear mixed models stratified by sex, we examined the association between CA and pubertal timing and tempo, adjusting for site, socioeconomic status, and age. Among the 1949 children who were 8 years or older by wave 3, cumulative CA was associated with higher PDS scores among girls compared with girls not exposed to CA (PDS score: 2.63 [95% confidence interval {CI} = 2.55-2.71] versus 2.48 [95% CI = 2.37-2.58]). In contrast, among boys, experiencing adversities was associated with lower pubertal developmental stage or later timing (PDS: 1.77 [95% CI = 1.67-1.87] versus 1.97 [95% CI = 1.85-2.10]) compared with those not exposed to adversities. Associations between CA and pubertal development may vary by sex. Understanding the etiological role of adversities on pubertal development and identifying targets for intervention are of utmost importance in ameliorating the impact of CA on child health.
Authors: Suglia SF; Chen C; Wang S; Cammack AL; April-Sanders AK; McGlinchey EL; Kubo A; Bird H; Canino G; Duarte CS
Psychosom Med. 2020 06;82(5):487-494.
Genetic predictors of circulating 25-hydroxyvitamin D and prognosis after colorectal cancer
Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in patients with colorectal cancer have been consistently associated with higher mortality in observational studies. It is unclear whether low 25(OH)D levels directly influence colorectal cancer mortality. To minimize bias, we use genetic variants associated with vitamin D levels to evaluate the association with overall and colorectal cancer-specific survival. Six genetic variants have been robustly identified to be associated with 25(OH)D levels in genome-wide association studies. On the basis of data from the International Survival Analysis in Colorectal Cancer Consortium, the individual genetic variants and a weighted genetic risk score were tested for association with overall and colorectal cancer-specific survival using Cox proportional hazards models in 7,657 patients with stage I to IV colorectal cancer, of whom 2,438 died from any cause and 1,648 died from colorectal cancer. The 25(OH)D decreasing allele of SNP rs2282679 (GC gene, encodes group-specific component/vitamin D-binding protein) was associated with poorer colorectal cancer-specific survival, although not significant after multiple-testing correction. None of the other five SNPs showed an association. The genetic risk score showed nonsignificant associations with increased overall [HR = 1.54; confidence interval (CI), 0.86-2.78] and colorectal cancer-specific mortality (HR = 1.76; 95% CI, 0.86-3.58). A significant increased risk of overall mortality was observed in women (HR = 3.26; 95% CI, 1.45-7.33; P heterogeneity = 0.01) and normal-weight individuals (HR = 4.14; 95% CI, 1.50-11.43, P heterogeneity = 0.02). Our results provided little evidence for an association of genetic predisposition of lower vitamin D levels with increased overall or colorectal cancer-specific survival, although power might have been an issue. Further studies are warranted to investigate the association in specific subgroups.
Authors: Neumeyer S; Sakoda LC; Chang-Claude J; et al.
Cancer Epidemiol Biomarkers Prev. 2020 06;29(6):1128-1134. Epub 2020-03-18.
Prenatal Depression and Diet Quality During Pregnancy
Maternal nutrition during pregnancy has a significant effect on the health of the offspring and mother, highlighting the need for identifying factors that may affect diet during pregnancy. Research in nonpregnant and pregnant populations suggest depression may play a role. To investigate the relationship between prenatal depression and diet quality during pregnancy overall and by race/ethnicity and to explore the relationships between prenatal depression and the 12 Healthy Eating Index 2010 dietary components. A cross-sectional secondary analysis of a cohort study of Kaiser Permanente Northern California women entering prenatal care between October 2011 and April 2013. Participants included 1,160 adult pregnant women. Poor diet quality was defined as a Healthy Eating Index 2010 score in the lowest quartile. Logistic regression was used to assess the relationship between prenatal depression (defined as a depression diagnosis, Patient Health Questionnaire score of 10 or greater or antidepressant medication dispensing between the last menstrual period and completion of the food frequency questionnaire) and poor diet quality overall and by race/ethnicity. Relationships between prenatal depression and each of the 12 Healthy Eating Index 2010 dietary components were assessed using t-tests and linear regression analyses. One hundred fifty-nine (14%) participants had prenatal depression. Women with prenatal depression had nearly two times the odds of poor diet quality (odds ratio 1.80, 95% CI 1.23 to 2.60) compared with women without prenatal depression, after adjusting for potential confounders. Differences emerged by race/ethnicity; after adjusting for potential confounders the adjusted odds of poor diet quality were significant only among Hispanic women. Hispanic women with prenatal depression had an increased odds of poor diet quality compared with Hispanic women without prenatal depression (odds ratio 2.66, 95% CI 1.15 to 6.06). Women with prenatal depression had a higher consumption of empty calories (from solid fats, alcohol, and added sugars; threshold for counting alcohol >13 g/1,000 kcal) (P=0.01) and lower consumption of greens and beans (P<0.05), total fruit (P<0.01), and whole fruit (P<0.01), compared with women without prenatal depression. Except for empty calories, these findings remained after adjusting for potential confounders. Study findings suggest that women with prenatal depression are at a higher risk of poor diet quality compared with women without prenatal depression, and the relationship is stronger among Hispanic women. Nutrition counseling interventions for women with depression should consider the use of culturally sensitive materials and target limiting empty calories from solid fats, alcohol, and added sugars and encourage eating more greens, beans, and fruit.
Authors: Avalos LA; Caan B; Nance N; Zhu Y; Li DK; Quesenberry C; Hyde RJ; Hedderson MM
J Acad Nutr Diet. 2020 06;120(6):972-984. Epub 2020-02-13.
A polygenic risk score for breast cancer in U.S. Latinas and Latin-American women
More than 180 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified; these SNPs can be combined into polygenic risk scores (PRS) to predict breast cancer risk. Because most SNPs were identified in predominantly European populations, little is known about the performance of PRS in non-Europeans. We tested the performance of a 180-SNP PRS in Latinas, a large ethnic group with variable levels of Indigenous American, European, and African ancestry. We conducted a pooled case-control analysis of US Latinas and Latin American women (4658 cases and 7622 controls). We constructed a 180-SNP PRS consisting of SNPs associated with breast cancer risk (P < 5 × 10-8). We evaluated the association between the PRS and breast cancer risk using multivariable logistic regression, and assessed discrimination using an area under the receiver operating characteristic curve. We also assessed PRS performance across quartiles of Indigenous American genetic ancestry. All statistical tests were two-sided. Of 180 SNPs tested, 142 showed directionally consistent associations compared with European populations, and 39 were nominally statistically significant (P < .05). The PRS was associated with breast cancer risk, with an odds ratio per SD increment of 1.58 (95% confidence interval [CI = 1.52 to 1.64) and an area under the receiver operating characteristic curve of 0.63 (95% CI = 0.62 to 0.64). The discrimination of the PRS was similar between the top and bottom quartiles of Indigenous American ancestry. The 180-SNP PRS predicts breast cancer risk in Latinas, with similar performance as reported for Europeans. The performance of the PRS did not vary substantially according to Indigenous American ancestry.
Authors: Shieh Y; Kushi LH; Neuhausen SL; et al.
J Natl Cancer Inst. 2020 06 01;112(6):590-598.
Validation of an Algorithm to Identify Patients at Risk for Colorectal Cancer Based on Laboratory Test and Demographic Data in Diverse, Community-Based Population
Approximately 30%-40% of screening-eligible adults in the United States are not up to date with colorectal cancer (CRC) screening. We aimed to validate a predictive score, generated by a machine learning algorithm with common laboratory test data, to identify patients at high risk for CRC in a large, community-based, ethnically diverse cohort. We performed a nested case-control study using data from members of Kaiser Permanente Northern California (1996-2015). Cases were cohort members who received a complete blood cell count at ages 50-75 y, did not have a prior or current diagnosis of CRC diagnosis at the time of the blood cell count, and were subsequently diagnosed with CRC. We used data from the cohort to validate the ability of an algorithm that uses laboratory and demographic information to identify patients at increased risk for CRC. Test performance was evaluated using area under the receiver operating characteristic curve (AUROC) and odds ratios (OR) with 95% CI values to compare high (defined as 97% specificity or more) vs low scores. A high score from the algorithm identified patients with a CRC diagnosis within the next 6 months with 35.4% sensitivity (95% CI, 33.8-36.7) and an AUROC of 0.78 (95% CI, 0.77-0.78). Patients with a high score had an increased risk of diagnosis with early-stage CRC (OR, 13.1; 95% CI, 11.8-14.3) and advanced stage CRC (OR, 24.8; 95% CI, 22.4-27.3) within the next 6 months. In patients with high scores, the ORs for proximal and distal cancers were 34.7 (95% CI, 31.5-37.7) and 12.1 (95% CI, 10.1-13.9), respectively. The algorithms accuracy decreased with the time interval between blood test result and CRC diagnosis; performance did not differ by sex or race. We validated a predictive model that uses complete blood cell count and demographic data to identify patients at high risk of CRC. The algorithm identified 3% of the population who require and investigation and identified 35% of patients who received a diagnosis of CRC within the next 6 months.
Authors: Schneider J; Layefsky E; Udaltsova N; Levin TR; Corley DA
Clin Gastroenterol Hepatol. 2020 Apr 29.
COVID-19: What Should Clinicians and Scientists Do and When?
Authors: Corley DA; Peek RM
Gastroenterology. 2020 Mar 19.
COVID-19: Long-term Planning for Procedure-based Specialties During Extended Mitigation and Suppression Strategies
Authors: Rouillard S; Liu VX; Corley DA
Gastroenterology. 2020 May 18.
Egocentric social networks, lifestyle behaviors, and body size in the Asian Community Health Initiative (CHI) cohort
Social networks have been shown to influence lifestyle behaviors in non-Latinx white (NLW) populations. We examined their influence in Asian American, Native Hawaiian and Pacific Islander (AANHPI) women. We included 477 AANHPI women from the Asian Community Health Initiative Study who provided egocentric (degree, density, composition) and epidemiologic (size, types of ties) social network data and data on alcohol intake, physical activity, smoking, diet, and body size. We used logistic regression to evaluate associations of social network measures and dichotomous outcomes, and linear regression for continuous outcomes. In multivariable-adjusted analyses, higher degree and/or proportion of friends were significantly related to higher Western diet, higher odds of any alcohol consumption, and lower odds of physical inactivity and body mass index (BMI)≥23 kg/m2. Additionally, a higher proportion of NLW in women’s networks was related to lower Asian diet but also lower waist size. Community participation was related to higher Western diet and lower Asian diet. By contrast, degree and/or proportion of relatives were positively related to BMI, waist size and to a higher odds of BMI≥23 kg/m2 and of ever smoking 100 cigarettes. Being married was related to fewer alcoholic drinks per week and higher Asian diet. A higher density of relationships with frequent contact was also associated with higher Asian diet. AANHPI women with larger proportions of friends and NLWs in their networks had more Western health behaviors and smaller body size. Norms for health behaviors and body size may be influenced by the size, composition, and structure of social networks, relevant to chronic disease prevention.
Authors: Kroenke CH; Le GM; Conroy SM; Canchola AJ; Shariff-Marco S; Gomez SL
PLoS ONE. 2020;15(5):e0232239. Epub 2020-05-06.
Pregnancy-related relapses and breastfeeding in a contemporary multiple sclerosis cohort
To determine whether women with multiple sclerosis (MS) diagnosed according to current criteria are at an increased risk of postpartum relapses and to assess whether this risk is modified by breastfeeding or MS disease-modifying therapies (DMTs), we examined the electronic health records (EHRs) of 466 pregnancies among 375 women with MS and their infants. We used prospectively collected information from the EHR at Kaiser Permanente Southern and Northern California between 2008 and 2016 of the mother and infant to identify treatment history, breastfeeding, and relapses. Multivariable models accounting for measures of disease severity were used. In the postpartum year, 26.4% relapsed, 87% breastfed, 36% breastfed exclusively for at least 2 months, and 58.8% did not use DMTs. At pregnancy onset, 67.2% had suboptimally controlled disease. Annualized relapse rates (ARRs) declined from 0.37 before pregnancy to 0.14-0.07 (p < 0.0001) during pregnancy, but in the postpartum period, we did not observe any rebound disease activity. The ARR was 0.27 in the first 3 months postpartum, returning to prepregnancy rates at 4-6 months (0.37). Exclusive breastfeeding reduced the risk of early postpartum relapses (adjusted hazard ratio = 0.37, p = 0.009), measures of disease severity increased the risk, and resuming modestly effective DMTs had no effect (time-dependent covariate, p = 0.62). Most women diagnosed with MS today can have children without incurring an increased risk of relapses. Women with suboptimal disease control before pregnancy may benefit from highly effective DMTs that are compatible with pregnancy and lactation. Women with MS should be encouraged to breastfeed exclusively.
Authors: Langer-Gould A; Smith JB; Albers KB; Xiang AH; Wu J; Kerezsi EH; McClearnen K; Gonzales EG; Leimpeter AD; Van Den Eeden SK
Neurology. 2020 05 05;94(18):e1939-e1949. Epub 2020-04-13.
Does weather trigger urologic chronic pelvic pain syndrome flares? A case-crossover analysis in the multidisciplinary approach to the study of the chronic pelvic pain research network
To investigate whether meteorological factors (temperature, barometric pressure, relative humidity, ultraviolet index [UVI], and seasons) trigger flares in male and female urologic chronic pelvic pain patients. We assessed flare status every 2 weeks in our case-crossover study of flare triggers in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain 1-year longitudinal study. Flare symptoms, flare start date, and exposures in the 3 days preceding a flare or the date of questionnaire completion were assessed for the first three flares and at three randomly selected nonflare times. We linked these data to daily temperature, barometric pressure, relative humidity, and UVI values by participants’ first 3 zip code digits. Values in the 3 days before and the day of a flare, as well as changes in these values, were compared to nonflare values by conditional logistic regression. Differences in flare rates by astronomical and growing seasons were investigated by Poisson regression in the full study population. A total of 574 flare and 792 nonflare assessments (290 participants) were included in the case-crossover analysis, and 966 flare and 5389 nonflare (409 participants) were included in the full study analysis. Overall, no statistically significant associations were observed for daily weather, no patterns of associations were observed for weather changes, and no differences in flare rates were observed by season. We found minimal evidence to suggest that weather triggers flares, although we cannot rule out the possibility that a small subset of patients is susceptible.
Authors: Li J; Langston ME; MAPP Research Network; et al.
Neurourol Urodyn. 2020 06;39(5):1494-1504. Epub 2020-05-04.
A population-based survey to assess the association between cannabis and quality of life among colorectal cancer survivors
As more states legalize cannabis for medical and recreational use, people increasingly use cannabis to treat medical conditions and associated symptoms. The prevalence and utility of cannabis for cancer-related symptoms may be clarified by examining cannabis use among patients with a common cancer diagnosis. We aimed to determine the prevalence of cannabis use among colorectal cancer (CRC) survivors and its associations with quality of life (QoL) and cancer-related symptomatology. A cross-sectional survey of patient-reported QoL outcomes and behaviors, including cannabis use, was conducted within the Patient Outcomes To Advance Learning network’s (PORTAL) CRC Cohort. The cohort included a population-based sample of healthcare system members ≥18 years old diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2016. We assessed the association between cannabis use and QoL using the European Organization for Research and Treatment of Cancer QLQ-C30 summary score. Of the 1784 respondents, 293 (16.4%) reported cannabis use following CRC diagnosis. Current tobacco smokers were more likely to use cannabis compared to former or never tobacco smokers (adjusted odds ratio [aOR] 2.71, 95% confidence interval [CI] 1.56 to 4.70). Greater alcohol use (> 4 drinks per month versus ≤4 drinks per month) was associated with cannabis use (aOR 2.17, 95% CI 1.65 to 2.85). There was an association between cannabis use and cancer stage at diagnosis, with stage 3 or 4 CRC patients more likely to use cannabis than stage 1 or 2 CRC patients (aOR 1.68, 95% CI 1.25 to 2.25). After adjusting for demographics, medical comorbidities, stage and site of CRC diagnosis, and prescription opioid use, people who used cannabis had significantly lower QoL than people who did not use cannabis (difference of - 6.14, 95% CI - 8.07 to - 4.20). Among CRC survivors, cannabis use was relatively common, associated with more advanced stages of disease, associated with tobacco and alcohol use, and not associated with better QoL. Clinicians should inquire about cannabis use among their patients and provide evidence-based recommendations for cancer-related symptoms.
Authors: Calcaterra SL; Burnett-Hartman AN; Powers JD; Corley DA; McMullen CM; Pawloski PA; Feigelson HS
BMC Cancer. 2020 May 03;20(1):373. Epub 2020-05-03.
Surveillance of Gastric Intestinal Metaplasia
Authors: Shah SC; Gawron AJ; Li D
Am J Gastroenterol. 2020 05;115(5):641-644.
Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations
We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.
Authors: Haque R; Skates SJ; Armstrong MA; Lentz SE; Anderson M; Jiang W; Alvarado MM; Chillemi G; Shaw SF; Kushi LH; Powell CB
Gynecol Oncol. 2020 05;157(2):521-528. Epub 2020-03-04.
Proton Pump Inhibitor Use and Risk of Gastric, Colorectal, Liver, and Pancreatic Cancers in a Community-Based Population
Proton pump inhibitors (PPIs) are commonly used for gastrointestinal disorders; given they increase the systemic levels of gastrin, a trophic hormone, there is a concern about their carcinogenicity. This study evaluated the association between PPI use and gastrointestinal cancers. We performed a nested case-control study in a large, community-based integrated healthcare setting. Cases were adults with gastric (n = 1,233), colorectal (n = 18,595), liver (n = 2,329), or pancreatic cancers (n = 567). Each case was matched with up to 10 controls by age, sex, race/ethnicity, medical facility, and enrollment duration. The primary exposure was defined as ≥2-year cumulative PPI supply. Data were obtained from pharmacy, cancer registry, and electronic medical record databases. Associations were evaluated using conditional logistic regression and adjusted for multiple confounders. We also evaluated the cancer risks separately by PPI dose, duration of use, and dose and duration. PPI use of ≥2-years was not associated with the risks of gastric (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.81-1.42), colorectal (OR: 1.05, 95% CI: 0.99-1.12), liver (OR: 1.14, 95% CI: 0.91-1.43), or pancreatic cancers (OR: 1.22, 95% CI: 0.89-1.67), compared to non-users. In exploratory analyses, elevated cancer risks were primarily restricted to those with ≥10 years of PPI use, but no consistent associations were found for increasing PPI dose and/or duration of use. PPI use of ≥2 years was not associated with increased risks of gastrointestinal cancers. The cancer risks associated with PPI use of ≥10 years requires further study.
Authors: Lee JK; Merchant SA; Schneider JL; Jensen CD; Fireman BH; Quesenberry CP; Corley DA
Am J Gastroenterol. 2020 05;115(5):706-715.
Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk
Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology. To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2. Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ). Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.
Authors: Xia Z; Sakoda LC; Peters U; et al.
Cancer Med. 2020 05;9(10):3563-3573. Epub 2020-03-24.
American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in familial adenomatous polyposis syndromes
Familial adenomatous polyposis (FAP) syndrome is a complex entity, which includes FAP, attenuated FAP, and MUTYH-associated polyposis. These patients are at significant risk for colorectal cancer and carry additional risks for extracolonic malignancies. In this guideline, we reviewed the most recent literature to formulate recommendations on the role of endoscopy in this patient population. Relevant clinical questions were how to identify high-risk individuals warranting genetic testing, when to start screening examinations, what are appropriate surveillance intervals, how to identify endoscopically high-risk features, and what is the role of chemoprevention. A systematic literature search from 2005 to 2018 was performed, in addition to the inclusion of seminal historical studies. Most studies were from worldwide registries, which have compiled years of data regarding the natural history and cancer risks in this cohort. Given that most studies were retrospective, recommendations were based on epidemiologic data and expert opinion. Management of colorectal polyps in FAP has not changed much in recent years, as colectomy in FAP is the standard of care. What is new, however, is the developing body of literature on the role of endoscopy in managing upper GI and small-bowel polyposis, as patients are living longer and improved endoscopic technologies have emerged.
Authors: Yang J; Lee JK; Samadder NJ; et al.
Gastrointest Endosc. 2020 05;91(5):963-982.e2. Epub 2020-03-10.
Alcohol and tobacco use in relation to mammographic density in 23,456 women
Percent density (PD) is a strong risk factor for breast cancer that is potentially modifiable by lifestyle factors. PD is a composite of the dense (DA) and nondense (NDA) areas of a mammogram, representing predominantly fibroglandular or fatty tissues, respectively. Alcohol and tobacco use have been associated with increased breast cancer risk. However, their effects on mammographic density (MD) phenotypes are poorly understood. We examined associations of alcohol and tobacco use with PD, DA, and NDA in a population-based cohort of 23,456 women screened using full-field digital mammography machines manufactured by Hologic or General Electric. MD was measured using Cumulus. Machine-specific effects were estimated using linear regression, and combined using random effects meta-analysis. Alcohol use was positively associated with PD (P trend = 0.01), unassociated with DA (P trend = 0.23), and inversely associated with NDA (P trend = 0.02) adjusting for age, body mass index, reproductive factors, physical activity, and family history of breast cancer. In contrast, tobacco use was inversely associated with PD (P trend = 0.0008), unassociated with DA (P trend = 0.93), and positively associated with NDA (P trend<0.0001). These trends were stronger in normal and overweight women than in obese women. These findings suggest that associations of alcohol and tobacco use with PD result more from their associations with NDA than DA. PD and NDA may mediate the association of alcohol drinking, but not tobacco smoking, with increased breast cancer risk. Further studies are needed to elucidate the modifiable lifestyle factors that influence breast tissue composition, and the important role of the fatty tissues on breast health.
Authors: McBride RB; Alexeeff SE; Sakoda LC; Habel LA; Sieh W; et al.
Cancer Epidemiol Biomarkers Prev. 2020 05;29(5):1039-1048. Epub 2020-02-17.
Identifying metabolomic profiles of inflammatory diets in postmenopausal women
We previously showed that a food-based empirical dietary inflammatory pattern (EDIP) score is associated with circulating inflammatory biomarkers. Metabolomic profiling of inflammatory diets may therefore provide insights on mechanisms contributing to disease etiology and prognosis. We aimed to elucidate metabolites associated with inflammatory diets among postmenopausal women, utilizing a robust study design that incorporates independent discovery and validation datasets. This baseline cross-sectional investigation evaluated associations between continuous EDIP scores calculated from food frequency questionnaires and 448 log-transformed plasma metabolites as outcomes in multivariable-adjusted linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Metabolite discovery was conducted among 1109 Women’s Health Initiative (WHI) Hormone Therapy trial participants and results were replicated in an independent dataset of 810 WHI Observational Study participants. Secondary analyses were stratified by standard body mass index (BMI, kg/m2) categories. In discovery and replication datasets statistical significance was based on false-discovery rate adjusted P < 0.05. After adjusting for energy intake, BMI, physical activity, and other confounding variables, 23 metabolites were significantly associated with EDIP score in the discovery dataset. Of these, the following ten were replicated: trigonelline, caffeine, acethylamino-6-amino-3-methyluracil, 7-methylxanthine, 1,7-dimethyluric acid, 3-methylxanthine, C18:3CE, glycine, associated with lower dietary inflammatory potential; whereas C52:3 triacylglycerol and linoleate associated with higher dietary inflammatory potential. Four of the ten were associated [glycine (inversely), caffeine, 1,7-dimethyluric acid, C52:3 triacylglycerol, (positively)], with C-reactive protein levels. In secondary analyses, associations showed differences by BMI category. Four metabolites, related to coffee/caffeine metabolism were inversely associated among normal weight women, and 83 metabolites associated with EDIP among overweight/obese women, including 40 (48%) that were also associated with C-reactive protein. Metabolites associated with coffee/caffeine and lipid metabolism may reflect the inflammatory potential of diet. Potential differences by BMI and the linkage to disease outcomes, require further study.
Authors: Tabung FK; Liang L; Rexrode KM; et al.
Clin Nutr. 2020 05;39(5):1478-1490. Epub 2019-06-17.
What Is Organized Screening and What Is Its Value?
Most screening in the United States occurs in an opportunistic fashion, although organized screening occurs in some integrated health care systems. Organized colorectal cancer (CRC) screening consists of an explicit screening policy, defined target population, implementation team, health care team for clinical care delivery, quality assurance infrastructure, and method for identifying cancer outcomes. Implementation of an organized screening program offers opportunities to systematically assess the success of the program and develop interventions to address identified gaps in an effort to optimize CRC outcomes. There is evidence of that organized screening is associated with improvements in screening participation and CRC mortality.
Authors: Dominitz JA; Levin TR
Gastrointest Endosc Clin N Am. 2020 Jul;30(3):393-411. Epub 2020-04-16.
Prediagnosis social support, social integration, living status, and colorectal cancer mortality in postmenopausal women from the women’s health initiative
We evaluated associations between perceived social support, social integration, living alone, and colorectal cancer (CRC) outcomes in postmenopausal women. The study included 1431 women from the Women’s Health Initiative who were diagnosed from 1993 through 2017 with stage I through IV CRC and who responded to the Medical Outcomes Study Social Support survey before their CRC diagnosis. We used proportional hazards regression to evaluate associations of social support (tertiles) and types of support, assessed up to 6 years before diagnosis, with overall and CRC-specific mortality. We also assessed associations of social integration and living alone with outcomes also in a subset of 1141 women who had information available on social ties (marital/partner status, community and religious participation) and living situation. In multivariable analyses, women with low (hazard ratio [HR], 1.52; 95% CI, 1.23-1.88) and moderate (HR, 1.21; 95% CI, 0.98-1.50) perceived social support had significantly higher overall mortality than those with high support (P [continuous] < .001). Similarly, women with low (HR, 1.42; 95% CI, 1.07-1.88) and moderate (HR, 1.28; 95% CI, 0.96-1.70) perceived social support had higher CRC mortality than those with high social support (P [continuous] = .007). Emotional, informational, and tangible support and positive interaction were all significantly associated with outcomes, whereas affection was not. In main-effects analyses, the level of social integration was related to overall mortality (P for trend = .02), but not CRC mortality (P for trend = .25), and living alone was not associated with mortality outcomes. However, both the level of social integration and living alone were related to outcomes in patients with rectal cancer. Women with low perceived social support before diagnosis have higher overall and CRC-specific mortality.
Authors: Kroenke CH; Paskett ED; Cené CW; Caan BJ; Luo J; Shadyab AH; Robinson JRM; Nassir R; Lane DS; Anderson GL
Cancer. 2020 04 15;126(8):1766-1775. Epub 2020-01-23.
Associations between nutritional factors and chemotherapy toxicity in older adults with solid tumors
Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors. This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity. Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1-52.1 kg/m2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2 ) and normal albumin levels (AOR, 0.41; P = .008). Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.
Authors: Dotan E; Caan B; Hurria A; et al.
Cancer. 2020 04 15;126(8):1708-1716. Epub 2020-01-24.
Reservations Regarding O-RADS Recommendations
Authors: Suh-Burgmann E; Flanagan T; Brasic N
Radiology. 2020 04;295(1):248-249. Epub 2020-02-25.
Election of Anil Rustgi and Raymond DuBois to the National Academy of Medicine
Authors: Corley DE; Peek RM
Gastroenterology. 2020 04;158(5):1196. Epub 2020-03-04.
Impact of the Affordable Care Act on Colorectal Cancer Outcomes: A Systematic Review
The Patient Protection and Affordable Care Act increases healthcare access and includes provisions that directly impact access to and cost of evidence-based colorectal cancer screening. The Affordable Care Act’s removal of cost sharing for colorectal cancer screening as well as Medicaid expansion have been hypothesized to increase screening and improve other health outcomes. However, since its passage in 2010, there is little consensus on the Affordable Care Act’s impact. Data from March 2010 to June 2019 were reviewed and 21 relevant studies were identified; 19 studies examined colorectal cancer screening with most finding increased screening rates. Eleven studies found significant increases, 5 found nonsignificant increases, 3 found nonsignificant decreases, and 1 study found a significant decrease in colorectal cancer screening. Three studies examined the impact on colorectal cancer incidence and stage of diagnosis, where a significant 2.4% increase in early diagnosis was found in one and a nonsignificant increase in incidence in another. However, survival improved after Medicaid expansion. Free preventive colorectal cancer screening and Medicaid expansion because of passage of the Affordable Care Act have been, in general, positively associated with modest improvements in screening rates across the country. Future studies are needed that investigate the longer-term impact of the Affordable Care Act on colorectal cancer morbidity and mortality rates, as screening is only the first step in treatment of cancerous and precancerous lesions, preventing them from progressing. Moreover, more studies examining subpopulations are needed to better assess where gaps in care remain.
Authors: Xu MR; Kelly AMB; Kushi LH; Reed ME; Koh HK; Spiegelman D
Am J Prev Med. 2020 04;58(4):596-603. Epub 2020-01-31.
ASGE guideline on minimum staffing requirements for the performance of GI endoscopy
Efforts to increase patient safety and satisfaction, a critical concern for health providers, require periodic evaluation of all factors involved in the provision of GI endoscopy services. We aimed to develop guidelines on minimum staffing requirements and scope of practice of available staff for the safe and efficient performance of GI endoscopy. The recommendations in this guideline were based on a systematic review of published literature, results from a nationwide survey of endoscopy directors, along with the expert guidance of the American Society for Gastrointestinal Endoscopy (ASGE) Standards of Practice Committee members, ASGE Practice Operation Committee members, and the ASGE Governing Board.
Authors: Jamil LH; Lee JK; Wani SB; et al.
Gastrointest Endosc. 2020 04;91(4):723-729.e17. Epub 2020-02-06.
The association of delay in curative intent treatment with survival among breast cancer patients: findings from the Women’s Health Initiative
Delays in adjuvant breast cancer (BC) therapy have been shown to worsen outcomes. However, thus far studies have only evaluated delays to initial treatment, or a particular modality, such as chemotherapy, leaving uncertainty about the role of delay to subsequent therapy and the effects of cumulative delay, on outcomes. We investigated the associations of delays across treatment modalities with survival. We included 3368 women with incident stage I-III BC in the Women’s Health Initiative (WHI) enrolled in fee-for-service Medicare who underwent definitive surgery. This prospective analysis characterized treatment delays by linking WHI study records to Medicare claims. Delays were defined as > 8 weeks to surgery, chemotherapy, and radiation from diagnosis or prior treatment. We used Cox proportional hazards models to estimate BC-specific mortality (BCSM) and all-cause mortality (ACM) in relation to treatment delays. We found 21.8% of women experienced delay to at least one therapy modality. In adjusted analysis, delay to chemotherapy was associated with a higher risk of BCSM (HR = 1.71; 95% CI 1.07-2.75) and ACM (HR = 1.39; 95% CI 1.02-1.90); delay in radiation increased BCSM risk (HR = 1.49; 95% CI 1.00-2.21) but not ACM risk (HR = 1.19; 95% CI 0.99-1.42). Delays across multiple treatment modalities increased BCSM risk threefold (95% CI 1.51-6.12) and ACM risk 2.3-fold (95% CI 1.50-3.50). A delay to a single treatment modality and delay to a greater extent an accumulation of delays were associated with higher BCSM and ACM after BC. Timely care throughout the continuum of breast cancer treatment is important for optimal outcomes.
Authors: Yung R; Kroenke CH; Reding KW; et al.
Breast Cancer Res Treat. 2020 Apr;180(3):747-757. Epub 2020-02-15.
Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk
Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.
Authors: Khankari NK; Sakoda LC; Zheng W; et al.
Cancer Epidemiol Biomarkers Prev. 2020 04;29(4):860-870. Epub 2020-02-12.
The effect of multiple recruitment contacts on response rates and patterns of missing data in a survey of bladder cancer survivors 6 months after cystectomy
The Bladder Cancer Quality of Life Study collected detailed and sensitive patient-reported outcomes from bladder cancer survivors in the period after bladder removal surgery, when participation in survey research may present a burden. This paper describes the study recruitment methods and examines the response rates and patterns of missing data. Detailed surveys focusing on quality of life, healthcare decision-making, and healthcare expenses were mailed to patients 5-7 months after cystectomy. We conducted up to 10 follow-up recruitment calls. We analyzed survey completion rates following each contact in relation to demographic and clinical characteristics, and patterns of missing data across survey content areas. The overall response rate was 71% (n = 269/379). This was consistent across patient clinical characteristics; response rates were significantly higher among patients over age 70 and significantly lower among racial and ethnic minority patients compared to non-Hispanic white patients. Each follow-up contact resulted in marginal survey completion rates of at least 10%. Rates of missing data were low across most content areas, even for potentially sensitive questions. Rates of missing data differed significantly by sex, age, and race/ethnicity. Despite the effort required to participate in research, this population of cancer survivors showed willingness to share detailed information about quality of life, health care decision-making, and expenses, soon after major cancer surgery. Additional contacts were effective at increasing participation. Response patterns differed by race/ethnicity and other demographic factors. Our data collection methods show that it is feasible to gather detailed patient-reported outcomes during this challenging period.
Authors: Bulkley JE; Kwan ML; McMullen CK; et al.
Qual Life Res. 2020 Apr;29(4):879-889. Epub 2019-12-06.
Cumulative Burden of Colorectal Cancer-Associated Genetic Variants is More Strongly Associated With Early-onset vs Late-onset Cancer
Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
Authors: Archambault AN; Sakoda LC; Corley DA; Hayes RB; et al.
Gastroenterology. 2020 04;158(5):1274-1286.e12. Epub 2019-12-19.
Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses
Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05-1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 × 10-4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 × 10-5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis.
Authors: Murphy N; Sakoda LC; Gunter MJ; et al.
Gastroenterology. 2020 04;158(5):1300-1312.e20. Epub 2019-12-27.
The Association of Abdominal Adiposity with Mortality in Patients with Stage I-III Colorectal Cancer
The quantity and distribution of adipose tissue may be prognostic measures of mortality in colorectal cancer patients, and such associations may vary by patient sex. This cohort included 3262 stage I-III colorectal cancer patients. Visceral and subcutaneous adipose tissues were quantified using computed tomography. The primary endpoint was all-cause mortality. Restricted cubic splines estimated statistical associations with two-sided P values. Visceral adipose tissue was prognostic of mortality in a reverse L-shaped pattern (nonlinear P?=?.02); risk was flat to a threshold (?260 cm2) then increased linearly. Subcutaneous adipose tissue was prognostic of mortality in a J-shaped pattern (nonlinear P?50 to ?560 cm2). Patient sex modified the prognostic associations between visceral adipose tissue (Pinteraction = .049) and subcutaneous adipose tissue (Pinteraction = .04) with mortality. Among men, visceral adiposity was associated with mortality in a J-shaped pattern (nonlinear P?=?.003), whereas among women, visceral adiposity was associated with mortality in a linear pattern (linear P?=?.008). Among men, subcutaneous adiposity was associated with mortality in an L-shaped pattern (nonlinear P?=?.01), whereas among women, subcutaneous adiposity was associated with mortality in a J-shaped pattern (nonlinear P?
Authors: Brown JC; Caan BJ; Prado CM; Cespedes Feliciano EM; Xiao J; Kroenke CH; Meyerhardt JA
J Natl Cancer Inst. 2020 04 01;112(4):377-383.
A Genome-wide Association Study of Prostate Cancer in Latinos
Latinos represent <1% of samples analyzed to date in genome-wide association studies of cancer. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts across populations. In the present study, we performed a GWAS of prostate cancer (PrCa) in 2,820 Latino PrCa cases and 5,293 controls to search for novel PrCa risk loci and to examine the generalizability of known PrCa risk loci in Latino men. We also conducted a genetic admixture-mapping scan to identify PrCa risk alleles associated with local ancestry. Genome-wide significant associations were observed with 84 variants all located at the known PrCa risk regions at 8q24 (128.484-128.548) and 10q11.22 (MSMB gene). In admixture mapping, we observed genome-wide significant associations with local African ancestry at 8q24. Of the 162 established PrCa risk variants that are common in Latino men, 135 (83.3%) had effects that were directionally consistent as previously reported, among which 55 (34.0%) were statistically significant with p < 0.05. A polygenic risk model of the known PrCa risk variants showed that, compared to men with average risk (25th-75th percentile of the polygenic risk score distribution), men in the top 10% had a 3.19-fold (95% CI: 2.65, 3.84) increased PrCa risk. In conclusion, we found that the known PrCa risk variants can effectively stratify PrCa risk in Latino men. Larger studies in Latino populations will be required to discover and characterize genetic risk variants for PrCa and improve risk stratification for this population.
Authors: Du Z; Van Den Eeden SK; Haiman CA; et al.
Int J Cancer. 2020 04 01;146(7):1819-1826. Epub 2019-07-03.
Post-cancer diagnosis dietary inflammatory potential is associated with survival among women diagnosed with colorectal cancer in the Women’s Health Initiative
Dietary factors may influence colorectal cancer (CRC) survival through effects on inflammation. We examined the association between post-CRC diagnosis inflammatory potential of diet and all-cause and cancer-specific mortality in the Women’s Health Initiative. The study included 463 postmenopausal women who developed CRC during follow-up and completed a food frequency questionnaire (FFQ), on average 1.7 years after diagnosis. Women were followed from CRC diagnosis until death, censoring, or the end of follow-up in October 2014. Energy-adjusted dietary inflammatory index (E-DII)® scores were calculated from the FFQ and dietary supplement inventory. Cox proportional hazards models were fitted to estimate multivariable-adjusted HRs and 95% confidence intervals (CIs) for all-cause, total cancer, and CRC-specific mortality with the most pro-inflammatory E-DII scores (tertile 3) as referent. After a median 11.6 years of follow-up, 162 deaths occurred, including 77 from CRC. Lowest tertile (i.e., most anti-inflammatory) E-DII scores from diet plus supplements were associated with significantly lower all-cause mortality (HRT1vsT3 = 0.49; 95% CI 0.31-0.79) compared to the most pro-inflammatory E-DII tertile. Modest associations with total cancer mortality or CRC-specific mortality were observed, though 95% CIs included 1. Consuming a dietary pattern and supplements with more anti-inflammatory potential after CRC diagnosis may improve overall survival among postmenopausal women.
Authors: Zheng J; Tabung FK; Zhang J; Murphy EA; Shivappa N; Ockene JK; Caan B; Kroenke CH; Hébert JR; Steck SE
Eur J Nutr. 2020 Apr;59(3):965-977. Epub 2019-04-06.
Cervical dystonia incidence and diagnostic delay in a multiethnic population
Current cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized. To determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization. We identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration. CD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68). CD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society.
Authors: LaHue SC; Tanner CM; Tanner CM; et al.
Mov Disord. 2020 03;35(3):450-456. Epub 2019-11-27.
Promises and Potential Pitfalls of Shared Decision-making in Cancer Screening
Authors: Haug U; Senore C; Corley DA
Gastroenterology. 2020 03;158(4):802-805. Epub 2019-12-05.
Cytological sampling of fallopian tubes using a hysteroscopic catheter: A multi-center study
To assess the feasibility of a novel hysteroscopic catheter to collect fallopian tube cytologic samples and to correlate cytologic findings with histopathology. This was a prospective, multicenter, single-arm pilot study. Women undergoing salpingo-oophorectomy for a pelvic mass suspicious for malignancy or for prevention of cancer for BRCA mutation carriers were recruited from 3 gynecologic oncology centers (October 2016-August 2017). Cytologic samples were collected from the fallopian tube using a novel FDA-cleared hysteroscopic catheter and evaluated by a pathologist blinded to surgical or pathologic findings. The correlation between cytologic results and final surgical pathology was assessed. Of the 50 patients enrolled, 42 were eligible. Hysteroscopies were completed in 40 patients with 78 fallopian tubes, of which 65 ostia (83%) were identified. Of these, 61 (72%) were successfully catheterized resulting in 44 (68%) cytology samples adequate for further evaluation: 5 were classified as positive (3 neoplastic and 2 malignant) and 39 as negative (34 benign and 5 reactive/atypical). A comparison of cytology results with fallopian tube histopathology showed a concordance rate of 95% (42/44). Of the two samples with discordant results, both had positive cytology but negative tubal pathology, and both were stage I ovarian cancers with malignant ovary histology. Deployment of the device yielded an evaluable cytologic sample in 68% of cases with a high rate of concordance with histopathology. Further evaluation of the device’s ability to detect malignancy in high risk populations is warranted.
Authors: Powell CB; Littell RD; Landen CN; Pramanik S; Hamilton IC; Suh-Burgmann EJ
Gynecol Oncol. 2020 03;156(3):636-640. Epub 2020-01-07.
Impact of observational training on endoscopic mucosal resection outcomes and competency for large colorectal polyps: single endoscopist experience
Background and study aims Endoscopic mucosal resection (EMR) is standard treatment for large colorectal polyps. However, it is a specialized technique with limited data on the effectiveness of training methods to acquire this skill. The aim of this study was to evaluate the impact of observational training on EMR outcomes and competency in an early-stage endoscopist. Patients and methods A single endoscopist completed comprehensive EMR training, which included knowledge acquisition and direct observation of EMR cases, and proctored supervision, during the third year of gastroenterology fellowship. After training, EMR was independently attempted on 142 consecutive, large (i. e., ≥ 20 mm), non-pedunculated colorectal polyps between July 2014 and December 2017 (mean age 61.7 years; mean polyp size 30.4 mm; en-bloc resection 55 %). Surveillance colonoscopy for evaluation of residual neoplasia was available for 86 % of the cases. Three primary outcomes were evaluated: endoscopic assessment of complete resection, rate of adverse events (AEs), and rate of residual neoplasia on surveillance colonoscopy. Results Complete endoscopic resection was achieved in 93 % of cases, the rates of AEs and residual neoplasia were 7.8 % and 7.3 %, respectively. The rate of complete resection remained stable (at 85 % or greater) with increasing experience while rates of AEs and residual neoplasia peaked and decreased after 60 cases. Conclusions An early-stage endoscopist can acquire the skills to perform effective EMR after completing observational training. At least 60 independent EMRs for large colorectal polyps were required to achieve a plateau for clinically meaningful outcomes.
Authors: Lee JK; Kidambi TD; Kaltenbach T; Bhat YM; Shergill A; McQuaid KR; Terdiman JP; Soetikno RM
Endosc Int Open. 2020 Mar;8(3):E346-E353. Epub 2020-02-21.
COPD and lung cancer incidence in the Women’s Health Initiative Observational Study: A brief report
Lung cancer is the leading cause of cancer mortality in both men and women in the United States. COPD is associated with lung cancer independently of cigarette smoking, but remains understudied in women. Utilizing data from the Women’s Health Initiative Observational Study (WHI-OS), this report investigates the association between COPD and development of lung cancer, with a focus on ethnicity and cancer subtype. The WHI-OS, part of the larger Women’s Health Initiative (WHI), is comprised of postmenopausal women between ages 50 and 79 years old at enrollment. Self-administered questionnaires were utilized to gather baseline demographic, socioeconomic, and behavioral information from participants. For this analysis, COPD status was determined at study entry (baseline) and on annual survey (incident). Information on the primary outcome of interest, diagnosis of lung cancer, was also collected annually. Of the 92,789 women examined, 1,536 developed lung cancer. Overall, women with COPD were 1.64 times more likely to develop lung cancer than those without COPD, after adjusting for smoking status and intensity, ethnicity, education, body mass index, and income (HR = 1.64, 95 % CI: 1.43, 1.89). The relationship between COPD and lung cancer was not found to be significantly different between ethnic groups (p-value = 0.697). The associations between COPD and lung cancer was similar across subtypes (HR range 1.31-2.16), after adjusting for smoking status and intensity. COPD increases risk of lung cancer in women, thus they may benefit from more intensive surveillance compared to similar women without COPD.
Authors: Nagasaka M; Lehman A; Chlebowski R; Haynes BM; Ho G; Patel M; Sakoda LC; Schwartz AG; Simon MS; Cote ML
Lung Cancer. 2020 03;141:78-81. Epub 2020-01-07.
Long-term Risk of Colorectal Cancer and Related Death After Adenoma Removal in a Large, Community-based Population
The long-term risks of colorectal cancer (CRC) and CRC-related death following adenoma removal are uncertain. Data are needed to inform evidence-based surveillance guidelines, which vary in follow-up recommendations for some polyp types. Using data from a large, community-based integrated health care setting, we examined the risks of CRC and related death by baseline colonoscopy adenoma findings. Participants at 21 medical centers underwent baseline colonoscopies from 2004 through 2010; findings were categorized as no-adenoma, low-risk adenoma, or high-risk adenoma. Participants were followed until the earliest of CRC diagnosis, death, health plan disenrollment, or December 31, 2017. Risks of CRC and related deaths among the high- and low-risk adenoma groups were compared with the no-adenoma group using Cox regression adjusting for confounders. Among 186,046 patients, 64,422 met eligibility criteria (54.3% female; mean age, 61.6 ± 7.1 years; median follow-up time, 8.1 years from the baseline colonoscopy). Compared with the no-adenoma group (45,881 patients), the high-risk adenoma group (7563 patients) had a higher risk of CRC (hazard ratio [HR] 2.61; 95% confidence interval [CI] 1.87-3.63) and related death (HR 3.94; 95% CI 1.90-6.56), whereas the low-risk adenoma group (10,978 patients) did not have a significant increase in risk of CRC (HR 1.29; 95% CI 0.89-1.88) or related death (HR 0.65; 95% CI 0.19-2.18). With up to 14 years of follow-up, high-risk adenomas were associated with an increased risk of CRC and related death, supporting early colonoscopy surveillance. Low-risk adenomas were not associated with a significantly increased risk of CRC or related deaths. These results can inform current surveillance guidelines for high- and low-risk adenomas.
Authors: Lee JK; Levin TR; Fireman BH; Quesenberry CP; Corley DA; et al.
Gastroenterology. 2020 03;158(4):884-894.e5. Epub 2019-10-04.
Risk of Mortality between Untreated and Treated Papillary Thyroid Cancer: A Matched Cohort Analysis
To examine the association between treatment status and mortality risk among patients with papillary thyroid cancer (PTC). We identified 3,679 adults with PTC. Thirty-one untreated patients were matched to 155 treated patients. Hazards ratios (HR) and 95% confidence intervals (CIs) were calculated to estimate all-cause and disease-specific mortality. A low-risk subgroup was analyzed for differences in all-cause mortality. The adjusted HRs (95% CIs) for all-cause mortality at 5 and 10 years were 4.2 (1.7-10.3) and 4.1 (1.9-9.4) and for disease- specific mortality were 14.1 (3.4-59.3) and 10.2 (2.9-36.4), respectively, for untreated versus treated patients. The adjusted HRs (95% CIs) for all- cause mortality was 0.7 (0.1-6.4) for low-risk untreated versus matched treated patients. Compared to treated patients, untreated PTC patients were at higher risk of death while low-risk untreated PTC patients had comparable rate of metastasis and no increased risk of all-cause mortality. Level of evidence: 3.
Authors: Lin JK; Sakoda LC; Darbinian J; Socarras M; Chiao W; Calixto N; Quesenberry C; Gurushanthaiah D; Wang KH; Durr M
Ann Otol Rhinol Laryngol. 2020 Mar;129(3):265-272. Epub 2019-10-28.
Evaluating screening participation, follow-up and outcomes for breast, cervical and colorectal cancer in the PROSPR consortium
Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium. We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40-74 years; cervical: ages 21-64 years; colorectal: ages 50-75 years). Metrics for screening participation, timely diagnostic evaluation, and diagnosed cancers in the screened and total populations are presented for the total eligible population and stratified by age group and cancer type. The overall screening-eligible populations in 2013 were 305 568 participants for breast, 3 160 128 for cervical, and 2 363 922 for colorectal cancer screening. Being up-to-date for testing was common for all three cancer types: breast (63.5%), cervical (84.6%), and colorectal (77.5%). The percentage of abnormal screens ranged from 10.7% for breast, 4.4% for cervical, and 4.5% for colorectal cancer screening. Abnormal breast screens were followed up diagnostically in almost all (96.8%) cases, and cervical and colorectal were similar (76.2% and 76.3%, respectively). Cancer rates per 1000 screens were 5.66, 0.17, and 1.46 for breast, cervical, and colorectal cancer, respectively. Comprehensive assessment of metrics by the Population-based Research Optimizing Screening through Personalized Regimens consortium enabled systematic identification of screening process steps in need of improvement. We encourage widespread use of common metrics to allow interventions to be tested across cancer types and health-care settings.
Authors: Barlow WE; Corley DA; Silverberg MJ; Tiro JA; et al.
J Natl Cancer Inst. 2020 03 01;112(3):238-246.
American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the management of acute colonic pseudo-obstruction and colonic volvulus
Colonic volvulus and acute colonic pseudo-obstruction (ACPO) are 2 causes of benign large-bowel obstruction. Colonic volvulus occurs most commonly in the sigmoid colon as a result of bowel twisting along its mesenteric axis. In contrast, the exact pathophysiology of ACPO is poorly understood, with the prevailing hypothesis being altered regulation of colonic function by the autonomic nervous system resulting in colonic distention in the absence of mechanical blockage. Prompt diagnosis and intervention leads to improved outcomes for both diagnoses. Endoscopy may play a role in the evaluation and management of both entities. The purpose of this document from the American Society for Gastrointestinal Endoscopy’s Standards of Practice Committee is to provide an update on the evaluation and endoscopic management of sigmoid volvulus and ACPO.
Authors: Naveed M; Qumseya BJ; Wani SB; et al.
Gastrointest Endosc. 2020 02;91(2):228-235. Epub 2019-11-30.
ASGE guideline on the management of achalasia
Achalasia is a primary esophageal motor disorder of unknown etiology characterized by degeneration of the myenteric plexus, which results in impaired relaxation of the esophagogastric junction (EGJ), along with the loss of organized peristalsis in the esophageal body. The criterion standard for diagnosing achalasia is high-resolution esophageal manometry showing incomplete relaxation of the EGJ coupled with the absence of organized peristalsis. Three achalasia subtypes have been defined based on high-resolution manometry findings in the esophageal body. Treatment of patients with achalasia has evolved in recent years with the introduction of peroral endoscopic myotomy. Other treatment options include botulinum toxin injection, pneumatic dilation, and Heller myotomy. This American Society for Gastrointestinal Endoscopy Standards of Practice Guideline provides evidence-based recommendations for the treatment of achalasia, based on an updated assessment of the individual and comparative effectiveness, adverse effects, and cost of the 4 aforementioned achalasia therapies.
Authors: Khashab MA; Lee JK; Wani S; et al.
Gastrointest Endosc. 2020 02;91(2):213-227.e6. Epub 2019-12-13.
Adjuvant endocrine therapy for breast cancer patients: impact of a health system outreach program to improve adherence
Reports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5 years of adjuvant endocrine therapy (AET). We examined the impact of an outreach program at Kaiser Permanente Northern California (KPNC) on adherence and discontinuation of AET among patients who initiated AET. We assembled a retrospective cohort of all KPNC patients diagnosed with HR+, stage I-III BC initiating AET before (n = 4287) and after (n = 3580) implementation of the outreach program. We compared adherence proportions and discontinuation rates before and after program implementation, both crude and adjusted for age, race/ethnicity, education, income, and stage. We conducted a pooled analysis of data from six Cancer Research Network (CRN) sites that had not implemented programs for improving AET adherence, using identical methods and time periods, to assess possible secular trends. In the pre-outreach period, estimated adherence in years 1, 2, and 3 following AET initiation was 75.2%, 71.0%, and 67.3%; following the outreach program, the estimates were 79.4%, 75.6%, and 72.2% (p-values < .0001 for pairwise comparisons). Results were comparable after adjusting for clinical and demographic factors. The estimated cumulative incidence of discontinuation was 0.22 (0.21-0.24) and 0.18 (0.17-0.19) at 3 years for pre- and post-outreach groups (p-value < .0001). We found no evidence of an increase in adherence between the study periods at the CRN sites with no AET adherence program. Adherence and discontinuation after AET initiation improved modestly following implementation of the outreach program.
Authors: Lee C; Check DK; Manace Brenman L; Kushi LH; Epstein MM; Neslund-Dudas C; Pawloski PA; Achacoso N; Laurent C; Fehrenbacher L; Habel LA
Breast Cancer Res Treat. 2020 Feb;180(1):219-226. Epub 2020-01-23.
Validity of state cancer registry treatment information for adolescent and young adult women
Population-based cancer registries collect information on first course of treatment that may be utilized in research on cancer care quality, yet few studies have investigated the validity of this information. We examined the accuracy and completeness of registry-based treatment information in a cohort of adolescent and young adult women. Women diagnosed with breast cancer, lymphoma, thyroid cancer, cervical/uterine cancer or ovarian cancer at ages 15-39 during 2003-2014 were identified using data from the North Carolina Central Cancer Registry (CCR) (N = 2342). CCR data were linked to Medicaid and private insurance claims data, and claims were reviewed for the 12 months following diagnosis to identify cancer treatments received. Using claims data as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of CCR data for receipt of chemotherapy, radiation and hormone therapy. We also compared dates of treatment initiation between the two data sources. For all cancer types combined, the sensitivity of the CCR data was high for chemotherapy (86%) and moderate for radiation (74%). PPVs were 82% and 83% for chemotherapy and radiation, respectively. Both the sensitivity (67%) and PPV (70%) were lower for hormone therapy for breast cancer. For all three treatment types, dates of initiation in the registry and the claims differed by ≤30 days for most women. In this cohort of young women, population-based cancer registry data on chemotherapy receipt was reasonably accurate and complete in comparison with insurance claims. Radiation and hormone therapy appeared to be less complete.
Authors: Anderson C; Baggett CD; Rao C; Moy L; Kushi LH; Chao CR; Nichols HB
Cancer Epidemiol. 2020 02;64:101652. Epub 2019-12-05.
Body Composition, Adherence to Anthracycline and Taxane-Based Chemotherapy, and Survival After Nonmetastatic Breast Cancer
Although most chemotherapies are dosed on body surface area or weight, body composition (ie, the amount and distribution of muscle and adipose tissues) is thought to be associated with chemotherapy tolerance and adherence. To evaluate whether body composition is associated with relative dose intensity (RDI) on anthracycline and taxane-based chemotherapy or hematologic toxic effects and whether lower RDI mediates the association of adiposity with mortality. An observational cohort study with prospectively collected electronic medical record data was conducted at Kaiser Permanente Northern California, a multicenter, community oncology setting within an integrated health care delivery system. Participants included 1395 patients with nonmetastatic breast cancer diagnosed between January 1, 2005, and December 31, 2013, and treated with anthracycline and taxane-based chemotherapy. Data analysis was performed between February 25 and September 4, 2019. Intramuscular, visceral, and subcutaneous adiposity as well as skeletal muscle were evaluated from clinically acquired computed tomographic scans at diagnosis. The primary outcome was low RDI (<0.85), which is the ratio of delivered to planned chemotherapy dose, derived from infusion records; in addition, hematologic toxic effects were defined based on laboratory test values. To evaluate associations with overall and breast cancer-specific mortality, logistic regression models adjusted for age and body surface area were fit as well as Cox proportional hazards models adjusted for age, race/ethnicity, adiposity, Charlson comorbidity index score, and tumor stage and subtype. The mediation proportion was computed using the difference method. The mean (SD) age at diagnosis of the 1395 women included in the study was 52.8 (10.2) years. Greater visceral (odds ratio [OR], 1.19; 95% CI, 1.02-1.39 per SD) and intramuscular (OR, 1.16; 95% CI, 1.01-1.34 per SD) adiposity were associated with increased odds of RDI less than 0.85. Greater muscle mass was associated with a decreased odds of hematologic toxic effects (OR, 0.84; 95% CI, 0.71-0.98 per SD). Relative dose intensity less than 0.85 was associated with a 30% increased risk of death (hazard ratio, 1.30; 95% CI, 1.02-1.65). Lower RDI partially explained the association of adiposity with breast cancer-specific mortality (mediation proportion, 0.20; 95% CI, 0.05-0.55). Excess adiposity, presenting as larger visceral or intramuscular adiposity, was associated with lower RDI. Lower RDI partially mediated the association of adiposity with worse breast cancer-specific survival. Body composition may help to identify patients likely to experience toxic effects and subsequent dose delays or reductions, which could compromise chemotherapeutic efficacy.
Authors: Cespedes Feliciano EM; Chen WY; Lee V; Albers KB; Prado CM; Alexeeff S; Xiao J; Shachar SS; Caan BJ
JAMA Oncol. 2020 02 01;6(2):264-270.
Longitudinal Evolution of Markers of Mineral Metabolism in Patients With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study
The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD. Retrospective analysis nested in a cohort study. Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847). Years before ESKD. Serial FGF-23, PTH, serum phosphate, and serum calcium levels. To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used “ESKD-anchored longitudinal analyses” to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD. Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased. Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.
Authors: Isakova T; Lo J; CRIC Study Investigators; et al.
Am J Kidney Dis. 2020 02;75(2):235-244. Epub 2019-10-23.
Re: Cancer outcomes in DCIS patients without locoregional treatment
Authors: Habel LA; Buist DSM
J Natl Cancer Inst. 2020 02 01;112(2):214-215.
Meta-analysis of 16 studies of the association of alcohol with colorectal cancer
Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.
Authors: McNabb S; Caan BJ; Peters U; et al.
Int J Cancer. 2020 02 01;146(3):861-873. Epub 2019-06-07.
DNA repair and cancer in colon and rectum: novel players in genetic susceptibility
Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 × 10-6 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 × 10-6 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 × 10-6 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.
Authors: Pardini B; Caan BJ; Landi S; et al.
Int J Cancer. 2020 01 15;146(2):363-372. Epub 2019-07-04.
Serum bone markers and risk of osteoporosis and fragility fractures in women who received endocrine therapy for breast cancer: a prospective study
Osteoporosis and fragility fracture are major bone toxicities of aromatase inhibitors (AIs) for postmenopausal hormone receptor-positive breast cancer. Except for a few small studies on bone turnover markers and reduced bone mineral density after AI treatment, data on the associations of bone markers and risk of osteoporosis or fracture from prospective studies are lacking. In a prospective study of 1709 women on AIs, two bone turnover markers, BALP and TRACP, and two bone regulatory markers, RANKL and OPG, were measured and examined in relation to risk of osteoporosis and fragility fractures during a median follow-up time of 6.1 years. Higher levels of BALP and TRACP were both associated with increased risk of osteoporosis and higher BALP/TRACP ratios were associated with lower risk of osteoporosis, but no associations were observed for fracture risk. Higher levels of OPG were associated with increased risk of fracture, whereas higher levels of RANKL were associated with lower risk. As a result, OPG/RANKL ratios were positively associated with fracture risk [hazard ratio (HR) = 2.49, 95% confidence interval (CI) 1.34-4.61]. After controlling for age and fracture history, the associations became non-significant but a suggestive trend remained (HR = 1.80, 95% CI 0.96-3.37). Our study provides suggestive evidence for the potential utility of OPG/RANKL ratios in predicting risk of fracture in women treated with AIs for breast cancer. Further validation may be warranted.
Authors: Yao S; Laurent CA; Roh JM; Lo J; Tang L; Hahn T; Ambrosone CB; Kushi LH; Kwan ML
Breast Cancer Res Treat. 2020 Jan 07.
Distinct trajectories of fruits and vegetables, dietary fat, and alcohol intake following a breast cancer diagnosis: the Pathways Study
To identify distinct diet trajectories after breast cancer (BC) diagnosis, and to examine the characteristics associated with diet trajectories. We analyzed 2865 Pathways Study participants who completed ≥ 2 food frequency questionnaires at the time of BC diagnosis (baseline), and at 6 and 24 months after baseline. Trajectory groups of fruit and vegetable (F/V) intake, % calories from dietary fat, and alcohol intake over 24 months were identified using group-based trajectory modeling. Associations between diet trajectories and sociodemographic, psychosocial, and clinical factors were analyzed using multinomial logistic regression. Analyses identified 3 F/V trajectory groups, 4 dietary fat groups, and 3 alcohol groups. All 3 F/V trajectory groups reported slightly increased F/V intake post-diagnosis (mean increase = 0.2-0.5 serving/day), while 2 groups (48% of participants) persistently consumed < 4 servings/day of F/V. Dietary fat intake did not change post-diagnosis, with 45% of survivors maintaining a high-fat diet (> 40% of calories from fat). While most survivors consumed < 1 drink/day of alcohol at all times, 21% of survivors had 1.4-3.0 drinks/day at baseline and temporarily decreased to 0.1-0.5 drinks/day at 6 months. In multivariable analysis, diet trajectory groups were significantly associated with education (ORs: 1.93-2.49), income (ORs: 1.32-2.57), optimism (ORs: 1.93-2.49), social support (OR = 1.82), and changes in physical well-being (ORs: 0.58-0.61) and neuropathy symptoms after diagnosis (ORs: 1.29-1.66). Pathways Study participants reported slightly increasing F/V and decreasing alcohol intake after BC diagnosis. Nearly half of survivors consumed insufficient F/V and excessive dietary fat. It is important to prioritize nutrition counseling and education in BC survivors.
Authors: Shi Z; Rundle A; Genkinger JM; Cheung YK; Ergas IJ; Roh JM; Kushi LH; Kwan ML; Greenlee H
Breast Cancer Res Treat. 2020 Jan;179(1):229-240. Epub 2019-10-10.
Neodymium Magnetic Bead Ingestion in a Toddler
Authors: Hui, Kenneth J; Arasu, Vignesh A; Vinson, David R; Cotton, Dale M
Perm J. 2020;24. Epub 2020-04-16.
Variation in Colorectal Cancer Stage and Mortality across Large Community-Based Populations: PORTAL Colorectal Cancer Cohort
Colorectal cancer (CRC) incidence and mortality can be reduced by effective screening and/or treatment. However, the influence of health care systems on disparities among insured patients is largely unexplored. To evaluate insured patients with CRC diagnosed between 2010 and 2014 across 6 diverse US health care systems in the Patient-Centered Outcomes Research Institute (PCORI) Patient Outcomes Research To Advance Learning (PORTAL) CRC cohort, we contrasted CRC stage; CRC mortality; all-cause mortality; and influences of demographics, stage, comorbidities, and treatment between health systems. Among 16,211 patients with CRC, there were significant differences between health care systems in CRC stage at diagnosis, CRC-specific mortality, and all-cause mortality. The unadjusted risk of CRC mortality varied from 27% lower to 21% higher than the reference system (hazard ratio [HR] = 0.73, 95% confidence interval = 0.66-0.80 to HR = 1.21, 95% confidence interval = 1.05-1.40; p < 0.01 across systems). Significant differences persisted after adjustment for demographics and comorbidities (p < 0.01); however, adjustment for stage eliminated significant differences (p = 0.24). All-cause mortality among patients with CRC differed approximately 30% between health care systems (HR = 0.89-1.17; p < 0.01). Adjustment for age eliminated significant differences (p = 0.48). Differences in CRC survival between health care systems were largely explained by stage at diagnosis, not demographics, comorbidity, or treatment. Given that stage is strongly related to early detection, these results suggest that variation in CRC screening systems represents a modifiable systems-level factor for reducing disparities in CRC survival.
Authors: Schneider, Jennifer L; Feigelson, Heather Spencer; Quinn, Virginia P; McMullen, Carmit; Pawloski, Pamela A; Powers, John D; Sterrett, Andrew T; Arterburn, David; Corley, Douglas A
Perm J. 2020;24.
Material and psychological financial hardship related to employment disruption among female adolescent and young adult cancer survivors
The importance of addressing adverse financial effects of cancer among adolescents and young adults (AYAs) is paramount as survival improves. In the current study, the authors examined whether cancer-related employment disruption was associated with financial hardship among female AYA cancer survivors in North Carolina and California. AYA cancer survivors identified through the North Carolina Central Cancer Registry and the Kaiser Permanente Northern/Southern California tumor registries responded to an online survey. Disrupted employment was defined as reducing hours, taking temporary leave, or stopping work completely because of cancer. Financial hardship was defined as material conditions or psychological distress related to cancer. Descriptive statistics and chi-square tests were used to characterize the invited sample and survey respondents. Marginal structural binomial regression models were used to estimate prevalence differences (PDs) and 95% confidence intervals (95% CIs). Among 1328 women employed at the time of their diagnosis, women were a median age of 34 years at the time of diagnosis and 7 years from diagnosis at the time of the survey and approximately 32% experienced employment disruption. A substantial percentage reported financial hardship related to material conditions (27%) or psychological distress (50%). In adjusted analyses, women with disrupted employment had a 17% higher burden of material conditions (95% CI, 10%-23%) and an 8% higher burden of psychological distress (95% CI, 1%-16%) compared with those without disruption. Financial hardship related to employment disruption among female AYA cancer survivors can be substantial. Interventions to promote job maintenance and transition back to the workforce after treatment, as well as improved workplace accommodations and benefits, present an opportunity to improve cancer survivorship.
Authors: Meernik, Clare; Kirchhoff, Anne C; Anderson, Chelsea; Edwards, Teresa P; Deal, Allison M; Baggett, Christopher D; Kushi, Lawrence H; Chao, Chun R; Nichols, Hazel B
Cancer. 2020 01 01;127(1):137-148. Epub 2020-10-12.
Interpersonal Trauma as a Marker of Risk for Urinary Tract Dysfunction in Midlife and Older Women
To examine relationships between interpersonal trauma exposures and urinary symptoms in community-dwelling midlife and older women. We analyzed cross-sectional data from a multiethnic cohort of women aged 40-80 years enrolled in an integrated health care system in California. Lifetime history of intimate partner violence (IPV) and sexual assault, current posttraumatic stress disorder (PTSD) symptoms, and current urinary symptoms were assessed using structured-item questionnaires. Multivariable-adjusted logistic regression models examined associations between traumatic exposures and PTSD symptoms with any weekly urinary incontinence, stress-type incontinence, urgency-type incontinence, and nocturia two or more times per night. Of the 1,999 participants analyzed, 21.7% women reported lifetime emotional IPV, 16.2% physical IPV, 19.7% sexual assault, and 22.6% reported clinically significant PTSD symptoms. Overall, 45% reported any weekly incontinence, 23% stress-type incontinence, 23% urgency-type incontinence, and 35% nocturia. Exposure to emotional IPV was associated with any weekly incontinence (odds ratio [OR] 1.33, 95% CI 1.04-1.70), stress-type incontinence (OR 1.30, 95% CI 1.00-1.65), urgency-type incontinence (OR 1.30, 95% CI 1.00-1.70), and nocturia (OR 1.73, 95% CI 1.36-2.19). Physical IPV exposure was associated with nocturia (OR 1.35, 95% CI 1.04-1.77), but not incontinence. Sexual assault history was not associated with weekly incontinence of any type or nocturia. Symptoms of PTSD were associated with all urinary symptoms assessed, including any weekly incontinence (OR 1.46, 95% CI 1.15-1.85), stress-type incontinence (OR 1.70, 95% CI 1.32-2.20), urgency-type incontinence (OR 1.60, 95% CI 1.24-2.06), and nocturia (OR 1.95, 95% CI 1.55-2.45). More than 20% of women in this multiethnic, community-based cohort reported a history of IPV, PTSD symptoms, or both, which were associated with symptomatic urinary tract dysfunction. Findings highlight the need to provide trauma-informed care of midlife and older women presenting with urinary symptoms.
Authors: Boyd BAJ; Gibson CJ; Van Den Eeden SK; McCaw B; Subak LL; Thom D; Huang AJ
Obstet Gynecol. 2020 01;135(1):106-112.
It’s Absolutely Relative: The Effect of Age on the BMI-Mortality Relationship in Postmenopausal Women
The use of relative and absolute effect estimates has important implications for the interpretation of study findings. Likewise, examining additive and multiplicative interaction can lead to differing conclusions about the joint effects of two exposure variables. The aim of this paper is to examine the relationship between BMI and mortality on the relative and absolute scales and investigate interaction between BMI and age. Data from 68,132 participants in the Women’s Health Initiative (WHI) study were used. The risk ratio and risk difference of BMI on mortality were estimated. A product term was also included to examine interaction between BMI and age on the multiplicative scale, and the relative excess risk of interaction was calculated to measure additive interaction. Results demonstrated that the mortality risk ratio decreased as women aged, but the mortality risk difference increased as women aged. Evidence of additive and multiplicative interaction between age and BMI was found. In postmenopausal women, the relative mortality risk associated with high BMI decreased with increasing age, but the absolute risk of high BMI increased with increasing age. This indicates the importance of considering the interaction between age and BMI to understand mortality risk in older women.
Authors: Banack HR; Kroenke CH; Caan B; Wactawski-Wende J; et al.
Obesity (Silver Spring). 2020 01;28(1):171-177. Epub 2019-12-04.
Decision Regret Related to Urinary Diversion Choice Among Cystectomy Patients
Patients who undergo cystectomy due to bladder cancer can elect an ileal conduit or a neobladder for urinary diversion. Decision regret related to this choice is an important and undesirable patient reported outcome. Our objective was to compare the severity of decision regret experienced by patients with a neobladder vs an ileal conduit. We analyzed data from a longitudinal cohort study of patients who underwent cystectomy from 2013 to 2015. We applied multivariable linear regression to examine associations of the urinary diversion method (neobladder vs ileal conduit) with decision regret measured with the DRS (Decision Regret Scale) 6 and 18 months after cystectomy. Covariates included demographic and clinical characteristics, health care utilization and complications after cystectomy, quality of life and factors related to the decision making process, including informed and shared decision making, and goal concordance. Of the 192 patients in our cohort 141 received an ileal conduit and 51 received a neobladder. We observed no significant difference in the DRS score in patients with a neobladder vs an ileal conduit at 6 or 18 months (b=-1.28, 95% CI -9.07-6.53, vs b=-1.55, 95% CI -12.48-9.38). However, informed decision making was negatively related to decision regret at 6 and 18 months (b=-13.08, 95% CI -17.05–9.11, and b=-8.54, 95% CI -4.26–2.63, respectively). Quality of life was negatively associated with decision regret at 18 months (b=-5.50, 95% CI -8.95–2.03). Patients treated with cystectomy who were more informed about bladder reconstruction options experienced less regret independent of the method selected. Efforts to inform and prepare patients for the bladder reconstruction decision may help prevent decision regret.
Authors: Check DK; Leo MC; Banegas MP; Bulkley JE; Danforth KN; Gilbert SM; Kwan ML; Rosetti MO; McMullen CK
J Urol. 2020 01;203(1):159-163. Epub 2019-08-23.
LIFE EXPECTANCY DISPARITIES AMONG ADULTS WITH HIV IN THE UNITED STATES AND CANADA: THE IMPACT OF A REDUCTION IN DRUG- AND ALCOHOL-RELATED DEATHS USING THE LIVES SAVED SIMULATION (LISSO) MODEL
Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic, drug- and alcohol-related deaths might be contributing to the disparities in life expectancy. We sought to estimate life expectancy at age 20 years in key populations (and their comparison groups) in 3 time periods (2004-2007, 2008-2011, and 2012-2015) and the potential increase in expected life expectancy with a simulated 20% reduction in drug- and alcohol-related deaths using the novel Lives Saved Simulation model. Among 92,289 PLWH, life expectancy increased in all key populations and comparison groups from 2004-2007 to 2012-2015. Disparities in survival of approximately a decade persisted among black versus white men who have sex with men and people with (vs. without) a history of injection drug use. A 20% reduction in drug- and alcohol-related mortality would have the greatest life-expectancy benefit for black men who have sex with men, white women, and people with a history of injection drug use. Our findings suggest that preventing drug- and alcohol-related deaths among PLWH could narrow disparities in life expectancy among some key populations, but other causes of death must be addressed to further narrow the disparities.
Authors: Althoff KN; Silverberg MJ; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA; et al.
Am J Epidemiol. 2019 12 31;188(12):2097-2109.
The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies
Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.
Authors: Watts EL; Habel LA; Schaefer CA; Van Den Eeden SK; Travis RC; et al.
Int J Cancer. 2019 12 15;145(12):3244-3256. Epub 2019-04-04.
AGA Clinical Practice Guidelines on Management of Gastric Intestinal Metaplasia
Authors: Gupta S; Li D; El Serag HB; Davitkov P; Altayar O; Sultan S; Falck-Ytter Y; Mustafa RA
Gastroenterology. 2019 Dec 06.
Understanding the natural history of papillary thyroid cancer: Case series
Papillary thyroid cancer (PTC) incidence continues to rise. We describe the natural history of untreated PTC patients. Retrospective case series of 31 untreated PTC patients. We identified 31 untreated patients from the Kaiser Permanente Cancer Registry with PTC from 1973 to 2010. Patients were categorized as low risk (n = 16), high risk (n = 12), or low risk but medically contraindicated for surgery (n = 3). At diagnosis, 7 (58.3%) in the high-risk group had cervical lymph node metastases and 5 (41.7%) had distant metastases, compared to none in the low-risk group. Among the latter, three (18.8%) patients developed tumor growth >3 mm and one (6.3%) developed regional lymph node metastases without distant metastases. The 10-year overall survival was 71% and 35% for the low-risk and high-risk groups, respectively. Patients with low-risk untreated PTC were less likely to develop new regional or distant metastases and had better overall survival than patients with high-risk untreated PTC. 4.
Authors: Lin JK; Sakoda LC; Darbinian J; Chiao W; Calixto N; Gurushanthaiah D; Wang KH; Durr M
Head Neck. 2019 12;41(12):4164-4170. Epub 2019-10-04.
Incidence rates of cardiovascular outcomes in a community-based population of cancer patients
There are limited data on the incidence of cardiovascular disease among cancer patients in the pre-tyrosine kinase inhibitor (TKI) era. Such data are important in order to contextualize the incidence of various cardiovascular outcomes among cancer patients enrolled in clinical trials of new agents and for postmarketing surveillance. A retrospective cohort study was conducted using data from the Kaiser Permanente Northern California (KPNC) population of cancer patients. The inclusion criterion was a KPNC Cancer Registry diagnosis of any of several selected solid and hematologic tumors between 1997 and 2009 not treated with a TKI. Endpoints were identified using ICD-9 codes and included acute coronary syndrome, heart failure, stroke, cardiac arrest, hypertension, venous thromboembolism, all-cause mortality, and cardiovascular mortality. Event rates were calculated according to type of cancer and number of cardiovascular risk factors. The study included almost 165 000 individuals with a broad variety of tumor types. The parent cohort was 54% female and 35% were ?70 years old. Cardiovascular risk factors such as diabetes mellitus (14% of patients with solid tumors, 15% of patients with liquid tumors), dyslipidemia (33%, 31%), hypertension (50%, 49%), and smoking (35%, 32%) were common. The most frequent adverse outcomes were incident hypertension (26.8-61.0 cases per 1000 person-years, depending on the type of cancer), heart failure (9.4-78.7), and acute coronary syndrome (2.6-48.1). These event rates are high compared to what has been reported in prior KPNC cohort studies of patients without cancer. The rates of acute coronary syndrome, heart failure, and ischemic stroke increased with increasing numbers of cardiovascular risk factors. In a population of patients with cancer not exposed to TKIs, cardiovascular risk factors and outcomes are very common, regardless of cancer type. These data can inform the evaluation of potential excess cardiovascular risks from new interventions.
Authors: Masson R; Titievsky L; Corley DA; Zhao W; Lopez AR; Schneider J; Zaroff JG
Cancer Med. 2019 12;8(18):7913-7923. Epub 2019-10-30.
A Scalable Database of Organ Doses for Common Diagnostic Fluoroscopy Procedures of Children: Procedures of Historical Practice for Use in Radiation Epidemiology Studies
Assessment of health effects from low-dose radiation exposures in patients undergoing diagnostic imaging is an active area of research. High-quality dosimetry information pertaining to these medical exposures is generally not readily available to clinicians or epidemiologists studying radiation-related health risks. The purpose of this study was to provide methods for organ dose estimation in pediatric patients undergoing four common diagnostic fluoroscopy procedures: the upper gastrointestinal (UGI) series, the lower gastrointestinal (LGI) series, the voiding cystourethrogram (VCUG) and the modified barium swallow (MBS). Abstracted X-ray film data and physician interviews were combined to generate procedure outlines detailing X-ray beam projections, imaged anatomy, length of X-ray exposure, and presence and amount of contrast within imaged anatomy. Monte Carlo radiation transport simulations were completed for each of the four diagnostic fluoroscopy procedures across the 162-member (87 males and 75 females) University of Florida/National Cancer Institute pediatric phantom library, which covers variations in both subject height and weight. Absorbed doses to 28 organs, including the active marrow and bone endosteum, were assigned for all 162 phantoms by procedure. Additionally, we provide dose coefficients (DCs) in a series of supplementary tables. The DCs give organ doses normalized to procedure-specific dose metrics, including: air kerma-area product (µGy/mGy · cm2), air kerma at the reference point (µGy/µGy), number of spot films (SF) (µGy/number of SFs) and total fluoroscopy time (µGy/s). Organs accumulating the highest absorbed doses per procedure were as follows: kidneys between 0.9-25.4 mGy, 1.1-16.6 mGy and 1.1-9.7 mGy for the UGI, LGI and VCUG procedures, respectively, and salivary glands between 0.2-3.7 mGy for the MBS procedure. Average values of detriment-weighted dose, a phantom-specific surrogate for the effective dose based on ICRP Publication 103 tissue-weighting factors, were 0.98 mSv, 1.16 mSv, 0.83 mSv and 0.15 mSv for the UGI, LGI, VCUG and MBS procedures, respectively. Scalable database of organ dose coefficients by patient sex, height and weight, and by procedure exposure time, reference point air kerma, kerma-area product or number of spot films, allows clinicians and researchers to compute organ absorbed doses based on their institution-specific and patient-specific dose metrics. In addition to informing on patient dosimetry, this work has the potential to facilitate exposure assessments in epidemiological studies designed to investigate radiation-related risks.
Authors: Marshall EL; Kwan ML; Bolch WE; et al.
Radiat Res. 2019 12;192(6):649-661. Epub 2019-10-14.
Effect of Sex, Age and Positivity Threshold on Fecal Immunochemical Test Accuracy: a Systematic Review and Meta-Analysis
Quantitative fecal immunochemical tests (FITs) for hemoglobin are commonly used for colorectal cancer (CRC) screening. We aimed to quantify the change in CRC and advanced adenoma detection and number of positive test results at different positivity thresholds and by sex and age. We searched MEDLINE and EMBASE, selecting articles of FIT for CRC detection in asymptomatic adults undergoing screening. We calculated sensitivity and specificity, as well as detected number of cancers, advanced adenomas, and positive test results at positivity thresholds ≤10 μg hemoglobin/g feces, 10 to ≤20 μg/g, 20 to ≤30 μg/g, and >30 μg/g. We also analyzed results from stratified by patient sex, age, and reference standard. Our meta-analysis comprised 46 studies with 2.4 million participants and 6478 detected cancers. Sensitivity for detection of CRC increased from 69% (95% confidence interval [CI], 63%-75%) at thresholds >10 μg/g and ≤20 μg/g to 80% (95% CI, 76%-83%) at thresholds ≤10 μg/g. At these threshold values, sensitivity for detection of advanced adenomas increased from 21% (95% CI, 18%-25%) to 31% (95% CI, 27%-35%), whereas specificity decreased from 94% (95% CI, 93%-96%) to 91% (95% CI, 89%-93%). In 3 studies stratified by sex, sensitivity of CRC detection was 77% in men (95% CI, 75%-79%) and 81% in women (95% CI, 60%-100%) (P = .68). In 3 studies stratified by age groups, sensitivity of CRC detection was 85% for ages 50-59 years (95% CI, 71%-99%) and 73% for ages 60-69 years (95% CI, 71%-75%) (P = .10). All studies with colonoscopy follow-up had similar sensitivity levels for detection of CRC to studies that analyzed 2-year registry follow-up data (74%; 95% CI, 68%-78% vs 75%; 95% CI, 73%-77%). In a meta-analysis of studies that analyzed detection of CRC and advanced adenomas at different FIT positivity thresholds, we found the sensitivity and specificity of detection to vary with positive cutoff value. It might be possible to decrease positive threshold values for centers with sufficient follow-up colonoscopy resources. More research is needed to precisely establish FIT thresholds for each sex and age subgroup. PROSPERO CRD42017068760.
Authors: Selby K; Levine EH; Doan C; Gies A; Brenner H; Quesenberry C; Lee JK; Corley DA
Gastroenterology. 2019 12;157(6):1494-1505. Epub 2019-08-22.
Post diagnosis loss of skeletal muscle, but not adipose tissue, is associated with shorter survival of patients with advanced pancreatic cancer
Pancreatic cancer is associated with development of cachexia, a wasting syndrome thought to limit survival. Few studies have longitudinally quantified peripheral tissues or identified biomarkers predictive of future tissue wasting. Adipose and muscle tissue were measured by computed tomography (CT) at diagnosis and 50 to 120 days later in 164 patients with advanced pancreatic cancer. Tissue changes and survival were evaluated by Cox proportional hazards regression. Baseline levels of circulating markers were examined in relation to future tissue wasting. Compared with patients in the bottom quartile of muscle change per 30 days (average gain of 0.8 ± 2.0 cm2), those in the top quartile (average loss of 12.9 ± 4.9 cm2) had a hazard ratio (HR) for death of 2.01 [95% confidence interval (CI), 1.12-3.62]. Patients in the top quartile of muscle attenuation change (average decrease of 4.9 ± 2.4 Hounsfield units) had an HR of 2.19 (95% CI, 1.18-4.04) compared with those in the bottom quartile (average increase of 2.4 ± 1.6 Hounsfield units). Changes in adipose tissue were not associated with survival. Higher plasma branched chain amino acids (BCAA; P = 0.004) and lower monocyte chemoattractant protein-1 (MCP-1; P = 0.005) at diagnosis were associated with greater future muscle loss. In patients with advanced pancreatic cancer, muscle loss and decrease in muscle density in 2 to 4 months after diagnosis were associated with reduced survival. BCAAs and MCP-1 levels at diagnosis were associated with subsequent muscle loss. BCAAs and MCP-1 levels at diagnosis could identify a high-risk group for future tissue wasting.
Authors: Babic A; Caan B; Wolpin BM; et al.
Cancer Epidemiol Biomarkers Prev. 2019 12;28(12):2062-2069. Epub 2019-09-18.
Diabetes in relation to Barrett’s esophagus and adenocarcinomas of the esophagus: A pooled study from the International Barrett’s and Esophageal Adenocarcinoma Consortium
Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear. Data were harmonized across 13 studies in the International Barrett’s and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett’s esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% CIs for self-reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random-effects meta-analysis. Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00-1.80; I2 = 48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05-1.55; I2 = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06-1.58; I2 = 34.9%). Regurgitation symptoms modified the diabetes-EA/EGJA association (P for interaction = .04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19-2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74-1.43). No consistent association was found between diabetes and BE. Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer.
Authors: Petrick JL; Corley DA; Cook MB; et al.
Cancer. 2019 12 01;125(23):4210-4223. Epub 2019-09-06.
Statins as a free pass: Body mass index and other cardiovascular risk factors among lipid-lowering medication users and nonusers in the California Men’s Health Study
To lower risk from cardiovascular disease (CVD), national guidelines recommend lifestyle changes followed by use of lipid-lowering medications when appropriate. Previous studies have questioned whether individuals taking these medications are less likely to modify their dietary intake and physical activity, resulting in increased body mass index (BMI). We assessed BMI and CVD clinical risk factors over time between lipid-lowering medication users and nonusers in a diverse cohort of middle-aged and older men. The cohort consisted of 63,357 men who enrolled in the California Men’s Health Study between 2002 and 2003 and were not taking lipid-lowering medications at baseline. Lipid-lowering medication use was determined over twelve years of follow-up. BMI and other CVD risk factors were assessed with longitudinal linear mixed effect models adjusting for possible confounders. Overall, lipid-lowering medication users had higher BMI than nonusers (p < .0001); however, there was a decrease over time for both groups (p < .0001). Total cholesterol, LDL-C, and triglycerides decreased for users and nonusers (p < .0001). While HDL-C was higher for nonusers (p < .05), over time this measure increased in both groups (p < .0001). We found no evidence of increases in BMI after initiation of lipid-lowering medication in this cohort. Instead, BMI decreased and several cholesterol-related CVD risk factors improved for lipid-lowering medication users and nonusers. This suggests that men placed on lipid-lowering medications do not view them as a panacea for their increased risk of cardiovascular disease. Instead, they appear to perceive them as one component of a multi-pronged strategy including lifestyle and nutrition as suggested by current guidelines.
Authors: Sidell MA; Ghai NR; Reynolds K; Jacobsen SJ; Scott R; Van Den Eeden S; Caan B; Quinn VP
Prev Med. 2019 12;129:105822. Epub 2019-08-27.
Is breast cancer in Asian and Asian American women a different disease?
Authors: Gomez SL; Yao S; Kushi LH; Kurian AW
J Natl Cancer Inst. 2019 12 01;111(12):1243-1244.
Exploring Care Attributes of Nephrologists Ranking Favorably on Measures of Value.
BACKGROUND: Despite growth in value-based payment, attributes of nephrology care associated with payer-defined value remains unexplored. n METHODS: Using national health insurance claims data from private preferred provider organization plans, we ranked nephrology practices using total cost of care and a composite of common quality metrics. Blinded to practice rankings, we conducted site visits at four highly ranked and three average ranked practices to identify care attributes more frequently present in highly ranked practices. A panel of nephrologists used a modified Delphi method to score each distinguishing attribute on its potential to affect quality and cost of care and ease of transfer to other nephrology practices. n RESULTS: Compared with average-value peers, high-value practices were located in areas with a relatively higher proportion of black and Hispanic patients and a lower proportion of patients aged >65 years. Mean risk-adjusted per capita monthly total spending was 24% lower for high-value practices. Twelve attributes comprising five general themes were observed more frequently in high-value nephrology practices: preventing near-term costly health crises, supporting patient self-care, maximizing effectiveness of office visits, selecting cost-effective diagnostic and treatment options, and developing infrastructure to support high-value care. The Delphi panel rated four attributes highly on effect and transferability: rapidly adjustable office visit frequency for unstable patients, close monitoring and management to preserve kidney function, early planning for vascular access, and education to support self-management at every contact. n CONCLUSIONS: Findings from this small-scale exploratory study may serve as a starting point for nephrologists seeking to improve on payer-specified value measures.
Authors: Brady, Brian M;Ragavan, Meera V;Simon, Melora;Chertow, Glenn M;Milstein, Arnold
J Am Soc Nephrol. 2019 Dec;30(12):2464-2472. doi: 10.1681/ASN.2019030219. Epub 2019 Nov 14.
Understanding racial disparities in renal cell carcinoma incidence: estimates of population attributable risk in two US populations
Renal cell carcinoma (RCC) incidence is higher among black than white Americans. The reasons for this disparity remain unclear. We calculated race- and sex-specific population attributable risk percentages (PAR%) and their 95% confidence intervals (CI) for hypertension and chronic kidney disease (CKD) among black and white subjects ≥ 50 years of age from the US Kidney Cancer Study (USKC; 965 cases, 953 controls), a case-control study in Chicago and Detroit, and a nested case-control study in the Kaiser Permanente Northern California health care network (KPNC; 2,162 cases, 21,484 controls). We also estimated PAR% for other modifiable RCC risk factors (cigarette smoking, obesity) in USKC. In USKC, the PAR% for hypertension was 50% (95% CI 24-77%) and 44% (95% CI 25-64%) among black women and men, respectively, and 29% (95% CI 13-44%) and 27% (95% CI 14-39%) for white women and men, respectively. In KPNC, the hypertension PAR% was 40% (95% CI 18-62%) and 23% (95% CI 2-44%) among black women and men, and 27% (95% CI 20-35%) and 19% (95% CI 14-24%) among white women and men, respectively. The PAR% for CKD in both studies ranged from 7 to 10% for black women and men but was negligible (
Authors: Callahan CL; Corley DA; Zhao WK; Hofmann JN; et al.
Cancer Causes Control. 2019 Nov 28.
Haloperidol and Prostate Cancer Prevention: More Epidemiologic Research Needed
The antipsychotic drug haloperidol has antiproliferative and growth-inhibiting properties on prostate cancer cell lines in vitro by binding the sigma 1 protein. Evidence is needed regarding a possible preventive association in men. To examine whether our epidemiologic data support an inverse association of haloperidol use with risk of prostate cancer. These case-control analyses used conditional logistic regression to estimate relative risk by odds ratios (ORs) adjusting for race/ethnicity and aspects of medical care related to detection of prostate cancer. We tested 3 other commonly used antipsychotic drugs, risperidone, quetiapine, and olanzapine, for sigma 1 protein binding and inhibition of clonogenic growth of prostate cancer cells. Use of any of these by men was considered use of a comparator drug. 1) association of haloperidol with prostate cancer; 2) sigma 1 binding and clonogenic growth. Probably owing to small numbers of haloperidol recipients, evidence of a preventive association was inconsistent, depending on the definition of long-term use. If duration of use was greater than 1 year, the odds ratio (OR) was 0.38 (95% confidence interval (CI) = 0.14-1.01) for haloperidol and 0.80 (95% CI = 0.66-0.98) for the comparator drug; if the duration of use was greater than 2 years, the OR was 0.66 (95% CI = 0.24-1.76) for haloperidol and 0.84 (95% CI = 0.66-1.08) for the comparator drug. Unlike haloperidol, risperidone, quetiapine, and olanzapine did not bind sigma 1 or inhibit clonogenic growth. Given the laboratory evidence, our ambiguous epidemiologic findings should encourage more epidemiologic evaluation of haloperidol use and risk of prostate cancer. Finding a negative association could be a scientific advance in prostate cancer prevention but would not be sufficient basis for recommending the prescription of haloperidol for that purpose.
Authors: Friedman GD; Habel LA; Achacoso N; Sanders CM; Oyer HM; Fireman B; Van Den Eeden SK; Kim FJ
Perm J. 2018;24. Epub 2019-11-22.
Rural-urban differences e-cigarette ever use, the perception of harm, and e-cigarette information seeking behaviors among U.S. adults in a nationally representative study.
Adults living in rural areas, compared to their urban counterparts, are at an increased risk of using tobacco-related products and mortality due to tobacco-related diseases. The harms and benefits of e-cigarette use are mixed, and similarly obscure messaging about these harms and benefits have a critical influence on e-cigarette uptake and perceptions. However, little is known about rural-urban differences in the prevalence of adult e-cigarette daily usage. Using the Health Information National Trends Survey-Food and Drug Administration (HINTS-FDA) cycles 1 and 2, we conducted weighted logistic regressions to assess rural-urban differences in the prevalence of adult e-cigarette daily usage, perceived harm, and e-cigarette information seeking behaviors. This analysis included adults aged 18 years and older in the United States (N = 4229). Both rural and urban respondents reported a similar history of e-cigarette use. Rural respondents were significantly more likely than urban respondents to trust religious organizations and leaders and tobacco companies for information about e-cigarettes. Rural and urban respondents were equally as likely to believe e-cigarettes are addictive, perceive e-cigarette use as harmful, and believe e-cigarettes are more harmful than tobacco cigarettes. Respondents were equally as likely to look for information on e-cigarettes, the health effects of e-cigarettes, and cessation; and, to seek e-cigarette information from healthcare professionals, family and friends, and health organizations and groups. Given our findings, it will be pertinent to continue to research the potential harms of e-cigarette use and develop accurate health communication messages to avoid rural-urban disparities observed for cigarette smoking-related outcomes.
Authors: Lewis-Thames, Marquita W; Langston, Marvin E; Fuzzell, Lindsay; Khan, Saira; Moore, Justin X; Han, Yunan
Preventive medicine. 2020 Jan ;130():105898. Epub 2019-11-21.
Detection of early stage ovarian cancer in a large community cohort
Although detecting ovarian cancer at early stage is a highly meaningful clinical goal, no studies have evaluated early stage disease presentation in a large community-based population and how it differs from that of late stage disease. Electronic medical records were evaluated for women diagnosed with ovarian or fallopian tube cancer in 2016 and 2017 to identify the first imaging study to detect disease. Women being followed prior to diagnosis for known genetic risk from BRCA or other mutation were excluded. The visit in which the imaging test was ordered and related encounters were reviewed to determine the indication for imaging. Patient characteristics, presenting symptoms and duration, and modality of first abnormal imaging were compared for early vs late stage ovarian cancer and by provider specialty. Of 540 women with ovarian cancer, 190 (35%) were diagnosed with early stage disease, of whom 141 (74%) were symptomatic, with 45% of women presenting to internists, 33% to gynecologists, and 20% to emergency medicine physicians. Pelvic ultrasonography detected only 23% of late stage cases whereas pelvic ultrasonography and abdominal pelvic computed tomography (CT) each detected 47% of early stage cases. While abdominal pain and bloating were common to both women with early and late stage cancer, women with early stage disease were younger (58 vs 64 years, P < .0001), more likely to present to gynecologists (33% vs 15%, P < .001) and complained more often of a palpable mass (17% vs 6%, P < .0001) or postmenopausal bleeding (11% vs 5%, P < .001). Excluding women with genetic predisposition to ovarian cancer known prior to diagnosis, approximately three out of four cases of early stage ovarian cancer are detected as the result of evaluation of symptoms and one in four cases are detected incidentally. Abdominal pelvic CT and pelvic ultrasonography each detect an equal proportion of early stage cases. In contrast to late stage presentation, women diagnosed with early stage disease present more often with complaints of a palpable mass or postmenopausal bleeding, particularly to gynecologists.
Authors: Suh-Burgmann EJ; Alavi M
Cancer Med. 2019 11;8(16):7133-7140. Epub 2019-09-30.
Morbidity and Mortality After Surgery for Nonmalignant Colorectal Polyps: A 10-Year Nationwide Analysis
Rates of surgery for nonmalignant colorectal polyps are increasing in the United States despite evidence that most polyps can be managed endoscopically. We aimed to determine nationally representative estimates and to identify predictors of in-hospital mortality and morbidity after surgery for nonmalignant colorectal polyps. Data were analyzed from the National Inpatient Sample for 2005-2014. All discharges for adult patients undergoing surgery for nonmalignant colorectal polyps were identified. Rates of in-hospital mortality and postoperative wound, infectious, urinary, pulmonary, gastrointestinal, or cardiovascular adverse events were calculated. Multivariable logistic regression using survey-weighted data was used to evaluate covariables associated with postoperative mortality and morbidity. An estimated 262,843 surgeries for nonmalignant colorectal polyps were analyzed. In-hospital mortality was 0.8% [95% confidence interval: 0.7%-0.9%] and morbidity was 25.3% [95% confidence interval: 24.2%-26.4%]. Postoperative mortality was associated with open surgical technique (vs laparoscopic), older age, black race (vs non-Hispanic white), Medicaid use, and burden of comorbidities. Female sex and private insurance were associated with lower risk. Patients developing a postoperative adverse event had a 106% increase in mean hospital length of stay (10.3 vs 5.0 days; P < 0.0001) and 91% increase in mean hospitalization cost ($77,015.24 vs $40,258.30; P < 0.0001). Surgery for nonmalignant colorectal polyps is associated with almost 1% mortality and common morbidity. These findings should inform risk vs benefit discussions for clinicians and patients, and although confounding by patient selection cannot be excluded, the risks associated with surgery support consideration of endoscopic resection as a potentially less invasive therapeutic option.
Authors: Ma C; Teriaky A; Sheh S; Forbes N; Heitman SJ; Jue TL; Munroe CA; Jairath V; Corley DA; Lee JK
Am J Gastroenterol. 2019 11;114(11):1802-1810.
Factors associated with employment discontinuation among older and working age survivors of oropharyngeal cancer
Oropharyngeal cancer survivors experience difficulty returning to work after treatment. To better understand specific barriers to returning to work, we investigated factors associated with discontinuing employment among older and working-age survivors. The sample included 675 oropharyngeal cancer survivors (median: 6 years posttreatment) diagnosed from 2000 to 2013 and employed at diagnosis. Relative risk models were constructed to examine the independent associations of demographic and health factors, and symptom experiences per the MD Anderson Symptom Inventory – Head and Neck Module (MDASI-HN) with posttreatment employment, overall and by age (<60 years vs ≥60 years at survey). Symptom interference was not statistically significantly associated with posttreatment employment status among respondents ≥60 years. Among working-age respondents <60 years, symptom interference was strongly associated with posttreatment employment. Efforts to assess and lessen symptom burden in working-age survivors should be evaluated as approaches to support regaining core functions needed for continued employment.
Authors: Check DK; Hutcheson KA; Poisson LM; Pocobelli G; Sakoda LC; Zaveri J; Chang SS; Chubak J
Head Neck. 2019 11;41(11):3948-3959. Epub 2019-09-06.
Intentional weight loss, weight cycling, and endometrial cancer risk: a systematic review and meta-analysis
Weight cycling, defined as intentional weight loss followed by unintentional weight regain, may attenuate the benefit of intentional weight loss on endometrial cancer risk. We summarized the literature on intentional weight loss, weight cycling after intentional weight loss, bariatric surgery, and endometrial cancer risk. A systematic search was conducted using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases published between January 2000 and November 2018. We followed Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) guidelines. We qualitatively summarized studies related to intentional weight loss and weight cycling due to the inconsistent definition, and quantitatively summarized studies when bariatric surgery was the mechanism of intentional weight loss. A total of 127 full-text articles were reviewed, and 13 were included (bariatric surgery n=7, self-reported intentional weight loss n=2, self-reported weight cycling n=4). Qualitative synthesis suggested that, compared with stable weight, self-reported intentional weight loss was associated with lower endometrial cancer risk (RR range 0.61-0.96), whereas self-reported weight cycling was associated with higher endometrial cancer risk (OR range 1.07-2.33). The meta-analysis yielded a 59% lower risk of endometrial cancer following bariatric surgery (OR 0.41, 95% CI 0.22 to 0.74). Our findings support the notion that intentional weight loss and maintenance of a stable, healthy weight can lower endometrial cancer risk. Strategies to improve awareness and maintenance of weight loss among women with obesity are needed to reduce endometrial cancer risk.
Authors: Zhang X; Rhoades J; Caan BJ; Cohn DE; Salani R; Noria S; Suarez AA; Paskett ED; Felix AS
Int J Gynecol Cancer. 2019 11;29(9):1361-1371. Epub 2019-08-26.
Immunotherapy-Associated Pseudomembranous Colitis
Authors: Kidambi TD; Chu P; Lee JK; Lin JL
Am J Gastroenterol. 2019 11;114(11):1708.
Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer: A case-control study nested within two prospective cohorts
Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case-control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p’-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p’-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.
Authors: Engel LS; Zabor EC; Satagopan J; Widell A; Rothman N; O'Brien TR; Zhang M; Van Den Eeden SK; Grimsrud TK
Int J Cancer. 2019 11 01;145(9):2360-2371. Epub 2019-02-14.
Environmental Tobacco Smoke Exposure in Relation to Family Characteristics, Stressors and Chemical Co-Exposures in California Girls
Childhood environmental tobacco smoke (ETS) exposure is a risk factor for adverse health outcomes and may disproportionately burden lower socioeconomic status groups, exacerbating health disparities. We explored associations of demographic factors, stressful life events, and chemical co-exposures, with cotinine levels, among girls in the CYGNET Study. Data were collected from families of girls aged 6-8 years old in Northern California, through clinic exams, questionnaires and biospecimens (n = 421). Linear regression and factor analysis were conducted to explore predictors of urinary cotinine and co-exposure body burdens, respectively. In unadjusted models, geometric mean cotinine concentrations were higher among Black (0.59 ug/g creatinine) than non-Hispanic white (0.27), Asian (0.32), or Hispanic (0.34) participants. Following adjustment, living in a rented home, lower primary caregiver education, and lack of two biologic parents in the home were associated with higher cotinine concentrations. Girls who experienced parental separation or unemployment in the family had higher unadjusted cotinine concentrations. Higher cotinine was also associated with higher polybrominated diphenyl ether and metals concentrations. Our findings have environmental justice implications as Black and socio-economically disadvantaged young girls experienced higher ETS exposure, also associated with higher exposure to other chemicals. Efforts to reduce ETS and co-exposures should account for other disparity-related factors.
Authors: Windham GC; Soriano JW; Dobraca D; Sosnoff CS; Hiatt RA; Kushi LH
Int J Environ Res Public Health. 2019 10 30;16(21). Epub 2019-10-30.
Detecting right ventricular dysfunction in patients diagnosed with low-risk pulmonary embolism: is routine computed tomographic pulmonary angiography sufficient?
Authors: Vinson DR; Arasu VA; Trujillo-Santos J
Eur Heart J. 2019 10 21;40(40):3356.
Selecting Active Surveillance: Decision-Making Factors for Men with a Low-Risk Prostate Cancer
Background. Men with a low-risk prostate cancer (PCa) should consider observation, particularly active surveillance (AS), a monitoring strategy that avoids active treatment (AT) in the absence of disease progression. Objective. To determine clinical and decision-making factors predicting treatment selection. Design. Prospective cohort study. Setting. Kaiser Permanente Northern California (KPNC). Patients. Men newly diagnosed with low-risk PCa between 2012 and 2014 who remained enrolled in KPNC for 12 months following diagnosis. Measurements. We used surveys and medical record abstractions to measure sociodemographic and clinical characteristics and psychological and decision-making factors. Men were classified as being on observation if they did not undergo AT within 12 months of diagnosis. We performed multivariable logistic regression analyses. Results. The average age of the 1171 subjects was 61.5 years (s = 7.2 years), and 81% were white. Overall, 639 (57%) were managed with observation; in adjusted analyses, significant predictors of observation included awareness of low-risk status (odds ratio 1.75; 95% confidence interval 1.04-2.94), knowing that observation was an option (3.62; 1.62-8.09), having concerns about treatment-related quality of life (1.21, 1.09-1.34), reporting a urologist recommendation for observation (8.20; 4.68-14.4), and having a lower clinical stage (T1c v. T2a, 2.11; 1.16-3.84). Conversely, valuing cancer control (1.54; 1.37-1.72) and greater decisional certainty (1.66; 1.18-2.35) were predictive of AT. Limitations. Results may be less generalizable to other types of health care systems and to more diverse populations. Conclusions. Many participants selected observation, and this was associated with tumor characteristics. However, nonclinical decisional factors also independently predicted treatment selection. Efforts to provide early decision support, particularly targeting knowledge deficits, and reassurance to men with low-risk cancers may facilitate better decision making and increase uptake of observation, particularly AS.
Authors: Hoffman RM; Lobo T; Van Den Eeden SK; Davis KM; Luta G; Leimpeter AD; Aaronson D; Penson DF; Taylor K
Med Decis Making. 2019 Oct 21:272989X19883242.
Guideline-concordant endometrial cancer treatment and survival in the Women’s Health Initiative Life and Longevity After Cancer study
In the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) cohort, we examined predictors of guideline-concordant treatment among endometrial cancer (EC) survivors and associations between receipt of guideline-concordant treatment and survival. Receipt of guideline-concordant EC treatment was defined according to year-specific National Comprehensive Cancer Network (NCCN) guidelines. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for predictors of guideline-concordant treatment receipt. We estimated multivariable-adjusted hazard ratios (HRs) and 95% CIs for relationships between guideline-concordant treatment and overall survival using Cox proportional hazards regression. We included 629 women with EC, of whom 83.6% (n = 526) received guideline-concordant treatment. Receipt of guideline-concordant treatment was less common among women with nonendometrioid histology (OR = 0.24, 95% CI = 0.13-0.45) but was more common among women living in the Midwest (OR = 2.09, 95% CI = 1.06-4.12) or West (OR = 3.02, 95% CI = 1.49-6.13) compared to the Northeast. In Cox regression models adjusted for age, histology and stage, receipt of guideline-concordant EC treatment was borderline associated with improved overall survival (HR = 0.80, 95% CI = 0.60-1.01) in the overall population. Guideline-concordant treatment was also linked with better overall survival among women with low-grade uterine-confined endometrioid EC or widely metastatic endometrioid EC. Guideline-concordant treatment varies by some patient characteristics and those women in receipt of guideline-concordant care had borderline improved survival. Studies evaluating regional differences in treatment along with randomized clinical trials to determine appropriate treatment regimens for women with aggressive tumor characteristics are warranted.
Authors: Felix AS; McLaughlin EM; Caan BJ; Cohn DE; Anderson GL; Paskett ED
Int J Cancer. 2019 Oct 16.
Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline
Recent 15-year updates of sigmoidoscopy screening trials provide new evidence on the effectiveness of colorectal cancer screening. Prompted by the new evidence, we asked: “Does colorectal cancer screening make an important difference to health outcomes in individuals initiating screening at age 50 to 79? And which screening option is best?” Numerous guidelines recommend screening, but vary on recommended test, age and screening frequency. This guideline looks at the evidence and makes recommendations on screening for four screening options: faecal immunochemical test (FIT) every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy. These recommendations apply to adults aged 50-79 years with no prior screening, no symptoms of colorectal cancer, and a life expectancy of at least 15 years. For individuals with an estimated 15-year colorectal cancer risk below 3%, we suggest no screening (weak recommendation). For individuals with an estimated 15-year risk above 3%, we suggest screening with one of the four screening options: FIT every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy (weak recommendation). With our guidance we publish the linked research, a graphic of the absolute harms and benefits, a clear description of how we reached our value judgments, and linked decision aids. A guideline panel including patients, clinicians, content experts and methodologists produced these recommendations using GRADE and in adherence with standards for trustworthy guidelines. A linked systematic review of colorectal cancer screening trials and microsimulation modelling were performed to inform the panel of 15-year screening benefits and harms. The panel also reviewed each screening option’s practical issues and burdens. Based on their own experience, the panel estimated the magnitude of benefit typical members of the population would value to opt for screening and used the benefit thresholds to inform their recommendations. Overall there was substantial uncertainty (low certainty evidence) regarding the 15-year benefits, burdens and harms of screening. Best estimates suggested that all four screening options resulted in similar colorectal cancer mortality reductions. FIT every two years may have little or no effect on cancer incidence over 15 years, while FIT every year, sigmoidoscopy, and colonoscopy may reduce cancer incidence, although for FIT the incidence reduction is small compared with sigmoidoscopy and colonoscopy. Screening related serious gastrointestinal and cardiovascular adverse events are rare. The magnitude of the benefits is dependent on the individual risk, while harms and burdens are less strongly associated with cancer risk. Based on benefits, harms, and burdens of screening, the panel inferred that most informed individuals with a 15-year risk of colorectal cancer of 3% or higher are likely to choose screening, and most individuals with a risk of below 3% are likely to decline screening. Given varying values and preferences, optimal care will require shared decision making.
Authors: Helsingen LM; Corley DA; Guyatt G; et al.
BMJ. 2019 Oct 02;367:l5515. Epub 2019-10-02.
Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors
Cardiovascular disease (CVD) is a major source of morbidity and mortality among breast cancer survivors. Although body mass index (BMI) is associated with CVD risk, adipose tissue distribution may better identify patients with a high risk of CVD after breast cancer. Among 2,943 patients with nonmetastatic breast cancer without prior CVD, we used International Classification of Diseases (9th and 10th revisions) codes to identify incidence of nonfatal stroke, myocardial infarction, heart failure, or CVD death. From clinically acquired computed tomography scans obtained near diagnosis, we measured visceral adiposity (centimeters squared), subcutaneous adiposity (centimeters squared), and intramuscular adiposity (fatty infiltration into muscle [Hounsfield Units, scored inversely]). We estimated hazard ratios (HRs) and 95% CIs per SD increase in adiposity accounting for competing risks and adjusting for demographics, smoking, cancer treatment, and pre-existing CVD risk factors. Mean (SD) age was 56 (12) years. Over a median follow-up of 6 years, 328 CVD events occurred. Each SD increase in visceral or intramuscular adiposity was associated with an increase in CVD risk (HR, 1.15 [95% CI, 1.03 to 1.29] and HR, 1.21 [95% CI, 1.06 to 1.37]), respectively). Excess visceral and intramuscular adiposity occurred across all BMI categories. Among normal-weight patients, each SD greater visceral adiposity increased CVD risk by 70% (HR, 1.70 [95% CI, 1.10 to 2.62]). Visceral and intramuscular adiposity were associated with increased CVD incidence after breast cancer diagnosis, independent of pre-existing CVD risk factors and cancer treatments. The increased CVD incidence among normal-weight patients with greater visceral adiposity would go undetected with BMI alone. Measures of adipose tissue distribution may help identify high-risk patients and tailor CVD prevention strategies.
Authors: Cespedes Feliciano EM; Chen WY; Bradshaw PT; Prado CM; Alexeeff S; Albers KB; Castillo AL; Caan BJ
J Clin Oncol. 2019 10 01;37(28):2528-2536. Epub 2019-08-01.
The Effect of Reverse Causality and Selective Attrition on the Relationship Between Body Mass Index and Mortality in Postmenopausal Women
Concerns about reverse causality and selection bias complicate the interpretation of studies of body mass index (BMI, calculated as weight (kg)/height (m)2) and mortality in older adults. The objective of this study was to investigate methodological explanations for the apparent attenuation of obesity-related risks in older adults. We used data from 68,132 participants in the Women’s Health Initiative (WHI) clinical trial for this analysis. All of the participants were postmenopausal women aged 50-79 years at baseline (1993-1998). To examine reverse causality and selective attrition, we compared rate ratios from inverse probability of treatment- and censoring-weighted Poisson marginal structural models with results from an unweighted adjusted Poisson regression model. The estimated mortality rate ratios and 95% confidence intervals for BMIs of 30.0-34.9, 35.0-39.9 and ≥40.0 were 0.86 (95% confidence interval (CI): 0.77, 0.96), 0.85 (95% CI: 0.72, 0.99), and 0.88 (95% CI: 0.72, 1.07), respectively, in the unweighted model. The corresponding mortality rate ratios were 0.96 (95% CI: 0.86, 1.07), 1.12 (95% CI: 0.97, 1.29), and 1.31 95% CI: (1.08, 1.57), respectively, in the marginal structural model. Results from the inverse probability of treatment- and censoring-weighted marginal structural model were attenuated in low BMI categories and increased in high BMI categories. The results demonstrate the importance of accounting for reverse causality and selective attrition in studies of older adults.
Authors: Banack HR; Kroenke CH; Caan B; Wactawski-Wende J; et al.
Am J Epidemiol. 2019 10 01;188(10):1838-1848.
An Environmental Scan of Biopsychosocial and Clinical Variables in Cohort Studies of Cancer Survivors
An inventory of cancer survivorship cohorts is necessary to identify important gaps in what is being studied among cancer survivors. We conducted an environmental scan of cancer survivor cohorts to determine the scope and scale of information collected on demographic, biopsychosocial, and selected clinical variables from cancer survivors. Cohorts were eligible for inclusion in the environmental scan if the study was conducted in the United States, reported in English, and consisted of data collected from cancer survivors postdiagnosis and followed for at least 1 year. Out of the 131 cohorts identified, 62 were eligible. There were 23 cancer sites represented, and more than half of the studies included breast cancer survivors (n = 34). The next most commonly included cancers were leukemia (n = 22) and lymphoma (n = 23). The majority (n = 59) collected information on clinical characteristics and basic diagnostic information, patient demographic characteristics (n = 57), patient-reported symptoms (n = 44), lifestyle (n = 45), and psychologic characteristics (n = 42). Half collected biospecimens (n = 35) and biomarkers (n = 35); fewer collected CAM use (n = 19) and social characteristics (n = 27). Extensive data are available in cancer cohorts to study important questions relevant to cancer survivors. Cohorts should consider collecting information on social and environmental factors, as well as biospecimen collection and biomarker analyses, and should include survivors from cancer sites less likely to be studied. This information can assist researchers in understanding the types of information currently being gathered from cancer survivors for further analysis and identify areas where more research is needed.
Authors: Krok-Schoen JL; Bernardo BM; Elena JW; Green PA; Hoover E; Peng J; Anderson GL; Caan B; Johnson LG; Paskett ED
Cancer Epidemiol Biomarkers Prev. 2019 10;28(10):1621-1641. Epub 2019-07-17.
Facebook advertising for recruitment of midlife women with bothersome vaginal symptoms: A pilot study
The MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) Network recruited into five randomized clinical trials (n = 100-350) through mass mailings. The fifth trial tested two interventions for postmenopausal vulvovaginal symptoms (itching, pain, irritation, dryness, or pain with sex) and thus required a high level of sensitivity to privacy concerns. For this trial, in addition to mass mailings we pilot tested a social media recruitment approach. We aimed to evaluate the feasibility of recruiting healthy midlife women with bothersome vulvovaginal symptoms to participate in the Vaginal Health Trial through Facebook advertising. As part of a larger advertising campaign that enrolled 302 postmenopausal women for the 12-week randomized, double-blind, placebo-controlled Vaginal Health Trial from April 2016 to February 2017, Facebook advertising was used to recruit 25 participants. The target population for recruitment by mailings and by Facebook ads included women aged 50-70 years and living within 20 miles of study sites in Minneapolis, MN and Seattle, WA. Design of recruitment letters and Facebook advertisements was informed by focus group feedback. Facebook ads were displayed in the “newsfeed” of targeted users and included a link to the study website. Response rates and costs are described for both online ads and mailing. Facebook ads ran in Minneapolis for 28 days and in Seattle for 15 days, with ads posted and removed from the site as needed based on clinic flow and a set budget limit. Our estimated Facebook advertising reach was over 200,000 women; 461 women responded and 25 were enrolled at a cost of US$14,813. The response rate per estimated reach was 0.22%; costs were US$32 per response and US$593 per randomized participant. The social media recruitment results varied by site, showing greater effectiveness in Seattle than in Minneapolis. We mailed 277,000 recruitment letters; 2166 women responded and 277 were randomized at a cost of US$98,682. The response rate per letter sent was 0.78%; costs were US$46 per response and US$356 per randomized participant. Results varied little across sites. Recruitment to a clinical trial testing interventions for postmenopausal vaginal symptoms is feasible through social media advertising. Variability in observed effectiveness and costs may reflect the small sample sizes and limited budget of the pilot recruitment study.
Authors: Guthrie KA; Caan B; Diem S; Ensrud KE; Greaves SR; Larson JC; Newton KM; Reed SD; LaCroix AZ
Clin Trials. 2019 10;16(5):476-480. Epub 2019-05-06.
No Association Between Vitamin D Status and Risk of Barrett’s Esophagus or Esophageal Adenocarcinoma-a Mendelian Randomization Study
Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett’s esophagus (BE). We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett’s and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.
Authors: Dong J; Corley DA; Thrift AP; et al.
Clin Gastroenterol Hepatol. 2019 10;17(11):2227-2235.e1. Epub 2019-02-01.
Simple Adnexal Cysts: SRU Consensus Conference Update on Follow-up and Reporting.
This multidisciplinary consensus update aligns prior Society of Radiologists in Ultrasound (SRU) guidelines on simple adnexal cysts with recent large studies showing exceptionally low risk of cancer associated with simple adnexal cysts. Most small simple cysts do not require follow-up. For larger simple cysts or less well-characterized cysts, follow-up or second opinion US help to ensure that solid elements are not missed and are also useful for assessing growth of benign tumors. In postmenopausal women, reporting of simple cysts greater than 1 cm should be done to document their presence in the medical record, but such findings are common and follow-up is recommended only for simple cysts greater than 3-5 cm, with the higher 5-cm threshold reserved for simple cysts with excellent imaging characterization and documentation. For simple cysts in premenopausal women, these thresholds are 3 cm for reporting and greater than 5-7 cm for follow-up imaging. If a cyst is at least 10%-15% smaller at any time, then further follow-up is unnecessary. Stable simple cysts at initial follow-up may benefit from a follow-up at 2 years due to measurement variability that could mask growth. Simple cysts that grow are likely cystadenomas. If a previously suspected simple cyst demonstrates papillary projections or solid areas at follow-up, then the cyst should be described by using standardized terminology. These updated SRU consensus recommendations apply to asymptomatic patients and to those whose symptoms are not clearly attributable to the cyst. These recommendations can reassure physicians and patients regarding the benign nature of simple adnexal cysts after a diagnostic-quality US examination that allows for confident diagnosis of a simple cyst. Patients will benefit from less costly follow-up, less anxiety related to these simple cysts, and less surgery for benign lesions.
Authors: Levine D; Suh-Burgmann EJ; Brown DL; et al.
Radiology. 2019 Nov;293(2):359-371. doi: 10.1148/radiol.2019191354. Epub 2019 Sep 24.
Chronotype, Social Jet Lag, and Cardiometabolic Risk Factors in Early Adolescence
Inadequate sleep duration and quality increase the risk of obesity. Sleep timing, while less studied, is important in adolescents because increasing evening preferences (chronotypes), early school start times, and irregular sleep schedules may cause circadian misalignment. To investigate associations of chronotype and social jet lag with adiposity and cardiometabolic risk in young adolescents. Starting in 1999, Project Viva recruited pregnant women from eastern Massachusetts. Mother-child in-person visits occurred throughout childhood. From January 23, 2012, to October 16, 2016, 804 adolescents aged 12 to 17 years completed 5 days or more of wrist actigraphy, questionnaires, and anthropometric measurements. A cross-sectional analysis using these data was conducted from April 31, 2018, to May 1, 2019. Chronotype, measured via a continuous scale with higher scores indicating greater evening preferences, and social jet lag, measured as the continuous difference in actigraphy sleep midpoint in hours from midnight on weekends vs weekdays, with higher values representing more delayed sleep timing on weekends. Adiposity, measured via anthropometry and dual-energy x-ray absorptiometry. For a subset of 479 adolescents with blood samples, cardiometabolic risk scores were computed as the mean of 5 sex- and cohort-specific z scores for waist circumference, systolic blood pressure, inversely scaled high-density lipoprotein cholesterol, and log-transformed triglycerides and homeostatic model of insulin resistance. Among the 804 adolescents in the study, 418 were girls and 386 were boys, with a mean (SD) age of 13.2 (0.9) years. In multivariable models adjusted for age, puberty, season, and sociodemographics, associations of chronotype and social jet lag with adiposity varied by sex. For girls, greater evening preference was associated with a 0.58-cm (95% CI, 0.12-1.03 cm; P = .04 for interaction) higher waist circumference and 0.16 kg/m2 (95% CI, 0.01-0.31 kg/m2; P = .03 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry; each hour of social jet lag was associated with a 1.19-cm (95% CI, 0.04-2.35 cm; P = .21 for interaction) higher waist circumference and 0.45 kg/m2 (95% CI, 0.09-0.82 kg/m2; P = .01 for interaction) higher fat mass index as measured by dual-energy x-ray absorptiometry. Associations of social jet lag and evening chronotypes persisted for many measures of adiposity after adjustment for sleep duration and other lifestyle behaviors. By contrast, no associations were observed in boys. There were no associations with the cardiometabolic risk score for either sex, although statistical power was low for this outcome. Evening chronotypes and social jet lag were associated with greater adiposity in adolescent girls but not adolescent boys. Interventions aimed at improving sleep schedules may be useful for obesity prevention, especially in girls.
Authors: Cespedes Feliciano EM; Rifas-Shiman SL; Quante M; Redline S; Oken E; Taveras EM
JAMA Pediatr. 2019 Sep 16.
Outcomes of direct oral anticoagulant- and warfarin-associated hemorrhage: A single center retrospective cohort study.
Authors: Cafuir L; Cheng E; Kempton C
Thromb Res. 2020 May;189:128-131. doi: 10.1016/j.thromres.2019.09.001. Epub 2019 Sep 3.
Trends in Use of Medical Imaging in US Health Care Systems and in Ontario, Canada, 2000-2016
Medical imaging increased rapidly from 2000 to 2006, but trends in recent years have not been analyzed. To evaluate recent trends in medical imaging. Retrospective cohort study of patterns of medical imaging between 2000 and 2016 among 16 million to 21 million patients enrolled annually in 7 US integrated and mixed-model insurance health care systems and for individuals receiving care in Ontario, Canada. Calendar year and country (United States vs Canada). Use of computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine imaging. Annual and relative imaging rates by imaging modality, country, and age (children [<18 years], adults [18-64 years], and older adults [≥65 years]). Overall, 135 774 532 imaging examinations were included; 5 439 874 (4%) in children, 89 635 312 (66%) in adults, and 40 699 346 (30%) in older adults. Among adults and older adults, imaging rates were significantly higher in 2016 vs 2000 for all imaging modalities other than nuclear medicine. For example, among older adults, CT imaging rates were 428 per 1000 person-years in 2016 vs 204 per 1000 in 2000 in US health care systems and 409 per 1000 vs 161 per 1000 in Ontario; for MRI, 139 per 1000 vs 62 per 1000 in the United States and 89 per 1000 vs 13 per 1000 in Ontario; and for ultrasound, 495 per 1000 vs 324 per 1000 in the United States and 580 per 1000 vs 332 per 1000 in Ontario. Annual growth in imaging rates among US adults and older adults slowed over time for CT (from an 11.6% annual percentage increase among adults and 9.5% among older adults in 2000-2006 to 3.7% among adults in 2013-2016 and 5.2% among older adults in 2014-2016) and for MRI (from 11.4% in 2000-2004 in adults and 11.3% in 2000-2005 in older adults to 1.3% in 2007-2016 in adults and 2.2% in 2005-2016 in older adults). Patterns in Ontario were similar. Among children, annual growth for CT stabilized or declined (United States: from 10.1% in 2000-2005 to 0.8% in 2013-2016; Ontario: from 3.3% in 2000-2006 to -5.3% in 2006-2016), but patterns for MRI were similar to adults. Changes in annual growth in ultrasound were smaller among adults and children in the United States and Ontario compared with CT and MRI. Nuclear medicine imaging declined in adults and children after 2006. From 2000 to 2016 in 7 US integrated and mixed-model health care systems and in Ontario, rates of CT and MRI use continued to increase among adults, but at a slower pace in more recent years. In children, imaging rates continued to increase except for CT, which stabilized or declined in more recent periods. Whether the observed imaging utilization was appropriate or was associated with improved patient outcomes is unknown.
Authors: Smith-Bindman R; Kwan ML; Kushi LH; Miglioretti DL; et al.
JAMA. 2019 09 03;322(9):843-856.
ASGE guideline on screening and surveillance of Barrett’s esophagus
Authors: ASGE STANDARDS OF PRACTICE COMMITTEE; Lee JK; ASGE Standards of Practice Committee Chair; et al.
Gastrointest Endosc. 2019 09;90(3):335-359.e2.
Pre-Diagnosis Exercise and Cardiovascular Events in Primary Breast Cancer: Women’s Health Initiative
The purpose of this study was to investigate whether pre-diagnosis exercise reduces the risk of subsequent cardiovascular events (CVEs) in women with primary breast cancer. Cardiovascular disease (CVD) is the leading nonmalignant cause of death in patients with cancer, and it is the leading cause of death in women with primary breast cancer who are older than 65 years of age. Using a prospective design, 4,015 patients with confirmed diagnosis of primary breast cancer enrolled in the Women’s Health Initiative (WHI) completed a self-report questionnaire assessing leisure-time physical activity (i.e., exercise) in metabolic equivalent task (MET) hours per week. Age- and multivariable-adjusted Cox proportional hazards models were used to estimate associations between pre-diagnosis exercise and new-onset CVEs (i.e., heart failure [HF], myocardial infarction [MI], angina, coronary revascularization, peripheral arterial disease [PAD], carotid artery disease, transient ischemic attack [TIA], stroke, and cardiovascular death). Median follow-up was 12.7 years and 8.2 years for cardiovascular disease (CVD) mortality and CVEs, respectively, with 324 CVEs, including 89 MIs, 49 new diagnoses of HF, and 215 CVD deaths. In multivariable analysis, the incidence of composite CVEs decreased across increasing total MET h/week categories (p = 0.016). Compared with <2.5 MET-hours per week, the adjusted hazard ratio (HR) was 0.80 (95% confidence interval [CI]: 0.59 to 1.09) for 2.5 to <8.6 MET h/week; 0.9 (95% CI: 0.64 to 1.17) for 8.6 to <18 MET h/week; and 0.63 (95% CI: 0.45 to 0.88) for ≥18 MET h/week. Pre-diagnosis exercise exposure is associated with a significant graded reduction in subsequent CVEs in long-term survivors of primary breast cancer.
Authors: Okwuosa, Tochi M; Ray, Roberta M; Palomo, Andres; Foraker, Randi E; Johnson, Lisa; Paskett, Electra D; Caan, Bette; Jones, Lee W
JACC CardioOncol. 2019 Sep;1(1):41-50. Epub 2019-09-24.
Clinical Molecular Marker Testing Data Capture to Promote Precision Medicine Research Within the Cancer Research Network
To evaluate health care systems for the availability of population-level data on the frequency of use and results of clinical molecular marker tests to inform precision cancer care. We assessed cancer-related molecular marker test data availability across 12 US health care systems in the Cancer Research Network. Overall, these systems provide care to a diverse population of more than 12 million people in the United States. We performed qualitative analyses of test data availability for five blood-based protein, nine germline, and 14 tissue-based tumor marker tests in each health care system’s electronic health record and tumor registry using key informants, test code lists, and manual review of data types and output. We then performed quantitative analyses to estimate the proportion of patients with cancer with test utilization data and results for specific molecular marker tests. Health systems were able to systematically capture population-level data on all five blood protein markers, six of 14 tissue-based tumor markers, and none of the nine germline markers. Successful, systematic data capture was achievable for tests with electronic data feeds for test results (blood protein markers) or through prior manual abstraction by tumor registrars (select tumor-based markers). For test results stored in scanned image files (particularly germline and tumor marker tests), information on which test was performed and test results was not readily accessible in an electronic format. Even in health care systems with sophisticated electronic health records, there were few codified data elements available for evaluating precision cancer medicine test use and results at the population level. Health care organizations should establish standards for electronic reporting of precision medicine tests to expedite cancer research and facilitate the implementation of precision medicine approaches.
Authors: Burnett-Hartman AN; Kushi LH; Corley DA; Lu CY; et al.
JCO Clin Cancer Inform. 2019 09;3:1-10.
Safety and Complications of Long-Term Proton Pump Inhibitor Therapy: Getting Closer to the Truth
Authors: Corley DA
Gastroenterology. 2019 09;157(3):604-607. Epub 2019-07-30.
Longitudinal study of age of menarche in association with childhood concentrations of persistent organic pollutants
Age at female puberty is associated with adult morbidities, including breast cancer and diabetes. Hormonally active chemicals are suspected of altering pubertal timing. We examined whether persistent organic pollutants (POPs) are associated with age at menarche in a longitudinal study. We analyzed data for females enrolled at age 6-8 years in the Breast Cancer and Environment Research Program from California and Ohio. Participants were followed annually 2004-2013 and provided serum (mean age 7.8 years) for measurement of polychlorinated biphenyl (PCB), organochlorine pesticide (OCP), and polybrominated diphenyl ether (PBDE) concentrations. Age of menarche was assigned based on parental and participant reported dates and ages of menarche. Adjusted hazard ratios (aHRs) for menarchal onset were calculated with Cox proportional regression. Body mass index (BMI), potentially on the causal pathway, was added to parallel analyses. Age of menarche was later with higher summed PCB levels (median 11.9 years in quartile 1 [Q1] versus 12.7 in quartile 4 [Q4]) and OCP levels (12.1 years versus 12.4, respectively). When adjusting for all covariates except BMI, higher POP concentrations were associated with later age at menarche (Q4 versus Q1 aHRs: PBDEs 0.75 [95% CI 0.58, 0.97], PCBs 0.67 [95% CI 0.5, 0.89], and OCPs 0.66 [95% CI 0.50, 0.89]). Additional adjustment for BMI attenuated aHRs; PCB aHR approached the null. Findings revealed later onset of menarche with higher concentrations of certain POPs, possibly through an association with BMI. Altered pubertal timing may have long lasting effects on reproductive health and disease risk, so continued attention is important for understanding the biological processes affected by hormonally active chemicals.
Authors: Attfield KR; Pinney SM; Sjödin A; Voss RW; Greenspan LC; Biro FM; Hiatt RA; Kushi LH; Windham GC
Environ Res. 2019 09;176:108551. Epub 2019-06-21.
A Cross-Sectional Analysis of Telomere Length and Sleep in the Women’s Health Initiative
Telomere length is a heritable marker of cellular age that is associated with morbidity and mortality. Poor sleep behaviors, which are also associated with adverse health events, may be related to leukocyte telomere length (LTL). We studied a subpopulation of 3,145 postmenopausal women (1,796 European-American (EA) and 1,349 African-American (AA)) enrolled in the Women’s Health Initiative in 1993-1998 with data on Southern blot-measured LTL and self-reported usual sleep duration and sleep disturbance. LTL-sleep associations were analyzed separately for duration and disturbance using weighted and confounder-adjusted linear regression models in the entire sample (AAs + EAs; adjusted for race/ethnicity) and in racial/ethnic strata, since LTL differs by ancestry. After adjustment for covariates, each additional daily hour of sleep beyond 5 hours, approximately, was associated with a 27-base-pair (95% confidence interval (CI): 6, 48) longer LTL in the entire sample. Associations between sleep duration and LTL were strongest among AAs (adjusted β = 37, 95% CI: 4, 70); a similar, nonsignificant association was observed for EAs (adjusted β = 20, 95% CI: -7, 48). Sleep disturbance was not associated with LTL in our study. Our models did not show departure from linearity (quadratic sleep terms: P ≥ 0.55). Our results suggest that longer sleep duration is associated with longer LTL in postmenopausal women.
Authors: Grieshober L; Kroenke CH; Ochs-Balcom HM; et al.
Am J Epidemiol. 2019 09 01;188(9):1616-1626.
Do breast quadrants explain racial disparities in breast cancer outcomes?
PURPOSE: Tumors of the inner quadrants of the breast are associated with poorer survival than those of the upper-outer quadrant. It is unknown whether racial differences in breast cancer outcomes are modified by breast quadrant, in addition to comparisons among Asian subgroups.METHODS: Using the Surveillance, Epidemiology, and End Results database, we analyzed data among women diagnosed with non-metastatic invasive breast cancer between 1990 and 2014. We performed Cox proportional hazards regression models to assess the associations of race with breast cancer-specific survival and overall survival, stratified by breast quadrants. The models were adjusted for age, year of the diagnosis, tumor size, grade, histological type, tumor laterality, lymph node, estrogen receptor, progesterone receptor, and treatments.RESULTS: Among 454,154 patients (73.0% White, 10.0% Black, 7.8% Asian/PI, and 9.2% Hispanic), 54.3% had tumors diagnosed in the upper-outer quadrant of the breast. Asian/PI women were more likely than White to have tumors diagnosed in the nipple/central portion of the breast and were less likely to have diagnosed in the upper-outer quadrant (P CONCLUSIONS: Differences in breast cancer survival by race could not be attributed to tumor locations. Understanding the cultural, biological, and lifestyle factors that vary between White, African American, and ethnic subgroups of Asian American women may help explain these survival differences.
Authors: Han, Yunan Y; Moore, Justin Xavier JX; Langston, Marvin M; Fuzzell, Lindsay L; Khan, Saira S; Lewis, Marquita W MW; Colditz, Graham A GA; Liu, Ying Y
Cancer causes & control : CCC. 2019 Nov ;30(11):1171-1182. Epub 2019-08-27.
Breastfeeding and timing of pubertal onset in girls: a multiethnic population-based prospective cohort study
Early puberty is associated with higher risk of adverse health and behavioral outcomes throughout adolescence and adulthood. US girls are experiencing earlier puberty with substantial racial/ethnic differences. We examined the association between breastfeeding and pubertal timing to identify modifiable risk factors of early puberty and potential sources of racial/ethnic differences in the timing of pubertal development. A prospective cohort study of 3331 racially/ethnically diverse girls born at Kaiser Permanente Northern California (KPNC) between 2004 and 06. All data were obtained from KPNC electronic clinical and administrative datasets. Mother-reported duration of breastfeeding was obtained from questionnaires administered at each ‘well-baby’ check-up exam throughout the baby’s first year and categorized as ‘Not breastfed’, ‘Breastfed < 6 months', and 'Breastfed ≥ 6 months'. Pubertal development data used Tanner stages assessed by pediatricians during routine pediatric checkups starting at age 6. Pubertal onset was defined as transition from Tanner Stage 1 to Tanner Stage 2+ for breast (thelarche) and pubic hair (pubarche). Weibull regression models accommodating for left, right, and interval censoring were used in all analyses. Models were adjusted for maternal age, education, race/ethnicity, parity and prepubertal body mass index (BMI). We also examined race/ethnicity as a potential effect modifier of these associations. Not breastfeeding was associated with earlier onset of breast and pubic hair development compared to breastfeeding ≥6 months (adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 1.07-1.46; HR: 1.24; 95% CI: 1.05-1.46, respectively). Breastfeeding for < 6 months was also associated with the risk of earlier pubic hair development (HR: 1.14; 95% CI: 1.00-1.30, compared to breastfeeding ≥6 months). Inclusion of girls' prepubertal BMI slightly attenuated the association between breastfeeding and timing of breast onset but remained significant. The association between not breastfeeding and early breast development may be stronger among African American girls (HR: 1.92; 95% CI: 1.01-3.66, no breastfeeding vs. ≥6 months) than other racial/ethnic groups. Breastfeeding is an independent predictor of pubertal onset in girls, and the strength of the association may vary by race/ethnicity. Providing breastfeeding support and lactation education for high risk mothers may help prevent earlier pubertal onset and promote positive health outcomes later in life.
Authors: Aghaee S; Deardorff J; Greenspan LC; Quesenberry CP; Kushi LH; Kubo A
BMC Pediatr. 2019 08 09;19(1):277. Epub 2019-08-09.
Trichomonas vaginalis infection and prostate-specific antigen concentration: Insights into prostate involvement and prostate disease risk.
BACKGROUND: The protist Trichomonas vaginalis causes a common, sexually transmitted infection and has been proposed to contribute to the development of chronic prostate conditions, including benign prostatic hyperplasia and prostate cancer. However, few studies have investigated the extent to which it involves the prostate in the current antimicrobial era. We addressed this question by investigating the relation between T. vaginalis antibody serostatus and serum prostate-specific antigen (PSA) concentration, a marker of prostate infection, inflammation, and/or cell damage, in young, male, US military members.METHODS: We measured T. vaginalis serum IgG antibodies and serum total PSA concentration in a random sample of 732 young, male US active duty military members. Associations between T. vaginalis serostatus and PSA were investigated by linear regression.RESULTS: Of the 732 participants, 341 (46.6%) had a low T. vaginalis seropositive score and 198 (27.0%) had a high score, with the remainder seronegative. No significant differences were observed in the distribution of PSA by T. vaginalis serostatus. However, slightly greater, nonsignificant differences were observed when men with high T. vaginalis seropositive scores were compared with seronegative men, and when higher PSA concentrations were examined (≥0.70 ng/mL). Specifically, 42.5% of men with high seropositive scores had a PSA concentration greater than or equal to 0.70 ng/mL compared with 33.2% of seronegative men (adjusted P = .125).CONCLUSIONS: Overall, our findings do not provide strong support for prostate involvement during T. vaginalis infection, although our suggestive positive findings for higher PSA concentrations do not rule out this possibility entirely. These suggestive findings may be relevant for prostate condition development because higher early- to mid-life PSA concentrations have been found to predict greater prostate cancer risk later in life.
Authors: Langston, Marvin E ME; Bhalla, Ankita A; Alderete, John F JF; Nevin, Remington L RL; Pakpahan, Ratna R; Hansen, Johannah J; Elliott, Debra D; De Marzo, Angelo M AM; Gaydos, Charlotte A CA; Isaacs, William B WB; Nelson, William G WG; Sokoll, Lori J LJ; Zenilman, Jonathan M JM; Platz, Elizabeth A EA; Sutcliffe, Siobhan S
The Prostate. 2019 Oct ;79(14):1622-1628. Epub 2019-08-02.
Colonoscopy Indication Algorithm Performance Across Diverse Health Care Systems in the PROSPR Consortium
Despite the importance of characterizing colonoscopy indication for quality monitoring and cancer screening program evaluation, there is no standard approach to documenting colonoscopy indication in medical records. We applied two algorithms in three health care systems to assign colonoscopy indication to persons 50-89 years old who received a colonoscopy during 2010-2013. Both algorithms used standard procedure, diagnostic, and laboratory codes. One algorithm, the KPNC algorithm, used a hierarchical approach to classify exam indication into: diagnostic, surveillance, or screening; whereas the other, the SEARCH algorithm, used a logistic regression-based algorithm to provide the probability that colonoscopy was performed for screening. Gold standard assessment of indication was from medical records abstraction. There were 1,796 colonoscopy exams included in analyses; age and racial/ethnic distributions of participants differed across health care systems. The KPNC algorithm’s sensitivities and specificities for screening indication ranged from 0.78-0.82 and 0.78-0.91, respectively; sensitivities and specificities for diagnostic indication ranged from 0.78-0.89 and 0.74-0.82, respectively. The KPNC algorithm had poor sensitivities (ranging from 0.11-0.67) and high specificities for surveillance exams. The Area Under the Curve (AUC) of the SEARCH algorithm for screening indication ranged from 0.76-0.84 across health care systems. For screening indication, the KPNC algorithm obtained higher specificities than the SEARCH algorithm at the same sensitivity. Despite standardized implementation of these indication algorithms across three health care systems, the capture of colonoscopy indication data was imperfect. Thus, we recommend that standard, systematic documentation of colonoscopy indication should be added to medical records to ensure efficient and accurate data capture.
Authors: Burnett-Hartman AN; Corley DA; Lee JK; Zheng Y; et al.
EGEMS (Wash DC). 2019 Aug 02;7(1):37. Epub 2019-08-02.
Germline Genetic Variants in GATA3 and Breast Cancer Treatment Outcomes in SWOG S8897 Trial and the Pathways Study
GATA3 is a critical transcription factor in maintaining the differentiated state of luminal mammary epithelial cells. We sought to determine the prognostic and predictive roles of GATA3 genotypes for breast cancer. Twelve single nucleotide polymorphisms (SNPs) were genotyped in 2 breast cancer cohorts, including the SWOG S8897 trial where patients were treated with adjuvant chemotherapy (CAF [cyclophosphamide, doxorubicin, 5-fluorouracil] vs. CMF [cyclophosphamide, methotrexate, 5-fluorouracil]) or untreated, and the observational Pathways Study. In the S8897 trial, rs3802604 and rs568727 were associated with disease-free survival and overall survival in the treated group, regardless of chemotherapy regimen. The GG genotype of rs3802604 conferred poorer overall survival (adjusted hazard ratio, 2.45; 95% confidence interval, 1.48-4.05) and disease-free survival (adjusted hazard ratio, 1.95; 95% confidence interval, 1.27-2.99) compared with the AA genotype. Similar associations were found for rs568727. In contrast, no association with either SNP was found in the untreated group. Subgroup analyses indicated that these 2 SNPs more strongly influenced outcomes in the patients who also received tamoxifen. However, the associations in the subgroup with tamoxifen treatment were not replicated in the Pathways Study, possibly owing to substantial differences between the 2 patient cohorts, such as chemotherapy regimen and length of follow-up. Results from joint analyses across these 2 cohorts were marginally significant, driven by the results in S8897. Bioinformatic analyses support potential functional disruption of the GATA3 SNPs in breast tissue. The present study provides some evidence for the predictive value of GATA3 genotypes for breast cancer adjuvant therapies. Future replication studies in appropriate patient populations are warranted.
Authors: Larsen V; Kwan ML; Ergas IJ; Yao S; et al.
Clin Breast Cancer. 2019 08;19(4):225-235.e2. Epub 2019-03-06.
Perfluorooctanoate and changes in anthropometric parameters with age in young girls in the Greater Cincinnati and San Francisco Bay Area
We conducted a study of per- and polyfluoroalkyl substance biomarkers, including PFOA, in girls from Greater Cincinnati (CIN, N = 353) and the San Francisco Bay Area (SFBA, N = 351). PFOA was measured in the baseline serum sample collected in 2004-2007 of 704 girls at age 6-8 years. Mixed effects models were used to derive the effect of PFOA on BMI, waist-to-height and waist-to-hip ratios over increasing age in this longitudinal cohort. Median PFOA serum concentrations were 7.3 (CIN) and 5.8 (SFBA) ng/mL, above the U.S. population median for children 12-19 years in 2005-2006 (3.8 ng/mL). Log-transformed serum PFOA had a strong inverse association with BMIz in the CIN girls (p = 0.0002) and the combined two-site data (p = 0.0008); the joint inverse effect of PFOA and Age*PFOA weakened at age at 10-11 years. However, in the SFBA group alone, the relationship was not significant (p = 0.1641) with no evidence of changing effect with age. The effect of PFOA on waist:height ratio was similar to BMIz at both sites, but we did not find a significant effect of PFOA on waist:hip ratio in either the CIN or SFBA girls. PFOA is associated with decreased BMI and waist:height ratio in young girls, but the strength of the relationship decreases with age. Site heterogeneity may be due to greater early life exposure in Cincinnati. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services.
Authors: Pinney SM; Windham GC; Xie C; Herrick RL; Calafat AM; McWhorter K; Fassler CS; Hiatt RA; Kushi LH; Biro FM; Breast Cancer and the Environment Research Program
Int J Hyg Environ Health. 2019 08;222(7):1038-1046. Epub 2019-07-09.
ASGE guideline on the role of endoscopy for bleeding from chronic radiation proctopathy
Chronic radiation proctopathy is a common sequela of radiation therapy for malignancies in the pelvic region. A variety of medical and endoscopic therapies have been used for the management of bleeding from chronic radiation proctopathy. In this guideline, we reviewed the results of a systematic search of the literature from 1946 to 2017 to formulate clinical questions and recommendations on the role of endoscopy for bleeding from chronic radiation proctopathy. The following endoscopic modalities are discussed in our document: argon plasma coagulation, bipolar electrocoagulation, heater probe, radiofrequency ablation, and cryoablation. Most studies were small observational studies, and the evidence for effectiveness of endoscopic therapy for chronic radiation proctopathy was limited because of a lack of controlled trials and comparative studies. Despite this limitation, our systematic review found that argon plasma coagulation, bipolar electrocoagulation, heater probe, and radiofrequency ablation were effective in the treatment of rectal bleeding from chronic radiation proctopathy.
Authors: Lee JK; Wani SB; et al.
Gastrointest Endosc. 2019 08;90(2):171-182.e1. Epub 2019-06-22.
Association of Daily Rest-Activity Patterns With Adiposity and Cardiometabolic Risk Measures in Teens
Emerging data indicate that the timing and rhythms of energetic behaviors may influence metabolism and obesity risk. Our aim was to derive diurnal rest-activity patterns from actigraphy in adolescents and analyze associations with adiposity measures and cardiometabolic risk factors. Adolescents in the Project Viva cohort wore a wrist actigraph over 7 days. We derived markers of daily rest-activity patterns from actigraphy using nonparametric models, generating measurements of relative amplitude (RA). RA reflects the normalized difference in activity measured during the most active 10-hour period and the least active 5-hour period, averaged over multiple 24-hour periods. Using multivariable-adjusted linear regression models, we estimated associations of RA and its components with markers of adiposity (body mass index, waist circumference, skinfolds, dual-energy X-ray absorptiometry fat mass) and cardiometabolic health (cardiometabolic risk score, derived as the mean of five sex-specific internal z-scores for waist circumference, systolic blood pressure, high-density lipoprotein cholesterol scaled inversely, and log-transformed triglycerides and homeostatic model assessment of insulin resistance). A total of 778 adolescents provided at least 5 days of valid actigraphy data. The average age was 13.2 (±.9) years, 52% were female, and the average RA was .9 (±.1). A higher RA reflecting higher activity during wakefulness and lower activity during the night was associated with more favorable indices of adiposity (e.g., -.35 kg/m2 lower body mass index per each .04 units increment of RA; 95% confidence interval: -.60 to -.09). In this large sample of adolescents, a higher RA emerged as a novel biomarker, associated with more favorable cardiometabolic profiles.
Authors: Quante M; Cespedes Feliciano EM; Rifas-Shiman SL; Mariani S; Kaplan ER; Rueschman M; Oken E; Taveras EM; Redline S
J Adolesc Health. 2019 08;65(2):224-231. Epub 2019-05-02.
Low-Literacy Instructions Enable Successful Completion of Fecal Immunohistochemical Tests
Authors: Lam AY; Lee JK
Clin Gastroenterol Hepatol. 2019 08;17(9):1729-1731. Epub 2019-05-02.
A summary of the Fight Colorectal Cancer working meeting: exploring risk factors and etiology of sporadic early-age onset colorectal cancer
Authors: Dwyer AJ; Lee J; Ahnen D; et al.
Gastroenterology. 2019 08;157(2):280-288. Epub 2019-05-13.
Sexual frequency and pain in a randomized clinical trial of vaginal estradiol tablets, moisturizer, and placebo in postmenopausal women
To evaluate the efficacy of two common interventions for bothersome postmenopausal vaginal symptoms on improving sexual frequency and pain. This is a post-hoc analysis of data from a 12-week double-blind placebo-controlled trial that randomized postmenopausal women (ages 45-70 years) with moderate-severe genitourinary discomfort to vaginal 10 μg estradiol tablet plus placebo gel (n = 102), placebo tablet plus vaginal moisturizer (n = 100), or dual placebo (n = 100). Outcomes were proportion of sexually active women at 12 weeks, frequency of sexual activity, and pain severity with sexual activity (0-3 scale). Consistent with the original study design, comparisons were made between each active arm and the dual placebo arm. Most women enrolled in the trial, 294/302 (97%), had sufficient data to be included in this analysis. Mean age of participants was 61 years, most were white (88%), college educated (66%), and most reported sexual activity in the month before enrollment (81%). After 12 weeks of treatment, a similar proportion of women in the vaginal estrogen and dual placebo groups reported sexual activity in the past week (50% and 40%; P = 0.10) and the past month (78% and 84%, P = 0.52). Mean (standard deviation) pain with sexual activity scores at 12 weeks were similar between vaginal estrogen (1.0 [1.0]) and placebo (0.9 [0.9], P = 0.52] groups. The proportion sexually active at 12 weeks (35%) and mean (standard deviation) pain severity in the vaginal moisturizer group (1.1 [0.9]) did not differ from placebo (P = 0.36). Compared to placebo, neither low-dose vaginal estradiol nor vaginal moisturizer treatment over 12 weeks resulted in significantly greater increases in the proportions of women reporting sexual activity or improvement in pain scores with sexual activity. Clinical trials.gov: NCT02516202.
Authors: Mitchell CM; Guthrie KA; Larson J; Diem S; LaCroix AZ; Caan B; Shifren JL; Woods NF; Heiman JR; Lindau ST; Reed SD
Menopause. 2019 08;26(8):816-822.
Validation of the Hepatocellular Carcinoma Early detection Screening (HES) algorithm in a Cohort of Veterans with Cirrhosis
Early detection of hepatocellular carcinoma (HCC) through surveillance reduces mortality associated with this cancer. Guidelines recommend HCC surveillance every 6 months for patients with cirrhosis, via ultrasonography, with or without measurement of serum level of alpha fetoprotein (AFP). We previously developed and internally validated an HCC early detection screening (HES) algorithm that included patient’s current level of AFP, rate of AFP change, age, level of alanine aminotransferase, and platelet count in a department of Veterans affairs (VA) cohort with active hepatitis C virus-related cirrhosis. HES score was associated with 3.84% absolute improvement in sensitivity of detection of HCC compared with AFP alone, at 90% specificity, within 6 months prior to diagnosis of this cancer. We externally validated the HES algorithm in a cohort of 38,431 patients with cirrhosis of any etiology evaluated at a VA medical center from 2010 through 2015. A total of 4804 cases of HCC developed during a median follow-up time of 3.12 years. At 90% specificity, the HES algorithm identified patients with HCC with 52.56% sensitivity, compared to 48.13% sensitivity for the AFP assay alone, within 6 months prior to diagnosis; this was an absolute improvement of 4.43% (P < .0005). In HCC screening, a positive result leads to follow-up evaluation by computed tomography or magnetic resonance imaging. We estimated that the number of HCC cases detected per 1000 imaging analyses was 198.57 for the HES algorithm vs 185.52 for the AFP assay alone, or detection of 13 additional cases of HCC (P < .0005). We validated the HES algorithm in detection of HCC in patients with cirrhosis of any etiology evaluated at VA medical centers. The algorithm offers a modest but useful advantage over AFP alone in HCC surveillance.
Authors: Tayob N; Christie I; Richardson P; Feng Z; White DL; Davila J; Corley DA; Kanwal F; El-Serag HB
Clin Gastroenterol Hepatol. 2019 08;17(9):1886-1893.e5. Epub 2018-12-14.
A Systematic Review and Meta-analysis of Associations between Clinical Prostatitis and Prostate Cancer: New Estimates Accounting for Detection Bias.
BACKGROUND: Previous meta-analyses have estimated summary positive associations between clinical prostatitis and prostate cancer. However, none have accounted for detection bias, the possibility for increased prostate cancer screening and detection in men with clinical prostatitis, in their pooled estimates.METHODS: We searched for studies that investigated the relation between clinical prostatitis and prostate cancer through November 2018. Random effects meta-analysis was used to calculate summary odds ratios (OR) among all studies and in strata defined by methods used to reduce detection bias.Results: Although an increased odds of prostate cancer was seen among men with a history of clinical prostatitis in all 38 eligible studies combined [OR, 2.05; 95% confidence interval (CI), 1.64-2.57], this estimate attenuated to null among studies that performed the most rigorous analyses to limit detection bias (OR, 1.16; 95% CI, 0.77-1.74).CONCLUSIONS: Our findings indicate that previously reported positive associations between clinical prostatitis and prostate cancer are likely due to detection bias.IMPACT: Studies using rigorous detection bias methods are warranted to replicate these findings, as well as to examine the possible relation between prostate inflammation and prostate cancer directly, rather than indirectly through the diagnosis of "prostatitis," which includes a large proportion of men without evidence of prostate inflammation.
Authors: Langston, Marvin E ME; Horn, Mara M; Khan, Saira S; Pakpahan, Ratna R; Doering, Michelle M; Dennis, Leslie K LK; Sutcliffe, Siobhan S
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019 Oct ;28(10):1594-1603. Epub 2019-07-23.
Association of imputed prostate cancer transcriptome with disease risk reveals novel mechanisms
Here we train cis-regulatory models of prostate tissue gene expression and impute expression transcriptome-wide for 233,955 European ancestry men (14,616 prostate cancer (PrCa) cases, 219,339 controls) from two large cohorts. Among 12,014 genes evaluated in the UK Biobank, we identify 38 associated with PrCa, many replicating in the Kaiser Permanente RPGEH. We report the association of elevated TMPRSS2 expression with increased PrCa risk (independent of a previously-reported risk variant) and with increased tumoral expression of the TMPRSS2:ERG fusion-oncogene in The Cancer Genome Atlas, suggesting a novel germline-somatic interaction mechanism. Three novel genes, HOXA4, KLK1, and TIMM23, additionally replicate in the RPGEH cohort. Furthermore, 4 genes, MSMB, NCOA4, PCAT1, and PPP1R14A, are associated with PrCa in a trans-ethnic meta-analysis (N = 9117). Many genes exhibit evidence for allele-specific transcriptional activation by PrCa master-regulators (including androgen receptor) in Position Weight Matrix, Chip-Seq, and Hi-C experimental data, suggesting common regulatory mechanisms for the associated genes.
Authors: Emami NC; Van Den Eeden SK; Witte JS; et al.
Nat Commun. 2019 07 15;10(1):3107. Epub 2019-07-15.
Trends in Medical Imaging During Pregnancy in the United States and Ontario, Canada, 1996 to 2016
The use of medical imaging has sharply increased over the last 2 decades. Imaging rates during pregnancy have not been quantified in a large, multisite study setting. To evaluate patterns of medical imaging during pregnancy. A retrospective cohort study was performed at 6 US integrated health care systems and in Ontario, Canada. Participants included pregnant women who gave birth to a live neonate of at least 24 weeks’ gestation between January 1, 1996, and December 31, 2016, and who were enrolled in the health care system for the entire pregnancy. Computed tomography (CT), magnetic resonance imaging, conventional radiography, angiography and fluoroscopy, and nuclear medicine. Imaging rates per pregnancy stratified by country and year of child’s birth. A total of 3?497?603 pregnancies in 2?211?789 women were included. Overall, 26% of pregnancies were from US sites. Most (92%) were in women aged 20 to 39 years, and 85% resulted in full-term births. Computed tomography imaging rates in the United States increased from 2.0 examinations/1000 pregnancies in 1996 to 11.4/1000 pregnancies in 2007, remained stable through 2010, and decreased to 9.3/1000 pregnancies by 2016, for an overall increase of 3.7-fold. Computed tomography rates in Ontario, Canada, increased more gradually by 2.0-fold, from 2.0/1000 pregnancies in 1996 to 6.2/1000 pregnancies in 2016, which was 33% lower than in the United States. Overall, 5.3% of pregnant women in US sites and 3.6% in Ontario underwent imaging with ionizing radiation, and 0.8% of women at US sites and 0.4% in Ontario underwent CT. Magnetic resonance imaging rates increased steadily from 1.0/1000 pregnancies in 1996 to 11.9/1000 pregnancies in 2016 in the United States and from 0.5/1000 pregnancies in 1996 to 9.8/1000 pregnancies in 2016 in Ontario, surpassing CT rates in 2013 in the United States and in 2007 in Ontario. In the United States, radiography rates doubled from 34.5/1000 pregnancies in 1996 to 72.6/1000 pregnancies in 1999 and then decreased to 47.6/1000 pregnancies in 2016; rates in Ontario slowly increased from 36.2/1000 pregnancies in 1996 to 44.7/1000 pregnancies in 2016. Angiography and fluoroscopy and nuclear medicine use rates were low (5.2/1000 pregnancies), but in most years, higher in Ontario than the United States. Imaging rates were highest for women who were younger than 20 years or aged 40 years or older, gave birth preterm, or were black, Native American, or Hispanic (US data only). Considering advanced imaging only, chest imaging of pregnant women was more likely to use CT in the United States and nuclear medicine imaging in Ontario. The use of CT during pregnancy substantially increased in the United States and Ontario over the past 2 decades. Imaging rates during pregnancy should be monitored to avoid unnecessary exposure of women and fetuses to ionizing radiation.
Authors: Kwan ML; Kushi LH; Radiation-Induced Cancers Study Team; et al.
JAMA Netw Open. 2019 07 03;2(7):e197249. Epub 2019-07-03.
Association of Normal-Weight Central Obesity With All-Cause and Cause-Specific Mortality Among Postmenopausal Women
Current public health guidelines for obesity prevention and control focus on promoting a normal body mass index (BMI), rarely addressing central obesity, which is reflected by high waist circumference (WC) and common in the general population. Studies of the association of normal-weight central obesity with long-term health outcomes are sparse. To examine associations of normal-weight central obesity with all-cause and cause-specific mortality in postmenopausal women in the United States. A nationwide prospective cohort study of 156?624 postmenopausal women enrolled in the Women’s Health Initiative at 40 clinical centers in the United States between 1993 and 1998. These women were observed through February 2017. Data analysis was performed from September 15, 2017, to March 13, 2019. Different combinations of BMI (calculated as weight in kilograms divided by height in meters squared; normal weight: BMI, 18.5-24.9; overweight: BMI, 25.0-29.9; and obesity: BMI, ?30) and WC (normal: WC, ?88 cm and high: WC, >88 cm). Mortality from all causes, cardiovascular disease, and cancer. Of the 156?624 women (mean [SD] age, 63.2 [7.2] years), during 2?811?187 person-years of follow-up, 43?838 deaths occurred, including 12?965 deaths from cardiovascular disease (29.6%) and 11?828 deaths from cancer (27.0%). Compared with women with normal weight and no central obesity and adjusted for demographic characteristics, socioeconomic status, lifestyle factors, and hormone use, the hazard ratio for all-cause mortality was 1.31 (95% CI, 1.20-1.42) among women with normal weight and central obesity, 0.91 (95% CI, 0.89-0.94) among women with overweight and no central obesity, 1.16 (95% CI, 1.13-1.20) for women with overweight and central obesity, 0.93 (95% CI, 0.89-0.94) for women with obesity and no central obesity, and 1.30 (95% CI, 1.27-1.34) for women with obesity and central obesity. Compared with normal weight without central obesity, normal-weight central obesity was associated with higher risk of cardiovascular disease mortality (hazard ratio, 1.25; 95% CI, 1.05-1.46) and cancer mortality (hazard ratio, 1.20; 95% CI, 1.01-1.43). Normal-weight central obesity in women was associated with excess risk of mortality, similar to that of women with BMI-defined obesity with central obesity. These findings underscore the need for future public health guidelines to include the prevention and control of central obesity, even in individuals with normal BMI.
Authors: Sun Y; Liu B; Snetselaar LG; Wallace RB; Caan BJ; Rohan TE; Neuhouser ML; Shadyab AH; Chlebowski RT; Manson JE; Bao W
JAMA Netw Open. 2019 07 03;2(7):e197337. Epub 2019-07-03.
Comparison of Universal Versus Age-Restricted Screening of Colorectal Tumors for Lynch Syndrome Using Mismatch Repair Immunohistochemistry: A Cohort Study
Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied. To compare the performance of age-restricted and universal LS screening using reflex mismatch repair (MMR) immunohistochemistry (IHC) of CRC tumors. Retrospective cohort study. A large, diverse, community-based health care system. 3891 persons with newly diagnosed CRC who had LS screening between 2011 and 2016. Diagnostic yield of different LS screening strategies. Sixty-three LS cases (diagnostic yield, 1.62%) were identified by universal screening, with only 5 (7.9%) detected after age 70 years and 1 (1.6%) detected after age 80 years. When all patients with CRC who had universal screening were used as the denominator, 58 LS cases (diagnostic yield, 1.49% [95% CI, 1.13% to 1.92%]) were identified in patients with CRC diagnosed at or before age 70 years, 60 LS cases (diagnostic yield, 1.54% [CI, 1.18% to 1.98%]) were identified in those with CRC diagnosed at or before age 75 years, and 62 LS cases (diagnostic yield, 1.59% [CI, 1.22% to 2.04%]) were identified in those with CRC diagnosed at or before age 80 years. Using 75 years as the upper age limit for screening missed 3 of 63 (4.8%) LS cases but resulted in 1053 (27.1%) fewer cases requiring tumor MMR IHC. Using 80 years as the upper age limit missed 1 of 63 (1.6%) LS cases and resulted in 668 (17.2%) fewer cases requiring tumor MMR IHC. Persons who were eligible for but did not complete germline analysis were excluded from calculations of performance characteristics. The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed. Kaiser Permanente Northern California Division of Research.
Authors: Li D; Levin TR; Corley DA; Bergoffen J; et al.
Ann Intern Med. 2019 07 02;171(1):19-26. Epub 2019-06-11.
An Exploratory Analysis of Real-World End Points for Assessing Outcomes Among Immunotherapy-Treated Patients With Advanced Non-Small-Cell Lung Cancer
This pilot study examined the ability to operationalize the collection of real-world data to explore the potential use of real-world end points extracted from data from diverse health care data organizations and to assess how these relate to similar end points in clinical trials for immunotherapy-treated advanced non-small-cell lung cancer. Researchers from six organizations followed a common protocol using data from administrative claims and electronic health records to assess real-world end points, including overall survival (rwOS), time to next treatment, time to treatment discontinuation (rwTTD), time to progression, and progression-free survival, among patients with advanced non-small-cell lung cancer treated with programmed death 1/programmed death-ligand 1 inhibitors in real-world settings. Data sets included from 269 to 6,924 patients who were treated between January 2011 and October 2017. Results from contributors were anonymized. Correlations between real-world intermediate end points (rwTTD and time to next treatment) and rwOS were moderate to high (range, 0.6 to 0.9). rwTTD was the most consistent end points as treatment detail was available in all data sets. rwOS at 1 year post-programmed death-ligand 1 initiation ranged from 40% to 57%. In addition, rwOS as assessed via electronic health records and claims data fell within the range of median OS values observed in relevant clinical trials. Data sources had been used extensively for research with ongoing data curation to assure accuracy and practical completeness before the initiation of this research. These findings demonstrate that real-world end points are generally consistent with each other and with outcomes observed in randomized clinical trials, which substantiates the potential validity of real-world data to support regulatory and payer decision making. Differences observed likely reflect true differences between real-world and protocol-driven practices.
Authors: Stewart M; Kushi L; Sakoda LC; Allen J; et al.
JCO Clin Cancer Inform. 2019 07;3:1-15.
Colorectal Cancer Screening in People With and Without HIV in an Integrated Health Care Setting
As people with HIV (PWH) live longer, age-appropriate colorectal cancer (CRC) screening is increasingly important. Limited data exist on CRC screening and outcomes comparing PWH and persons without HIV. Large integrated health care system. This study included PWH and demographically matched persons without HIV who were aged 50-75 years during 2005-2016 and had no previous CRC screening. We evaluated time to first CRC screening (fecal test, sigmoidoscopy, or colonoscopy). We also assessed detection of adenoma and CRC with sigmoidoscopy or colonoscopy by HIV status, accounting for CRC risk factors including sex, age, race/ethnicity, number of outpatient visits, smoking, body mass index, type-2 diabetes, and inflammatory bowel disease. Among PWH, we evaluated whether CD4 count (<200/200-499/≥500 cells/µL) was associated with adenoma and CRC. Among 3177 PWH and 29,219 persons without HIV, PWH were more likely to be screened (85.6% vs. 79.1% within 5 years, P < 0.001). Among those with sigmoidoscopy or colonoscopy, adenoma was detected in 161 (19.6%) PWH and 1498 (22.6%) persons without HIV, and CRC was detected in 4 (0.5%) PWH and 69 (1.0%) persons without HIV. In adjusted analyses, we found no difference in prevalence of either adenoma or CRC by HIV status (adjusted prevalence ratio = 0.97, 95% confidence interval: 0.83 to 1.12). Lower CD4 count did not increase likelihood of adenoma or CRC. Within an integrated health care system with an organized CRC screening program, we found no disparities in CRC screening uptake or outcomes among people with and without HIV, and CD4 count did not influence CRC risk among PWH.
Authors: Lam JO; Hurley LB; Udaltsova N; Alexeeff SE; Klein DB; Corley DA; Silverberg MJ
J Acquir Immune Defic Syndr. 2019 07 01;81(3):284-291.
Treatment patterns and survival differ between early-onset and late-onset colorectal cancer patients: the patient outcomes to advance learning network
Our objective was to describe differences in treatment patterns and survival between early-onset (< 50 years old) and late-onset colorectal cancer (CRC) patients in community-based health systems. We used tumor registry and electronic health record data to identify and characterize patients diagnosed with adenocarcinoma of the colon or rectum from 2010 to 2014 at six US health systems in the patient outcomes to advance learning (PORTAL) network. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the distribution of tumor characteristics and treatment patterns in early-onset versus late-onset CRC. Cox regression models were used to estimate adjusted hazard ratios (HRs) and CIs comparing survival between early- and late-onset CRC patients. There were 1,424 early-onset and 10,810 late-onset CRC cases in our analyses. Compared to late-onset CRC, early-onset CRC was significantly associated with advanced-stage disease, high-grade histology, signet ring histology, and rectal or left colon location. After adjusting for differences in tumor and patient characteristics, early-onset patients were more likely than late-onset patients to have > 12 lymph nodes examined (OR 1.60, CI 1.37-1.87), to receive systemic therapy (chemotherapy or immunotherapy) within 6 months of diagnosis (OR 2.84, CI 2.40-3.37), and to have a reduced risk of CRC-specific death (HR 0.66, CI 0.56-0.79). Early-onset CRC is associated with aggressive tumor characteristics, distal location, and systemic therapy use. Despite some adverse risk factors, these patients tend to have better survival than older onset patients.
Authors: Burnett-Hartman AN; Powers JD; Chubak J; Corley DA; Ghai NR; McMullen CK; Pawloski PA; Sterrett AT; Feigelson HS
Cancer Causes Control. 2019 Jul;30(7):747-755. Epub 2019-05-17.
Body Composition and Cardiovascular Events in Patients With Colorectal Cancer: A Population-Based Retrospective Cohort Study
Patients with colorectal cancer (CRC) are up to 4-fold more likely than individuals without a history of cancer to develop cardiovascular disease. Clinical care guidelines recommend that physicians counsel patients with CRC regarding the association between obesity (defined using body mass index [BMI] calculated as weight in kilograms divided by height in meters squared) and cardiovascular disease risk; however, this recommendation is based on expert opinion. To determine which measures of body composition are associated with major adverse cardiovascular events (MACEs) in patients with CRC. Population-based retrospective cohort study of 2839 patients with stage I to III CRC diagnosed between January 2006 and December 2011 at an integrated health care system in North America. The primary exposures were BMI and computed tomography-derived body composition measurements (eg, adipose tissue compartments and muscle characteristics) obtained at the diagnosis of CRC. The primary outcome was time to the first occurrence of MACE after diagnosis of CRC, including myocardial infarction, stroke, and cardiovascular death. In this population-based cohort study of 2839 participants with CRC (1384 men and 1455 women), the average age (SD) was 61.9 (11.5) years (range, 19-80 years). A substantial number of patients were former (1127; 40%) or current smokers (340; 12%), with hypertension (1150; 55%), hyperlipidemia (1389; 49%), and type 2 diabetes (573; 20%). The cumulative incidence of MACE 10 years after diagnosis of CRC was 19.1%. Body mass index was positively correlated with some computed tomography-derived measures of body composition. However, BMI was not associated with MACE; contrasting BMI categories of greater than or equal to 35 vs 18.5 to 24.9, the hazard ratio (HR) was 1.23 (95% CI, 0.85-1.77; P = .50 for trend). Visceral adipose tissue area was associated with MACE; contrasting the highest vs lowest quintile, the HR was 1.54 (95% CI, 1.02-2.31; P = .04 for trend). Subcutaneous adipose tissue area was not associated with MACE; contrasting the highest vs lowest quintile, the HR was 1.15 (95% CI, 0.78-1.69; P = .65 for trend). Muscle mass was not associated with MACE; contrasting the highest vs lowest quintile, the HR was 0.96 (95% CI, 0.57-1.61; P = .92 for trend). Muscle radiodensity was associated with MACE; contrasting the highest (ie, less lipid stored in the muscle) vs lowest quintile, the HR was 0.67 (95% CI, 0.44-1.03; P = .02 for trend). Visceral adiposity and muscle radiodensity appear to be risk factors for MACE. Body mass index may have limited use for determining cardiovascular risk in this patient population.
Authors: Brown JC; Caan BJ; Prado CM; Weltzien E; Xiao J; Cespedes Feliciano EM; Kroenke CH; Meyerhardt JA
JAMA Oncol. 2019 Jul 01;5(7):967-972.
Muscle segmentation in axial computed tomography (CT) images at the lumbar (L3) and thoracic (T4) levels for body composition analysis
In diseases such as cancer, patients suffer from degenerative loss of skeletal muscle (cachexia). Muscle wasting and loss of muscle function/performance (sarcopenia) can also occur during advanced aging. Assessing skeletal muscle mass in sarcopenia and cachexia is therefore of clinical interest for risk stratification. In comparison with fat, body fluids and bone, quantifying the skeletal muscle mass is more challenging. Computed tomography (CT) is one of the gold standard techniques for cancer diagnostics and analysis of progression, and therefore a valuable source of imaging for in vivo quantification of skeletal muscle mass. In this paper, we design a novel deep neural network-based algorithm for the automated segmentation of skeletal muscle in axial CT images at the third lumbar (L3) and the fourth thoracic (T4) levels. A two-branch network with two training steps is investigated. The network’s performance is evaluated for three trained models on separate datasets. These datasets were generated by different CT devices and data acquisition settings. To ensure the model’s robustness, each trained model was tested on all three available test sets. Errors and the effect of labeling protocol in these cases were analyzed and reported. The best performance of the proposed algorithm was achieved on 1327 L3 test samples with an overlap Jaccard score of 98% and sensitivity and specificity greater than 99%.
Authors: Dabiri S; Popuri K; Cespedes Feliciano EM; Caan BJ; Baracos VE; Beg MF
Comput Med Imaging Graph. 2019 07;75:47-55. Epub 2019-05-09.
Systematic review and meta-analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease
Janus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease. To determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). PubMed, Embase and CENTRAL were systematically searched to November 1, 2018. Randomised placebo-controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC were eligible. Open-label extension studies without a placebo comparator arm were excluded. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random-effects model. A total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomised to placebo (n = 844), tofacitinib (n = 1882), filgotinib (n = 130), peficitinib (n = 176), upadacitinib (n = 387) or TD-1473 (n = 31). JAK inhibitor treatment was associated with induction of clinical remission in CD (RR, relative risk 1.38 [95% confidence interval CI 1.04-1.83], P = 0.025, I2 = 14%) and UC (RR 3.07 [95% CI 2.03-4.63], P < 0.001, I2 = 0%). In UC, JAK inhibitor treatment was associated with induction of endoscopic remission (endoscopic Mayo subscore MCSe = 0/1) (RR 2.43 [95% CI 1.64-3.59], P < 0.001, I2 = 27%) and mucosal healing (MCSe = 0) (RR 5.50 [95% CI 2.46-12.32], P < 0.001, I2 = 0%). JAK inhibitor treatment increased the risk of infection compared to placebo (RR 1.40 [95% CI 1.18-1.67], P < 0.001, I2 = 0%), particularly for herpes zoster. JAK inhibitors are effective for inducing clinical remission in CD and induction of clinical and endoscopic remission in UC, although are associated with an increased risk of infectious complications.
Authors: Ma C; Lee JK; Mitra AR; Teriaky A; Choudhary D; Nguyen TM; Vande Casteele N; Khanna R; Panaccione R; Feagan BG; Jairath V
Aliment Pharmacol Ther. 2019 07;50(1):5-23. Epub 2019-05-23.
Incorporation of a Molecular Prognostic Classifier Improves Conventional Non-Small Cell Lung Cancer Staging
Despite adoption of molecular biomarkers in the management of NSCLC, the recently adopted eighth edition of the TNM staging system utilized only clinicopathologic characteristics and validated improvement in risk stratification of early-stage disease has remained elusive. We therefore evaluated the integration of a clinically validated molecular prognostic classifier into conventional staging. A novel staging system, the TNMB (with the B denoting biology) system, which integrates a 14-gene molecular prognostic classifier into the eighth edition of the TNM staging system, was developed by using data from 321 patients with NSCLC at the University of California, San Francisco. The TNMB staging system was subsequently validated in an independent, multicenter cohort of 1373 patients, and its implementation was compared with adoption of the seventh and eighth edition staging systems utilizing metrics of reclassification. Compared with staging according to the eighth edition of the TNM system, the TNMB staging system enhanced the identification of high-risk patients, with a net reclassification improvement of 0.33 (95% confidence interval [CI]: 0.24-0.41). It better predicted differences in survival, with a relative integrated discrimination improvement of 22.1% (95% CI: 8.8%-35.3%), and it improved agreement between observed and predicted survival, with a decrease in the reclassification calibration statistic of from 39 to 21. The seventh and eighth editions failed to change the net reclassification improvement (0.01 [95% CI: -0.04 to 0.03] and 0.03 [95% CI: 0.00 to 0.06], respectively) or relative integrated discrimination improvement (2.1% [95% CI: -5.8 to 9.9] and -2.5% [95% CI: -17.6 to 12.4], respectively); in addition, the eighth edition worsened calibration, with an increase in the reclassification calibration statistic from 23 to 25. Incorporation of a molecular prognostic classifier significantly improved identification of high-risk patients and survival predictions compared with when conventional staging is used. The TNMB staging system may lead to improved survival of early-stage disease through more effective application of adjuvant therapy.
Authors: Kratz JR; Van Den Eeden SK; Mann MJ; et al.
J Thorac Oncol. 2019 07;14(7):1223-1232. Epub 2019-04-05.
Development of a goal elicitation measure to support bladder cancer patients’ choice about urinary diversion
Patient centered care aims to align treatment with patient goals, especially when treatment options have equivalent clinical outcomes. For surgeries with lasting impacts that alignment is critical. To our knowledge no psychometrically tested preference elicitation measures exist to support patients with bladder cancer treated with cystectomy, who can often choose between ileal conduit and neobladder diversions. In this study we created a scale to measure how patient goals align with each type of urinary diversion and the associated surgical outcomes. We performed formative research through focus groups and clinician outreach to adapt a goal dissonance measure. We mailed a survey to adult Kaiser Permanente® members who underwent cystectomy for bladder cancer between January 2013 and June 2015. Eligible patients were identified through electronic health records and chart review. Surveys were mailed 5 to 7 months postoperatively. We administered our 10-item decision dissonance scale along with other decision making measures. We explored goal alignment as well as dissonance. Psychometric analysis included factor analysis, evaluation of scale scores between surgery groups and evaluation with other decision making scores. We identified 10 goals associated with ileal conduit or neobladder diversion. Using survey data on 215 patients our scale differentiated patient goals associated with each diversion choice. On average patients with a neobladder strongly valued neobladder aligned goals such as maintaining body integrity and volitional voiding through the urethra. Patients with an ileal conduit had neutral values on average across all goals. Our measure lays the foundation for a simple value elicitation approach which could facilitate shared decision making about urinary diversion choice.
Authors: Leo MC; Gilbert SM; Wendel CS; Krouse RS; Grant M; Danforth KN; Kwan ML; Harrison TN; Bulkley JE; McMullen CK
J Urol. 2019 07;202(1):83-89. Epub 2019-06-07.
Blood pressure lowering medication initiation and fracture risk: a SWAN pharmacoepidemiology study
We examined the fracture risk after initiation of blood pressure-lowering drugs compared with initiation of antidepressants. Multivariable regression models demonstrated an increased risk of fracture among women initiating a blood pressure-lowering medication (HR 1.73, 95% CI 1.02-2.95). This is likely related to an increased risk of falls. Initiation of blood pressure-lowering drugs has been associated with fractures in several studies, presumably due to an increase in the risk of falls. However, these studies used self-controlled designs without active comparators. We examined the risk of fractures after initiation of blood pressure lowering drugs compared with initiation of antidepressants. Women participants in the Study of Women Across the Nation (SWAN) were potentially eligible if they initiated blood pressure-lowering or antidepressant drugs during follow-up. To reduce the risk of confounding, we estimated a propensity score that included potential confounders including age, menopausal status, osteoporosis, and osteoporosis medication use. The propensity score was used to match subjects in both groups and we then constructed multivariable logistic regression models comparing the risk of any fracture. Sensitivity analyses assessed a limited range of fractures less likely related to trauma. Among the 3302 potentially eligible women participating in the SWAN cohort, we were able to propensity-score match 289 women who initiated a blood pressure-lowering medication with 289 who initiated an antidepressant. Multivariable logistic regression models demonstrated an increased risk of fracture among women initiating a blood pressure lowering medication (OR 1.74, 95% CI 1.02-2.95). After excluding fractures of the digits and face, the results were similar (OR 1.57, 95% CI 0.88-2.81). There was evidence of an increased risk in fractures among women initiating blood pressure-lowering medications compared to those initiating antidepressants. This is likely related to an increased risk of falling.
Authors: Solomon DH; Ruppert K; Kazlauskaite R; Finkelstein JS; Habel LA
Arch Osteoporos. 2019 06 28;14(1):73. Epub 2019-06-28.
Identifying Metabolomic Profiles of Insulinemic Dietary Patterns
The food-based empirical dietary index for hyperinsulinemia (EDIH) score assesses the insulinemic potential of diet. This cross-sectional study evaluated associations between EDIH scores from food frequency questionnaires with c-peptide concentrations and with 448 metabolites, from fasting plasma samples, in multivariable linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Using a robust two-stage study design, discovery of metabolite associations was conducted among 1109 Women’s Health Initiative (WHI) Hormone Therapy (HT) trial participants and results replicated in an independent dataset of 810 WHI Observational Study (OS) participants. In both discovery and replication datasets, statistical significance was based on the false-discovery rate adjusted P < 0.05. In the multivariable-adjusted analyses, EDIH was significantly associated with c-peptide concentrations among 919 women (HT & OS) with c-peptide data. On average, c-peptide concentrations were 18% higher (95% CI, 6%, 32%; P-trend < 0.0001) in EDIH quintile 5 compared to quintile 1. Twenty-six metabolites were significantly associated with EDIH in the discovery dataset, and 19 of these were replicated in the validation dataset. Nine metabolites were found to decrease in abundance with increasing EDIH scores and included: C14:0 CE, C16:1 CE, C18:1 CE, C18:3 CE, C20:3 CE, C20:5 CE, C36:1 PS plasmalogen, trigonelline, and eicosapentanoate, whereas the 10 metabolites observed to increase with increasing EDIH scores were: C18:2 SM, C36:3 DAG, C36:4 DAG-A, C51:3 TAG, C52:3 TAG, C52:4, TAG, C54:3 TAG, C54:4 TAG, C54:6 TAG, and C10:2 carnitine. Cholesteryl esters, phospholipids, acylglycerols, and acylcarnitines may constitute circulating metabolites that are associated with insulinemic dietary patterns.
Authors: Tabung FK; Balasubramanian R; Liang L; Clinton SK; Cespedes Feliciano EM; Manson JE; Van Horn L; Wactawski-Wende J; Clish CB; Giovannucci EL; Rexrode KM
Metabolites. 2019 Jun 24;9(6). Epub 2019-06-24.
Telomere length and socioeconomic status at neighborhood and individual levels among 80,000 adults in the Genetic Epidemiology Research on Adult Health and Aging cohort
Telomere length (TL) may serve as a biologic marker of aging. We examined neighborhood and individual-level socioeconomic status (SES) in relation to TL. The study included 84,996 non-Hispanic white subjects from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, part of the Research Program on Genes, Environment and Health. Relative TL (T/S) was log2 transformed to improve normality and standardized to have mean 0 and variance 1. Neighborhood SES was measured using the Neighborhood Deprivation Index (NDI), and individual SES was measured by self-reported education level. We fit linear regression models of TL on age, sex, smoking, body mass index, comorbidities, NDI, and education level. We tested for differences in the associations by sex and nonlinearity in the association of NDI with TL. Each SD increase in NDI was associated with a decrease of 0.0192 in standardized TL, 95% confidence interval (CI) = -0.0306, -0.0078. There was no evidence of nonlinearity in the association of NDI with TL. We further found that less than high school education was associated with a decrease of 0.1371 in standardized TL, 95% CI = -0.1919, -0.0823 as compared to a college education. There were no differences in the associations by sex. We found evidence that both lower neighborhood SES and lower individual-level SES are associated with shorter TL among non-Hispanic whites. Our findings suggest that socioeconomic factors may influence aging by contributing to shorter TL.
Authors: Alexeeff, Stacey E; Schaefer, Catherine A; Risch, Neil; Sakoda, Lori C; Quesenberry, Charles P; Van Den Eeden, Stephen K; et al.
Environ Epidemiol. 2019 Jun;3(3):e049. Epub 2019-05-01.
Reproductive Factors and Mammographic Density: Associations Among 24,840 Women and Comparison of Studies Using Digitized Film-Screen Mammography and Full-Field Digital Mammography
Breast density is a modifiable factor that is strongly associated with breast cancer risk. We sought to understand the influence of newer technologies of full-field digital mammography (FFDM) on breast density research and to determine whether results are comparable across studies using FFDM and previous studies using traditional film-screen mammography. We studied 24,840 screening-age (40-74 years) non-Hispanic white women who were participants in the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California and underwent screening mammography with either Hologic (Hologic, Inc., Marlborough, Massachusetts) or General Electric (General Electric Company, Boston, Massachusetts) FFDM machines between 2003 and 2013. We estimated the associations of parity, age at first birth, age at menarche, and menopausal status with percent density and dense area as measured by a single radiological technologist using Cumulus software (Canto Software, Inc., San Francisco, California). We found that associations between reproductive factors and mammographic density measured using processed FFDM images were generally similar in magnitude and direction to those from prior studies using film mammography. Estimated associations for both types of FFDM machines were in the same direction. There was some evidence of heterogeneity in the magnitude of the effect sizes by machine type, which we accounted for using random-effects meta-analysis when combining results. Our findings demonstrate the robustness of quantitative mammographic density measurements across FFDM and film mammography platforms.
Authors: Alexeeff SE; Habel LA; et al.
Am J Epidemiol. 2019 06 01;188(6):1144-1154.
ASGE guideline on the role of endoscopy in the evaluation and management of choledocholithiasis
Each year choledocholithiasis results in biliary obstruction, cholangitis, and pancreatitis in a significant number of patients. The primary treatment, ERCP, is minimally invasive but associated with adverse events in 6% to 15%. This American Society for Gastrointestinal Endoscopy (ASGE) Standard of Practice (SOP) Guideline provides evidence-based recommendations for the endoscopic evaluation and treatment of choledocholithiasis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the contemporary literature regarding the following topics: EUS versus MRCP for diagnosis, the role of early ERCP in gallstone pancreatitis, endoscopic papillary dilation after sphincterotomy versus sphincterotomy alone for large bile duct stones, and impact of ERCP-guided intraductal therapy for large and difficult choledocholithiasis. Comprehensive systematic reviews were also performed to assess the following: same-admission cholecystectomy for gallstone pancreatitis, clinical predictors of choledocholithiasis, optimal timing of ERCP vis-à-vis cholecystectomy, management of Mirizzi syndrome and hepatolithiasis, and biliary stent therapy for choledocholithiasis. Core clinical questions were derived using an iterative process by the ASGE SOP Committee. This body developed all recommendations founded on the certainty of the evidence, balance of risks and harms, consideration of stakeholder preferences, resource utilization, and cost-effectiveness.
Authors: ASGE Standards of Practice Committee; Lee JK; Wani SB; et al.
Gastrointest Endosc. 2019 06;89(6):1075-1105.e15. Epub 2019-04-09.
Lack of Standardized Terminology in Ultrasound Reports for Ovarian Cysts
Authors: Suh-Burgmann E; Herrinton L
JAMA Intern Med. 2019 06 01;179(6):847-848.
Adipose Tissue Distribution and Survival Among Women with Nonmetastatic Breast Cancer
Previous studies of breast cancer survival have not considered specific depots of adipose tissue such as subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). This study assessed these relationships among 3,235 women with stage II and III breast cancer diagnosed between 2005 and 2013 at Kaiser Permanente Northern California and between 2000 and 2012 at Dana Farber Cancer Institute. SAT and VAT areas (in centimeters squared) were calculated from routine computed tomography scans within 6 (median: 1.2) months of diagnosis, covariates were collected from electronic health records, and vital status was assessed by death records. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression. SAT and VAT ranged from 19.0 to 891 cm2 and from 0.484 to 454 cm2 , respectively. SAT was related to increased risk of death (127-cm2 increase; HR [95% CI]: 1.13 [1.02-1.26]), but no relationship was found with VAT (78.18-cm2 increase; HR [95% CI]: 1.02 [0.91-1.14]). An association with VAT was noted among women with stage II cancer (stage II: HR: 1.17 [95% CI: 0.99-1.39]; stage III: HR: 0.90 [95% CI: 0.76-1.07]; P interaction < 0.01). Joint increases in SAT and VAT were associated with mortality above either alone (simultaneous 1-SD increase: HR 1.19 [95% CI: 1.05-1.34]). SAT may be an underappreciated risk factor for breast cancer-related death.
Authors: Bradshaw PT; Cespedes Feliciano EM; Prado CM; Alexeeff S; Albers KB; Chen WY; Caan BJ
Obesity (Silver Spring). 2019 06;27(6):997-1004. Epub 2019-04-25.
Benign Papillary Breast Mass Lesions: Favorable Outcomes with Surgical Excision or Imaging Surveillance
There is no consensus regarding the management of benign papillary breast lesions diagnosed on image-guided core needle biopsy (IGCNB). This is a retrospective review of 407 patients within Kaiser Permanente Northern California diagnosed between 2012 and 2013. The study focused on patients presenting with a mass lesion and who were diagnosed with a benign papillary breast lesion (BPBL) on IGCNB. Patients who did not have surgical excision of the IGCNB papilloma were followed for at least 2 years. A total of 327 patients (80%) underwent surgical excision, 61 patients (15%) had follow-up imaging, and 19 patients (5%) had no surgery or imaging. Overall among women with surgical excision, 9.5% had a high-risk lesion, 3.4% had in situ cancer, and 2.4% had invasive cancer. An upgrade to an in situ cancer or invasive cancer was more common among women with a lesion greater than 1 cm, a palpable breast mass, age > 50 years, or if the lesion was > 5 cm from the nipple. No cancers were diagnosed in 61 women followed by imaging surveillance. This is the largest, single-cohort study of benign papillary mass lesions diagnosed on IGCNB. On surgical excision, the overall rate of upgrade to in situ cancer and invasive cancer was low, and almost all cancers diagnosed had favorable features. Because no cancers were found in women who were followed by imaging, we conclude that outcomes for BPBL diagnosed on IGCNB are favorable whether surgical excision or surveillance is the treatment choice.
Authors: Kuehner G; Darbinian J; Habel L; Axelsson K; Butler S; Chang S; Chen R; Fehrenbacher L
Ann Surg Oncol. 2019 Jun;26(6):1695-1703. Epub 2019-02-08.
Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ? 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
Authors: Walsh N; Van Den Eeden SK; Stolzenberg-Solomon RZ; et al.
J Natl Cancer Inst. 2019 12 01;111(12):1243-1244.
Mendelian randomization analysis of C-reactive protein on colorectal cancer risk
Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P?=?7.5?×?10-4, and P?=?0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR)?=?1.04; 95% confidence interval (CI): 0.97, 1.12; P?=?0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.
Authors: Wang X; Caan B; White E; et al.
Int J Epidemiol. 2019 06 01;48(3):767-780.
Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: a study within the National Cancer Institute Cohort Consortium
Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk. This nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy. Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORsquartile 4 vs 1=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker-cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity-oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk. This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.
Authors: Cook MB; Kroenke CH; Campbell PT; et al.
Gut. 2019 06;68(6):960-968. Epub 2018-08-18.
Disparities in Health Information-Seeking Behaviors and Fatalistic Views of Cancer by Sexual Orientation Identity: A Nationally Representative Study of Adults in the United States.
Purpose: A lack of national data makes it difficult to estimate, but LGB adults appear to have a higher risk of cancer. Although limited research exists to explain the disparity, we aimed to explore potential differences in access to and utilization of health information and in cancer-related beliefs and behaviors. Methods: We used data from the Health Information National Trends Survey 5, Cycle 1 conducted from January 25 through May 5, 2017. Using survey-weighted logistic regression, we explored potential differences in health information-seeking behavior, trusted sources of health care information, engagement with the health care system, awareness of cancer risk factors, cancer fatalism, cancer-related health behaviors, and historical cancer screening between 117 LGB and 2857 heterosexual respondents. Results: LGB respondents were more likely to report looking for information about health or medical topics than heterosexual respondents (adjusted odds ratio [aOR]: 3.12; confidence interval [95% CI]: 1.07-9.06), but less likely to seek health information first from a doctor (aOR: 0.17; 95% CI: 0.06-0.50) after adjusting for age, race, and sex. LGB persons were less likely to report that they trust receiving health or medical information from friends and family and more likely to be worried about getting cancer (aOR: 2.30; 95% CI: 1.04-5.05). Conclusions: Our findings indicate a growing need for the production of tailored cancer prevention and control materials for members of sexual minority groups. More work is needed to understand barriers that LGB populations face in accessing this health information and building informative social support networks.
Authors: Langston, Marvin E ME; Fuzzell, Lindsay L; Lewis-Thames, Marquita W MW; Khan, Saira S; Moore, Justin X JX
LGBT health. 2019 Oct ;6(4):192-201. Epub 2019-05-20.
Effectiveness of a Patient Education Class to Enhance Knowledge about Lung Cancer Screening: a Quality Improvement Evaluation
Best practices to facilitate high-quality shared decision-making for lung cancer screening (LCS) are not well established. In our LCS program, patients are first referred to attend a free group education class on LCS, taught by designated clinician specialists, before a personal shared decision-making visit is scheduled. We conducted an evaluation on the effectiveness of this class to enhance patient knowledge and shared decision-making about LCS. For quality improvement purposes, participants were asked to complete one-page surveys immediately before and after class to assess knowledge and decision-making capacity regarding LCS. To evaluate knowledge gained, we tabulated the distributions of correct, incorrect, unsure, and missing responses to eight true-false statements included on both pre- and post-class surveys and assessed pre-post differences in the number of correct responses. To evaluate decision-making capacity, we tabulated the distributions of post-class responses to items on decision uncertainty. From June 2017 to August 2018, 680 participants completed both pre- and post-class surveys. Participants had generally poor baseline knowledge about LCS. The proportion who responded correctly to each knowledge-related statement increased pre- to post-class, with a mean difference of 0.9 (paired t test, p
Authors: Sakoda LC; Meyer MA; Chawla N; Sanchez MA; Blatchins MA; Nayak S; San K; Zin GK; Minowada G; Permanente Medical Group Lung Cancer Screening Task Force
J Cancer Educ. 2019 May 09.
Predictors of Long-Term Survival among High-Grade Serous Ovarian Cancer Patients
Relatively little is known about factors associated with long-term survival (LTS) following a diagnosis of ovarian cancer. We conducted a retrospective study of high-grade serous ovarian cancer (HGSOC) to explore predictors of LTS (defined as ≥7 years of survival) using electronic medical record data from a network of integrated health care systems. Multivariable logistic regression with forward selection was used to compare characteristics of women who survived ≥7 years after diagnosis (n = 148) to those who died within 7 years of diagnosis (n = 494). Our final model included study site, age, stage at diagnosis, CA-125, comorbidity score, receipt of chemotherapy, BMI, and four separate comorbid conditions: weight loss, depression, hypothyroidism, and liver disease. Of these, only younger age, lower stage, and depression were statistically significantly associated with LTS. We did not identify any new characteristics associated with HGSOC survival. Prognosis of ovarian cancer generally remains poor. Large, pooled studies of ovarian cancer are needed to identify characteristics that may improve survival.
Authors: Clarke CL; Kushi LH; Chubak J; Pawloski PA; Bulkley JE; Epstein MM; Burnett-Hartman AN; Powell B; Pearce CL; Spencer Feigelson H
Cancer Epidemiol Biomarkers Prev. 2019 05;28(5):996-999. Epub 2019-04-09.
Time to Follow-up After Colorectal Cancer Screening by Health Insurance Type
The purpose of this study was to test the hypothesis that patients with Medicaid insurance or Medicaid-like coverage would have longer times to follow-up and be less likely to complete colonoscopy compared with patients with commercial insurance within the same healthcare systems. A total of 35,009 patients aged 50-64years with a positive fecal immunochemical test were evaluated in Northern and Southern California Kaiser Permanente systems and in a North Texas safety-net system between 2011 and 2012. Kaplan-Meier estimation was used between 2016 and 2017 to calculate the probability of having follow-up colonoscopy by coverage type. Among Kaiser Permanente patients, Cox regression was used to estimate hazard ratios and 95% CIs for the association between coverage type and receipt of follow-up, adjusting for sociodemographics and health status. Even within the same integrated system with organized follow-up, patients with Medicaid were 24% less likely to complete follow-up as those with commercial insurance. Percentage receiving colonoscopy within 3 months after a positive fecal immunochemical test was 74.6% for commercial insurance, 63.10% for Medicaid only, and 37.5% for patients served by the integrated safety-net system. This study found that patients with Medicaid were less likely than those with commercial insurance to complete follow-up colonoscopy after a positive fecal immunochemical test and had longer average times to follow-up. With the future of coverage mechanisms uncertain, it is important and timely to assess influences of health insurance coverage on likelihood of follow-up colonoscopy and identify potential disparities in screening completion.
Authors: Breen N; Corley DA; PROSPR consortium; et al.
Am J Prev Med. 2019 05;56(5):e143-e152.
Germline BRCA1 Deletion as Driver Mutation for Metastatic Urachal Adenocarcinoma in Patient Who Achieved Complete Response to Rucaparib
Authors: Seto T; Pujare D; Song MN; Lee J; Huber R; Sam D; Pan M
J Oncol Pract. 2019 05;15(5):293-295. Epub 2019-04-02.
Interaction of body mass index or waist-to-hip ratio and sun exposure associated with nonmelanoma skin cancer: A prospective study from the Women’s Health Initiative
The incidence of nonmelanoma skin cancer (NMSC) exceeds the incidence of all other types of cancers combined. Cumulative sun exposure and intermittent sun exposure are known risk factors for the development of NMSC. Because obesity has been shown to decrease the risk of NMSC incidence, this study investigated whether the risk of NMSC with sun exposure was consistent across different levels of body size. Body size was assessed with the body mass index (BMI) and the waist-to-hip ratio (WHR). Sun exposure was assessed in watts and langleys and by the amount of time spent outdoors per day in the summer during a person’s 30s. Among 71,645 postmenopausal women eligible for inclusion in this study, 13,351 participants (18.6%) developed NMSC. A BMI ? 25 kg/m2 or a WHR ? 0.80 was associated with lower NMSC hazard rates (hazard ratio for BMI, 0.78; hazard ratio for WHR, 0.89); however, the association between higher levels of sun exposure and a higher risk of NMSC was more apparent among women with a BMI ? 25 kg/m2 or a WHR ? 0.80 in comparison with those of a normal weight (P for interaction for BMI < .001; P for interaction for WHR = .022). Although most studies have considered sun exposure as a covariate, none have addressed the potential interaction of body size with sun exposure; therefore, the effect size of being overweight or obese may have been overestimated. In comparison to the normal-weight group, those in the overweight group had increasingly higher hazard rates with increasing sun exposure. Further studies are warranted to investigate how increased weight interacts with sun exposure to influence skin cancer pathogenesis.
Authors: Chan AA; Noguti J; Pak Y; Qi L; Caan B; Going S; Han J; Chlebowski RT; Lee DJ
Cancer Causes Control. 2020 Jan;31(1):85-93. Epub 2019-11-28.
SeqSQC: A Bioconductor Package for Evaluating the Sample Quality of Next-generation Sequencing Data
As next-generation sequencing (NGS) technology has become widely used to identify genetic causal variants for various diseases and traits, a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data, sample quality issues, such as gender mismatch, abnormal inbreeding coefficient, cryptic relatedness, and population outliers, can also have fundamental impact on downstream analysis. However, there is a lack of tools specialized in identifying problematic samples from NGS data, often due to the limitation of sample size and variant counts. We developed SeqSQC, a Bioconductor package, to automate and accelerate sample cleaning in NGS data of any scale. SeqSQC is designed for efficient data storage and access, and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQC is available at https://bioconductor.org/packages/SeqSQC.
Authors: Liu Q; Hu Q; Yao S; Kwan ML; Roh JM; Zhao H; Ambrosone CB; Kushi LH; Liu S; Zhu Q
Genomics Proteomics Bioinformatics. 2019 04;17(2):211-218. Epub 2019-04-05.
Will a Proton Pump Inhibitor and an Aspirin Keep the Doctor Away for Patients With Barrett’s Esophagus?
Authors: Fitzgerald RC; Corley DA
Gastroenterology. 2019 04;156(5):1228-1231. Epub 2019-03-05.
Early-onset triple-negative breast cancer in multiracial/ethnic populations: Distinct trends of prevalence of truncation mutations
Young black women are at higher risk of triple-negative breast cancer (TNBC); however, a majority of the genetic studies on cancer predisposition were carried out in White populations. The underrepresentation of minority racial/ethnic populations in cancer genetic studies may have led to disproportionate gaps in our knowledge of cancer predisposition genes in these populations. We surveyed the protein-truncating mutations at the exome-wide scale and in known breast cancer predisposition genes among 170 patients of multiple racial/ethnic groups with early-onset (≤age 50) TNBC from two independent cohorts. Black patients, on average, had a higher number of truncating mutations than Whites at the exome-wide level, but fewer truncating mutations in the panel of known breast cancer genes. White TNBC patients showed a strong enrichment of truncating variants in known breast cancer genes, whereas no such enrichment was found among Black patients. Our findings indicate likely more breast cancer disposition genes yet to be discovered in minority racial/ethnic groups, and the current multigene panels may result in unequal benefits from cancer genetic testing.
Authors: Liu Q; Yao S; Zhao H; Hu Q; Kwan ML; Roh JM; Ambrosone CB; Kushi LH; Liu S; Zhu Q
Cancer Med. 2019 04;8(4):1845-1853. Epub 2019-03-12.
Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer
Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10- 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10- 4, replication P = 6.7 × 10- 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. This study is the first to implement PrediXcan in a large colorectal cancer study and findings highlight the utility of integrating transcriptome data in GWAS for discovery of, and biological insight into, risk loci.
Authors: Bien SA; Caan BJ; Peters U; et al.
Hum Genet. 2019 Apr;138(4):307-326. Epub 2019-02-28.
Collaborating on Data, Science, and Infrastructure: The 20-Year Journey of the Cancer Research Network
The Cancer Research Network (CRN) is a consortium of 12 research groups, each affiliated with a nonprofit integrated health care delivery system, that was first funded in 1998. The overall goal of the CRN is to support and facilitate collaborative cancer research within its component delivery systems. This paper describes the CRN’s 20-year experience and evolution. The network combined its members’ scientific capabilities and data resources to create an infrastructure that has ultimately supported over 275 projects. Insights about the strengths and limitations of electronic health data for research, approaches to optimizing multidisciplinary collaboration, and the role of a health services research infrastructure to complement traditional clinical trials and large observational datasets are described, along with recommendations for other research consortia.
Authors: Doria-Rose VP; Corley DA; Kushi LH; Greene SM; et al.
EGEMS (Wash DC). 2019 Mar 29;7(1):7. Epub 2019-03-29.
Developing a Prognostic Information System for Personalized Care in Real Time
Electronic medical records hold promise to transform clinical practice. However, technological and other barriers may preclude using them to guide care in real time. We used the Virtual Data Warehouse (VDW) to develop a tool that enables physicians to generate real-time, personalized prognostic information about survival after cancer. Patients with cancer often ask their oncologists, “Have you ever seen a patient like me?” To help oncologists answer this question, we developed a prototype Prognostic Information System (PRISM), a web-based tool that gathers data about the index patient from Kaiser Permanente’s clinical information systems, selects a historical cohort of similar patients, and displays the survival curve of the similar patients relative to key points in their treatment course. The prototype was developed by a multidisciplinary team with expertise in oncology, research, and technology. We have completed two rounds of user testing and refinement. Successful development rested on: (1) executive support and a clinical champion; (2) collaboration among experts from multiple disciplines; (3) starting with simple cases rather than ambitious ones; (4) extensive research experience with the Virtual Data Warehouse, related databases, and an existing query tool; and (5) following agile software development principles, especially iterative user testing. Clinical data stored in health care systems’ electronic medical records can be used to personalize clinical care in real time. Development of prognostic information systems can be accelerated by collaborations among researchers, technology specialists, and clinicians and by use of existing technology like the Virtual Data Warehouse.
Authors: Lieu TA; Neugebauer R; Van Den Eeden SK; Baer DM; et al.
EGEMS (Wash DC). 2019 Mar 25;7(1):2. Epub 2019-03-25.
Maternal Gestational Weight Gain, Obesity, and the Timing of Pubertal Onset in Daughters
Early puberty is associated with adverse health outcomes, but little is known regarding early life determinants influencing pubertal timing. We examined the associations between maternal gestational weight gain (GWG) and the timing of the onset of breast development (thelarche) and pubic hair development (pubarche) in a cohort of 2,070 girls born in a Kaiser Permanente Northern California facility between 2005-06. Using Weibull regression models accommodating interval censoring, and adjusting for important confounders, we found that excessive GWG was associated with increased risk of early thelarche (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.26-1.78) and early pubarche (HR: 1.35; 95% CI: 1.10-1.66). Inadequate GWG was associated with early thelarche (HR: 1.36; 95% CI: 1.08-1.71). The associations between excess or inadequate GWG and risk of earlier thelarche were stronger if mothers were obese before or at the beginning of pregnancy (body mass index ≥30) (HR: 2.01; 95% CI: 1.53-2.63; HR: 2.08; 95% CI: 1.45-2.98, respectively]. Similar associations were found for pubarche outcome. Inclusion of girls’ prepubertal body mass index slightly attenuated these associations, but they remained significant. Monitoring of maternal weight before and throughout pregnancy may help prevent early pubertal onset and subsequent negative health outcomes.
Authors: Aghaee S; Laurent CA; Deardorff J; Ferrara A; Greenspan LC; Quesenberry CP; Kushi LH; Kubo A
Am J Epidemiol. 2019 Mar 15.
Cervical Cancer Screening Research in the PROSPR I Consortium: Rationale, Methods, and Baseline Findings from a U.S. Cohort
Little is known about the effect of evolving risk-based cervical cancer screening and management guidelines on United States (US) clinical practice and patient outcomes. We describe the National Cancer Institute’s Population-based Research Optimizing Screening through Personalized Regimens (PROSPR I) consortium, methods and baseline findings from its cervical sites: Kaiser Permanente Washington, Kaiser Permanente Northern California, Kaiser Permanente Southern California, Parkland Health & Hospital System/University of Texas Southwestern (Parkland-UTSW) and New Mexico HPV Pap Registry housed by University of New Mexico (UNM-NMHPVPR). Across these diverse healthcare settings, we collected data on human papillomavirus (HPV) vaccinations, screening tests/results, diagnostic and treatment procedures/results and cancer diagnoses on nearly 4.7 million women aged 18-89 years from 2010 to 2014. We calculated baseline (2012 for UNM-NMHPVPR; 2010 for other sites) frequencies for sociodemographics, cervical cancer risk factors and key screening process measures for each site’s cohort. Healthcare delivery settings, cervical cancer screening strategy, race/ethnicity and insurance status varied among sites. The proportion of women receiving a Pap test during the baseline year was similar across sites (26.1-36.1%). Most high-risk HPV tests were performed either reflexively or as cotests, and utilization pattern varied by site. Prevalence of colposcopy or biopsy was higher at Parkland-UTSW (3.6%) than other sites (1.3-1.4%). Incident cervical cancer was rare. HPV vaccination among age-eligible women not already immunized was modest across sites (0.1-7.2%). Cervical PROSPR I makes available high-quality, multilevel, longitudinal screening process data from a large and diverse cohort of women to evaluate and improve the effectiveness of US cervical cancer screening delivery.
Authors: Kamineni A; Silverberg MJ; Corley DA; PROSPR consortium; et al.
Int J Cancer. 2019 03 15;144(6):1460-1473. Epub 2018-12-20.
Why What You May Not Know About Fecal Immunochemical Testing Matters
Authors: Allison J
Ann Intern Med. 2019 03 05;170(5):342-343. Epub 2019-02-26.
Opportunities to Improve Detection and Treatment of Depression among Patients with Breast Cancer Treated in an Integrated Delivery System
Patients with cancer commonly experience depression. If not addressed, depression can lead to reduced quality of life and survival. Given the introduction of national initiatives to improve management of psychiatric symptoms among patients with cancer, we examined patterns of depression detection and treatment over time, and with respect to patient characteristics. This cross-sectional study linked data from the Pathways Study, a prospective cohort study of women diagnosed with breast cancer at Kaiser Permanente Northern California between 2005 and 2013, with data from Kaiser Permanente Northern California’s electronic medical record. Pathways participants eligible for this analysis had no known prior depression but reported depressive symptoms at baseline. We used modified Poisson regression to assess the association of cancer diagnosis year and other patient characteristics with receipt of a documented clinician response to depressive symptoms (depression diagnosis, mental health referral, or antidepressant prescription). Of the 725 women in our sample, 34% received a clinician response to depression. We observed no statistically significant association of breast cancer diagnosis year with clinician response. Characteristics associated with clinician response included Asian race (adjusted risk ratio, Asian vs. white: 0.44, 95% CI: 0.29-0.68) and depression severity (adjusted risk ratio, mild-moderate vs. severe depression: 1.45, 95% CI: 1.11-1.88). Most patients in our sample did not receive a clinician response to their study-reported depression, and rates of response do not appear to have improved over time. Asian women, and those with less severe depression, appeared to be at increased risk of having unmet mental health care needs.
Authors: Check DK; Kwan ML; Chawla N; Dusetzina SB; Valice E; Ergas IJ; Roh JM; Kolevska T; Rosenstein DL; Kushi LH
J Pain Symptom Manage. 2019 03;57(3):587-595. Epub 2018-12-01.
The association of medical and demographic characteristics with sarcopenia and low muscle radiodensity in patients with nonmetastatic colorectal cancer
Sarcopenia and low skeletal muscle radiodensity (SMD) have been associated with adverse outcomes in patients with colorectal cancer (CRC); however, factors contributing to these 2 muscle abnormalities are unclear. The aim of this study was to investigate the association of medical and demographic characteristics with muscle abnormalities among patients with nonmetastatic CRC. Patients with stage I-III invasive CRC (2006-11) who had diagnostic computed tomography (CT) available from Kaiser Permanente Northern California electronic medical records were included. CT-assessed sarcopenia and low SMD were defined according to optimal stratification. Logistic regressions including age, stage, site, total adipose tissue (TAT), race/ethnicity, neutrophil-lymphocyte ratio, smoking history, alcohol use, and Charlson Comorbidity Score were performed to identify characteristics associated with muscle abnormalities. The study included 3262 patients (49.9% females) with a mean ± SD age of 62.6 ± 11.4 y. Sarcopenia and low SMD were highly prevalent (42.4% and 29.6%, respectively). Age and sex interactions were noted for muscle mass, but not SMD. Age was associated with higher odds of muscle abnormalities in a dose-response manner. Compared with those aged ≤50 y, patients aged 70-80 y had considerably higher odds (OR: 6.19; 95% CI: 4.72, 8.11) of sarcopenia, and low SMD (OR: 17.81; 95% CI: 11.73, 27.03). High TAT was related to a higher odds of low SMD (OR: 9.62; 95% CI: 7.37, 12.56), but lower odds of sarcopenia (OR: 0.59; 95% CI: 0.48, 0.71). Compared with Caucasians, African Americans had lower odds of sarcopenia and low SMD. Patients with a higher neutrophil-lymphocyte ratio had higher odds of having both muscle abnormalities. Patients who were smokers or had any comorbidity had higher odds of low SMD, but not sarcopenia. Muscle abnormalities were common in patients with nonmetastatic CRC, with great variability in muscle mass and SMD across age, TAT, and race/ethnicity. Factors associated with muscle abnormalities may be used to facilitate risk stratification and the guidance of targeted strategies to counteract these abnormalities.
Authors: Xiao J; Caan BJ; Cespedes Feliciano EM; Meyerhardt JA; Kroenke CH; Baracos VE; Weltzien E; Kwan ML; Alexeeff SE; Castillo AL; Prado CM
Am J Clin Nutr. 2019 03 01;109(3):615-625.
AUTHOR REPLY
Authors: Kwan ML; Danforth KN; Aaronson DS; Wagner MD; Williams SG; McMullen CK
Urology. 2019 Mar;125:229.
Associations Between Timing of Meals, Physical Activity, Light Exposure, and Sleep With Body Mass Index in Free-Living Adults
This study tested if the timing of meals, physical activity, light exposure, and sleep cluster within individuals and are associated with body mass index (BMI) in a sample of free-living adults (N = 125). Data were collected between November 2015 and March 2016 at the University of California, San Diego, Children’s Hospital of Philadelphia, and Washington University in St Louis. Height and weight were measured, and BMI (kg/m2) was calculated. Sleep timing was estimated using actigraphy, and timing of meals, physical activity, and light exposure were self-reported using a smartphone application. General linear models estimated the mean BMI across time categories of behaviors, adjusting for covariates. A latent class analysis was used to identify patterns of timing variables that clustered within individuals and test for associations between identified patterns and BMI. Later exposure to outdoor light was associated with a lower BMI (P trend < .01). The timing of other behaviors was not independently associated with BMI. The latent class analysis identified 2 distinct groups related to behavioral timing, reflecting an "early bird" and "night owl" phenotype. These phenotypes were not associated with BMI (P > .05). Timing of exposures to light, meals, sleep, and physical activity were not strongly associated with BMI in this sample.
Authors: Marinac CR; Quante M; Mariani S; Weng J; Redline S; Cespedes Feliciano EM; Hipp JA; Wang D; Kaplan ER; James P; Mitchell JA
J Phys Act Health. 2019 03 01;16(3):214-221. Epub 2019-02-24.
Factors that Influence Selection of Urinary Diversion among Bladder Cancer Patients in Three Community-Based Integrated Health Care Systems
To assess the relative contributions of patient and surgeon factors for predicting selection of ileal conduit (IC), neobladder (NB), or continent pouch (CP) urinary diversions (UD) for patients diagnosed with muscle-invasive/high-risk nonmuscle invasive bladder cancer. This information is needed to enhance research comparing cancer survivors’ outcomes across different surgical treatment options. Bladder cancer patients’ age ?21 years with cystectomy/UD performed from January 2010 to June 2015 in 3 Kaiser Permanente regions were included. All patient and surgeon data were obtained from electronic health records. A mixed effects logistic regression model was used treating surgeon as a random effect and region as a fixed effect. Of 991 eligible patients, 794 (80%) received IC. One hundred sixty-nine surgeons performed the surgeries and accounted for a sizeable proportion of the variability in patient receipt of UD (intraclass correlation coefficient?=?0.26). The multilevel model with only patient factors showed good fit (area under the curve?=?0.93, Hosmer-Lemeshow test P?=?.44), and older age, female sex, estimated glomerular filtration rate <45, 4+ comorbidity index score, and stage III/IV tumors were associated with higher odds of receiving an IC vs neobladder/continent pouch. However, including surgeon factors (annual cystectomy volume, specialty training, clinical tenure) had no association (P?=?.29). In this community setting, patient factors were major predictors of UD received. Surgeons also played a substantial role, yet clinical training and experience were not major predictors. Surgeon factors such as beliefs about UD options and outcomes should be explored.
Authors: Kwan ML; McMullen CK; et al.
Urology. 2019 03;125:222-229. Epub 2018-11-22.
Effects of Electronic Chromoendoscopy on Detection of Adenomas During Colonoscopy
I-scan is an electronic chromoendoscopy technology that improves resolution of epithelial and mucosal surfaces and vessels. We performed a randomized controlled trial to compare detection of adenomas by i-scan vs standard high-definition white-light (HDWL) colonoscopy. From February 1 through December 31, 2017, 740 outpatients (50-75 years old) undergoing screening and surveillance for colorectal neoplasia were randomly assigned to groups that received colonoscopies with i-scan 1 (surface and contrast enhancement) or HDWL. When lesions and polyps were detected, endoscopists could switch between i-scan 1 and HDWL imaging to confirm their finding; polyps were collected and analyzed by histology. The primary outcome was adenoma detection rate (ADR, proportion of subjects with at least 1 adenoma of any size); secondary outcomes included detection of sessile serrated polyps and neoplasias, along with location, size, and morphology of polyps. We performed intent to treat and per-protocol analyses (on 357 patients evaluated by i-scan and 358 evaluated by HDWL colonoscopy) to assess the primary and secondary outcomes. There were no differences in baseline characteristics between the groups. In the intent to treat analysis, the ADR was significantly higher in the i-scan 1 group (47.2%) than in the HDWL colonoscopy group (37.7%) (P = .01). In the per-protocol analysis, the ADR in the i-scan 1 group (47.6%) was also significantly higher than in the HDWL group (37.2%) (P = .005), but this effect was not consistent among all endoscopists. There was no difference between groups in detection of sessile serrated polyps. However, the rate of neoplasia detection was significantly higher in the i-scan 1 group (56.4%) than in the than the HDWL group (46.1%) (P = .005). In secondary analyses, the increase in ADR was associated with improved detection of diminutive flat adenomas in the right colon. In a prospective randomized trial, higher proportions of patients with adenomas were identified in a group that underwent colonoscopy with i-scan 1 than in a group evaluated by HDWL colonoscopy. This effect was mainly due to improved detection of diminutive, flat right sided adenomas. I-scan 1 technology may benefit some endoscopists. ClinicalTrials.gov no: NCT02811419.
Authors: Kidambi TD; Terdiman JP; El-Nachef N; Singh A; Kattah MG; Lee JK
Clin Gastroenterol Hepatol. 2019 03;17(4):701-708.e1. Epub 2018-06-20.
Reply to Liu et al.: Tissue specificity of SIM1 gene expression and erectile dysfunction
Authors: Jorgenson E; Van Den Eeden SK; et al.
Proc Natl Acad Sci USA. 2019 02 26;116(9):3349-3350. Epub 2019-02-12.
Changes in physical and mental health are associated with cardiovascular disease incidence in postmenopausal women
physical and mental health are important risk factors for cardiovascular disease (CVD) incidence and death among postmenopausal women. The objective of this study was to assess whether changes in physical and mental health were associated with CVD incidence and death. in the Women’s Health Initiative Observational Study, 48,906 women (50-79 years) had complete data at baseline on physical and mental health (assessed with Short Form-36) and key covariates. Changes in self-reported physical and mental health were calculated between baseline and year 3. Incident CVD and death between year 3 and end of the study were verified with medical records. over a median 8.2-year follow-up, 2,319 women developed CVD, and 1,571 women died, including 361 CVD deaths. Women with continued poor health and those with worsened health had significantly increased risk of CVD incidence, CVD-specific death and all-cause death relative to women with continued good health. Both major and minor declines in physical health were associated with an increased risk of these outcomes relative to women with no change in physical health. Only major declines in mental health were associated with poor prognosis. changes in physical and mental health over 3 years were independently associated with subsequent CVD events.
Authors: Saquib N; Brunner R; Desai M; Kroenke C; Martin LW; Daviglus M; Allen NB; Robinson J; Tindle H; Stefanick ML
Age Ageing. 2019 Feb 11.
Perioperative Intravesical Chemotherapy for Patients with Non-Muscle Invasive Bladder Cancer: Understanding the Extent of and Sources of Variation in Guideline-Recommended Use
To examine intravesical chemotherapy (IVC) use according to non-muscle-invasive bladder cancer patient disease risk, and the contributions of multilevel factors to variation in proficient use among patients with low-intermediate disease. This study included 988 patients diagnosed with non-muscle-invasive bladder cancer in an integrated health system in Northern California from 2015-2017. We calculated IVC receipt by disease risk, and among patients with low-intermediate risk disease, assessed the relationship between multilevel factors and IVC receipt using a logistic regression model with random intercepts for provider and service area, and patient-, provider-, and service area-level fixed effects. We further assessed the association of provider- and service area-level factors with IVC use by examining intraclass correlation coefficients. Similar proportions of low-intermediate (36%) and high-risk (34%) patients received IVC. In the multivariate analysis, including low-intermediate risk patients, service area volume was strongly and statistically significantly associated with IVC use (adjusted odds ratio, high- vs low-volume: 0.08, 95% Confidence Interval: 0.01-0.58). Provider- and service area-level intraclass correlation coefficients were large, (38%, P = .0009 and 39% P = .03, respectively) indicating that much of the variance in IVC use was explained by factors at these levels. Our findings highlight opportunities to improve proficient use of IVC. Future research should assess provider- and practice-level barriers to IVC use among low-intermediate risk patients.
Authors: Check DK; Aaronson DS; Nielsen ME; Lee VS; Ergas IJ; Roh JM; Kushi LH; Tang L; Kwan ML
Urology. 2019 02;124:107-112. Epub 2018-10-23.
The Be-Well Study: a prospective cohort study of lifestyle and genetic factors to reduce the risk of recurrence and progression of non-muscle-invasive bladder cancer
Bladder cancer is one of the top five cancers diagnosed in the U.S. with a high recurrence rate, and also one of the most expensive cancers to treat over the life-course. However, there are few observational, prospective studies of bladder cancer survivors. The Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study) is a National Cancer Institute-funded, multi-center prospective cohort study of non-muscle-invasive bladder cancer (NMIBC) patients (Stage Ta, T1, Tis) enrolled from the Kaiser Permanente Northern California (KPNC) and Southern California (KPSC) health care systems, with genotyping and biomarker assays performed at Roswell Park Comprehensive Cancer Center. The goal is to investigate diet and lifestyle factors in recurrence and progression of NMIBC, with genetic profiles considered, and to build a resource for future NMIBC studies. Recruitment began in February 2015. As of 30 June 2018, 1,281 patients completed the baseline interview (774 KPNC, 511 KPSC) with a recruitment rate of 54%, of whom 77% were male and 23% female, and 80% White, 6% Black, 8% Hispanic, 5% Asian, and 2% other race/ethnicity. Most patients were diagnosed with Ta (69%) or T1 (27%) tumors. Urine and blood specimens were collected from 67% and 73% of consented patients at baseline, respectively. To date, 599 and 261 patients have completed the 12- and 24-month follow-up questionnaires, respectively, with additional urine and saliva collection. The Be-Well Study will be able to answer novel questions related to diet, other lifestyle, and genetic factors and their relationship to recurrence and progression among early-stage bladder cancer patients.
Authors: Kwan ML; Kushi LH; Ergas IJ; Quesenberry CP; Tang L; et al.
Cancer Causes Control. 2019 Feb;30(2):187-193. Epub 2019-01-17.
Strategies to Improve Follow-up After Positive Fecal Immunochemical Tests in a Community-Based Setting: A Mixed-Methods Study
The effectiveness of fecal immunochemical test (FIT) screening for colorectal cancer depends on timely colonoscopy follow-up of positive tests, although limited data exist regarding effective system-level strategies for improving follow-up rates. Using a mixed-methods design (qualitative and quantitative), we first identified system-level strategies that were implemented for improving timely follow-up after a positive FIT test in a large community-based setting between 2006 and 2016. We then evaluated changes in time to colonoscopy among FIT-positive patients across 3 periods during the study interval, controlling for screening participant age, sex, race/ethnicity, comorbidity, FIT date, and previous screening history. Implemented strategies over the study period included setting a goal of colonoscopy follow-up within 30 days of a positive FIT, tracking FIT-positive patients, early telephone contact to directly schedule follow-up colonoscopies, assigning the responsibility for follow-up tracking and scheduling to gastroenterology departments (vs primary care), and increasing colonoscopy capacity. Among 160,051 patients who had a positive FIT between 2006 and 2016, 126,420 (79%) had a follow-up colonoscopy within 180 days, including 67% in 2006-2008, 79% in 2009-2012, and 83% in 2013-2016 (P < 0.001). Follow-up within 180 days in 2016 varied moderately across service areas, between 72% (95% CI 70-75) and 88% (95% CI 86-91), but there were no obvious differences in the pattern of strategies implemented in higher- vs lower-performing service areas. The implementation of system-level strategies coincided with substantial improvements in timely colonoscopy follow-up after a positive FIT. Intervention studies are needed to identify the most effective strategies for promoting timely follow-up.
Authors: Selby K; Jensen CD; Zhao WK; Lee JK; Slam A; Schottinger JE; Bacchetti P; Levin TR; Corley DA
Clin Transl Gastroenterol. 2019 02;10(2):e00010.
Long-term Risk of Colorectal Cancer and Related Deaths After a Colonoscopy With Normal Findings
Guidelines recommend a 10-year rescreening interval after a colonoscopy with normal findings (negative colonoscopy results), but evidence supporting this recommendation is limited. To examine the long-term risks of colorectal cancer and colorectal cancer deaths after a negative colonoscopy result, in comparison with individuals unscreened, in a large, community-based setting. A retrospective cohort study was conducted in an integrated health care delivery organization serving more than 4 million members across Northern California. A total of 1?251?318 average-risk screening-eligible patients (age 50-75 years) between January 1, 1998, and December 31, 2015, were included. The study was concluded on December 31, 2016. Screening was examined as a time-varying exposure; all participants contributed person-time unscreened until they were either screened or censored. If the screening received was a negative colonoscopy result, the participants contributed person-time in the negative colonoscopy results group until they were censored. Using Cox proportional hazards regression models, the hazard ratios (HRs) for colorectal cancer and related deaths were calculated according to time since negative colonoscopy result (or since cohort entry for those unscreened). Hazard ratios were adjusted for age, sex, race/ethnicity, Charlson comorbidity score, and body mass index. Of the 1?251?318 patients, 613?692 were men (49.0%); mean age was 55.6 (7.0) years. Compared with the unscreened participants, those with a negative colonoscopy result had a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, and although reductions in risk were attenuated with increasing years of follow-up, there was a 46% lower risk of colorectal cancer (hazard ratio, 0.54; 95% CI, 0.31-0.94) and 88% lower risk of related deaths (hazard ratio, 0.12; 95% CI, 0.02-0.82) at the current guideline-recommended 10-year rescreening interval. A negative colonoscopy result in average-risk patients was associated with a lower risk of colorectal cancer and related deaths for more than 12 years after examination, compared with unscreened patients. Our study findings may be able to inform guidelines for rescreening after a negative colonoscopy result and future studies to evaluate the costs and benefits of earlier vs later rescreening intervals.
Authors: Lee JK; Levin TR; Fireman BH; Quesenberry CP; Corley DA; et al.
JAMA Netw Open. 2019 09 04;2(9):e1911513. Epub 2019-09-04.
Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index: A Secondary Analysis of a Randomized Clinical Trial and Observational Study
Obesity is associated with an increased risk of breast cancer, including the estrogen receptor (ER)-positive subtype in postmenopausal women. Whether excess adiposity is associated with increased risk in women with a normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown. To investigate the association between body fat and breast cancer risk in women with normal BMI. This ad hoc secondary analysis of the Women’s Health Initiative (WHI) clinical trial and observational study cohorts was restricted to postmenopausal participants with a BMI ranging from 18.5 to 24.9. Women aged 50 to 79 years were enrolled from October 1, 1993, through December 31, 1998. Of these, 3460 participants underwent body fat measurement with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up. At a median follow-up of 16 years (range, 9-20 years), 182 incident breast cancers had been ascertained, and 146 were ER positive. Follow-up was complete on September 30, 2016, and data from October 1, 1993, through September 30, 2016, was analyzed August 2, 2017, through August 21, 2018. Body fat levels were measured at baseline and years 1, 3, 6, and 9 using DXA. Information on demographic data, medical history, and lifestyle factors was collected at baseline. Invasive breast cancers were confirmed via central review of medical records by physician adjudicators. Blood analyte levels were measured in subsets of participants. Among the 3460 women included in the analysis (mean [SD] age, 63.6 [7.6] years), multivariable-adjusted hazard ratios for the risk of invasive breast cancer were 1.89 (95% CI, 1.21-2.95) for the highest quartile of whole-body fat and 1.88 (95% CI, 1.18-2.98) for the highest quartile of trunk fat mass. The corresponding adjusted hazard ratios for ER-positive breast cancer were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31), respectively. Similar positive associations were observed for serial DXA measurements in time-dependent covariate analyses. Circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides were higher, whereas levels of high-density lipoprotein cholesterol and sex hormone-binding globulin were lower in those in the uppermost vs lowest quartiles of trunk fat mass. In postmenopausal women with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors. Normal BMI categorization may be an inadequate proxy for the risk of breast cancer in postmenopausal women. ClinicalTrials.gov identifier: NCT00000611.
Authors: Iyengar NM; Kroenke CH; Feliciano EC; Dannenberg AJ; et al.
JAMA Oncol. 2019 02 01;5(2):155-163.
Non-alcoholic fatty liver disease and colorectal cancer survival
Liver diseases including non-alcoholic fatty liver disease (NAFLD) and ensuing alterations to the micro-environment may affect development of liver metastasis. Mirroring the rise in obesity rates, prevalence of NAFLD is increasing globally. Our objective was to examine the association between NAFLD and mortality in colorectal cancer patients. Colorectal Cancer-Sarcopenia and Near-term Survival (C-SCANS) is a retrospective cohort study which included 3,262 stage I-III patients, aged 18-80 years, and diagnosed between 2006 and 2011 at Kaiser Permanente Northern California. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI). After up to 10 years of follow-up, 879 deaths, including 451 from CRC were identified. Cases diagnosed with NAFLD before and within 1 month after CRC diagnosis (pre-existing NAFLD; n?=?83) had a HR of 1.64 (95% CI 1.06-2.54) for overall and a HR of 1.85 (95% CI 1.03-3.30) for CRC-specific mortality compared to those without NAFLD. Findings did not differ significantly by sex, stage, tumor location, and smoking status, and were also similar when restricted to obese patients only. Independent of body mass index and prognostic indicators, CRC patients with pre-existing NAFLD had a worse prognosis than those without NAFLD.
Authors: Wu K; Zhai MZ; Weltzien EK; Cespedes Feliciano EM; Meyerhardt JA; Giovannucci E; Caan BJ
Cancer Causes Control. 2019 Feb;30(2):165-168. Epub 2018-11-15.
Balancing Adherence and Expense: The Cost-Effectiveness of Two-Sample vs One-Sample Fecal Immunochemical Test
Colorectal cancer (CRC) causes more than 50,000 deaths each year in the United States but early detection through screening yields survival gains; those diagnosed with early stage disease have a 5-year survival greater than 90%, compared to 12% for those diagnosed with late stage disease. Using data from a large integrated health system, this study evaluates the cost-effectiveness of fecal immunochemical testing (FIT), a common CRC screening tool. A probabilistic decision-analytic model was used to examine the costs and outcomes of positive test results from a 1-FIT regimen compared with a 2-FIT regimen. The authors compared 5 diagnostic cutoffs of hemoglobin concentration for each test (for a total of 10 screening options). The principal outcome from the analysis was the cost per additional advanced neoplasia (AN) detected. The authors also estimated the number of cancers detected and life-years gained from detecting AN. The following costs were included: program management of the screening program, patient identification, FIT kits and their processing, and diagnostic colonoscopy following a positive FIT. Per-person costs ranged from $33 (1-FIT at 150ng/ml) to $92 (2-FIT at 50ng/ml) across screening options. Depending on willingness to pay, the 1-FIT 50 ng/ml and the 2-FIT 50 ng/ml are the dominant strategies with cost-effectiveness of $11,198 and $28,389, respectively, for an additional AN detected. The estimates of cancers avoided per 1000 screens ranged from 1.46 to 4.86, depending on the strategy and the assumptions of AN to cancer progression.
Authors: Smith DH; O'Keeffe Rosetti M; Mosen DM; Rosales AG; Keast E; Perrin N; Feldstein AC; Levin TR; Liles EG
Popul Health Manag. 2019 02;22(1):83-89. Epub 2018-06-21.
Novel Common Genetic Susceptibility Loci for Colorectal Cancer
Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
Authors: Schmit SL; Caan BJ; Gruber SB; et al.
J Natl Cancer Inst. 2019 02 01;111(2):146-157.
Recovering from Cystectomy: Patient Perspectives
Bladder cancer patients who undergo cystectomy and urinary diversion face functional and quality-of-life challenges. Little is known about these patients’ experiences during decision-making, surgery, and recovery, or how they vary by treatment setting. To learn about patients’ experiences with treatment choice, surgical care, and recovery across health settings. Understanding patient experiences is essential to closing care gaps and developing patient-reported measures. We conducted focus groups with cystectomy patients and family caregivers at a large comprehensive health care system (N = 32 patients) and an NCI-designated comprehensive cancer center (N = 25 patients and 5 caregivers). Using standard qualitative methods, we identified themes that are not well-represented in existing research. Across both systems, patients described variable experiences in decision-making about their cystectomy and urinary diversion. Some felt overwhelmed by information; others felt poorly informed. Many found self-care equipment challenging; many felt they knew little about what to expect regarding chemotherapy, recovery, and transitioning home. At times, health care personnel could not help manage patients’ ostomies or catheterization equipment. Our study also contributes a grounded theoretical framework for describing meaningful domains of patient experience with cystectomy and urinary diversion. We identified a common trajectory that includes decision-making, surgery and post-operative recovery, mastery of self-care, and reintegration. Patients with radical cystectomy and urinary diversion report a wide variety of experiences not captured by quantitative measures. These findings demonstrate that many cystectomy patients could benefit from additional post-operative support. We offer a framework to measure patient-centered domains in future research.
Authors: McMullen CK; Kwan ML; Colwell JC; Munneke JR; Davis JV; Firemark A; Brooks N; Grant M; Gilbert SM; Altschuler A
Bladder Cancer. 2019 Jan 31;5(1):51-61. Epub 2019-01-31.
Identification of novel common breast cancer risk variants at the 6q25 locus among Latinas
Breast cancer is a partially heritable trait and genome-wide association studies (GWAS) have identified over 180 common genetic variants associated with breast cancer. We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25, with the protective minor allele originating from indigenous American ancestry. Here we report on fine mapping of the 6q25 locus in an expanded sample of Latinas. We performed GWAS in 2385 cases and 6416 controls who were either US Latinas or Mexican women. We replicated the top SNPs in 2412 cases and 1620 controls of US Latina, Mexican, and Colombian women. In addition, we validated the top novel variants in studies of African, Asian and European ancestry. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model-based approach. We identified a novel set of SNPs at the 6q25 locus associated with genome-wide levels of significance (p = 3.3 × 10- 8 – 6.0 × 10- 9) not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD (r2 > 0.9) with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.76 (0.70-0.84). In a replication in women of Latin American origin, we also observed a consistent effect (OR 0.88; 95% CI 0.78-0.99; p = 0.037). We also performed a meta-analysis of these SNPs in East Asians, African ancestry and European ancestry populations and also observed a consistent effect (rs3778609, OR 0.95; 95% CI 0.91-0.97; p = 0.0017). Our study adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.
Authors: Hoffman J; Kushi L; Ziv E; et al.
Breast Cancer Res. 2019 01 14;21(1):3. Epub 2019-01-14.
A Randomized Controlled Trial of mHealth Mindfulness Intervention for Cancer Patients and Informal Cancer Caregivers: A Feasibility Study Within an Integrated Health Care Delivery System
To assess feasibility and preliminary efficacy of a mobile/online-based (mHealth) mindfulness intervention for cancer patients and their caregivers to reduce distress and improve quality of life (QoL). Two-arm randomized controlled trial within Kaiser Permanente Northern California targeting cancer patients who received chemotherapy and their informal caregivers. The intervention group received a commercially available mindfulness program for 8 weeks. The wait-list control group received usual care. We assessed feasibility using retention and adherence rates and obtained participant-reported data on distress, QoL, sleep, mindfulness, and posttraumatic growth before and immediately after the intervention. Ninety-seven patients (median age 59 years; female 69%; 65% whites) and 31 caregivers (median age 63 years; female 58%; 77% whites) were randomized. Among randomized participants, 74% of the patients and 84% of the caregivers completed the study. Among those in the intervention arm who initiated the mindfulness program, 65% practiced at least 50% of the days during the intervention period. We observed significantly greater improvement in QoL among patients in the intervention arm compared with controls. Caregivers in the intervention group experienced increased mindfulness compared with controls. Participants appreciated the convenience of the intervention and the mindfulness skills they obtained from the program. We demonstrated the feasibility of conducting a randomized trial of an mHealth mindfulness intervention for cancer patients and their informal caregivers. Results from fully powered efficacy trials would inform the potential for clinicians to use this scalable intervention to help improve QoL of those affected by cancer and their caregivers.
Authors: Kubo A; Kurtovich E; McGinnis M; Aghaee S; Altschuler A; Quesenberry C; Kolevska T; Avins AL
Integr Cancer Ther. 2019 Jan-Dec;18:1534735419850634.
Gabapentin and Cancer Risk: Updated Findings from Kaiser Permanente Northern California
Epidemiologic analyses of gabapentin use and cancer risk in Kaiser Permanente Northern California were previously carried out in a collaborative study and independently evaluated in a UK database. To update these epidemiologic analyses with 7.5 more years of follow-up. Case-control analyses using conditional logistic regression to estimate relative risk by odds ratios using the prior collaboration’s criteria for identifying positive drug-cancer associations and our more stringent criteria requiring stronger association, lower p values, and evidence of dose response. New associations were reanalyzed with additional control for limited measures of smoking and alcohol use. Gabapentin-cancer associations. No previously found associations met our stringent criteria, but cancers of the mouth/pharynx, esophagus, liver, and vagina did. All odds ratios for 3 or more and 8 or more prescriptions were moderately reduced by control for smoking and alcohol. Substantial elevations of risk of mouth/pharynx, liver, and vaginal cancers were associated with only 1 prescription dispensed. Sensitivity analyses aimed at possible confounding and other biases did not change our conclusions but did reveal a markedly increased risk of vaginal cancer in gabapentin users with epilepsy compared with users without. The reduced magnitude of relative risk with control for smoking and alcohol use suggests confounding by known risk factors. Biologically implausible elevated risk from just 1 prescription suggests confounding by indication. Either or both of these concerns applies to each of the 4 cancer sites associated with gabapentin use. Updated analyses show little if any evidence for carcinogenic effects of gabapentin.
Authors: Friedman GD; Achacoso N; Habel LA
Perm J. 2019;23.
Discovery of common and rare genetic risk variants for colorectal cancer
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P?
Authors: Huyghe JR; Caan BJ; Sakoda LC; Peters U; et al.
Nat Genet. 2019 01;51(1):76-87. Epub 2018-12-03.
Diet-related inflammation and risk of prostate cancer in the California Men’s Health Study
The purpose of the study was to examine the relationship between proinflammatory diet and prostate cancer risk. Energy-adjusted Dietary Inflammatory Index (E-DII) scores were computed among 40,161 participants in the California Men’s Health Study. Over 9.7 ± 3.8 years of follow-up, 2707 incident prostate cancer cases were diagnosed and categorized as low-, intermediate-, or high-risk, based on disease grade and stage. Accelerated failure-time models assessed time to diagnosis of prostate cancer. Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (95% CI). Nonlinear effects of E-DII were modeled as third-order polynomials. Time to prostate cancer diagnosis did not differ by E-DII quartile. The HR for high-risk prostate cancer increased in the third E-DII quartile (HRQ3 vs. Q1 = 1.36; 95% CI: 1.04-1.76), but not in the fourth (HRQ4 vs. Q1 = 0.99; 95% CI: 0.74-1.32, Ptrend = .74), suggesting a nonlinear dose-response. HR curves for prostate cancer increased exponentially above an E-DII threshold of ?+3.0. HR curves for high-risk prostate cancer had a much steeper incline above an E-DII threshold of ?+2.5. Curves were higher among Blacks and Whites relative to other races and among overweight or obese men. No relationship was observed between E-DII scores and intermediate- or low-risk disease. Relationships between proinflammatory diet and prostate cancer risk may be nonlinear, with an increased risk above an E-DII threshold of ?+2.5.
Authors: McMahon DM; Burch JB; Hébert JR; Hardin JW; Zhang J; Wirth MD; Youngstedt SD; Shivappa N; Jacobsen SJ; Caan B; Van Den Eeden SK
Ann Epidemiol. 2019 01;29:30-38. Epub 2018-11-02.
Lead exposure during childhood and subsequent anthropometry through adolescence in girls
Cross-sectional studies suggest that postnatal blood lead (PbB) concentrations are negatively associated with child growth. Few studies prospectively examined this association in populations with lower PbB concentrations. We investigated longitudinal associations of childhood PbB concentrations and subsequent anthropometric measurements in a multi-ethnic cohort of girls. Data were from The Breast Cancer and the Environment Research Program at three sites in the United States (U.S.): New York City, Cincinnati, and San Francisco Bay Area. Girls were enrolled at ages 6-8?years in 2004-2007. Girls with PbB concentrations collected at ?10?years old (mean 7.8?years, standard deviation (SD) 0.82) and anthropometry collected at ?3 follow-up visits were included (n?=?683). The median PbB concentration was 0.99??g/d (10th percentile?=?0.59??g/dL and 90th percentile?=?2.00??g/dL) and the geometric mean was 1.03??g/dL (95% Confidence Interval (CI): 0.99, 1.06). For analyses, PbB concentrations were dichotomized as <1??g/dL (n?=?342) and ?1??g/dL (n?=?341). Anthropometric measurements of height, body mass index (BMI), waist circumference (WC), and percent body fat (%BF) were collected at enrollment and follow-up visits through 2015. Linear mixed effects regression estimated how PbB concentrations related to changes in girls' measurements from ages 7-14?years. At 7?years, mean difference in height was -2.0?cm (95% CI: -3.0, -1.0) for girls with ?1??g/dL versus <1??g/dL PbB concentrations; differences persisted, but were attenuated, with age to -1.5?cm (95% CI: -2.5, -0.4) at 14?years. Mean differences for BMI, WC, and BF% at 7?years between girls with ?1??g/dL versus <1??g/dL PbB concentrations were -0.7?kg/m2 (95% CI: -1.2, -0.2), -2.2?cm (95% CI: -3.8, -0.6), and -1.8% (95% CI: -3.2, -0.4), respectively. Overall, these differences generally persisted with advancing age and at 14?years, differences were -0.8?kg/m2 (95% CI: -1.5, -0.02), -2.9?cm (95% CI: -4.8, -0.9), and -1.7% (95% CI: -3.1, -0.4) for BMI, WC, and BF%, respectively. These findings suggest that higher concentrations of PbB during childhood, even though relatively low by screening standards, may be inversely associated with anthropometric measurements in girls.
Authors: Deierlein AL; Kushi LH; Breast Cancer and Environment Research Program; et al.
Environ Int. 2019 01;122:310-315. Epub 2018-11-29.
Receipt of Colonoscopy Following Diagnosis of Advanced Adenomas: An Analysis within Integrated Healthcare Delivery Systems
To reduce colorectal cancer incidence and mortality, experts recommend surveillance colonoscopy 3 years after advanced adenoma removal. Little is known about adherence to that interval. We describe patterns of and factors associated with subsequent colonoscopy among persons with ?3 adenomas and/or ?1 adenoma with villous/tubulovillous histology in four U.S. integrated healthcare delivery systems. We report Kaplan-Meier estimators of the cumulative percentage of patients undergoing colonoscopy 6 months to 3.5 years after an index colonoscopy with high-risk findings. Combining data from three healthcare systems, we used multivariable logistic regression with inverse probability of censoring weights to estimate ORs and 95% confidence intervals (CI) for associations between patient characteristics and receipt of subsequent colonoscopy. Among 6,909 persons with advanced adenomas, the percent receiving a subsequent colonoscopy 6 months to 3.5 years later ranged from 18.3% (95% CI: 11.7%-27.8%) to 59.5% (95% CI: 53.8%-65.2%) across healthcare systems. Differences remained significant in the multivariable model. Patients with ?3 adenomas were more likely than those with 1 to 2 villous/tubulovillous adenomas to undergo subsequent colonoscopy. Subsequent colonoscopy was also more common for patients ages 60-74 and less common for patients ages 80 to 89 compared with those ages 50 to 54 years at their index colonoscopy. Sex, race/ethnicity, and comorbidity index score were generally not associated with subsequent colonoscopy receipt. Colonoscopy within the recommended interval following advanced adenoma was underutilized and varied by healthcare system, age, and number of adenomas. Strategies to improve adherence to surveillance colonoscopy following advanced adenomas are needed.
Authors: Chubak J; Corley DA; PROSPR consortium; et al.
Cancer Epidemiol Biomarkers Prev. 2019 01;28(1):91-98. Epub 2018-11-20.
Associations of Intimate Partner Violence, Sexual Assault, and Posttraumatic Stress Disorder With Menopause Symptoms Among Midlife and Older Women
Little is known about the prevalence of traumatic exposures among midlife and older women and the association of these traumatic exposures with health issues. To examine the associations of intimate partner violence (IPV), sexual assault, and posttraumatic stress with menopause symptoms among midlife and older women. A cross-sectional analysis of data from a multiethnic cohort of 2016 women 40 to 80 years of age in the Kaiser Permanente Northern California health care system was conducted from November 15, 2008, to March 30, 2012. Statistical analysis was conducted from June 8, 2016, to September 6, 2017. Lifetime physical or emotional IPV, sexual assault, and current symptoms of posttraumatic stress disorder, assessed with standardized questionnaires. Difficulty sleeping, vasomotor symptoms, and vaginal symptoms, assessed with standardized questionnaires. Among the 2016 women enrolled, the mean (SD) age was 60.5 (9.5) years, and 792 of 2011 with race/ethnicity data (39.4)% were non-Latina white (403 [20.0%] Latina, 429 [21.3%] black, and 387 [19.2%] Asian). Lifetime emotional IPV was reported by 423 women (21.0%), lifetime physical IPV was reported by 316 women (15.7%), sexual assault was reported by 382 women (18.9%), and 450 of 2000 women (22.5%) had current clinically significant symptoms of posttraumatic stress disorder. In multivariable analyses adjusted for age, race/ethnicity, educational level, body mass index, menopause status, hormone therapy, and parity, symptoms of posttraumatic stress disorder were associated with difficulty sleeping (odds ratio [OR], 3.02; 95% CI, 2.22-4.09), vasomotor symptoms (hot flashes: OR, 1.69; 95% CI, 1.34-2.12; night sweats: OR, 1.72; 95% CI, 1.37-2.15), and vaginal symptoms (vaginal dryness: OR, 1.73; 95% CI, 1.37-2.18; vaginal irritation: OR, 2.20; 95% CI, 1.66-2.93; pain with intercourse: OR, 2.16; 95% CI, 1.57-2.98). Emotional IPV was associated with difficulty sleeping (OR, 1.36; 95% CI, 1.09-1.71), night sweats (OR, 1.50; 95% CI, 1.19-1.89), and pain with intercourse (OR, 1.60; 95% CI, 1.14-2.25). Physical IPV was associated with night sweats (OR, 1.33; 95% CI, 1.03-1.72). Sexual assault was associated with vaginal symptoms (vaginal dryness: OR, 1.41; 95% CI, 1.10-1.82; vaginal irritation: OR, 1.42; 95% CI, 1.04-1.95; pain with intercourse: OR, 1.44; 95% CI, 1.00-2.06). Lifetime history of IPV or sexual assault and current clinically significant symptoms of posttraumatic stress disorder are common and are associated with menopause symptoms. These findings highlight the need for greater recognition of these exposures by clinicians caring for midlife and older women.
Authors: Gibson CJ; Huang AJ; McCaw B; Subak LL; Thom DH; Van Den Eeden SK
JAMA Intern Med. 2019 01 01;179(1):80-87.
Modifiable Failures in the Colorectal Cancer Screening Process and Their Association with Risk of Death
Colorectal cancer (CRC) deaths occur when patients do not receive screening or have inadequate follow-up of abnormal results or when the screening test fails. We have few data on the contribution of each to CRC-associated deaths or factors associated with these events. We performed a retrospective cohort study of patients in the Kaiser Permanente Northern and Southern California systems (55-90 years old) who died of CRC from 2006 through 2012 and had ?5 years of enrollment before diagnosis. We compared data from patients with those from a matched cohort of cancer-free patients in the same system. Receipt, results, indications, and follow-up of CRC tests in the 10-year period before diagnosis were obtained from electronic databases and chart audits. Of 1750 CRC deaths, 75.9% (n = 1328) occurred in patients who were not up to date in screening and 24.1% (n = 422) occurred in patients who were up to date. Failure to screen was associated with fewer visits to primary care physicians. Of 3486 cancer-free patients, 44.6% were up to date in their screening. Patients who were up to date in their screening had a lower risk of CRC death (odds ratio, 0.38; 95% confidence interval, 0.33-0.44). Failure to screen, or failure to screen at appropriate intervals, occurred in a 67.8% of patients who died of CRC vs 53.2% of cancer-free patients; failure to follow-up on abnormal results occurred in 8.1% of patients who died of CRC vs 2.2% of cancer-free patients. CRC death was associated with higher odds of failure to screen or failure to screen at appropriate intervals (odds ratio, 2.40; 95% confidence interval, 2.07-2.77) and failure to follow-up on abnormal results (odds ratio, 7.26; 95% confidence interval, 5.26-10.03). Being up to date on screening substantially decreases the risk of CRC death. In 2 health care systems with high rates of screening, most people who died of CRC had failures in the screening process that could be rectified, such as failure to follow-up on abnormal findings; these significantly increased the risk for CRC death.
Authors: Doubeni CA; Levin TR; Corley DA; et al.
Gastroenterology. 2019 01;156(1):63-74.e6. Epub 2018-09-27.
Colorectal Cancer Screening Participation Among Asian Americans Overall and Subgroups in an Integrated Health Care Setting with Organized Screening
Screening reduces colorectal cancer deaths, but?<50% of Asian Americans are screening up-to-date according to surveys, with variability across Asian subgroups. We examined colorectal cancer screening participation among Asian Americans overall and Asian subgroups in a large integrated health care system with organized screening. Data were electronically accessed to characterize screening in 2016 for Asians overall and subgroups relative to the National Colorectal Cancer Roundtable target of ?80% screening and compared with non-Hispanic whites. Screening up-to-date was defined as a colonoscopy with 10 years, a sigmoidoscopy within 5 years, or a fecal immunochemical test (FIT) completed in 2016. Among 436,398 patients, 69,826 (16.0%) were Asian, of whom 79.8% were screening up-to-date vs. 77.6% of non-Hispanic whites (p?
Authors: Ghai NR; Jensen CD; Corley DA; Doubeni CA; Schottinger JE; Zauber AG; Lee AT; Contreras R; Levin TR; Lee JK; Quinn VP
Clin Transl Gastroenterol. 2018 09 21;9(9):186. Epub 2018-09-21.
Index colonoscopy-related risk factors for postcolonoscopy colorectal cancers
Postcolonoscopy colorectal cancers (PCCRCs) are defined as those detected ≤10 years after an index colonoscopy negative for cancer, but modifiable risk factors are not well established in large, community-based populations. We evaluated risk factors from the index colonoscopy for PCCRCs diagnosed 1 to 10 years after an index colonoscopy using a case-control design. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for potential confounders. A proximal polyp ≥10 mm (OR, 8.18; 95% CI, 4.59-14.60), distal polyp ≥10 mm (OR, 3.30; 95% CI, 1.65-6.58), adenoma with (OR, 3.23; 95% CI, 1.83-5.68) and without advanced histology (OR, 1.87; 95% CI, 1.37-2.55), and an incomplete colonoscopy (OR, 5.52; 95% CI, 2.98-10.21) were associated with PCCRC. Risk factors for early versus late cancers (12-36 months vs >36 months to 10 years after examination) included incomplete polyp excision in the colonic segment of the subsequent cancer (OR, 4.76; 95% CI, 2.35-9.65); failure to examine the segment (OR, 2.42; 95% CI, 1.27-4.60); and a polyp ≥10 mm in the segment (OR, 2.38; 95% CI, 1.53-3.70). A total of 559 of 1206 patients with PCCRC (46.4%) had 1 or more risk factors that were significant for PCCRC (incomplete examination, large polyp, or any adenoma). In a large community-based study with comprehensive capture of PCCRCs, almost half of PCCRCs had potentially modifiable factors related to polyp surveillance or removal and examination completeness. These represent potential high-yield targets to further increase the effectiveness of colorectal cancer screening.
Authors: Tollivoro TA; Levin TR; Fireman B; Quesenberry CP; Corley DA; et al.
Gastrointest Endosc. 2019 01;89(1):168-176.e3. Epub 2018-08-23.
Health care improvement and survivorship priorities of colorectal cancer survivors: findings from the PORTAL colorectal cancer cohort survey
Few population-level surveys have explored patient-centered priorities for improving colorectal cancer survivors’ care. Working with patients, we designed a survey to identify care improvement and survivorship priorities. We surveyed a random sample of 4000 patients from a retrospective, population-based cohort of colorectal cancer survivors diagnosed during 2010-2014. The survey included two multiple response questions: “What would you have changed about your cancer diagnosis and treatment experience?” and “What are your biggest health or lifestyle concerns (other than having cancer) since being diagnosed?” Multivariable regression identified characteristics associated with endorsement of health care experience and survivorship concerns. Survey response rate was 50.2% (2000/3986). Fifty-three percent reported at least one unmet need, most commonly for more information about life after treatment (26.7%). Survivors of rectal cancer reported more needs than respondents with colon cancer; persons of color reported more needs than non-Hispanic whites; individuals without high school diplomas reported more needs than individuals with more education. Fear of recurrence was the most common health/lifestyle concern (58.9%). Respondents under age 65 reported nearly all health/lifestyle concerns more often than respondents over age 74. Rectal cancer survivors reported more concerns about activity limitation, changes, and body function and appearance than colon cancer survivors. Persons of color were more likely to report financial concerns than non-Hispanic whites. The greatest needs for intervention are among survivors of rectal cancer, survivors of minority racial/ethnic background, and survivors of younger age. Survivors with low educational attainment and those with higher stage disease could also benefit.
Authors: McMullen C; Corley DA; Feigelson HS; et al.
Support Care Cancer. 2019 Jan;27(1):147-156. Epub 2018-06-12.
Bariatric Surgery and the Risk of Cancer in a Large Multisite Cohort
To determine whether bariatric surgery is associated with a lower risk of cancer. Obesity is strongly associated with many types of cancer. Few studies have examined the relationship between bariatric surgery and cancer risk. We conducted a retrospective cohort study of patients undergoing bariatric surgery between 2005 and 2012 with follow-up through 2014 using data from a large integrated health insurance and care delivery systems with 5 study sites. The study included 22,198 subjects who had bariatric surgery and 66,427 nonsurgical subjects matched on sex, age, study site, body mass index, and Elixhauser comorbidity index. Multivariable Cox proportional-hazards models were used to examine incident cancer up to 10 years after bariatric surgery compared to the matched nonsurgical patients. After a mean follow-up of 3.5 years, we identified 2543 incident cancers. Patients undergoing bariatric surgery had a 33% lower hazard of developing any cancer during follow-up [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.60, 0.74, P < 0.001) compared with matched patients with severe obesity who did not undergo bariatric surgery, and results were even stronger when the outcome was restricted to obesity-associated cancers (HR 0.59, 95% CI 0.51, 0.69, P < 0.001). Among the obesity-associated cancers, the risk of postmenopausal breast cancer (HR 0.58, 95% CI 0.44, 0.77, P < 0.001), colon cancer (HR 0.59, 95% CI 0.36, 0.97, P = 0.04), endometrial cancer (HR 0.50, 95% CI 0.37, 0.67, P < 0.001), and pancreatic cancer (HR 0.46, 95% CI 0.22, 0.97, P = 0.04) was each statistically significantly lower among those who had undergone bariatric surgery compared with matched nonsurgical patients. In this large, multisite cohort of patients with severe obesity, bariatric surgery was associated with a lower risk of incident cancer, particularly obesity-associated cancers, such as postmenopausal breast cancer, endometrial cancer, and colon cancer. More research is needed to clarify the specific mechanisms through which bariatric surgery lowers cancer risk.
Authors: Schauer DP; Feigelson HS; Koebnick C; Caan B; Weinmann S; Leonard AC; Powers JD; Yenumula PR; Arterburn DE
Ann Surg. 2019 01;269(1):95-101.
Accurate Identification of Colonoscopy Quality and Polyp Findings Using Natural Language Processing
The aim of this study was to test the ability of a commercially available natural language processing (NLP) tool to accurately extract examination quality-related and large polyp information from colonoscopy reports with varying report formats. Colonoscopy quality reporting often requires manual data abstraction. NLP is another option for extracting information; however, limited data exist on its ability to accurately extract examination quality and polyp findings from unstructured text in colonoscopy reports with different reporting formats. NLP strategies were developed using 500 colonoscopy reports from Kaiser Permanente Northern California and then tested using 300 separate colonoscopy reports that underwent manual chart review. Using findings from manual review as the reference standard, we evaluated the NLP tool’s sensitivity, specificity, positive predictive value (PPV), and accuracy for identifying colonoscopy examination indication, cecal intubation, bowel preparation adequacy, and polyps ≥10 mm. The NLP tool was highly accurate in identifying examination quality-related variables from colonoscopy reports. Compared with manual review, sensitivity for screening indication was 100% (95% confidence interval: 95.3%-100%), PPV was 90.6% (82.3%-95.8%), and accuracy was 98.2% (97.0%-99.4%). For cecal intubation, sensitivity was 99.6% (98.0%-100%), PPV was 100% (98.5%-100%), and accuracy was 99.8% (99.5%-100%). For bowel preparation adequacy, sensitivity was 100% (98.5%-100%), PPV was 100% (98.5%-100%), and accuracy was 100% (100%-100%). For polyp(s) ≥10 mm, sensitivity was 90.5% (69.6%-98.8%), PPV was 100% (82.4%-100%), and accuracy was 95.2% (88.8%-100%). NLP yielded a high degree of accuracy for identifying examination quality-related and large polyp information from diverse types of colonoscopy reports.
Authors: Lee JK; Jensen CD; Levin TR; Zauber AG; Doubeni CA; Zhao WK; Corley DA
J Clin Gastroenterol. 2019 01;53(1):e25-e30.
Associations of evolutionary-concordance diet, Mediterranean diet and evolutionary-concordance lifestyle pattern scores with all-cause and cause-specific mortality.
Various individual diet and lifestyle factors are associated with mortality. Investigating these factors collectively may help clarify whether dietary and lifestyle patterns contribute to life expectancy. We investigated the association of previously described evolutionary-concordance and Mediterranean diet pattern scores and a novel evolutionary-concordance lifestyle pattern score with all-cause and cause-specific mortality in the prospective Iowa Women’s Health Study (1986-2012). We created the diet pattern scores from Willett FFQ responses, and the lifestyle pattern score from self-reported physical activity, BMI and smoking status, and assessed their associations with mortality, using multivariable Cox proportional hazards regression. Of the 35 221 55- to 69-year-old cancer-free women at baseline, 18 687 died during follow-up. The adjusted hazard ratios (HR) and 95 % CI for all-cause, all CVD, and all-cancer mortality among participants in the highest relative to the lowest quintile of the evolutionary-concordance lifestyle score were, respectively, 0.52 (95 % CI 0.50, 0.55), 0.53 (95 % CI 0.49, 0.57) and 0.51 (95 % CI 0.46, 0.57). The corresponding findings for the Mediterranean diet score were HR 0.85 (95 % CI 0.82, 0.90), 0.83 (95 % CI 0.76, 0.90) and 0.93 (95 % CI 0.84, 1.03), and for the evolutionary-concordance diet score they were close to null and not statistically significant. The lowest estimated risk was among those in the highest joint quintile of the lifestyle score and either diet score (both Pinteraction <0.01). Our findings suggest that (1) a more Mediterranean-like diet pattern and (2) a more evolutionary-concordant lifestyle pattern, alone and in interaction with a more evolutionary-concordant or Mediterranean diet pattern, may be inversely associated with mortality.
Authors: Cheng E; Um CY; Prizment A; Lazovich D; Bostick RM
Br J Nutr. 2018 Dec 18:1-10. doi: 10.1017/S0007114518003483.
The evolution of body composition in oncology-epidemiology, clinical trials, and the future of patient care: facts and numbers
There is growing interest from the oncology community to understand how body composition measures can be used to improve the delivery of clinical care for the 18.1 million individuals diagnosed with cancer annually. Methods that distinguish muscle from subcutaneous and visceral adipose tissue, such as computed tomography (CT), may offer new insights of important risk factors and improved prognostication of outcomes over alternative measures such as body mass index. In a meta-analysis of 38 studies, low muscle area assessed from clinically acquired CT was observed in 27.7% of patients with cancer and associated with poorer overall survival [hazard ratio: 1.44, 95% CI: 1.32-1.56]. Therapeutic interventions such as lifestyle and pharmacotherapy that modify all aspects of body composition and reduce the incidence of poor clinical outcomes are needed in patients with cancer. In a meta-analysis of six randomized trials, resistance training exercise increased lean body mass assessed from dual-energy X-ray absorptiometry [mean difference (MD): +1.07 kg, 95% CI: 0.76-1.37; P < 0.001] and walking distance [MD: +143 m, 95% CI: 70-216; P < 0.001] compared with usual care control in patients with non-metastatic cancer. In a meta-analysis of five randomized trials, anamorelin (a ghrelin agonist) significantly increased lean body mass [MD: +1.10 kg, 95% CI: 0.35-1.85; P = 0.004] but did not improve handgrip strength [MD: 0.52 kg, 95% CI: -0.09-1.13; P = 0.09] or overall survival compared with placebo [HR: 0.99, 95% CI: 0.85-1.14; P = 0.84] in patients with advanced or metastatic cancer. Early screening to identify individuals with occult muscle loss, combined with multimodal interventions that include lifestyle therapy with resistance exercise training and dietary supplementation combined with pharmacotherapy, may be necessary to provide a sufficient stimulus to prevent or slow the cascade of tissue wasting. Rapid, cost-efficient, and feasible methods to quantify muscle and adipose tissue distribution are needed if body composition assessment is to be integrated into large-scale clinical workflows. Fully automated analysis of body composition from clinically acquired imaging is one example. The study of body composition is one of the most provocative areas in oncology that offers tremendous promise to help patients with cancer live longer and healthier lives.
Authors: Brown JC; Cespedes Feliciano EM; Caan BJ
J Cachexia Sarcopenia Muscle. 2018 Dec;9(7):1200-1208. Epub 2019-01-13.
Patterns of medication adherence in a multi-ethnic cohort of prevalent statin users diagnosed with breast, prostate, or colorectal cancer
To investigate the implications of a cancer diagnosis on medication adherence for pre-existing comorbid conditions, we explored statin adherence patterns prior to and following a new diagnosis of breast, colorectal, or prostate cancer among a multi-ethnic cohort. We identified adults enrolled at Kaiser Permanente Northern California who were prevalent statin medication users, newly diagnosed with breast, colorectal, or prostate cancer between 2000 and 2012. Statin adherence was measured using the proportion of days covered (PDC) during the 2-year pre-cancer diagnosis and the 2-year post-cancer diagnosis. Adherence patterns were assessed using generalized estimating equations, for all cancers combined and stratified by cancer type and race/ethnicity, adjusted for demographic, clinical, and tumor characteristics. Among 10,177 cancer patients, statin adherence decreased from pre- to post-cancer diagnosis (adjusted odds ratio (ORadj):0.91, 95% confidence interval (95% CI):0.88-0.94). Statin adherence decreased from pre- to post-cancer diagnosis among breast (ORadj:0.94, 95% CI:0.90-0.99) and colorectal (ORadj:0.79, 95% CI:0.74-0.85) cancer patients. No difference in adherence was observed among prostate cancer patients (ORadj:1.01, 95% CI:0.97-1.05). Prior to cancer diagnosis, adherence to statins was generally higher among non-Hispanic whites and multi-race patients than other groups. However, statin adherence after diagnosis decreased only among these two populations (ORadj:0.85, 95% CI:0.85-0.92 and ORadj:0.86, 95% CI:0.76-0.97), respectively. We found substantial variation in statin medication adherence following diagnosis by cancer type and race/ethnicity among a large cohort of prevalent statin users in an integrated health care setting. Improving our understanding of comorbidity management and polypharmacy across diverse cancer patient populations is warranted to develop tailored interventions that improve medication adherence and reduce disparities in health outcomes.
Authors: Banegas MP; Emerson MA; Adams AS; Achacoso NS; Chawla N; Alexeeff S; Habel LA
J Cancer Surviv. 2018 12;12(6):794-802. Epub 2018-10-18.
In Screening for Colorectal Cancer, Is the FIT Right for the Right Side of the Colon?
Authors: Doubeni CA; Levin TR
Ann Intern Med. 2018 11 06;169(9):650-651. Epub 2018-10-02.
Novel variant of unknown significance in MUTYH in a patient with MUTYH-associated polyposis: a case to reclassify
MUTYH-associated polyposis (MAP) is a hereditary cancer syndrome that is caused by biallelic pathogenic variants in the MUTYH gene and should be evaluated for in patients with an attenuated colonic polyposis phenotype. Monoallelic pathogenic variants in MUTYH are associated with a moderate increased risk of colorectal cancer but not with the polyposis phenotype. We present a case of a patient presenting with multiple colonic adenomatous polyps, whose germline testing revealed a heterozygous pathogenic variant in MUTYH in exon 13, c.1187G > A (p.Gly396Asp) as well as a heterozygous variant of unknown significance (VUS) in MUTYH in exon 14, c.1379T > C (p.Leu460Ser). We interpret the VUS as pathogenic in light of the patient’s phenotype; the fact that the VUS was in trans with a known pathogenic variant; and because all the in silico predictors suggested, it was likely to be deleterious. This case highlights the importance of a gastroenterologist recognizing the indication for genetic testing in a patient with greater than ten adenomas, the importance of a genetic counselor in interpretation of results, and is the first report of the specific variant in the literature with clinical information to suggest that it is likely pathogenic.
Authors: Kidambi TD; Goldberg D; Nussbaum R; Blanco A; Umetsu SE; Terdiman JP; Lee JK
Clin J Gastroenterol. 2018 Dec;11(6):457-460. Epub 2018-05-15.
Examining the role of access to care: Racial/ethnic differences in receipt of resection for early-stage non-small cell lung cancer among integrated system members and non-members
To examine the role of uniform access to care in reducing racial/ethnic disparities in receipt of resection for early stage non-small cell lung cancer (NSCLC) by comparing integrated health system member patients to demographically similar non-member patients. Using data from the California Cancer Registry, we conducted a retrospective cohort study of patients from four racial/ethnic groups (White, Black, Hispanic, Asian/Pacific Islander), aged 21-80, with a first primary diagnosis of stage I or II NSCLC between 2004 and 2011, in counties served by Kaiser Permanente Northern California (KPNC) at diagnosis. Our cohort included 1565 KPNC member and 4221 non-member patients. To examine the relationship between race/ethnicity and receipt of surgery stratified by KPNC membership, we used modified Poisson regression to calculate risk ratios (RR) adjusted for patient demographic and tumor characteristics. Black patients were least likely to receive surgery regardless of access to integrated care (64-65% in both groups). The magnitude of the black-white difference in the likelihood of surgery receipt was similar for members (RR: 0.82, 95% CI: 0.73-0.93) and non-members (RR: 0.86, 95% CI: 0.80-0.94). Among members, roughly equal proportions of Hispanic and White patients received surgery; however, among non-members, Hispanic patients were less likely to receive surgery (non-members, RR: 0.93, 95% CI: 0.86-1.00; members, RR: 0.98, 95% CI: 0.89-1.08). Disparities in surgical treatment for NSCLC were not reduced through integrated health system membership, suggesting that factors other than access to care (e.g., patient-provider communication) may underlie disparities. Future research should focus on identifying such modifiable factors.
Authors: Check DK; Albers KB; Uppal KM; Suga JM; Adams AS; Habel LA; Quesenberry CP; Sakoda LC
Lung Cancer. 2018 Nov;125:51-56. Epub 2018-09-11.
Prospective Validation of a Standardized Ultrasonography-Based Ovarian Cancer Risk Assessment System
To evaluate the performance of a system that standardizes ovarian cancer risk assessment and reporting on ultrasonography. We conducted a prospective community-based cohort study of average-risk women undergoing ultrasonography in 2016 using a reporting system that requires adnexal masses to be categorized as 1, 2, 3, or X based on standardized ultrasound criteria including size, presence of solid components, and vascularity assessed by Doppler. With a median follow-up of 18 months, the risk of ovarian cancer or borderline tumor diagnosis for each category was determined. Among 43,606 women undergoing ultrasonography, 6,838 (16%) had an abnormal adnexal mass reported: 70% were category 1, 21% category 2, 3.7% category 3, and 5.4% category X. Among these women, 89 (1.3%) were subsequently diagnosed with ovarian cancer and 59 (0.9%) with borderline tumors. The risks of ovarian cancer diagnosis associated with masses reported as categories 1, 2, 3, and X were 0.2% (95% CI 0.05-0.3%), 1.3% (95% CI 0.7-1.9%), 6.0% (95% CI 3.0-8.9%), and 13.0% (95% CI 9.5-16.4%), respectively; risks of either ovarian cancer or borderline tumor were 0.4% (95% CI 0.2-0.6%), 2.3% (95% CI 1.6-3.1%), 10.4% (95% CI 6.6-14.1%), and 18.9% (95% CI 14.9-23.0%) respectively. Among 36,768 (84%) women with normal or benign adnexal findings reported, 38 women were diagnosed with ovarian cancer, for a risk of 0.1% (95% CI 0.07-0.14%). In a community-based setting with low ovarian cancer prevalence, our standardized reporting system differentiated adnexal masses into four categories with distinct levels of risk with 9-10% of women having higher risk masses and 70% of women having masses associated with a risk of cancer similar to that of normal ultrasound findings. The system supports risk-based management by providing clinicians a more consistent assessment of risk based on ultrasound characteristics.
Authors: Suh-Burgmann E; Flanagan T; Osinski T; Alavi M; Herrinton L
Obstet Gynecol. 2018 11;132(5):1101-1111.
The Utility and Cross-Validation of a Composite Physical Activity Score in Relation to Cardiovascular Health Indicators: Coronary Artery Risk Development in Young Adults
Single-method assessment of physical activity (PA) has limitations. The utility and cross-validation of a composite PA score that includes reported and accelerometer-derived PA data has not been evaluated. Participants attending the Year 20 exam were randomly assigned to the derivation (two-thirds) or validation (one-third) data set. Principal components analysis was used to create a composite score reflecting Year 20 combined reported and accelerometer PA data. Generalized linear regression models were constructed to estimate the variability explained (R2) by each PA assessment strategy (self-report only, accelerometer only, composite score, or self-report plus accelerometer) with cardiovascular health indicators. This process was repeated in the validation set to determine cross-validation. At Year 20, 3549 participants (45.2 [3.6] y, 56.7% female, and 53.5% black) attended the clinic exam and 2540 agreed to wear the accelerometer. Higher R2 values were obtained when combined assessment strategies were used; however, the approach yielding the highest R2 value varied by cardiovascular health outcome. Findings from the cross-validation also supported internal study validity. Findings support continued refinement of methodological approaches to combine data from multiple sources to create a more robust estimate that reflects the complexities of PA behavior.
Authors: Pettee Gabriel K; Pérez A; Jacobs DR; Lee J; Kohl HW; Sternfeld B
J Phys Act Health. 2018 11 01;15(11):847-856. Epub 2018-10-19.
A Prospective Study to Establish a New-Onset Diabetes Cohort: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer
The National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases initiated the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) in 2015 (the CPDPC’s origin, structure, governance, and research objectives are described in another article in this journal). One of the key objectives of CPDPC is to assemble a cohort of 10,000 subjects 50 years or older with new-onset diabetes, called the NOD cohort. Using a define, enrich, and find early detection approach, the aims of the NOD study are to (a) estimate the 3-year probability of pancreatic ductal adenocarcinoma (PDAC) in NOD (define), (b) establish a biobank of clinically annotated biospecimens from presymptomatic PDAC and control new-onset type 2 diabetes mellitus subjects, (c) conduct phase 3 validation studies of promising biomarkers for identification of incident PDAC in NOD patients (enrich), and (d) provide a platform for development of a future interventional screening protocol for early detection of PDAC in patients with NOD that incorporates imaging studies and/or clinical algorithms (find). It is expected that 85 to 100 incidences of PDAC will be diagnosed during the study period in this cohort of 10,000 patients.
Authors: Maitra A; Van Den Eeden SK; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC); et al.
Pancreas. 2018 Nov/Dec;47(10):1244-1248.
PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer
Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.
Authors: Yadav D; Van Den Eeden SK; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC); et al.
Pancreas. 2018 Nov/Dec;47(10):1229-1238.
Influence of Varying Quantitative Fecal Immunochemical Test Positivity Thresholds on Colorectal Cancer Detection: A Community-Based Cohort Study
The fecal immunochemical test (FIT) is commonly used for colorectal cancer (CRC) screening. Despite demographic variations in stool hemoglobin concentrations, few data exist regarding optimal positivity thresholds by age and sex. To identify programmatic (multitest) FIT performance characteristics and optimal FIT quantitative hemoglobin positivity thresholds in a large, population-based, screening program. Retrospective cohort study. Kaiser Permanente Northern and Southern California. Adults aged 50 to 75 years who were eligible for screening and had baseline quantitative FIT results (2013 to 2014) and 2 years of follow-up. Nearly two thirds (411 241) had FIT screening in the previous 2 years. FIT programmatic sensitivity for CRC and number of positive test results per cancer case detected, overall and by age and sex. Of 640 859 persons who completed a baseline FIT and were followed for 2 years, 481 817 (75%) had at least 1 additional FIT and 1245 (0.19%) received a CRC diagnosis. Cancer detection (programmatic sensitivity) increased at lower positivity thresholds, from 822 in 1245 (66.0%) at 30 µg/g to 925 (74.3%) at 20 µg/g and 987 (79.3%) at 10 µg/g; the number of positive test results per cancer case detected increased from 43 at 30 µg/g to 52 at 20 µg/g and 85 at 10 µg/g. Reducing the positivity threshold from 20 to 15 µg/g would detect 3% more cancer cases and require 23% more colonoscopies. At the conventional FIT threshold of 20 µg/g, programmatic sensitivity decreased with increasing age (79.0%, 73.4%, and 68.9% for ages 50 to 59, 60 to 69, and 70 to 75 years, respectively; P = 0.009) and was higher in men than women (77.0% vs. 70.6%; P = 0.011). Information on advanced adenoma was lacking. Increased cancer detection at lower positivity thresholds is counterbalanced by substantial increases in positive tests. Tailored thresholds may provide screening benefits that are more equal among different demographic groups, depending on local resources. National Cancer Institute.
Authors: Selby K; Lee JK; Levin TR; Corley DA; et al.
Ann Intern Med. 2018 10 02;169(7):439-447. Epub 2018-09-18.
Effects of Organized Colorectal Cancer Screening on Cancer Incidence and Mortality in a Large, Community-based Population
Little information is available on the effectiveness of organized colorectal cancer (CRC) screening on screening uptake, incidence, and mortality in community-based populations. We contrasted screening rates, age-adjusted annual CRC incidence, and incidence-based mortality rates before (baseline year 2000) and after (through 2015) implementation of organized screening outreach, from 2007 through 2008 (primarily annual fecal immunochemical testing and colonoscopy), in a large community-based population. Among screening-eligible individuals 51-75 years old, we calculated annual up-to-date status for cancer screening (by fecal test, sigmoidoscopy, or colonoscopy), CRC incidence, cancer stage distributions, and incidence-based mortality. Initiation of organized CRC screening significantly increased the up-to-date status of screening, from 38.9% in 2000 to 82.7% in 2015 (P < .01). Higher rates of screening were associated with a 25.5% reduction in annual CRC incidence between 2000 and 2015, from 95.8 to 71.4 cases/100,000 (P < .01), and a 52.4% reduction in cancer mortality, from 30.9 to 14.7 deaths/100,000 (P < .01). Increased screening was initially associated with increased CRC incidence, due largely to greater detection of early-stage cancers, followed by decreases in cancer incidence. Advanced-stage CRC incidence rates decreased 36.2%, from 45.9 to 29.3 cases/100,000 (P < .01), and early-stage CRC incidence rates decreased 14.5%, from 48.2 to 41.2 cases/100,000 (P < .04). Implementing an organized CRC screening program in a large community-based population rapidly increased screening participation to the ≥80% target set by national organizations. Screening rates were sustainable and associated with substantial decreases in CRC incidence and mortality within short time intervals, consistent with early detection and cancer prevention.
Authors: Levin TR; Corley DA; Lee JK; Quesenberry CP; Fireman BH; Doubeni CA; et al.
Gastroenterology. 2018 11;155(5):1383-1391.e5. Epub 2018-07-19.
Clinical implications of low skeletal muscle mass in early-stage breast and colorectal cancer
Although obesity has now been widely accepted to be an important risk factor for cancer survival, the associations between BMI and cancer mortality have not been consistently linear. Although morbid obesity has clearly been associated with worse survival, some studies have suggested a U-shaped association with no adverse association with overweight or lower levels of obesity. This ‘obesity paradox’ may be due to the fact that BMI likely incompletely captures key measures of body composition, including distribution of skeletal muscle and adipose tissue. Fat and lean body mass can be measured using clinically acquired computed tomography scans. Many of the earlier studies focused on patients with metastatic cancer. However, skeletal muscle loss in the metastatic setting may reflect end-stage disease processes. Therefore, this article focuses on the clinical implication of low skeletal muscle mass in early-stage non-metastatic breast and colorectal cancer where measures of body composition have been shown to be strong predictors of disease-free survival and overall survival and also chemotherapy toxicity and operative risk.
Authors: Cespedes Feliciano E; Chen WY
Proc Nutr Soc. 2018 11;77(4):382-387. Epub 2018-06-04.
Photosensitizing Antihypertensive Drug Use and Risk of Cutaneous Squamous Cell Carcinoma
Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown. To examine the association between AD use and cSCC risk among a cohort of non-Hispanic white individuals with hypertension enrolled in a comprehensive integrated healthcare delivery system in northern California (n = 28 357). Electronic pharmacy data were used to determine exposure to ADs, which were classified as photosensitizing, nonphotosensitizing or unknown, based on published literature. We identified patients who developed a cSCC during follow-up (n = 3010). We used Cox modelling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Covariates included age, sex, smoking, comorbidities, history of cSCC and actinic keratosis, survey year, healthcare utilization, length of health plan membership and history of photosensitizing AD use. Compared with nonuse of ADs, risk of cSCC was increased with ever having used photosensitizing ADs (aHR = 1·17, 95% CI 1·07-1·28) and ever having used ADs of unknown photosensitizing potential (aHR = 1·11, 95% CI 1·02-1·20), whereas no association was seen with ever having used nonphotosensitizing ADs (aHR = 0·99; 95% CI 0·91-1·07). Additionally, there was a modest increased risk with an increased number of prescriptions for photosensitizing ADs (aHR = 1·12, 95% CI 1·02-1·24; aHR = 1·19, 95% CI 1·06-1·34; aHR = 1·41, 95% CI 1·20-1·67 for one to seven, eight to 15 and ≥ 16 fills, respectively). These findings provide moderate support for an increased cSCC risk among individuals treated with photosensitizing ADs.
Authors: Su KA; Habel LA; Achacoso NS; Friedman GD; Asgari MM
Br J Dermatol. 2018 11;179(5):1088-1094. Epub 2018-08-14.
Gastroesophageal Reflux Frequency, Severity, Age of Onset, Family History and Acid Suppressive Therapy Predict Barrett Esophagus in a Large Population
To identify risk factors associated with Barrett esophagus (BE) for potential improved surveillance and risk reduction. Gastroesophageal reflux disease (GERD) is a known risk factor for esophageal adenocarcinoma, but the ability of GERD symptom frequency and severity to predict presence of its putative precursor lesion, BE, is less well-defined in large, community-based populations. We conducted a case-control study within the Kaiser Permanente Northern California population. Cases had new diagnoses of BE. To identify risk factors in the general population, we contrasted cases with population controls; to identify risk factors only among patients with GERD, we contrasted cases with GERD patients who lacked BE. We interviewed 953 patients; 320 patients with BE, 316 patients with GERD who lacked BE and 317 population controls. Compared with population controls, BE risk was highest among patients with the most frequent and severe GERD symptoms [odds ratio (OR), 27.00; 95% confidence interval (CI), 14.52-50.21], nocturnal symptoms (OR, 5.40; 95% CI, 3.81-7.72), and family history of GERD (OR, 2.55; 95% CI, 1.80-3.62) or BE (OR, 10.08; 95% CI, 2.83-35.84). Although at least weekly proton pump inhibitor (PPI) use was a risk factor for BE (OR, 9.85; 95% CI, 6.54-14.84), among PPI users in the general population, GERD symptoms were not strongly associated with the risk of BE. Compared with GERD controls, cases were more likely to have onset of GERD symptoms before 30 years of age (OR, 1.93; 95% CI, 1.15-3.22) and a family history of BE (OR, 3.64; 95% CI, 1.50-8.83). Severe and frequent GERD symptoms are strongly associated with increased risk of BE in the general population, especially in the absence of frequent PPI use. Among people with GERD, family history of BE and early age of symptom onset were stronger predictors of BE. These findings may improve identification of patients at highest risk for BE.
Authors: Bakr O; Zhao W; Corley D
J Clin Gastroenterol. 2018 Nov/Dec;52(10):873-879.
Genetic variation in the SIM1 locus is associated with erectile dysfunction
Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10-25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10-14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function.
Authors: Jorgenson E; Yin J; Shan J; Hoffmann TJ; Thai KK; Van Den Eeden SK; et al.
Proc Natl Acad Sci USA. 2018 Oct 23;115(43):11018-11023. Epub 2018-10-08.
Differences in molecular features of triple-negative breast cancers based on the age at diagnosis
Although the proportion of triple-negative breast cancers (TNBCs) diagnosed among older women is low, the number of TNBC cases is substantial because of the high incidence of breast cancer after the age of 65 years. The molecular features of TNBC in this age group have not been well described. This study examined a population-based cohort of women with stage I to III TNBC diagnosed between the ages of 25 and 91 years with the PAM50 gene expression subtyping assay. The concordance between the TNBC classification by immunohistochemistry and the gene expression classification by PAM50, the expression of individual genes, and 5-year recurrence and breast cancer mortality in older women (?65 years old) and younger women (<50 years old) was assessed. The molecular subtype distribution in TNBC was significantly different according to the age at diagnosis. TNBC was more likely to be classified as basal-like in women younger than 50 years (sensitivity, 0.91; 95% confidence interval, 0.77-0.97) than women 65 years old or older (sensitivity, 0.72; 95% confidence interval, 0.48-0.87); 35% of clinical TNBC cases in the latter group were the human epidermal growth factor receptor 2 (HER2)-enriched subtype by molecular classification. Older women with TNBC also had significantly higher expression of ERBB2 and lower expression of all 10 proliferation-associated genes tested (P < .01). The risk of breast cancer death within 5 years was significantly higher in women with TNBC in comparison with women with hormone receptor-positive cancers in all age groups. This study revealed differences in molecular subtypes among clinical TNBC cases based on patient age. A potentially targetable HER2-enriched group raises the possible need for intrinsic subtyping in older women with TNBC.
Authors: Gulbahce HE; Bernard PS; Weltzien EK; Factor RE; Kushi LH; Caan BJ; Sweeney C
Cancer. 2018 12 15;124(24):4676-4684. Epub 2018-10-12.
Negative withdrawal time: simple and efficient
Authors: Kidambi TD; Terdiman JP; Lee JK
Gastrointest Endosc. 2018 10;88(4):781.
Obesity and renal cell carcinoma risk by histologic subtype: A nested case-control study and meta-analysis
Although obesity is an established risk factor for renal cell carcinoma (RCC), it is unclear whether this relationship varies across histologic subtypes. We conducted a nested case-control study within the Kaiser Permanente Northern California (KPNC) health care network, and meta-analysis combining our results with those of previously published studies. Our KPNC study included 685 RCC cases [421 clear cell; 65 papillary; 24 chromophobe; 35 other; 141 not otherwise specified (NOS)] and 4266 controls. Subtype-specific odds ratios (ORs) and 95% confidence intervals (CIs) for categories of body mass index (BMI) and were computed from the case-control data using polytomous logistic regression. Findings from this and other relevant studies were combined by meta-analysis using a random effects model. In the KPNC study, obesity (BMI ≥ 30 kg/m2) was associated with clear cell RCC (OR 1.5, 95% CI 1.1-2.1) and chromophobe RCC (OR 2.5, 95%CI 0.8-8.1), but not with papillary RCC (OR 1.0, 95% CI 0.5-1.9). In meta-analysis including three additional studies, a similar pattern of summary relative risks (SRR) for obesity was observed across subtypes (clear cell: SRR 1.8, 95% CI 1.5-2.2; chromophobe: SRR 2.2, 95% CI 1.3-3.7; papillary, SRR 1.2, 95% CI 0.8-1.6). These findings support the hypothesis that histologic subtypes of RCC possess distinct etiologic pathways, with obesity important for the development of clear cell and, possibly, chromophobe RCC, but not papillary RCC.
Authors: Callahan CL; Hofmann JN; Corley DA; Zhao WK; Shuch B; Chow WH; Purdue MP
Cancer Epidemiol. 2018 10;56:31-37. Epub 2018-07-18.
Changes in Overall Diet Quality in Relation to Survival in Postmenopausal Women with Breast Cancer: Results from the Women’s Health Initiative
Lifestyle factors are important for cancer survival. However, empirical evidence regarding the effects of dietary changes on mortality in breast cancer survivors is sparse. The objective was to examine the associations of changes in overall diet quality, indicated by the Healthy Eating Index (HEI)-2010 score, with mortality in breast cancer survivors. This was a prospective cohort study from September 1993 through September 30, 2015. This study included 2,295 postmenopausal women who were diagnosed with invasive breast cancer and completed a food frequency questionnaire both before and after the diagnosis of breast cancer in the Women’s Health Initiative. The HEI-2010 score (maximum score of 100) was calculated based on consumption of 12 dietary components. The outcomes were mortality from all causes, breast cancer, and causes other than breast cancer. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios of mortality from all causes, breast cancer, and other causes. Over 12 years of follow-up, 763 deaths occurred. Compared with women with relatively stable diet quality (±14.9% change in HEI-2010 score), women who decreased diet quality (≥15% decrease in HEI-2010 score) had a higher risk of death from breast cancer (adjusted hazard ratio 1.66, 95% CI 1.09 to 2.52). Increased diet quality (≥15% increase in HEI-2010 score) was not significantly associated with lower risk of death. These associations persisted after additional adjustment for change in body mass index. Among women with breast cancer, decreased diet quality after breast cancer diagnosis was associated with higher risk of death from breast cancer.
Authors: Sun Y; Caan BJ; Snetselaar LG; et al.
J Acad Nutr Diet. 2018 10;118(10):1855-1863.e6. Epub 2018-05-30.
The Stockholm-3 (STHLM3) Model can Improve Prostate Cancer Diagnostics in Men Aged 50-69 yr Compared with Current Prostate Cancer Testing
Prostate cancer screening is associated with low specificity, unnecessary biopsies, and overdiagnosis. We have previously shown that the Stockholm-3 model (S3M) can reduce biopsies compared with using prostate-specific antigen (PSA) ≥3ng/ml as an indication for biopsy. Urologists in today’s current prostate cancer testing (CPT) have access to numerous variables in addition to PSA (eg, age, ethnicity, family history, free PSA, PSA velocity, digital rectal examination, and prostate volume) to support biopsy decisions. We estimated the number of prostate cancers diagnosed and prostate biopsies performed if S3M replaced CPT in Stockholm, Sweden, by comparing biopsy results in 56 282 men who underwent PSA testing according to CPT in Stockholm in 2011 with the 47 688 men enrolled in the STHLM3 validation cohort 2012-2015. With the same sensitivity as CPT to diagnose Gleason score ≥7 prostate cancer, S3M was estimated to reduce the number of men biopsied by 53% (95% confidence interval [CI]: 41-65%), avoid 76% (95% CI: 67-81%) of negative biopsies, and reduce Gleason score 6 cancers by 23% (95% CI: 6-40%). S3M has the potential to improve prostate cancer diagnostics by better selecting men with high risk of GS ≥7 prostate cancer. PATIENT SUMMARY: We modeled the effect the Stockholm-3 model would have on prostate cancer diagnostics if it replaced current clinical practice. We found that Stockholm-3 model may substantially reduce the number of biopsies, while maintaining the same sensitivity to diagnose clinically significant prostate cancer.
Authors: Eklund M; StLezin M; Grönberg H; et al.
Eur Urol Focus. 2018 09;4(5):707-710. Epub 2016-11-23.
Overdiagnosis in Colorectal Cancer Screening: Time to Acknowledge a Blind Spot
Authors: Kalager M; Wieszczy P; Lansdorp-Vogelaar I; Corley DA; Bretthauer M; Kaminski MF
Gastroenterology. 2018 Sep;155(3):592-595. Epub 2018-08-01.
World Endoscopy Organization Consensus Statements on Post-Colonoscopy and Post-Imaging Colorectal Cancer
Colonoscopy examination does not always detect colorectal cancer (CRC)- some patients develop CRC after negative findings from an examination. When this occurs before the next recommended examination, it is called interval cancer. From a colonoscopy quality assurance perspective, that term is too restrictive, so the term post-colonoscopy colorectal cancer (PCCRC) was created in 2010. However, PCCRC definitions and methods for calculating rates vary among studies, making it impossible to compare results. We aimed to standardize the terminology, identification, analysis, and reporting of PCCRCs and CRCs detected after other whole-colon imaging evaluations (post-imaging colorectal cancers [PICRCs]). A 20-member international team of gastroenterologists, pathologists, and epidemiologists; a radiologist; and a non-medical professional met to formulate a series of recommendations, standardize definitions and categories (to align with interval cancer terminology), develop an algorithm to determine most-plausible etiologies, and develop standardized methodology to calculate rates of PCCRC and PICRC. The team followed the Appraisal of Guidelines for Research and Evaluation II tool. A literature review provided 401 articles to support proposed statements; evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The statements were voted on anonymously by team members, using a modified Delphi approach. The team produced 21 statements that provide comprehensive guidance on PCCRCs and PICRCs. The statements present standardized definitions and terms, as well as methods for qualitative review, determination of etiology, calculation of PCCRC rates, and non-colonoscopic imaging of the colon. A 20-member international team has provided standardized methods for analysis of etiologies of PCCRCs and PICRCs and defines its use as a quality indicator. The team provides recommendations for clinicians, organizations, researchers, policy makers, and patients.
Authors: Rutter MD; Corley DA; Sanduleanu S; et al.
Gastroenterology. 2018 09;155(3):909-925.e3. Epub 2018-06-27.
The use of 5-alpha reductase inhibitors to manage benign prostatic hyperplasia and the risk of all-cause mortality
To compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. We employed a retrospective matched cohort study in 4 regions of an integrated healthcare system. Men aged 50 years and older who initiated pharmaceutical treatment for BPH and/or lower urinary tract symptoms between 1992 and 2008 and had at least 3 consecutive prescriptions that were eligible and followed through 2010 (N = 174,895). Adjusted hazard ratios were used to estimate the risk of mortality due to all-causes associated with 5ARI use (with or without concomitant ABs) as compared to AB use. In this large and diverse sample with 543,523 person-years of follow-up, 35,266 men died during the study period, 18.9% of the 5ARI users and 20.4% of the AB users. After adjustment for age, medication initiation year, race, region, prior AB history, Charlson score, and comorbidities, 5ARI use was not associated with an increased risk of mortality when compared to AB use (Adjusted hazard ratios: 0.64, 95% confidence interval: 0.62, 0.66). Among men receiving medications for BPH in community practice settings, 5ARI use was not associated with an increased risk of mortality when compared to AB use. These data provide reassurance about the safety of using 5ARIs in general practice to manage BPH and/or lower urinary tract symptoms.
Authors: Wallner LP; Van Den Eeden SK; Jacobsen SJ; et al.
Urology. 2018 Sep;119:70-78. Epub 2018-06-12.
Stratified probabilistic bias analysis for BMI-related exposure misclassification in postmenopausal women
There is widespread concern about the use of body mass index (BMI) to define obesity status in postmenopausal women because it may not accurately represent an individual’s true obesity status. The objective of the present study is to examine and adjust for exposure misclassification bias from using an indirect measure of obesity (BMI) compared with a direct measure of obesity (percent body fat). We used data from postmenopausal non-Hispanic black and non-Hispanic white women in the Women’s Health Initiative (n=126,459). Within the Women’s Health Initiative, a sample of 11,018 women were invited to participate in a sub-study involving dual-energy x-ray absorptiometry scans. We examined indices of validity comparing BMI-defined obesity (≥30 kg/m), with obesity defined by percent body fat. We then used probabilistic bias analysis models stratified by age and race to explore the effect of exposure misclassification on the obesity-mortality relationship. Validation analyses highlight that using a BMI cutpoint of 30 kg/m to define obesity in postmenopausal women is associated with poor validity. There were notable differences in sensitivity by age and race. Results from the stratified bias analysis demonstrated that failing to adjust for exposure misclassification bias results in attenuated estimates of the obesity-mortality relationship. For example, in non-Hispanic white women 50-59 years of age, the conventional risk difference was 0.017 (95% confidence interval = 0.01, 0.023) and the bias-adjusted risk difference was 0.035 (95% simulation interval = 0.028, 0.043). These results demonstrate the importance of using quantitative bias analysis techniques to account for nondifferential exposure misclassification of BMI-defined obesity. See video abstract at, https://links.lww.com/EDE/B385.
Authors: Banack HR; Cespedes Feliciano EM; Caan BJ; Kroenke CH; Wactawski-Wende J; et al.
Epidemiology. 2018 09;29(5):604-613.
The Obesity Paradox in Cancer: How Important Is Muscle?
Although higher body mass index (BMI) increases the incidence of many cancers, BMI can also exhibit a null or U-shaped relationship with survival among patients with existing disease; this association of higher BMI with improved survival is termed the obesity paradox. This review discusses possible explanations for the obesity paradox, the prevalence and consequences of low muscle mass in cancer patients, and future research directions. It is unlikely that methodological biases, such as reverse causality or confounding, fully explain the obesity paradox. Rather, up to a point, higher BMI may truly be associated with longer survival in cancer patients. This is due, in part, to the limitations of BMI, which scales weight to height without delineating adipose tissue distribution or distinguishing between adipose and muscle tissue. Thus, cancer patients with higher BMIs often have higher levels of protective muscle. We assert that more precise measures of body composition are required to clarify the relationship of body size to cancer outcomes, inform clinical decision-making, and help tailor lifestyle interventions.
Authors: Cespedes Feliciano EM; Kroenke CH; Caan BJ
Annu Rev Nutr. 2018 08 21;38:357-379. Epub 2018-05-04.
Evolutionary-Concordance Lifestyle and Diet and Mediterranean Diet Pattern Scores and Risk of Incident Colorectal Cancer in Iowa Women.
Background: Whereas diet and lifestyle are strongly implicated in the etiology of colorectal cancer, single exposures generally are weakly and inconsistently associated with the disease. Exposure patterns may be more helpful for investigating diet and lifestyle-colorectal cancer associations. Evolutionary-concordance diet and Mediterranean diet pattern scores were previously found to be inversely associated with colorectal adenoma.Methods: To investigate associations of these diet scores and an evolutionary-concordance lifestyle score (comprising smoking status, physical activity, and body mass index) with incident colorectal cancer, we analyzed data from the prospective Iowa Women’s Health Study. Diet and lifestyle scores were calculated for each participant and categorized into quintiles, and associations estimated using Cox proportional hazards models.Results: Of the 35,221 55- to 69-year-old cancer-free women at baseline, 1,731 developed colorectal cancer during follow-up. The multivariable-adjusted HR comparing persons in the highest relative to the lowest quintile of the lifestyle score was 0.66 (95% confidence interval, 0.56-0.78; P trend < 0.01). Although the estimated associations of the evolutionary-concordance diet and Mediterranean diet scores alone with colorectal cancer were null, relative to those in the lowest tertiles of both the evolutionary-concordance diet and lifestyle scores, those in the highest tertiles of both scores were at the lowest risk (P interaction < 0.01).Conclusions: Our findings suggest that a more evolutionary-concordant lifestyle, alone and in interaction with a more evolutionary-concordant diet pattern, may be inversely associated with colorectal cancer risk.Impact: These results support further investigation of colorectal cancer etiology using evolutionary-concordance dietary and lifestyle pattern scores. Cancer Epidemiol Biomarkers Prev; 27(10); 1195-202. (c)2018 AACR.
Authors: Cheng E; Um CY; Prizment AE; Lazovich D; Bostick RM
Cancer Epidemiol Biomarkers Prev. 2018 Oct;27(10):1195-1202. doi: 10.1158/1055-9965.EPI-17-1184. Epub 2018 Aug 14.
Age of Menarche in a Longitudinal US Cohort
Menarche is a critical milestone in a woman’s life, and historically has been determined using several approaches. The goals of this study were to: (1) determine age at menarche from multiple reports of parents and adolescent participants in a prospective study; (2) examine factors affecting age at menarche; and (3) determine correlates of menarche and pubertal tempo. Longitudinal observational study. Three sites of the Breast Cancer and the Environment Research Program. Girls enrolled at 6-8 years of age. Parental and participant reported age of menarche, and tempo of puberty. There were 946 girls who were assigned an age of menarche. The correlation between parent and participant reports was high (Spearman R = 0.799, P < .001), and the difference was insignificant. Median age at menarche overall was 12.25 years. Compared with black participants, Hispanic girls were more likely to have menarche earlier, whereas white and Asian girls were more likely to have menarche later. Age of menarche was highly correlated with age of breast development (Spearman R = 0.547; P < .001), and inversely with body mass index (Spearman R = -0.403; P < .001). Tempo (interval of age of breast development to menarche) was slower in those with earlier breast development. Parental and adolescent reports of menarche are highly correlated. Earlier breast maturation was associated with slower tempo through puberty. Body mass index had a greater effect on age at menarche than did race and ethnicity.
Authors: Biro FM; Pajak A; Wolff MS; Pinney SM; Windham GC; Galvez MP; Greenspan LC; Kushi LH; Teitelbaum SL
J Pediatr Adolesc Gynecol. 2018 Aug;31(4):339-345. Epub 2018-05-24.
Urinary biomarkers of polycyclic aromatic hydrocarbons in pre- and peri-pubertal girls in Northern California: Predictors of exposure and temporal variability
Polycyclic aromatic hydrocarbons (PAHs), a class of chemicals produced as combustion by-products, have been associated with endocrine disruption. To understand exposure in children, who have been less studied than adults, we examined PAH metabolite concentrations by demographic characteristics, potential sources of exposure, and variability over time, in a cohort study of pre- and peri-pubertal girls in Northern California. Urinary concentrations of ten PAH metabolites and cotinine were quantified in 431 girls age 6-8 years at baseline. Characteristics obtained from parental interview, physical exam, and linked traffic data were examined as predictors of PAH metabolite concentrations using multivariable linear regression. A subset of girls (n = 100) had repeat measures of PAH metabolites in the second and fourth years of the study. We calculated the intraclass correlation coefficient (ICC), Spearman correlation coefficients, and how well the quartile ranking by a single measurement represented the four-year average PAH biomarker concentration. Eight PAH metabolites were detected in ≥ 95% of the girls. The most consistent predictors of PAH biomarker concentrations were cotinine concentration, grilled food consumption, and region of residence, with some variation by demographics and season. After adjustment, select PAH metabolite concentrations were higher for Hispanic and Asian girls, and lower among black girls; 2-naphthol concentrations were higher in girls from lower income households. Other than 1-naphthol, there was modest reproducibility over time (ICCs between 0.18 and 0.49) and the concentration from a single spot sample was able to reliably rank exposure into quartiles consistent with the multi-year average. These results confirm diet and environmental tobacco smoke exposure as the main sources of PAHs. Controlling for these sources, differences in concentrations still existed by race for specific PAH metabolites and by income for 2-naphthol. The modest temporal variability implies adequate exposure assignment using concentrations from a single sample to define a multi-year exposure timeframe for epidemiologic exposure-response studies.
Authors: Dobraca D; Lum R; Sjödin A; Calafat AM; Laurent CA; Kushi LH; Windham GC
Environ Res. 2018 08;165:46-54. Epub 2018-04-14.
Understanding racial/ethnic differences in breast cancer-related physical well-being: the role of patient-provider interactions
Racial/ethnic differences in cancer symptom burden are well documented, but limited research has evaluated modifiable factors underlying these differences. Our objective was to examine the role of patient-provider interactions to help explain the relationship between race/ethnicity and cancer-specific physical well-being (PWB) among women with breast cancer. The Pathways Study is a prospective cohort study of 4505 women diagnosed with breast cancer at Kaiser Permanente Northern California between 2006 and 2013. Our analysis included white, black, Hispanic, and Asian participants who completed baseline assessments of PWB, measured using the Functional Assessment of Cancer Therapy for Breast Cancer, and patient-provider interactions, measured by the Interpersonal Processes of Care Survey (IPC) (N = 4002). Using step-wise linear regression, we examined associations of race/ethnicity with PWB, and changes in associations when IPC domains were added. We observed racial/ethnic differences in PWB, with minorities reporting lower scores than whites (beta, black: - 1.79; beta, Hispanic: - 1.92; beta, Asian: - 1.68; p < 0.0001 for all comparisons). With the addition of health and demographic covariates to the model, associations between race/ethnicity and PWB score became attenuated for blacks and Asians (beta: - 0.63, p = 0.06; beta: - 0.68, p = 0.02, respectively) and, to a lesser extent, for Hispanic women (beta: - 1.06, p = 0.0003). Adjusting for IPC domains did not affect Hispanic-white differences (beta: - 1.08, p = 0.0002), and slightly attenuated black-white differences (beta: - 0.51, p = 0.14). Asian-white differences narrowed substantially (beta: - 0.31, p = 0.28). IPC domains, including those capturing perceived discrimination, respect, and clarity of communication, appeared to partly explain PWB differences for black and Asian women. Results highlight opportunities to improve providers' interactions with minority patients, and communication with minority patients about their supportive care needs.
Authors: Check DK; Chawla N; Kwan ML; Pinheiro L; Roh JM; Ergas IJ; Stewart AL; Kolevska T; Ambrosone C; Kushi LH
Breast Cancer Res Treat. 2018 Aug;170(3):593-603. Epub 2018-04-05.
Personal and clinical social support and adherence to adjuvant endocrine therapy among hormone receptor-positive breast cancer patients in an integrated health care system
We evaluated associations between personal and clinical social support and non-adherence to adjuvant endocrine therapy (AET) in a large, Northern California breast cancer (BC) cohort from an integrated healthcare network. This study included 3382 women from the Pathways Study diagnosed from 2005 to 2013 with stages I-III hormone receptor-positive BC and who responded to the Medical Outcomes Study Social Support and Interpersonal Processes of Care surveys, approximately 2 months post-diagnosis. We used logistic regression to evaluate associations between tertiles of social support and non-initiation (< 2 consecutive prescription fills within a year after diagnosis). Among those who initiated treatment, we used proportional hazards regression to evaluate associations with discontinuation (≥ 90 day gap) and non-adherence (< 80% medical possession ratio). Of those who initiated AET (79%), approximately one-fourth either discontinued AET or were non-adherent. AET non-initiation was more likely in women with moderate (adjusted OR 1.18, 95% CI 0.96-1.46) or low (OR 1.30, 95% CI 1.05-1.62) versus high personal social support (P trend = 0.02). Women with moderate (HR 1.20, 95% CI 0.99-1.45) or low (HR 1.32, 95% CI 1.09-1.60) personal social support were also more likely to discontinue treatment (P trend = 0.01). Furthermore, women with moderate (HR 1.25, 95% CI 1.02-1.53) or low (HR 1.38, 95% CI 1.12-1.70) personal social support had higher non-adherence (P trend = 0.007). Associations with clinical social support and outcomes were similar. Notably, high clinical social support mitigated the risk of discontinuation when patients' personal support was moderate or low (P value = 0.04). Women with low personal or clinical social support had higher AET non-adherence. Clinician teams may need to fill support gaps that compromise treatment adherence.
Authors: Kroenke CH; Hershman DL; Gomez SL; Adams SR; Eldridge EH; Kwan ML; Ergas IJ; Kubo A; Kushi LH
Breast Cancer Res Treat. 2018 Aug;170(3):623-631. Epub 2018-04-18.
Risk of diabetes complications among those with diabetes receiving androgen deprivation therapy for localized prostate cancer
Androgen deprivation therapy (ADT), used increasingly in the treatment of localized prostate cancer, is associated with substantial long-term adverse consequences, including incident diabetes. While previous studies have suggested that ADT negatively influences glycemic control in existing diabetes, its association with diabetes complications has not been investigated. In this study, we examined the association between ADT use and diabetes complications in prostate cancer patients. A retrospective cohort study was conducted among men with newly diagnosed localized prostate cancer between 1995 and 2008, enrolled in three integrated health care systems. Men had radical prostatectomy or radiotherapy (curative intent therapy), existing type II diabetes mellitus (T2DM), and were followed through December 2010 (n = 5,336). Cox proportional hazards models were used to examine associations between ADT use and diabetes complications (any complication), and individual complications (diabetic neuropathy, diabetic retinopathy, diabetic amputation or diabetic cataract) after prostate cancer diagnosis. ADT use was associated with an increased risk of any diabetes complication after prostate cancer diagnosis (adjusted hazard ratio, AHR, 1.12, 95% CI 1.03-1.23) as well as an increased risk of each individual complication compared to non-use. ADT use in men with T2DM, who received curative intent therapy for prostate cancer, was associated with an increased risk of diabetes complications. These findings support those of previous studies, which showed that ADT worsened diabetes control. Additional, larger studies are required to confirm these findings and to potentially inform the development of a risk-benefit assessment for men with existing T2DM, before initiating ADT.
Authors: Bradley MC; Zhou Y; Freedman AN; Yood MU; Quesenbery CP; Haque R; Van Den Eeden SK; Cassidy-Bushrow AE; Aaronson D; Potosky AL
Cancer Causes Control. 2018 08;29(8):785-791. Epub 2018-06-29.
Helicobacter pylori Infection Is Associated With Reduced Risk of Barrett’s Esophagus: An Analysis of the Barrett’s and Esophageal Adenocarcinoma Consortium
Epidemiological studies of Helicobacter pylori infection and risk of Barrett’s esophagus (BE) have reported conflicting results. We examined the association between H. pylori infection and BE and sought to determine whether the association is mediated by gastroesophageal reflux disease (GERD) and to identify potential effect modifiers. We used individual level data from 1308 patients with BE (cases), 1388 population-based controls, and 1775 GERD controls in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON). We estimated study-specific odds ratios (ORs) and 95% CIs using multivariable logistic regression models and obtained summary risk estimates using a random-effects meta-analytic approach. We examined potential effect modification by waist-to-hip ratio (WHR), body mass index (BMI), and smoking status by conducting stratified analyses. For comparisons with population-based controls, H. pylori infection was inversely associated with the risk of BE (adjusted OR = 0.44, 95% CI = 0.36-0.55), with no evidence of between-study heterogeneity (I2 = 0%). A stronger inverse association between H. pylori and BE was observed among individuals with the CagA-positive strain (P for interaction = 0.017). We found no evidence of interaction between WHR, BMI, smoking status, and H. pylori infection on the risk of BE. There was no association between H. pylori infection and BE for comparisons with GERD controls (OR = 0.96, 95% CI = 0.67-1.37; I2 = 48%). This study provides the strongest evidence yet that H. pylori infection is strongly inversely associated with BE. This effect is probably mediated by a decrease in GERD in infected patients, since the protective effect disappears in patients with GERD symptoms.
Authors: Wang Z; Shaheen NJ; Whiteman DC; Anderson LA; Vaughan TL; Corley DA; El-Serag HB; Rubenstein JH; Thrift AP
Am J Gastroenterol. 2018 08;113(8):1148-1155. Epub 2018-06-08.
Antidepressant Use and Risk of Colorectal Cancer in The Women’s Health Initiative
Background: Some prior studies have reported reduced colorectal cancer risk among individuals using antidepressant medications, especially selective serotonin reuptake inhibitors (SSRIs). Yet most studies have not considered the potential role of depression or other confounders in their analyses.Methods: We utilized prospectively collected data from 145,190 participants in the Women’s Health Initiative, among whom 2,580 incident colorectal cancer cases were diagnosed. Antidepressant use and depressive symptoms were assessed at baseline and follow-up study visits. Cox proportional hazards regression models with adjustment for depressive symptoms and other covariates were utilized to estimate HRs and 95% confidence intervals (CIs) for associations between antidepressant use and colorectal cancer.Results: Antidepressant use was reported by 6.9% of participants at baseline, with SSRIs the most common class of antidepressant used. In multivariable analyses, including adjustment for depressive symptomology, we observed no statistically significant association between antidepressant use overall (HR = 0.90; 95% CI, 0.75-1.09) or with SSRIs specifically (HR = 1.08; 95% CI, 0.85-1.37) and colorectal cancer risk. A borderline significant reduction in colorectal cancer risk was observed for use of tricyclic antidepressants (HR = 0.76; 95% CI, 0.56-1.04). Severe depressive symptoms were independently associated with a 20% increased risk of colorectal cancer (HR = 1.21; 95% CI, 1.09-1.48). Results were similar for separate evaluations of colon and rectal cancer.Conclusions: We observed no evidence of an association between antidepressant use, overall or by therapeutic class, and colorectal cancer risk.Impact: These results suggest that antidepressants may not be useful as chemopreventive agents for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(8); 892-8. ©2018 AACR.
Authors: Kiridly-Calderbank JF; Sturgeon SR; Kroenke CH; Reeves KW
Cancer Epidemiol Biomarkers Prev. 2018 08;27(8):892-898. Epub 2018-05-22.
Associations of pre-existing co-morbidities with skeletal muscle mass and radiodensity in patients with non-metastatic colorectal cancer
Co-morbidities and computerized tomography-measured muscle abnormalities are both common in cancer patients and independently adversely influence clinical outcomes. Muscle abnormalities are also evident in other diseases, such as diabetes and obesity. This study examined for the first time the association between co-morbidities and muscle abnormalities in patients diagnosed with colorectal cancer (CRC). This cross-sectional study included 3051 non-metastatic patients with Stages I-III CRC. Muscle abnormalities, measured at diagnosis, were defined as low skeletal muscle mass index (SMI) or low skeletal muscle radiodensity (SMD) quantified using computerized tomography images using optimal stratification. Co-morbidities included in the Charlson index were ascertained. χ2 tests were used to compare the prevalence of co-morbidities by the presence or absence of each muscle abnormality. Logistic regressions were performed to evaluate which co-morbidities predicted muscle abnormalities adjusting for age, sex, body mass index, weight change, cancer stage, cancer site, race/ethnicity, and smoking. Mean age was 63 years; 50% of patients were male. The prevalence of low SMI and low SMD were 43.1% and 30.2%, respectively. Co-morbidities examined were more prevalent in patients with low SMD than in those with normal SMD, and most remained independent predictors of low SMD after adjustment for covariates. Co-morbidities associated with higher odds of low SMD included myocardial infarction [odds ratio (OR) = 1.77, P = 0.023], congestive heart failure (OR = 3.27, P < 0.001), peripheral vascular disease (OR = 2.15, P = 0.002), diabetes with or without complications (OR = 1.61, P = 0.008; OR = 1.46, P = 0.003, respectively), and renal disease (OR = 2.21, P < 0.001). By contrast, only diabetes with complications was associated with lower odds of low SMI (OR = 0.64, P = 0.007). Prevalence of muscle abnormalities was high in patients with non-metastatic CRC. Pre-existing co-morbidities were associated with low SMD, suggestive of a potential shared mechanism between fat infiltration into muscle and each of these co-morbidities.
Authors: Xiao J; Caan BJ; Weltzien E; Cespedes Feliciano EM; Kroenke CH; Meyerhardt JA; Baracos VE; Kwan ML; Castillo AL; Prado CM
J Cachexia Sarcopenia Muscle. 2018 08;9(4):654-663. Epub 2018-04-19.
Screening for low muscularity in colorectal cancer patients: a valid, clinic-friendly approach that predicts mortality
Low skeletal muscle quantified using computed tomography (CT) scans is associated with morbidity and mortality among cancer patients. However, existing methods to assess skeletal muscle from CT are time-consuming, expensive, and require training. Clinic-friendly tools to screen for low skeletal muscle in cancer patients are urgently needed. We included 807 scans from non-metastatic colorectal cancer patients. With the digital ruler available in most radiological software, we implemented an abbreviated method to assess skeletal muscle area at the third lumbar vertebra (L3), which consisted of assessing the height and width of the psoas and paraspinal muscles and computing their combined ‘linear area’ in centimetres squared (cm2 ). A subset of CT scans was assessed twice by two analysts to compute intra-rater and inter-rater reliability. We derived cut-points for ‘low’ linear area using optimal stratification and then calculated the sensitivity and specificity of these cut-points relative to standard methods (total L3 cross-sectional area assessed with Slice-O-Matic research software). We further evaluated the association of low linear area with death from any cause after colorectal cancer diagnosis in Cox proportional hazards models adjusting for demographics, smoking, body mass index category, and tumour characteristics. The linear area was highly correlated with total cross-sectional area assessed using standard methods [r = 0.92; 95% confidence interval (CI): 0.91, 0.93] overall and within subgroups defined by age, sex, and body mass index group. Intra-rater and inter-rater reliability were equally high (both intra-class correlations = 0.98). Cut-points for low linear area were sensitive (0.75; 95% CI: 0.70, 0.80) and specific (0.77; 95% CI: 0.73, 0.80) for identifying low skeletal muscle relative to the standard of total L3 cross-sectional area. The hazard ratio and 95% CI for death associated with a low linear area were hazard ratio = 1.66; 95% CI: 1.22, 2.25. Clinic-friendly methods that assess linear area from CT scans are an accurate screening tool to identify low skeletal muscle among non-metastatic colorectal cancer patients. These linear measures are associated with mortality after colorectal cancer, suggesting they could be clinically useful both to improve prognostication and to provide a practical screening tool to identify cancer patients who require nutrition or exercise intervention.
Authors: Cespedes Feliciano EM; Avrutin E; Caan BJ; Boroian A; Mourtzakis M
J Cachexia Sarcopenia Muscle. 2018 Jul 31.
A conceptual model of social networks and mechanisms of cancer mortality, and potential strategies to improve survival
Women with larger personal social networks have better breast cancer survival and a lower risk of mortality. However, little work has examined the mechanisms through which social networks influence breast cancer outcomes and cancer outcomes more generally, potentially limiting the development of feasible, clinically effective interventions. In fact, much of the emphasis in cancer research regarding the influence of social relationships on cancer outcomes has focused on the benefits of the provision of social support to patients, especially through peer support groups, and only more recently through patient navigation. Though critically important, there are other ways through which social relationships might influence outcomes, around which interventions might be developed. In addition to social support, these include social resources, social norms, social contagion, social roles, and social burdens and obligations. This narrative review addresses how social networks may influence cancer outcomes and discusses potential strategies for improving outcomes given these relationships. The paper (a) describes background and limitations of previous research, (b) outlines terms and provides a conceptual model that describes interrelationships between social networks and relevant variables and their hypothesized influence on cancer outcomes, (c) clarifies social and psychosocial mechanisms through which social networks affect downstream factors, (d) describes downstream behavioral, treatment, and physiological factors through which these subsequently influence recurrence and mortality, and (e) describes needed research and potential opportunities to enhance translation. Though most literature in this area pertains to breast cancer, this review has substantial relevance for cancer outcomes generally. Further clarification and research regarding potential mechanisms are needed to translate epidemiological findings on social networks into clinical and community strategies to improve cancer outcomes.
Authors: Kroenke CH
Transl Behav Med. 2018 07 17;8(4):629-642.
Muscle radiodensity and mortality in patients with colorectal cancer
Low skeletal muscle radiodensity (SMD) is related to higher mortality in several cancers, but the association with colorectal cancer (CRC) prognosis is unclear. This observational study included 3262 men and women from the Kaiser Permanente Northern California population diagnosed between 2006 and 2011 with AJCC stages I to III CRC. The authors evaluated hazard ratios (HRs) of low SMD for all-cause and CRC-specific mortality, assessed by computed tomography using optimal stratification, compared with patients with normal SMD. They also evaluated the cross-classification of categories of low versus normal SMD and muscle mass (MM) with outcomes. The median follow-up was 6.9 years. Optimal stratification cutpoints for SMD were 32.5 in women and 35.5 in men. In multivariate-adjusted analyses, among patients with CRC, those with low SMD demonstrated higher overall (HR, 1.61; 95% confidence interval [95% CI], 1.36-1.90) and CRC-specific (HR, 1.74; 95% CI, 1.38-2.21) mortality when compared with those with normal SMD levels. Patients with low SMD and low MM (ie, sarcopenia) were found to have the highest overall (HR, 2.02; 95% CI, 1.65-2.47) and CRC-specific (HR, 2.54; 95% CI, 1.91-3.37) mortality rates. In patients with CRC, those with low SMD were found to have elevated risks of disease-specific and overall mortality, independent of MM or adiposity. Clinical practice should incorporate body composition measures into the evaluation of the health status of patients with CRC. Cancer 2018;124:3008-15. © 2018 American Cancer Society.
Authors: Kroenke CH; Prado CM; Meyerhardt JA; Weltzien EK; Xiao J; Cespedes Feliciano EM; Caan BJ
Cancer. 2018 07 15;124(14):3008-3015. Epub 2018-05-24.
The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs
The TGFβ-signaling pathway plays an important role in the pathogenesis of colorectal cancer (CRC). Loss of function of several genes within this pathway, such as bone morphogenetic proteins (BMPs) have been seen as key events in CRC progression. In this study we comprehensively evaluate differential gene expression (RNASeq) of 81 genes in the TGFβ-signaling pathway and evaluate how dysregulated genes are associated with miRNA expression (Agilent Human miRNA Microarray V19.0). We utilize paired carcinoma and normal tissue from 217 CRC cases. We evaluate the associations between differentially expressed genes and miRNAs and sex, age, disease stage, and survival months. Thirteen genes were significantly downregulated and 14 were significantly upregulated after considering fold change (FC) of > 1.50 or < 0.67 and multiple comparison adjustment. Bone morphogenetic protein genes BMP5, BMP6, and BMP2 and growth differentiation factor GDF7 were downregulated. BMP4, BMP7, INHBA (Inhibin beta A), TGFBR1, TGFB2, TGIF1, TGIF2, and TFDP1 were upregulated. In general, genes with the greatest dysregulation, such as BMP5 (FC 0.17, BMP6 (FC 0.25), BMP2 (FC 0.32), CDKN2B (FC 0.32), MYC (FC 3.70), BMP7 (FC 4.17), and INHBA (FC 9.34) showed dysregulation in the majority of the population (84.3, 77.4, 81.1, 80.2, 82.0, 51.2, and 75.1% respectively). Four genes, TGFBR2, ID4, ID1, and PITX2, were un-associated or slightly upregulated in microsatellite-stable (MSS) tumors while downregulated in microsatellite-unstable (MSI) tumors. Eight dysregulated genes were associated with miRNA differential expression. E2F5 and THBS1 were associated with one or two miRNAs; RBL1, TGFBR1, TGIF2, and INHBA were associated with seven or more miRNAs with multiple seed-region matches. Evaluation of the joint effects of mRNA:miRNA identified interactions that were stronger in more advanced disease stages and varied by survival months. These data support an interaction between miRNAs and genes in the TGFβ-signaling pathway in association with CRC risk. These interactions are associated with unique clinical characteristics that may provide targets for further investigations.
Authors: Pellatt AJ; Mullany LE; Herrick JS; Sakoda LC; Wolff RK; Samowitz WS; Slattery ML
J Transl Med. 2018 07 09;16(1):191. Epub 2018-07-09.
Conflicts of Interest in Nutrition Research
Authors: Ludwig DS; Kushi LH; Heymsfield SB
JAMA. 2018 07 03;320(1):93.
Objective Sleep Characteristics and Cardiometabolic Health in Young Adolescents
: media-1vid110.1542/5778442247001PEDS-VA_2017-4085Video Abstract BACKGROUND AND OBJECTIVES: Shorter sleep duration is associated with childhood obesity. Few studies measure sleep quantity and quality objectively or examine cardiometabolic biomarkers other than obesity. This cross-sectional study of 829 adolescents derived sleep duration, efficiency and moderate-to-vigorous physical activity from >5 days of wrist actigraphy recording for >10 hours/day. The main outcome was a metabolic risk score (mean of 5 sex-specific z-scores for waist circumference, systolic blood pressure, high-density lipoprotein cholesterol scaled inversely, and log-transformed triglycerides and homeostatic model assessment of insulin resistance), for which higher scores indicate greater metabolic risk. Secondary outcomes included score components and dual-energy radiograph absorptiometry fat mass. We measured socioeconomic status, race and/or ethnicity, pubertal status, and obesity-related behaviors (television-viewing and fast food and sugar-sweetened beverage consumption) using questionnaires. The sample was 51.5% girls; mean (SD) age 13.2 (0.9) years, median (interquartile range) sleep duration was 441.1 (54.8) minutes per day and sleep efficiency was 84.0% (6.3). Longer sleep duration was associated with lower metabolic risk scores (-0.11 points; 95% CI: -0.19 to -0.02, per interquartile range). Associations with sleep efficiency were similar and persisted after adjustment for BMI z score and physical activity, television-viewing, and diet quality. Longer sleep duration and greater sleep efficiency were also favorably associated with waist circumference, systolic blood pressure, high-density lipoprotein cholesterol, and fat mass. Longer sleep duration and higher sleep efficiency were associated with a more favorable cardiometabolic profile in early adolescence, independent of other obesity-related behaviors. These results support the need to assess the role of sleep quantity and quality interventions as strategies for improving cardiovascular risk profiles of adolescents.
Authors: Cespedes Feliciano EM; Quante M; Rifas-Shiman SL; Redline S; Oken E; Taveras EM
Pediatrics. 2018 07;142(1). Epub 2018-06-15.
Associations Between Maternal Obesity and Pregnancy Hyperglycemia and Timing of Pubertal Onset in Adolescent Girls: A Population-Based Study
Early puberty is associated with adverse health outcomes. We investigated whether in utero exposure to maternal obesity is associated with daughters’ pubertal timing using 15,267 racially/ethnically diverse Kaiser Permanente Northern California members aged 6-11 years with pediatrician-assessed Tanner staging (2003-2017). We calculated maternal body mass index (BMI; weight (kg)/height (m)2) during pregnancy from the electronic health record data. Using a proportional hazards model with interval censoring, we examined the associations between maternal obesity and girls’ pubertal timing, as well as effect modification by race/ethnicity and mediation by prepubertal BMI. Maternal obesity (BMI ≥30) and overweight (BMI 25-29.9) were associated with earlier onset of breast development in girls (hazard ratio (HR) = 1.39 (95% confidence interval (CI): 1.30, 1.49) and HR = 1.21 (95% CI: 1.13, 1.29), respectively), after adjustment for girl’s race/ethnicity, maternal age, education, parity, and smoking during pregnancy. There was interaction by race/ethnicity for associations between maternal obesity and girls’ pubic hair onset: Associations were strongest among Asian and non-Hispanic white girls (HR = 1.53 (95% CI: 1.24, 1.90) and HR = 1.34 (95% CI: 1.18, 1.52), respectively) and absent for African-American girls. Adjustment for girl’s prepubertal BMI only slightly attenuated associations. Our results suggest the importance of maternal metabolic factors during pregnancy in the timing of girls’ puberty and potential differences in the associations by race/ethnicity.
Authors: Kubo A; Deardorff J; Laurent CA; Ferrara A; Greenspan LC; Quesenberry CP; Kushi LH
Am J Epidemiol. 2018 07 01;187(7):1362-1369.
Mutation analysis of adenomas and carcinomas of the colon: early and late drivers
Colorectal cancer (CRC) accounts for about 8% of all new cancer cases diagnosed in the US. We used whole exome sequence data from triplet samples (colon carcinoma, colon adenoma, and normal tissue) from 18 individuals to assess gene mutation rates. Of the 2 204 genes that were mutated, APC, TTN, TP53, KRAS, OBSCN, SOX9, PCDH17, SIGLEC10, MYH6, and BRD9 were consistent with genes being an early driver of carcinogenesis, in that they were mutated in multiple adenomas and multiple carcinomas. Fifty-two genes were mutated in ≥12.5% of microsatellite stable (MSS) carcinomas but not in any of the adenomas, in line with the profile of a late driver event involved in tumor progression. Thirty-eight genes were sequenced in a larger independent set of 148 carcinoma/normal tissue pairs to obtain more precise mutation frequencies. Eight of the genes, APC, TP53, ATM, CSMD3, LRP1B, RYR2, BIRC6, and MUC17, contained mutations in >20% of the carcinomas. Interestingly, mutations in four genes in addition to APC that are associated with dysregulation of Wnt signaling, were all classified as early driver events. Most of the genes that are commonly associated with colon cancer, including APC, TP53, and KRAS, were all classified as being early driver genes being mutated in both adenomas and carcinomas. Classifying genes as potential early and late driver events points to candidate genes that may help dissect pathways involved in both tumor initiation and progression.
Authors: Wolff RK; Hoffman MD; Wolff EC; Herrick JS; Sakoda LC; Samowitz WS; Slattery ML
Genes Chromosomes Cancer. 2018 07;57(7):366-376. Epub 2018-04-30.
Mapping hot spots of breast cancer mortality in the United States: place matters for Blacks and Hispanics.
PURPOSE: The goals of this study were to identify geographic and racial/ethnic variation in breast cancer mortality, and evaluate whether observed geographic differences are explained by county-level characteristics.METHODS: We analyzed data on breast cancer deaths among women in 3,108 contiguous United States (US) counties from years 2000 through 2015. We applied novel geospatial methods and identified hot spot counties based on breast cancer mortality rates. We assessed differences in county-level characteristics between hot spot and other counties using Wilcoxon rank-sum test and Spearman correlation, and stratified all analysis by race/ethnicity.RESULTS: Among all women, 80 of 3,108 (2.57%) contiguous US counties were deemed hot spots for breast cancer mortality with the majority located in the southern region of the US (72.50%, p value CONCLUSIONS: We observed geographic and racial/ethnic disparities in breast cancer mortality: NH-Black and Hispanic breast cancer deaths were more concentrated in southern, lower SES counties.
Authors: Moore, Justin Xavier JX; Royston, Kendra J KJ; Langston, Marvin E ME; Griffin, Russell R; Hidalgo, Bertha B; Wang, Henry E HE; Colditz, Graham G; Akinyemiju, Tomi T
Cancer causes & control : CCC. 2018 Aug ;29(8):737-750. Epub 2018-06-19.
Influence of smoking, body mass index and other factors on the preventive effect of nonsteroidal anti-inflammatory drugs on colorectal cancer risk
Nonsteroidal anti-inflammatory drugs (NSAIDs) use has consistently been associated with lower risk of colorectal cancer (CRC); however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the interaction between regular use of NSAIDs and other lifestyle and dietary factors on CRC risk among 11,894 cases and 15,999 controls. Fixed-effects meta-analyses were used for stratified analyses across studies for each risk factor and to summarize the estimates from interactions. Regular use of any NSAID, aspirin, or non-aspirin NSAIDs was significantly associated with a lower risk of CRC within almost all subgroups. However, smoking status and BMI were found to modify the NSAID-CRC association. Aspirin use was associated with a 29% lower CRC risk among never-smokers (OR = 0.71; 95% CI: 0.64, 0.79), compared to 19% and 17% lower CRC risk among smokers of pack-years below median (OR = 0.81; 95% CI: 0.71, 0.92) and above median (OR = 0.83; 95% CI: 0.74, 0.94), respectively (p-interaction = 0.048). The association between any NSAID use and CRC risk was also attenuated with increasing BMI (p-interaction = 0.075). Collectively, these results suggest that obese individuals and heavy smokers are unlikely to benefit as much as other groups from the prophylactic effect of aspirin against CRC.
Authors: Wang X; Caan B; White E; et al.
Cancer Res. 2018 Jun 19.
The p53-signaling pathway and colorectal cancer: Interactions between downstream p53 target genes and miRNAs
We examined expression of genes in the p53-signaling pathway. We determine if genes that have significantly different expression in carcinoma tissue compared to normal mucosa also have significantly differentially expressed miRNAs. We utilize a sample of 217 CRC cases. We focused on fold change (FC) > 1.50 or
Authors: Slattery ML; Mullany LE; Wolff RK; Sakoda LC; Samowitz WS; Herrick JS
Genomics. 2018 Jun 01.
Comparing Reported Dietary Supplement Intakes between Two 24-Hour Recall Methods: The Automated Self-Administered 24-Hour Dietary Assessment Tool and the Interview-Administered Automated Multiple Pass Method
The Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24) includes a highly standardized multipass web-based recall that, like the Automated Multiple Pass Method (AMPM), captures detailed information about dietary intake using multiple probes and reminders to enhance recall of intakes. The primary distinction between ASA24 and AMPM is that the ASA24 user interface guides participants, thus removing the need for interviewers. The objective of this study was to compare dietary supplement use reported on self-administered (ASA24-2011) vs interviewer-administered (AMPM) 24-hour recalls. The Food Reporting Comparison Study was an evaluation study designed to compare self-reported intakes captured using the self-administered ASA24 vs data collected via interviewer-administered AMPM recalls. Between 2010 and 2011, 1081 women and men were enrolled from three integrated health care systems that belong to the National Cancer Institute-funded Cancer Research Network: Security Health Plan Marshfield Clinic, Wisconsin; Henry Ford Health System, Michigan; and Kaiser Permanente Northern California, California. Quota sampling was used to ensure a balance of age, sex, and race/ethnicity. Participants were randomly assigned to four groups, and each group was asked to complete two dietary recalls: group 1, two ASA24s; group 2, two AMPMs; group 3, ASA24 first and AMPM second; and group 4, AMPM first and ASA24 second. Dietary supplements were coded using the 2007-2008 National Health and Nutrition Examination Survey Dietary Supplement Database. Analyses used the two one-sided tests, known as TOST, to assess equivalence of reported supplement use between methods. Complete 24-hour dietary recalls that included both dietary and supplement intake data were available for 1076 participants (507 men and 569 women). The proportions reporting supplement use via ASA24 and AMPM were 46% and 43%, respectively. These proportions were equivalent, with a small effect size of less than 20%. There were two exceptions in subgroup analyses: reported use among those 40 to 59 years of age and reported use by non-Hispanic black subjects were higher for ASA24 than AMPM. This study provides evidence that there is little difference in reported supplement use by mode of administration (ie, interview-administered vs self-administered recall).
Authors: Pannucci TE; Kushi LH; Subar AF; et al.
J Acad Nutr Diet. 2018 06;118(6):1080-1086.
Mendelian randomisation study of age at menarche and age at menopause and the risk of colorectal cancer
Substantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent. We used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index. Genetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results. Our study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk.
Authors: Neumeyer S; Caan BJ; Chang-Claude J; et al.
Br J Cancer. 2018 06;118(12):1639-1647. Epub 2018-05-24.
Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer
Sarcopenia (low muscle mass), poor muscle quality (low muscle radiodensity), and excess adiposity derived from computed tomography (CT) has been related to higher mortality in patients with metastatic breast cancer, but the association with prognosis in patients with nonmetastatic breast cancer is unknown. To evaluate associations of all 3 body composition measures, derived from clinically acquired CT at diagnosis, with overall mortality in nonmetastatic breast cancer. This observational study included 3241 women from Kaiser Permanente of Northern California and Dana Farber Cancer Institute diagnosed from January 2000 to December 2013 with stages II or III breast cancer. We calculated hazard ratios (HRs) to evaluate the associations of all-cause mortality with sarcopenia, low muscle radiodensity, and total adipose tissue (TAT). Models were adjusted for sociodemographics, tumor characteristics, treatment, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), and other body composition measures. We also evaluated the cross-classification of categories of sarcopenia (yes/no) and tertiles of TAT, with outcomes. Overall survival time and all-cause mortality. Median (range) age of 3241 women included in this study was 54 (18-80) years, and median follow-up was 6.0 years; 1086 patients (34%) presented with sarcopenia, and 1199 patients (37%) had low muscle radiodensity. Among patients with nonmetastatic breast cancer, those with sarcopenia showed higher overall mortality (HR, 1.41; 95% CI, 1.18-1.69) compared with those without sarcopenia. Patients in the highest tertile of TAT also showed higher overall mortality (HR, 1.35; 95% CI, 1.08-1.69) compared with those in the lowest tertile. Low radiodensity was not associated with survival. In analyses of sarcopenia and TAT, highest mortality was seen in patients with sarcopenia and high TAT (HR, 1.89; 95% CI, 1.30-2.73); BMI alone was not significantly related to overall mortality and did not appropriately identify patients at risk of death owing to their body composition. Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes.
Authors: Caan BJ; Cespedes Feliciano EM; Prado CM; Alexeeff S; Kroenke CH; Bradshaw P; Quesenberry CP; Weltzien EK; Castillo AL; Olobatuyi TA; Chen WY
JAMA Oncol. 2018 06 01;4(6):798-804.
Reparameterization of PAM50 expression identifies novel breast tumor dimensions and leads to discovery of a genomewide significant breast cancer locus at 12q15
Background: Breast tumor subtyping has failed to provide impact in susceptibility genetics. The PAM50 assay categorizes breast tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like. However, tumors are often more complex than simple categorization can describe. The identification of heritable tumor characteristics has potential to decrease heterogeneity and increase power for gene finding.Methods: We used 911 sporadic breast tumors with PAM50 expression data to derive tumor dimensions using principal components (PC). Dimensions in 238 tumors from high-risk pedigrees were compared with the sporadic tumors. Proof-of-concept gene mapping, informed by tumor dimension, was performed using Shared Genomic Segment (SGS) analysis.Results: Five dimensions (PC1-5) explained the majority of the PAM50 expression variance: three captured intrinsic subtype, two were novel (PC3, PC5). All five replicated in 745 TCGA tumors. Both novel dimensions were significantly enriched in the high-risk pedigrees (intrinsic subtypes were not). SGS gene-mapping in a pedigree identified a 0.5 Mb genome-wide significant region at 12q15 This region segregated through 32 meioses to 8 breast cancer cases with extreme PC3 tumors (P = 2.6 × 10-8).Conclusions: PC analysis of PAM50 gene expression revealed multiple independent, quantitative measures of tumor diversity. These tumor dimensions show evidence for heritability and potential as powerful traits for gene mapping.Impact: Our study suggests a new approach to describe tumor expression diversity, provides new avenues for germline studies, and proposes a new breast cancer locus. Similar reparameterization of expression patterns may inform other studies attempting to model the effects of tumor heterogeneity. Cancer Epidemiol Biomarkers Prev; 27(6); 644-52. ©2018 AACR.
Authors: Madsen MJ; Kushi LH; Caan BJ; Camp NJ; et al.
Cancer Epidemiol Biomarkers Prev. 2018 06;27(6):644-652. Epub 2018-04-12.
Social relationships, inflammation markers, and breast cancer incidence in the Women’s Health Initiative
Previous research has reported associations between social relationships and carcinogenesis. Inflammation is a potential mediator of these associations. To clarify these links for one tumor site, we examined associations between social relationships, circulating inflammation markers, and breast cancer incidence. Among 132,262 participants from the prospective Women’s Health Initiative, we used linear and logistic regression to evaluate associations between social relationship characteristics (social support, social strain, social network size) and inflammation markers of C-reactive protein (CRP) and white blood cell count (WBC). Cox regression was used to evaluate associations between inflammation markers and breast cancer incidence, as well as associations between social relationship characteristics and breast cancer incidence with and without adjustment for inflammation markers. Larger social networks were associated with lower continuous CRP (beta = -0.22, 95% CI -0.36, -0.08) and WBC (beta = -0.23, 95% CI -0.31, -0.16). Greater social strain was associated with higher continuous CRP (beta = 0.24, 95% CI 0.14, 0.33) and WBC (beta = 0.09, 95% CI 0.04, 0.14). When WBC was dichotomized at 10,000 cells/uL, high WBC was associated with greater hazards of in situ breast cancer (HR = 1.65, 95% CI 1.17, 2.33) but not invasive breast cancer. Social relationship characteristics were not associated with incidence of invasive or in situ breast cancer. Larger social networks were associated with lower inflammation and greater social strain was associated with higher inflammation. Higher inflammation might be associated with development of in situ breast cancer, but this appeared to be due to factors other than social relationships.
Authors: Busch EL; Whitsel EA; Kroenke CH; Yang YC
Breast. 2018 Jun;39:63-69. Epub 2018-03-31.
Determining Risk of Colorectal Cancer and Starting Age of Screening Based on Lifestyle, Environmental, and Genetic Factors
Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening. We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry. In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62-0.64) for men and 0.62 (95% confidence interval, 0.61-0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk. We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies.
Authors: Jeon J; Caan B; Colorectal Transdisciplinary Study and Genetics and Epidemiology of Colorectal Cancer Consortium; et al.
Gastroenterology. 2018 06;154(8):2152-2164.e19. Epub 2018-02-17.
The combined association of modifiable risk factors with breast cancer risk in the Women’s Health Initiative
Although several modifiable risk factors have been independently associated with risk of breast cancer, few studies have investigated their joint association with breast cancer risk. Using a healthy lifestyle index (HLI) score, we assessed the association of a combination of selected modifiable risk factors (diet, alcohol, physical activity, BMI, and smoking) with risk of invasive breast cancer in the Women’s Health Initiative (WHI). This study comprised 131,833 postmenopausal women, of whom 8,168 had breast cancer, who were enrolled in the WHI Observational Study or the WHI clinical trials. Cox proportional hazards regression was used to estimate the HRs and 95% confidence intervals (CI) for the association of the score with the risk of developing breast cancer overall and according to specific breast cancer clinicopathologic characteristics. There was a 4% reduction in the risk of breast cancer per unit increase in the HLI score. Compared with those with an HLI score in the lowest quintile level, those in the highest quintile level had 30%, 37%, and 30% lower risk for overall, ER+/PR+, and HER2+ breast cancer, respectively (HR = 0.70; 95% CI, 0.64-0.76; 0.63, 0.57-0.69; and 0.70; 0.55-0.90, respectively). We also observed inverse associations between the score and risk of breast cancer irrespective of nodal status, tumor grade, and stage of the disease. Most individual lifestyle factors were independently associated with the risk of breast cancer. Our findings support the view that promoting healthy lifestyle practices may be beneficial with respect to lowering risk of breast cancer among postmenopausal women. Cancer Prev Res; 11(6); 317-26. ©2018 AACRSee related editorial by Friedenreich and McTiernan, p. 313.
Authors: Arthur R; Wassertheil-Smoller S; Manson JE; Luo J; Snetselaar L; Hastert T; Caan B; Qi L; Rohan T
Cancer Prev Res (Phila). 2018 06;11(6):317-326. Epub 2018-02-26.
Cardiovascular disease incidence in adolescent and young adult cancer survivors: a retrospective cohort study
Few population-based studies have focused on cardiovascular disease (CVD) risk in adolescent and young adult (AYA; 15-39 years) cancer survivors and none have considered whether CVD risk differs by sociodemographic factors. Analyses focused on 79,176 AYA patients diagnosed with 14 first primary cancers in 1996-2012 and surviving > 2 years after diagnosis with follow-up through 2014. Data were obtained from the California Cancer Registry and State hospital discharge data. CVD included coronary artery disease, heart failure, and stroke. The cumulative incidence of developing CVD accounted for the competing risk of death. Multivariable Cox proportional hazards regression evaluated factors associated with CVD and the impact of CVD on mortality. Overall, 2249 (2.8%) patients developed CVD. Survivors of central nervous system cancer (7.3%), acute lymphoid leukemia (6.9%), acute myeloid leukemia (6.8%), and non-Hodgkin lymphoma (4.1%) had the highest 10-year CVD incidence. In multivariable models, African-Americans (hazard ratio (HR) = 1.55, 95% confidence interval (CI) = 1.33-1.81; versus non-Hispanic Whites), those with public/no health insurance (HR = 1.78, 95% CI = 1.61-1.96; versus private) and those who resided in lower socioeconomic status neighborhoods had a higher CVD risk. These sociodemographic differences in CVD incidence were apparent across most cancer sites. The risk of death was increased by eightfold or higher among AYAs who developed CVD. While cancer therapies are known to increase the risk of CVD, this study additionally shows that CVD risk varies by sociodemographic factors. The identification and mitigation of CVD risk factors in these subgroups may improve long-term patient outcomes.
Authors: Keegan THM; Kushi LH; Li Q; Brunson A; Chawla X; Chew HK; Malogolowkin M; Wun T
J Cancer Surviv. 2018 06;12(3):388-397. Epub 2018-02-09.
Optimism, Pessimism, Cynical Hostility, and Biomarkers of Metabolic Function in the Women’s Health Initiative
Psychological attitudes reflecting expectations about the future (optimism, pessimism) and people (cynical hostility) independently predict incident cardiovascular disease and possibly diabetes, but underlying biologic pathways are incompletely understood. Herein we examined the cross-sectional relationship between optimism, pessimism, and cynicism and biomarkers of metabolic function in the Women’s Health Initiative. Among 3443 postmenopausal women, biomarkers of metabolic function (fasting insulin [FINS] and glucose) were measured at baseline and used to calculate insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) and pancreatic β-cell activity (homeostasis model assessment of β-cell function [HOMA-B]). Psychological attitudes were assessed by the Life Orientation Test, Revised (full scale, and optimism and pessimism subscales) and the Cook-Medley cynicism subscale. Multivariable linear regression modeled the association of psychological attitudes with biomarker levels, adjusting for sociodemographics, health conditions, and health behaviors. Because obesity promotes insulin resistance and obese individuals tend to report higher levels of pessimism and cynical hostility, an interaction with body mass index (BMI) was explored. In fully adjusted models, only pessimism remained independently associated with higher FINS and insulin resistance (HOMA-IR). Scoring 1 point higher on the pessimism subscale was associated with a 1.2% higher FINS, whereas scoring 1 SD higher was associated with a 2.7% higher FINS (P = 0.03); results were similar for HOMA-IR. An interaction term with BMI was not significant. In multivariable models, higher dispositional pessimism was associated with worse metabolic function; these findings were not modified by obesity status. Results extend prior work by linking pessimism to an objective biomarker of insulin resistance in elderly women.
Authors: Tindle HA; Kroenke CH; Freiberg MS; et al.
J Diabetes. 2018 Jun;10(6):512-523. Epub 2017-09-29.
Sustained influence of infections on prostate-specific antigen concentration: An analysis of changes over 10 years of follow-up.
BACKGROUND: To extend our previous observation of a short-term rise in prostate-specific antigen (PSA) concentration, a marker of prostate inflammation and cell damage, during and immediately following sexually transmitted and systemic infections, we examined the longer-term influence of these infections, both individually and cumulatively, on PSA over a mean of 10 years of follow-up in young active duty U.S. servicemen.METHODS: We measured PSA in serum specimens collected in 1995-7 (baseline) and 2004-6 (follow-up) from 265 men diagnosed with chlamydia (CT), 72 with gonorrhea (GC), 37 with non-chlamydial, non-gonococcal urethritis (NCNGU), 58 with infectious mononucleosis (IM), 91 with other systemic or non-genitourinary infections such as varicella; and 125-258 men with no infectious disease diagnoses in their medical record during follow-up (controls). We examined the influence of these infections on PSA change between baseline and follow-up.RESULTS: The proportion of men with any increase in PSA (>0 ng/mL) over the 10-year average follow-up was significantly higher in men with histories of sexually transmitted infections (CT, GC, and NCNGU; 67.7% vs 60.8%, P = 0.043), systemic infections (66.7% vs 54.4%, P = 0.047), or any infections (all cases combined; 68.5% vs 54.4%, P = 0.003) in their military medical record compared to controls.CONCLUSIONS: While PSA has been previously shown to rise during acute infection, these findings demonstrate that PSA remains elevated over a longer period. Additionally, the overall infection burden, rather than solely genitourinary-specific infection burden, contributed to these long-term changes, possibly implying a role for the cumulative burden of infections in prostate cancer risk.
Authors: Langston, Marvin E ME; Pakpahan, Ratna R; Nevin, Remington L RL; De Marzo, Angelo M AM; Elliott, Debra J DJ; Gaydos, Charlotte A CA; Isaacs, William B WB; Nelson, William G WG; Sokoll, Lori J LJ; Zenilman, Jonathan M JM; Platz, Elizabeth A EA; Sutcliffe, Siobhan S
The Prostate. 2018 09 ;78(13):1024-1034. Epub 2018-05-30.
The deterioration of muscle mass and radiodensity is prognostic of poor survival in stage I-III colorectal cancer: a population-based cohort study (C-SCANS)
Muscle abnormalities such as low muscle mass and low muscle radiodensity are well known risk factors for unfavourable cancer prognosis. However, little is known in regard to the degree and impact of longitudinal changes in muscle mass and radiodensity within the context of cancer. Here, we explore the relationship between muscle wasting and mortality in a large population-based study of patients with non-metastatic colorectal cancer (CRC). A total of 1924 patients with stage I-III CRC who underwent surgical resection in the Kaiser Permanente Northern California Health System were included. Muscle mass and radiodensity were quantified using computed tomography images obtained at diagnosis and after approximately 14 months. Cox proportional-hazards models were used to estimate hazard ratios for all-cause mortality. The hazard ratio for all-cause mortality among patients with the largest deterioration in muscle mass (≥2 SD; ≥11.4% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 5.7%) was 2.15 [95% confidence interval (CI): 1.59-2.92; P
Authors: Brown JC; Caan BJ; Weltzien E; Cespedes Feliciano EM; Kroenke CH; Castillo A; Kwan ML; Prado CM; et al.
J Cachexia Sarcopenia Muscle. 2018 May 15.
Participation in medical activities beyond standard consultations by Swiss general practitioners: a cross-sectional study
Few data exist to support the observation that general practitioners (GPs) occupy many important positions in our communities or to characterize which GPs devote more of their time to such activities. We sought to characterize community-based complementary medical activities performed by GPs in the canton Vaud, Switzerland. All GPs in a region were invited to participate in a cross-sectional study (n = 600) examining engagement in complementary activities beyond standard ambulatory consultations. Categories included teaching, care giving in specific structures, roles as medical experts or company doctors, community care giving, and others completed by the GP. GPs were asked the number of hours devoted monthly to each activity and whether or not they are remunerated for this work. One hundred and sixty-eight GPs responded (28%), with 149 (92%) reporting that they were engaged in at least one activity beyond their in-office consultations, including 117 (72%) in community care-giving (ex: care for addictions or refugees). Altogether, GPs spend on average 5.8 h a week on these activities. One-hundred and twenty-three GPs (82%) were remunerated for at least one of their complementary engagements. Predictors of participation in a larger number of complementary activities were working in a rural area (IRR 1.29, 95% CI 1.05 to 1.57) and having a higher weekly workload (IRR 1.01 for each additional hour, 95% CI 1.01 to 1.02). The vast majority of GPs engage in activities beyond their standard clinic tasks and they are typically reimbursed. GPs in rural areas and those who work more hours per week are more likely to engage in complementary activities.
Authors: Jakob J; Cohidon C; Cornuz J; Selby K
BMC Fam Pract. 2018 May 03;19(1):52. Epub 2018-05-03.
A Mixed-Effects Model for Powerful Association Tests in Integrative Functional Genomics
Genome-wide association studies (GWASs) have successfully identified thousands of genetic variants for many complex diseases; however, these variants explain only a small fraction of the heritability. Recently, genetic association studies that leverage external transcriptome data have received much attention and shown promise for discovering novel variants. One such approach, PrediXcan, is to use predicted gene expression through genetic regulation. However, there are limitations in this approach. The predicted gene expression may be biased, resulting from regularized regression applied to moderately sample-sized reference studies. Further, some variants can individually influence disease risk through alternative functional mechanisms besides expression. Thus, testing only the association of predicted gene expression as proposed in PrediXcan will potentially lose power. To tackle these challenges, we consider a unified mixed effects model that formulates the association of intermediate phenotypes such as imputed gene expression through fixed effects, while allowing residual effects of individual variants to be random. We consider a set-based score testing framework, MiST (mixed effects score test), and propose two data-driven combination approaches to jointly test for the fixed and random effects. We establish the asymptotic distributions, which enable rapid calculation of p values for genome-wide analyses, and provide p values for fixed and random effects separately to enhance interpretability over GWASs. Extensive simulations demonstrate that our approaches are more powerful than existing ones. We apply our approach to a large-scale GWAS of colorectal cancer and identify two genes, POU5F1B and ATF1, which would have otherwise been missed by PrediXcan, after adjusting for all known loci.
Authors: Su YR; Caan B; Hsu L; et al.
Am J Hum Genet. 2018 05 03;102(5):904-919.
MicroRNA-messenger RNA interactions involving JAK-STAT signaling genes in colorectal cancer
JAK-STAT signaling influences many downstream processes that, unchecked, contribute to carcinogenesis and metastasis. MicroRNAs (miRNAs) are hypothesized as a mechanism to prevent uncontrolled growth from continuous JAK-STAT activation. We investigated differential expression between paired carcinoma and normal colorectal mucosa of messenger RNAs (mRNAs) and miRNAs using RNA-Seq and Agilent Human miRNA Microarray V19.0 data, respectively, using a negative binomial mixed effects model to test 122 JAK-STAT-signaling genes in 217 colorectal cancer (CRC) cases. Overall, 42 mRNAs were differentially expressed with a fold change of >1.50 or <0.67, remaining significant with a false discovery rate of < 0.05; four were dysregulated in microsatellite stable (MSS) tumors, eight were for microsatellite unstable (MSI)-specific tumors. Of these 54 mRNAs, 17 were associated with differential expression of 46 miRNAs, comprising 116 interactions: 16 were significant overall, one for MSS tumors only. Twenty of the 29 interactions with negative beta coefficients involved miRNA seed sequence matches with mRNAs, supporting miRNA-mediated mRNA repression; 17 of these mRNAs encode for receptor molecules. Receptor molecule degradation is an established JAK-STAT signaling control mechanism; our results suggest that miRNAs facilitate this process. Interactions involving positive beta coefficients may illustrate downstream effects of disrupted STAT activity, and subsequent miRNA upregulation.
Authors: Mullany LE; Herrick JS; Sakoda LC; Samowitz W; Stevens JR; Wolff RK; Slattery ML
Genes Cancer. 2018 May;9(5-6):232-246.
A Cohort Study of Metformin and Colorectal Cancer Risk among Patients with Diabetes Mellitus
Background: Several epidemiologic studies have reported strong inverse associations between metformin use and risk of colorectal cancer, although time-related biases, such as immortal time bias, may in part explain these findings. We reexamined this association using methods to minimize these biases.Methods: A cohort study was conducted among 47,351 members of Kaiser Permanente Northern California with diabetes and no history of cancer or metformin use. Follow-up for incident colorectal cancer occurred from January 1, 1997, until June 30, 2012. Cox regression was used to calculate HRs and 95% confidence intervals (CIs) for colorectal cancer risk associated with metformin use (ever use, total duration, recency of use, and cumulative dose).Results: No association was observed between ever use of metformin and colorectal cancer risk (HR, 0.90; 95% CI, 0.76-1.07) and there was no consistent pattern of decreasing risk with increasing total duration, dose, or recency of use. However, long-term use (≥5.0 years) appeared to be associated with reduced risk of colorectal cancer in the full population (HR, 0.78; 95% CI, 0.60-1.02), among current users (HR, 0.78; 95% CI, 0.59-1.04), and in men (HR, 0.65; 95% CI, 0.45-0.94) but not in women. Higher cumulative doses of metformin were associated with reduced risk. In initial users of sulfonylureas, switching to or adding metformin was also associated with decreased colorectal cancer risk.Conclusions: Our findings showed an inverse association between long-term use of metformin and colorectal cancer risk. Findings, especially the risk reduction among men, need to be confirmed in large, well-conducted studies.Impact: If our findings are confirmed, metformin may have a role in the chemoprevention of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 525-30. ©2018 AACRSee related commentary by Jackson and García-Albéniz, p. 520.
Authors: Bradley MC; Ferrara A; Achacoso N; Ehrlich SF; Quesenberry CP; Habel LA
Cancer Epidemiol Biomarkers Prev. 2018 05;27(5):525-530.
Timely follow-up of positive cancer screening results: A systematic review and recommendations from the PROSPR Consortium
Timely follow-up for positive cancer screening results remains suboptimal, and the evidence base to inform decisions on optimizing the timeliness of diagnostic testing is unclear. This systematic review evaluated published studies regarding time to follow-up after a positive screening for breast, cervical, colorectal, and lung cancers. The quality of available evidence was very low or low across cancers, with potential attenuated or reversed associations from confounding by indication in most studies. Overall, evidence suggested that the risk for poorer cancer outcomes rises with longer wait times that vary within and across cancer types, which supports performing diagnostic testing as soon as feasible after the positive result, but evidence for specific time targets is limited. Within these limitations, we provide our opinion on cancer-specific recommendations for times to follow-up and how existing guidelines relate to the current evidence. Thresholds set should consider patient worry, potential for loss to follow-up with prolonged wait times, and available resources. Research is needed to better guide the timeliness of diagnostic follow-up, including considerations for patient preferences and existing barriers, while addressing methodological weaknesses. Research is also needed to identify effective interventions for reducing wait times for diagnostic testing, particularly in underserved or low-resource settings. CA Cancer J Clin 2018;68:199-216. © 2018 American Cancer Society.
Authors: Doubeni CA; Corley DA; Armstrong K; et al.
CA Cancer J Clin. 2018 05;68(3):199-216. Epub 2018-03-30.
Patterns and predictors or repeat fecal immunochemical and occult blood test screening in four large health care systems in the United States
Effectiveness of fecal occult blood test (FOBT) for colorectal cancer (CRC) screening depends on annual testing, but little is known about patterns of repeat stool-based screening within different settings. Our study’s objective was to characterize screening patterns and identify factors associated with repeat screening among patients who completed an index guaiac FOBT (gFOBT) or fecal immunochemical test (FIT). We performed a multi-center retrospective cohort study among people who completed a FOBT between January 2010 and December 2011 to characterize repeat screening patterns over the subsequent 3 years. We studied at 4 large health care delivery systems in the United States. Logistic regression analyses were used to identify factors associated with repeat screening patterns. We included individuals aged 50-71 years who completed an index FOBT and had at least 3 years of follow-up. We excluded people with a history of CRC, colonoscopy within 10 years or flexible sigmoidoscopy within 5 years before the index test, or positive index stool test. Consistent screening was defined as repeat FOBT within every 15 months and inconsistent screening as repeat testing at least once during follow-up but less than consistent screening. Among 959,857 eligible patients who completed an index FIT or gFOBT, 344,103 had three years of follow-up and met inclusion criteria. Of these, 46.6% had consistent screening, 43.4% inconsistent screening, and 10% had no repeat screening during follow-up. Screening patterns varied substantially across healthcare systems, with consistent screening proportions ranging from 1 to 54.3% and no repeat screening proportions ranging from 6.9 to 42.8%. Higher consistent screening proportions were observed in health systems with screening outreach and in-reach programs, whereas the safety-net health system, which uses opportunistic clinic-based screening, had the lowest consistent screening. Consistent screening increased with older age but was less common among racial/ethnic minorities and patients with more comorbidities. Adherence with annual FOBT screening is highly variable across healthcare delivery systems. Settings with more organized screening programs performed better than those with opportunistic screening, but evidence-based interventions are needed to improve CRC screening adherence in all settings.
Authors: Singal AG; Corley DA; Halm EA; et al.
Am J Gastroenterol. 2018 05;113(5):746-754. Epub 2018-02-27.
LSD1 activates a lethal prostate cancer gene network independently of its demethylase function
Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1’s binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.
Authors: Sehrawat A; Van Den Eeden SK; Alumkal JJ; et al.
Proc Natl Acad Sci USA. 2018 05 01;115(18):E4179-E4188. Epub 2018-03-26.
Large-Scale Implementation of Structured Reporting of Adnexal Masses on Ultrasound
The aim of this article is to describe the development and implementation of structured reporting of adnexal mass findings on pelvic ultrasound in a large integrated health care delivery system. A structured reporting system that includes standardized terminology for describing adnexal masses on ultrasound was developed by a multidisciplinary team of radiologists, gynecologists, and gynecologic oncologists on the basis of literature review and internal data. The system uses a reporting template that requires radiologists to assign abnormal adnexal masses to one of five possible categories on the basis of standardized criteria: category 0, 1, 2, or 3 for masses <10 cm, to reflect increasing concern for malignancy, and category X for masses >10 cm. Unique predefined hashtags were linked to each category to enable electronic data extraction, and a hard stop feature was installed that prevents reports from being finalized without a category designation. In 2014, after a 3-month pilot study, large-scale implementation was supported by an educational campaign consisting of web-based conferences, e-mail announcements, and local presentations. Clinical management recommendations on the basis of category and other clinical factors were provided in a separate practice resource for clinicians. Analysis of adherence revealed that 93% of the approximately 12,000 reports describing abnormal adnexal masses in 2016 included category designations. Feedback from referring providers via an anonymous survey indicated high levels of satisfaction with reports. Multidisciplinary collaboration and leveraging of technology enabled large-scale implementation of structured reporting with high levels of adherence among radiologists and improved satisfaction among referring providers.
Authors: Suh-Burgmann EJ; Flanagan T; Lee N; Osinski T; Sweet C; Lynch M; Caponigro M; Mehta J; Alavi M; Herrinton LJ
J Am Coll Radiol. 2018 May;15(5):755-761. Epub 2018-03-20.
Lifestyle and nutritional modifiable factors in the prevention and treatment of bladder cancer
Bladder cancer is one of the top 5 most common cancers diagnosed in the U.S. It is also one of the most expensive cancers to treat through the life course given its high rate of recurrence. While cigarette smoking and occupational exposures have been firmly established as risk factors, it is less certain whether modifiable lifestyle factors such as diet and physical activity play roles in bladder cancer etiology and prognosis. This literature review based on a PubMed search summarizes the research to date on key dietary factors, types of physical activity, and smoking in relation to bladder cancer incidence, and discusses the potential public health implications for formalized smoking cessation programs among recently diagnosed patients. Overall, population-based research in bladder cancer is growing, and will be a key platform to inform patients diagnosed and living with bladder cancer, as well as their treating clinicians, how lifestyle changes can lead to the best outcomes possible.
Authors: Kwan ML; Garren B; Nielsen ME; Tang L
Urol Oncol. 2018 Apr 24.
An Empirical Dietary Inflammatory Pattern Score Is Associated with Circulating Inflammatory Biomarkers in a Multi-Ethnic Population of Postmenopausal Women in the United States
The empirical dietary inflammatory pattern (EDIP) score has been associated with concentrations of circulating inflammatory biomarkers in European Americans. We used the EDIP score, a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating concentrations of inflammatory biomarkers, to test the hypothesis that a pro-inflammatory dietary pattern is associated with inflammatory biomarker concentrations in a US multi-ethnic population. In this cross-sectional study, we calculated EDIP scores using baseline food frequency questionnaire data from 31,472 women, aged 50-79 y, in the Women’s Health Initiative observational study and clinical trials. Circulating biomarkers outcomes at baseline were: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, TNF receptor (TNFR) 1 and 2, and adiponectin. We used multivariable-adjusted linear regression analyses to estimate absolute concentrations and relative differences in biomarker concentrations, overall and in subgroups of race/ethnicity and BMI (body mass index) categories. Independent of energy intake, BMI, physical activity, and other potential confounding variables, higher EDIP scores were significantly associated with higher (lower for adiponectin) absolute concentrations of all 6 biomarkers. On the relative scale, the percentage of difference in the concentration of biomarkers, among women in the highest compared to the lowest EDIP quintile, was: CRP, +13% (P-trend
Authors: Tabung FK; Cespedes Feliciano EM; Rexrode KM; et al.
J Nutr. 2018 Apr 20.
The Plausibility of the Obesity Paradox in Cancer-Response-Reply to Point
Authors: Cespedes Feliciano EM; Kroenke CH; Caan BJ
Cancer Res. 2018 04 15;78(8):1904-1905.
The Importance of Body Composition in Explaining the Overweight Paradox in Cancer-Counterpoint
Despite a greater risk of cancer associated with higher BMI, overweight (BMI 25-<30 kg/m2) and class I obese (BMI 30-<35 kg/m2) patients often have a paradoxically lower risk of overall mortality after a cancer diagnosis, a phenomenon called the "obesity paradox." Only when patients exceed a BMI ≥35 kg/m2 are elevations in mortality risk consistently noted. This paradox has been dismissed as the result of methodologic bias, which we will describe and debate here. However, even if such bias influences associations, there is growing evidence that body composition may in part explain the paradox. This phenomenon may more accurately be described as a BMI paradox. That is, BMI is a poor proxy for adiposity and does not distinguish muscle from adipose tissue, nor describe adipose tissue distribution. Low muscle mass is associated with higher risk of recurrence, overall and cancer-specific mortality, surgical complications, and treatment-related toxicities. Patients with who are overweight or obese have on average higher levels of muscle than their normal-weight counterparts. Also, there is some evidence that patients with moderate levels of subcutaneous adipose tissue may have lower mortality. More research utilizing body composition is needed to clarify the effects of adiposity on cancer mortality. Cancer Res; 78(8); 1906-12. ©2018 AACR.
Authors: Caan BJ; Cespedes Feliciano EM; Kroenke CH
Cancer Res. 2018 04 15;78(8):1906-1912.
Cardiometabolic risk factors and survival after breast cancer in the Women’s Health Initiative
Few studies have examined the relationship between cardiometabolic risk factors linked to metabolic syndrome and mortality among women with breast cancer. We used the Women’s Health Initiative to evaluate the relationship between cardiometabolic risk factors, including waist circumference (WC), blood pressure, cholesterol level, and presence of type 2 diabetes, and their relation with death from breast cancer, cardiovascular disease (CVD), and other causes among 8641 women with local or regional stage invasive breast cancer. Cox proportional hazards models were used to estimate hazard ratios, and 95% confidence intervals, adjusted for important predictors of survival. After a median of 11.3 years, there were 2181 total deaths, 619 (28.4%) of which were due to breast cancer. Most participants (55.7%) had at least 2 cardiometabolic risk factors, and 4.9% had 3 or 4. Having a larger number of risk factors was associated with higher risk of CVD and other-cause mortality (P trend < .001 for both), but not with breast cancer mortality (P trend = .86). Increased WC was associated with a higher risk of CVD (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.05-1.57) and other-cause mortality (HR, 1.32; 95% CI, 1.16-1.49) and only with a small and nonsignificant higher risk of breast cancer mortality (HR, 1.19; 95% CI, 0.93-1.52). The results did not differ in analyses stratified by race, hormone receptor status, or after an analysis of cases diagnosed within 5 years after baseline. Among women with early stage breast cancer, cardiometabolic risk factors are significantly associated with cardiovascular and other-cause mortality, but not breast cancer mortality. Cancer 2018;124:1798-807. © 2018 American Cancer Society.
Authors: Simon MS; Cespedes Feliciano EM; Caan B; et al.
Cancer. 2018 04 15;124(8):1798-1807. Epub 2018-01-16.
Yield of Colonoscopy After a Positive Result From a Fecal Immunochemical Test OC-Light.
BACKGROUND & AIMS: The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening. The OC-Light FIT is 1 of 2 FITs recommended for CRC screening by the Preventive Services Task Force guidelines. However, little is known about its ability to detect CRC in large average-risk populations.METHODS: We performed a retrospective cohort study of patients (50-75 years old) in the San Francisco Health Network who were screened for CRC by OC-Light FIT from August 2010 through June 2015. Patients with a positive result were referred for colonoscopy. We used electronic health records to identify participants with positive FIT results, and collected results from subsequent colonoscopies and pathology analyses. The FIT positive rate was calculated by dividing the number of positive FIT results by the total number of FIT tests completed. The primary outcome was the positive rate from OC-Light FIT and yield of neoplasms at colonoscopy. Secondary outcomes were findings from first vs subsequent rounds of testing, and how these varied by sex and race.RESULTS: We collected result from 35,318 FITs, performed on 20,886 patients; 2930 patients (8.3%) had a positive result, and 1558 patients completed the follow-up colonoscopy. A positive result from the FIT identified patients with CRC with a positive predictive value of 3.0%, and patients with advanced adenoma with a positive predictive value of 20.8%. The FIT positive rate was higher during the first round of testing (9.4%) compared to subsequent rounds (7.4%) (P < .01). The yield of CRC in patients with a positive result from the first round of the FIT was 3.7%, and decreased to 1.8% for subsequent rounds (P = .02).CONCLUSIONS: In a retrospective analysis of patients in a diverse safety-net population who underwent OC-Light FIT for CRC screening, we found that approximately 3% of patients with a positive result from a FIT to have CRC and approximately 21% to have advanced adenoma.
Authors: Alsayid, Muhammad M; Singh, Maneesh H MH; Issaka, Rachel R; Laleau, Victoria V; Day, Lukejohn L; Lee, Jeffrey J; Allison, James J; Somsouk, Ma M
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018 Oct ;16(10):1593-1597.e1. Epub 2018-04-13.
Learning to De-Adopt Ineffective Healthcare Practices
Authors: Selby K; Barnes GD
Am J Med. 2018 Apr 09.
Dysregulated genes and miRNAs in the apoptosis pathway in colorectal cancer patients
Apoptosis is genetically regulated and involves intrinsic and extrinsic pathways. We examined 133 genes within these pathways to identify whether they are expressed differently in colorectal carcinoma (CRC) and normal tissue (N = 217) and if they are associated with similar differential miRNA expression. Gene expression data (RNA-Seq) and miRNA expression data (Agilent Human miRNA Microarray V19.0) were generated. We focused on dysregulated genes with a fold change (FC) of > 1.50 or < 0.67, that were significant after adjustment for multiple comparisons. miRNA:mRNA seed-region matches were determined. Twenty-three genes were significantly downregulated (FC < 0.67) and 18 were significantly upregulated (FC > 1.50). Of these 41 genes, 11 were significantly associated with miRNA differential expression. BIRC5 had the greatest number of miRNA associations (14) and the most miRNAs with a seed-region match (10). Four of these matches, miR-145-5p, miR-150-5p, miR-195-5p, and miR-650, had a negative beta coefficient. CSF2RB was associated with ten total miRNAs (five with a seed-region match, and one miRNA, miR-92a-3p, with a negative beta coefficient). Of the three miRNAs associated with CTSS, miR-20b-5p, and miR-501-3p, had a seed-region match and a negative beta coefficient between miRNA:mRNA pairs. Several miRNAs that were associated with dysregulated gene expression, seed-region matches, and negative beta coefficients also were associated with CRC-specific survival. Our data suggest that miRNAs could influence several apoptosis-related genes. BIRC5, CTSS, and CSF2R all had seed-region matches with miRNAs that would favor apoptosis. Our study identifies several miRNA associated with apoptosis-related genes, that if validated, could be important therapeutic targets.
Authors: Slattery ML; Mullany LE; Sakoda LC; Wolff RK; Samowitz WS; Herrick JS
Apoptosis. 2018 04;23(3-4):237-250.
Girls’ Sleep Trajectories Across the Pubertal Transition: Emerging Racial/Ethnic Differences
This study aims to examine the longitudinal association between puberty and sleep in a diverse sample of girls and explore racial/ethnic differences in this association. Using latent growth curve modeling, the present study measured pubertal development (timing and rate) and sleep (wake time and bedtime) in 1,239 socioeconomically and ethnically diverse girls starting when they were 6-8 years old and followed longitudinally for up to 8 years. Pubertal assessment was conducted annually in clinic by physical examination, classified by sexual maturation stage for breast and pubic hair development by trained raters. In line with previous research, black girls had the earliest pubertal development, followed by Hispanic, white, and Asian girls. Black girls, on average, reported significantly shorter sleep duration than Hispanic (β = -.20, p < .001), Asian (β = -.29, p = .002), and white (β = -.35, p < .001) girls. In a series of dual-process models, we found that early pubertal timing predicted shorter sleep duration for early-maturing black girls (breast development: β = .13, p = .005; pubic hair development: β = .14, p = .012). There was no evidence of any association between pubertal rate and sleep. All models controlled for family socioeconomic status and body mass index. Sleep is essential for many aspects of youth development, including emotional, cognitive, and physical functioning. Developmental changes associated with puberty may put some early maturing girls at risk of shorter sleep duration in adolescence and exacerbate racial/ethnic disparities in health and well-being.
Authors: Hoyt LT; Kushi LH; Hiatt RA; et al.
J Adolesc Health. 2018 04;62(4):496-503.
Changes in bone mineral density in women with breast cancer receiving aromatase inhibitor therapy
We assessed bone mineral density (BMD) change with aromatase inhibitor (AI) treatment in a contemporary cohort of women with breast cancer treated in Kaiser Permanente Northern California. Percent and estimated annual percent changes in BMD at the total hip and lumbar spine were examined in 676 women receiving AI therapy who had two serial BMD reports available (at least 1 year apart) before and after AI initiation (N = 317) or during continued AI therapy (N = 359). BMD changes were examined at the total hip and lumbar spine and compared by age and clinical subgroups. Women experienced BMD declines after AI initiation or continued therapy, with median annual percent change – 1.2% (interquartile range, IQR – 2.4 to – 0.1%) at the hip and – 1.0% (IQR – 2.3 to 0.1%) at the spine after AI initiation, and – 1.1% (IQR – 2.4 to 0.1%) at the hip and – 0.9% (IQR – 2.4 to 0.5%) at the spine during continued therapy. Higher levels of bone loss were observed among younger (< 55 years) compared with older (≥ 75 years) women at the hip (- 1.6% vs. - 0.8%) and at the spine (- 1.5% vs. - 0.5%) after AI initiation, and at the hip (- 1.4% vs. - 1.2%) and at the spine (- 2.4% vs. - 0.001%) during continued therapy. Small but consistent declines in total hip and lumbar spine BMD were present in breast cancer patients following AI therapy initiation or continued AI therapy. Although the overall rates of osteoporosis were low, greater estimated levels of annual bone loss were evident among women < 55 years.
Authors: Kwan ML; Yao S; Laurent CA; Roh JM; Quesenberry CP; Kushi LH; Lo JC
Breast Cancer Res Treat. 2018 Apr;168(2):523-530. Epub 2017-12-16.
Association between post-cancer diagnosis dietary inflammatory potential and mortality among invasive breast cancer survivors in the Women’s Health Initiative
Background: Inflammation is important in chronic disease and can be modulated by dietary exposures. Our aim was to examine whether the inflammatory potential of diet after cancer diagnosis, assessed using the dietary inflammatory index (DII), is associated with all-cause and cause-specific mortality among women diagnosed with invasive breast cancer in the Women’s Health Initiative (WHI).Methods: Our analytic cohort included 2,150 postmenopausal women, ages 50 to 79 years at baseline, who developed invasive breast cancer during follow-up and completed a food frequency questionnaire (FFQ) on average 1.5 years after diagnosis. Women were followed from breast cancer diagnosis until death or the end of follow-up by October 2014. Energy-adjusted DII (E-DII) scores were calculated from food plus supplements using a nutrient-density approach. Cox proportional hazards models were fit to estimate multivariable-adjusted HRs and 95% confidence intervals (CIs) for all-cause, breast cancer-specific, and cardiovascular disease (CVD) mortality.Results: After a median 13.3 years of follow-up, 580 deaths from any cause occurred, including 212 breast cancer deaths and 103 CVD deaths. Lower (i.e., more anti-inflammatory) E-DII scores were associated with a lower risk of CVD mortality (HRQ1VSQ4 = 0.44; 95% CI, 0.24-0.82; Ptrend = 0.005), but not with breast cancer-specific mortality (HRQ1VSQ4 = 0.96; 95% CI, 0.62-1.49; Ptrend = 0.96) or all-cause mortality (HRQ1VSQ4 = 0.82; 95% CI, 0.63-1.05; Ptrend = 0.17).Conclusions: Consuming a more anti-inflammatory diet after breast cancer diagnosis may be a means for reducing risk of death from CVD.Impact: Survival after invasive breast cancer diagnosis may be improved by consumption of an anti-inflammatory diet. Cancer Epidemiol Biomarkers Prev; 27(4); 454-63. ©2018 AACR.
Authors: Zheng J; Tabung FK; Zhang J; Liese AD; Shivappa N; Ockene JK; Caan B; Kroenke CH; Hébert JR; Steck SE
Cancer Epidemiol Biomarkers Prev. 2018 04;27(4):454-463. Epub 2018-01-22.
The relationship between non-steroidal anti-inflammatory drug use and age-related macular degeneration
To describe the relationship between the incidence of age-related macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use. Prospective cohort study. This study consisted of participants in the California Men’s Health Study. Those who completed surveys in 2002-2003 and 2006 were included. Men who self-reported use of aspirin, ibuprofen, naproxen, valdecoxib, celecoxib, and/or rofecoxib at least 3 days per week were considered NSAID users. Patients were categorized as non-users, former users, new users, or longer-term users based on survey responses. NSAID use was also categorized by type: any NSAIDs, aspirin, and/or non-aspirin NSAIDs. Age, race/ethnicity, smoking status, education, income, alcohol use, and Charlson comorbidity index score were included in the multivariate analysis as risk factors for AMD. A total of 51 371 men were included. Average follow-up time was 7.4 years. There were 292 (0.6%) and 1536 (3%) cases of exudative and nonexudative AMD, respectively. Longer-term use of any NSAID was associated with lower risk of exudative AMD (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.96, P = .029). New users of any NSAIDs (HR = 0.79, 95% CI 0.68-0.93, P = .0039) and aspirin (HR = 0.82, 95% CI 0.70-0.97, P = .018) had a lower risk of nonexudative AMD, although this trend did not persist in longer-term users. The relationship between exudative or nonexudative AMD and the remaining categories of NSAID use were not significant. The overall impact of NSAIDs on AMD incidence is small; however, the lower risk of exudative AMD in longer-term NSAID users may point to a protective effect and deserves further study as a possible mechanism to modulate disease risk.
Authors: Modjtahedi BS; Fong DS; Jorgenson E; Van Den Eeden SK; Quinn V; Slezak JM
Am J Ophthalmol. 2018 04;188:111-122. Epub 2018-01-31.
A Pilot Mobile-based Mindfulness Intervention for Cancer Patients and their Informal Caregivers
Authors: Kubo A; Altschuler A; Kurtovich E; Hendlish S; Laurent CA; Kolevska T; Li Y; Avins A
Mindfulness (N Y). 2018 Dec;9(6):1885-1894. Epub 2018-03-24.
Development and validation of the SIMPLE endoscopic classification of diminutive and small colorectal polyps.
BACKGROUND: Prediction of histology of small polyps facilitates colonoscopic treatment. The aims of this study were: 1) to develop a simplified polyp classification, 2) to evaluate its performance in predicting polyp histology, and 3) to evaluate the reproducibility of the classification by trainees using multiplatform endoscopic systems.METHODS: In phase 1, a new simplified endoscopic classification for polyps - Simplified Identification Method for Polyp Labeling during Endoscopy (SIMPLE) - was created, using the new I-SCAN OE system (Pentax, Tokyo, Japan), by eight international experts. In phase 2, the accuracy, level of confidence, and interobserver agreement to predict polyp histology before and after training, and univariable/multivariable analysis of the endoscopic features, were performed. In phase 3, the reproducibility of SIMPLE by trainees using different endoscopy platforms was evaluated.RESULTS: Using the SIMPLE classification, the accuracy of experts in predicting polyps was 83 % (95 % confidence interval [CI] 77 % - 88 %) before and 94 % (95 %CI 89 % - 97 %) after training (P = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value after training were 97 %, 88 %, 95 %, and 91 %. The interobserver agreement of polyp diagnosis improved from 0.46 (95 %CI 0.30 - 0.64) before to 0.66 (95 %CI 0.48 - 0.82) after training. The trainees demonstrated that the SIMPLE classification is applicable across endoscopy platforms, with similar post-training accuracies for narrow-band imaging NBI classification (0.69; 95 %CI 0.64 - 0.73) and SIMPLE (0.71; 95 %CI 0.67 - 0.75).CONCLUSIONS: Using the I-SCAN OE system, the new SIMPLE classification demonstrated a high degree of accuracy for adenoma diagnosis, meeting the ASGE PIVI recommendations. We demonstrated that SIMPLE may be used with either I-SCAN OE or NBI.
Authors: Iacucci, Marietta M; Trovato, Cristina C; Daperno, Marco M; Akinola, Oluseyi O; Greenwald, David D; Gross, Seth A SA; Hoffman, Arthur A; Lee, Jeffrey J; Lethebe, Brendan C BC; Lowerison, Mark M; Nayor, Jennifer J; Neumann, Helmut H; Rath, Timo T; Sanduleanu, Silvia S; Sharma, Prateek P; Kiesslich, Ralf R; Ghosh, Subrata S; Saltzman, John R JR;
Endoscopy. 2018 Aug ;50(8):779-789. Epub 2018-03-23.
Predictors of Follow-Up Visits Post Radical Prostatectomy.
Long-term follow-up care among prostate cancer patients is important as biochemical recurrence can occur many years after diagnosis, with 20%-30% of men experiencing biochemical recurrence within 10 years of treatment. This study examined predictors of follow-up care among 1,158 radical prostatectomy patients, treated at the Washington University in St. Louis, within 6 months, 1 year, and 2 years post surgery. Predictors examined included age at surgery, race (Black vs. White), rural/urban status, education, marital status, and prostate cancer aggressiveness. Multivariable logistic regression was used to assess the association between the predictors and follow-up visits with a urologist in 6 months, the 1st year, and the 2nd year post surgery. In a secondary analysis, any follow-up visit with a prostate-specific antigen (PSA) test was included, regardless of provider type. Men that were Black ( 6 months OR: 0.60; 95% CI [0.36, 0.99], 1 year OR: 0.34; 95% CI [0.20, 0.59], 2 year OR: 0.41; 95% CI [0.25, 0.68]), resided in a rural residence ( 1 year OR: 0.61; 95% CI [0.44, 0.85], 2 year OR: 0.41; 95% CI [0.25, 0.68]), or were unmarried ( 2 year OR: 0.69; 95% CI [0.49, 0.97]) had a reduced odds of follow-up visits with a urologist. In models where any follow-up visit with a PSA test was examined, race remained a significant predictor of follow-up. The results indicate that Black men, men residing in a rural residence, and unmarried men may not receive adequate long-term follow-up care following radical prostatectomy. These men represent a high-risk group that could benefit from increased support post treatment.
Authors: Khan, Saira S; Hicks, Veronica V; Rancilio, Danielle D; Langston, Marvin M; Richardson, Katina K; Drake, Bettina F BF
American journal of men's health. 2018 07 ;12(4):760-765. Epub 2018-03-14.
Quality of life among men with low-risk prostate cancer during the first year following diagnosis: the PREPARE prospective cohort study
As many as 40% of men diagnosed with prostate cancer have low-risk disease, which results in the need to decide whether to undergo active treatment (AT) or active surveillance (AS). The treatment decision can have a significant effect on general and prostate-specific quality of life (QOL). The purpose of this study was to assess the QOL among men with low-risk prostate cancer during the first year following diagnosis. In a prospective cohort study, we conducted pretreatment telephone interviews (N = 1,139; 69.3% response rate) with low-risk PCa patients (PSA ≤ 10, Gleason ≤ 6) and a follow-up assessment 6-10 months postdiagnosis (N = 1057; 93%). We assessed general depression, anxiety, and physical functioning, prostate-specific anxiety, and prostate-specific QOL at both interviews. Clinical variables were obtained from the medical record. Men were 61.7 (SD = 7.2) years old, 82% white, 39% had undergone AT (surgery or radiation), and 61.0% had begun AS. Linear regression analyses revealed that at follow-up, the AS group reported significantly better sexual, bowel, urinary, and general physical function (compared to AT), and no difference in depression. However, the AS group did report greater general anxiety and prostate-specific anxiety at follow-up, compared to AT. Among men with low-risk PCa, adjusting for pretreatment functioning, the AS group reported better prostate-related QOL, but were worse off on general and prostate-specific anxiety compared to men on AT. These results suggest that, within the first year postdiagnosis, men who did not undergo AT may require additional support in order to remain comfortable with this decision and to continue with AS when it is clinically indicated.
Authors: Taylor KL; Luta G; Hoffman RM; Davis KM; Lobo T; Zhou Y; Leimpeter A; Shan J; Jensen RE; Aaronson DS; Van Den Eeden SK
Transl Behav Med. 2018 03 01;8(2):156-165.
Development, Validation, and Dissemination of a Breast Cancer Recurrence Detection and Timing Informatics Algorithm
This study developed, validated, and disseminated a generalizable informatics algorithm for detecting breast cancer recurrence and timing using a gold standard measure of recurrence coupled with data derived from a readily available common data model that pools health insurance claims and electronic health records data. The algorithm has two parts: to detect the presence of recurrence and to estimate the timing of recurrence. The primary data source was the Cancer Research Network Virtual Data Warehouse (VDW). Sixteen potential indicators of recurrence were considered for model development. The final recurrence detection and timing models were determined, respectively, by maximizing the area under the ROC curve (AUROC) and minimizing average absolute error. Detection and timing algorithms were validated using VDW data in comparison with a gold standard recurrence capture from a third site in which recurrences were validated through chart review. Performance of this algorithm, stratified by stage at diagnosis, was compared with other published algorithms. All statistical tests were two-sided. Detection model AUROCs were 0.939 (95% confidence interval [CI] = 0.917 to 0.955) in the training data set (n = 3370) and 0.956 (95% CI = 0.944 to 0.971) and 0.900 (95% CI = 0.872 to 0.928), respectively, in the two validation data sets (n = 3370 and 3961, respectively). Timing models yielded average absolute prediction errors of 12.6% (95% CI = 10.5% to 14.5%) in the training data and 11.7% (95% CI = 9.9% to 13.5%) and 10.8% (95% CI = 9.6% to 12.2%) in the validation data sets, respectively, and were statistically significantly lower by 12.6% (95% CI = 8.8% to 16.5%, P < .001) than those estimated using previously reported timing algorithms. Similar covariates were included in both detection and timing algorithms but differed substantially from previous studies. Valid and reliable detection of recurrence using data derived from electronic medical records and insurance claims is feasible. These tools will enable extensive, novel research on quality, effectiveness, and outcomes for breast cancer patients and those who develop recurrence.
Authors: Ritzwoller DP; Hassett MJ; Uno H; Cronin AM; Carroll NM; Hornbrook MC; Kushi LC
J Natl Cancer Inst. 2018 03 01;110(3):273-281.
Feasibility of analyzing DNA copy number variation in breast cancer tumor specimens from 1950 to 2010: how old is too old?
The purpose of the study was to assess the feasibility of quantifying long-term trends in breast tumor DNA copy number variation (CNV) profiles. We evaluated CNV profiles in formalin-fixed paraffin-embedded (FFPE) tumor specimens from 30 randomly selected Kaiser Permanente Northern California health plan women members diagnosed with breast cancer from 1950 to 2010. Assays were conducted for five cases per decade who had available tumor blocks and pathology reports. As compared to the tumors from the 1970s to 2000s, the older tumors dating back to the 1950s and 1960s were much more likely to (1) fail quality control, and (2) have fewer CNV events (average 23 and 31 vs. 58 to 69), fewer CNV genes (average 5.1 and 3.7k vs. 8.1 to 10.3k), shorter CNV length (average 2,440 and 3,300k vs. 5,740 to 9,280k), fewer high frequency Del genes (37 and 25% vs. 54 to 76%), and fewer high frequency high_Amp genes (20% vs. 56 to 73%). On average, assay interpretation took an extra 60 min/specimen for cases from the 1960s versus 20 min/specimen for the most recent tumors. Assays conducted in the mid-2010s for CNVs may be feasible for FFPE tumor specimens dating back to the 1980s, but less feasible for older specimens.
Authors: Krieger N; Nabavi S; Waterman PD; Achacoso NS; Acton L; Schnitt SJ; Habel LA
Cancer Causes Control. 2018 03;29(3):305-314. Epub 2018-02-09.
Research Strategies for Nutritional and Physical Activity Epidemiology and Cancer Prevention
Very large international and ethnic differences in cancer rates exist, are minimally explained by genetic factors, and show the huge potential for cancer prevention. A substantial portion of the differences in cancer rates can be explained by modifiable factors, and many important relationships have been documented between diet, physical activity, and obesity, and incidence of important cancers. Other related factors, such as the microbiome and the metabolome, are emerging as important intermediary components in cancer prevention. It is possible with the incorporation of newer technologies and studies including long follow-up and evaluation of effects across the life cycle, additional convincing results will be produced. However, several challenges exist for cancer researchers; for example, measurement of diet and physical activity, and lack of standardization of samples for microbiome collection, and validation of metabolomic studies. The United States National Cancer Institute convened the Research Strategies for Nutritional and Physical Activity Epidemiology and Cancer Prevention Workshop on June 28-29, 2016, in Rockville, Maryland, during which the experts addressed the state of the science and areas of emphasis. This current paper reflects the state of the science and priorities for future research. Cancer Epidemiol Biomarkers Prev; 27(3); 233-44. ©2017 AACR.
Authors: Mahabir S; Kushi LH; Prentice RL; et al.
Cancer Epidemiol Biomarkers Prev. 2018 03;27(3):233-244. Epub 2017-12-18.
Diagnosis of sessile serrated adenoma after educational training in a large, community-based, integrated healthcare setting
Sessile serrated adenomas (SSAs) are precursors of 15% to 30% of colorectal cancers but are frequently underdiagnosed. We sought to measure the SSA detection rate (SDR) and predictors of SSA detection after educational training for community gastroenterologists and pathologists. Colonoscopy and pathology data (2010-2014) from 3 medical centers at Kaiser Permanente Northern California were accessed electronically. Gastroenterologists and pathologists attended a training session on SSA diagnosis in 2012. Mean SDRs and patient-level predictors of SSA detection post-training (2013-2014) were investigated. Mean SDRs increased from .6% in 2010-2012 to 3.7% in 2013-2014. The increase in the detection of proximal SSAs was accompanied by a decrease in the detection of proximal hyperplastic polyps (HPs). Among 34,161 colonoscopies performed in 2013 to 2014, SDRs for screening, fecal immunochemical test positivity, surveillance, and diagnostic indication were 4.2%, 4.5%, 4.9%, and 3.0%, respectively. SSA detection was lower among Asians (adjusted odds ratio [aOR], .46; 95% confidence interval [CI], .31-.69) and Hispanics (aOR, .59; 95% CI, .36-.95) compared with non-Hispanic whites and higher among patients with synchronous conventional adenoma (aOR, 1.46; 95% CI, 1.15-1.86), HP (aOR, 1.74; 95% CI, 1.30-2.34), and current smokers (aOR, 1.78; 95% CI, 1.17-2.72). SDRs varied widely among experienced gastroenterologists, even after training (1.1%-8.1%). There was a moderately strong correlation between adenoma detection rate (ADR) and SDR for any SSA (r = .64, P = .0003) and for right-sided SSAs (r = .71, P < .0001). Educational training significantly increased the detection of SSA, but a wide variation in SDR remained across gastroenterologists. SSA detection was inversely associated with Asian and Hispanic race/ethnicity and positively associated with the presence of conventional adenoma, HP, and current smoking. There was a moderately strong correlation between ADR and SDR.
Authors: Li D; Corley DA; Levin TR; et al.
Gastrointest Endosc. 2018 Mar;87(3):755-765.e1. Epub 2017-08-24.
Visceral adiposity and cancer survival: a review of imaging studies
Although obesity is a well-known risk factor for cancer, the association between obesity and cancer survival remains controversial. This is partially due to the inability of conventional obesity measures to directly assess adiposity or adipose tissue distribution. As a metabolic organ, visceral adipose tissue (VAT) secrets a variety of cytokines and cytokine-like factors, potentially affecting cancer survival. The objective of this review was to investigate the influence of imaging-assessed VAT on cancer survival. A total of 22 studies assessing the impact of visceral adiposity on survival were included. Negative associations between VAT and survival were more frequently observed among patients with colorectal (four of six studies) and pancreatic (three of five studies) cancers, compared to higher VAT predicting longer survival in most studies of renal cell carcinoma patients (four of five studies). Methodological limitations, including unstandardised VAT measurement methods, lack of other body composition measurement (i.e. muscle mass), small sample size and heterogeneous cohort characteristics, may explain controversial findings related to the impact of VAT on cancer survival.
Authors: Xiao J; Mazurak VC; Olobatuyi TA; Caan BJ; Prado CM
Eur J Cancer Care (Engl). 2018 Mar;27(2):e12611. Epub 2016-12-06.
Cancer incidence and mortality risks in a large US Barrett’s oesophagus cohort
Barrett’s oesophagus (BE) increases the risk of oesophageal adenocarcinoma by 10-55 times that of the general population, but no community-based cancer-specific incidence and cause-specific mortality risk estimates exist for large cohorts in the USA. Within Kaiser Permanente Northern California (KPNC), we identified patients with BE diagnosed during 1995-2012. KPNC cancer registry and mortality files were used to estimate standardised incidence ratios (SIR), standardised mortality ratios (SMR) and excess absolute risks. There were 8929 patients with BE providing 50 147 person-years of follow-up. Compared with the greater KPNC population, patients with BE had increased risks of any cancer (SIR=1.40, 95% CI 1.31 to 1.49), which slightly decreased after excluding oesophageal cancer. Oesophageal adenocarcinoma risk was increased 24 times, which translated into an excess absolute risk of 24 cases per 10 000 person-years. Although oesophageal adenocarcinoma risk decreased with time since BE diagnosis, oesophageal cancer mortality did not, indicating that the true risk is stable and persistent with time. Relative risks of cardia and stomach cancers were increased, but excess absolute risks were modest. Risks of colorectal, lung and prostate cancers were unaltered. All-cause mortality was slightly increased after excluding oesophageal cancer (SMR=1.24, 95% CI 1.18 to 1.31), but time-stratified analyses indicated that this was likely attributable to diagnostic bias. Cause-specific SMRs were elevated for ischaemic heart disease (SMR=1.39, 95% CI 1.18 to 1.63), respiratory system diseases (SMR=1.51, 95% CI 1.29 to 1.75) and digestive system diseases (SMR=2.20 95% CI 1.75 to 2.75). Patients with BE had a persistent excess risk of oesophageal adenocarcinoma over time, although their absolute excess risks for this cancer, any cancer and overall mortality were modest.
Authors: Cook MB; Coburn SB; Lam JR; Taylor PR; Schneider JL; Corley DA
Gut. 2018 03;67(3):418-529. Epub 2017-01-04.
Do not leave FIT positives alone!
Authors: Zorzi M; Hassan C; Selby K; Rugge M
Am J Gastroenterol. 2018 Feb 23.
Personalized cancer screening: helping primary care rise to the challenge
With their longitudinal patient relationships, primary care physicians and their care teams are uniquely situated to promote preventive medicine, including cancer screening. A confluence of forces is driving the demand for the personalization of cancer screening recommendations. Recommendations are increasingly based on individual patient preferences, medical history, genetic and environmental risk factors, and level of interaction with the healthcare system. Current examples include choices between colonoscopy, fecal testing, and emerging tests for colorectal cancer (CRC) screening; the use of genetic information and availability of home self-testing in cervical cancer screening; the integration of multiple risk factors and patient preferences to decide the intensity and length of breast cancer screening; and the issues of smoking cessation and competing priorities when deciding whether or not to pursue lung cancer screening. These changes will inevitably increase the burden on primary care of providing high-quality cancer screening to their patients. To address, primary care physicians need access to continuously updated evidence reviews including prioritization of strongly supported recommendations, training in shared decision-making and tools for preference diagnosis, and an electronic health record (EHR) and reimbursement model that allow for population health management and team-based care. Only by reinforcing cancer screening in primary care can we ensure that personalized cancer screening is accessible and evidence-based.
Authors: Selby K; Bartlett-Esquilant G; Cornuz J
Public Health Rev. 2018;39:4. Epub 2018-02-21.
Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
Authors: Klein AP; Van Den Eeden SK; Amundadottir LT; et al.
Nat Commun. 2018 02 08;9(1):556. Epub 2018-02-08.
The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression
The nuclear factor-kappa B (NF-κB) signalling pathway is a regulator of immune response and inflammation that has been implicated in the carcinogenic process. We examined differentially expressed genes in this pathway and miRNAs to determine associations with colorectal cancer (CRC). We used data from 217 CRC cases to evaluate differences in NF-κB signalling pathway gene expression between paired carcinoma and normal mucosa and identify miRNAs that are associated with these genes. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were analysed. We evaluated genes most strongly associated and differentially expressed (fold change (FC) of > 1.5 or < 0.67) that were statistically significant after adjustment for multiple comparisons. Of the 92 genes evaluated, 22 were significantly downregulated and nine genes were significantly upregulated in all tumours. Two additional genes (CD14 and CSNK2A1) were dysregulated in MSS tumours and two genes (CARD11 and VCAM1) were downregulated and six genes were upregulated (LYN, TICAM2, ICAM1, IL1B, CCL4 and PTGS2) in MSI tumours. Sixteen of the 21 dysregulated genes were associated with 40 miRNAs. There were 76 miRNA:mRNA associations of which 38 had seed-region matches. Genes were associated with multiple miRNAs, with TNFSRF11A (RANK) being associated with 15 miRNAs. Likewise several miRNAs were associated with multiple genes (miR-150-5p with eight genes, miR-195-5p with four genes, miR-203a with five genes, miR-20b-5p with four genes, miR-650 with six genes and miR-92a-3p with five genes). Focusing on the genes and their associated miRNAs within the entire signalling pathway provides a comprehensive understanding of this complex pathway as it relates to CRC and offers insight into potential therapeutic agents.
Authors: Slattery ML; Mullany LE; Sakoda L; Samowitz WS; Wolff RK; Stevens JR; Herrick JS
J Cancer Res Clin Oncol. 2018 Feb;144(2):269-283. Epub 2017-11-29.
The Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) Study: Description and Baseline Characteristics of Participants
Background: The Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study offers an important opportunity to advance cancer research by extending the original WHI studies to examine survivorship in women diagnosed with cancer during their participation in WHI.Methods: The goals of LILAC are to (i) obtain cancer treatment information and long-term cancer outcomes for women diagnosed with one of eight selected cancers (breast, endometrial, ovarian, lung, and colorectal cancers, and melanoma, lymphoma, and leukemia); (ii) augment the existing WHI biorepository with fixed tumor tissue from the solid tumor sites for cancers diagnosed since 2002; and (iii) develop, refine, and validate methods to use administrative data to capture treatment and recurrence data. Methods for accomplishing these goals are described, as are results from the initial LILAC participant survey.Results: A total of 9,934 WHI participants living with cancer were eligible for LILAC participation, of which 78% (N = 7,760) agreed to participate. Among the three most prevalent cancer types, 54% are breast cancer survivors, 11% are melanoma survivors, and 10% are survivors of colorectal cancer.Conclusions: In addition to describing this resource, we present pertinent lessons that may assist other investigators interested in embedding survivorship research into existing large epidemiologic cohorts.Impact: The LILAC resource offers a valuable opportunity for researchers to study cancer survivorship and issues pertinent to cancer survivors in future studies. Cancer Epidemiol Biomarkers Prev; 27(2); 125-37. ©2017 AACR.
Authors: Paskett ED; Caan BJ; Johnson L; Bernardo BM; Young GS; Pennell ML; Ray RM; Kroenke CH; Porter PL; Anderson GL
Cancer Epidemiol Biomarkers Prev. 2018 02;27(2):125-137. Epub 2018-01-29.
Effect of Time to Diagnostic Testing for Breast, Cervical, and Colorectal Cancer Screening Abnormalities on Screening Efficacy: A Modeling Study
Background: Patients who receive an abnormal cancer screening result require follow-up for diagnostic testing, but the time to follow-up varies across patients and practices.Methods: We used a simulation study to estimate the change in lifetime screening benefits when time to follow-up for breast, cervical, and colorectal cancers was increased. Estimates were based on four independently developed microsimulation models that each simulated the life course of adults eligible for breast (women ages 50-74 years), cervical (women ages 21-65 years), or colorectal (adults ages 50-75 years) cancer screening. We assumed screening based on biennial mammography for breast cancer, triennial Papanicolaou testing for cervical cancer, and annual fecal immunochemical testing for colorectal cancer. For each cancer type, we simulated diagnostic testing immediately and at 3, 6, and 12 months after an abnormal screening exam.Results: We found declines in screening benefit with longer times to diagnostic testing, particularly for breast cancer screening. Compared to immediate diagnostic testing, testing at 3 months resulted in reduced screening benefit, with fewer undiscounted life years gained per 1,000 screened (breast: 17.3%, cervical: 0.8%, colorectal: 2.0% and 2.7%, from two colorectal cancer models), fewer cancers prevented (cervical: 1.4% fewer, colorectal: 0.5% and 1.7% fewer, respectively), and, for breast and colorectal cancer, a less favorable stage distribution.Conclusions: Longer times to diagnostic testing after an abnormal screening test can decrease screening effectiveness, but the impact varies substantially by cancer type.Impact: Understanding the impact of time to diagnostic testing on screening effectiveness can help inform quality improvement efforts. Cancer Epidemiol Biomarkers Prev; 27(2); 158-64. ©2017 AACR.
Authors: Rutter CM; Tosteson ANA; Tosteson ANA; et al.
Cancer Epidemiol Biomarkers Prev. 2018 02;27(2):158-164. Epub 2017-11-17.
Effectiveness of screening colonoscopy in reducing the risk of death from right and left colon cancer: a large community-based study
Screening colonoscopy’s effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers. We conducted a nested case-control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55-90 years old on their colorectal cancer death date during 2006-2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures. We analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53). Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population.
Authors: Doubeni CA; Corley DA; Levin TR; Fletcher RH; et al.
Gut. 2018 02;67(2):291-298. Epub 2016-10-12.
Expression of Wnt-signaling pathway genes and their associations with miRNAs in colorectal cancer
The Wnt-signaling pathway functions in regulating cell growth and thus is involved in the carcinogenic process of several cancers, including colorectal cancer. We tested the hypothesis that multiple genes in this signaling pathway are dysregulated and that miRNAs are associated with these dysregulated genes. We used data from 217 colorectal cancer (CRC) cases to evaluate differences in Wnt-signaling pathway gene expression between paired CRC and normal mucosa and identify miRNAs that are associated with these genes. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were analyzed. We focused on genes most strongly associated with CRC (fold change (FC) of >1.5 or <0.67) and that were statistically significant after adjustment for multiple comparisons. Of the 138 Wnt-signaling pathway genes examined, 27 were significantly down-regulated (FC<0.67) and 32 genes were significantly up-regulated (FC>1.50) after adjusting for multiple comparisons. Thirteen of the 66 Wnt-signaling genes that were differentially expressed in CRC tumors were associated with differential expression of miRNAs. A total of 93 miRNA:mRNA associations were detected for these 13 genes. Of these 93 associations, 36 miRNA seed-region matches were observed, suggesting that miRNAs have both direct and indirect effects on Wnt-signaling pathway genes. In summary, our data supports the hypothesis that the Wnt-signaling pathway is dysregulated in CRC and suggest that miRNAs may importantly influence that dysregulation.
Authors: Slattery ML; Mullany LE; Sakoda LC; Samowitz WS; Wolff RK; Stevens JR; Herrick JS
Oncotarget. 2018 Jan 19;9(5):6075-6085. Epub 2017-12-23.
Identification of fluorescence in situ hybridization assay markers for prediction of disease progression in prostate cancer patients on active surveillance
Prostate Cancer (PCa) is the second most prevalent cancer among U.S. males. In recent decades many men with low risk PCa have been over diagnosed and over treated. Given significant co-morbidities associated with definitive treatments, maximizing patient quality of life while recognizing early signs of aggressive disease is essential. There remains a need to better stratify newly diagnosed men according to the risk of disease progression, identifying, with high sensitivity and specificity, candidates for active surveillance versus intervention therapy. The objective of this study was to select fluorescence in situ hybridization (FISH) panels that differentiate non-progressive from progressive disease in patients with low and intermediate risk PCa. We performed a retrospective case-control study to evaluate FISH biomarkers on specimens from PCa patients with clinically localised disease (T1c-T2c) enrolled in Watchful waiting (WW)/Active Surveillance (AS). The patients were classified into cases (progressed to clinical intervention within 10 years), and controls (did not progress in 10 years). Receiver Operating Characteristic (ROC) curve analysis was performed to identify the best 3-5 probe combinations. FISH parameters were then combined with the clinical parameters ─ National Comprehensive Cancer Network (NNCN) risk categories ─ in the logistic regression model. Seven combinations of FISH parameters with the highest sensitivity and specificity for discriminating cases from controls were selected based on the ROC curve analysis. In the logistic regression model, these combinations contributed significantly to the prediction of PCa outcome. The combination of NCCN risk categories and FISH was additive to the clinical parameters or FISH alone in the final model, with odds ratios of 5.1 to 7.0 for the likelihood of the FISH-positive patients in the intended population to develop disease progression, as compared to the FISH-negative group. Combinations of FISH parameters discriminating progressive from non-progressive PCa were selected based on ROC curve analysis. The combination of clinical parameters and FISH outperformed clinical parameters alone, and was complimentary to clinical parameters in the final model, demonstrating potential utility of multi-colour FISH panels as an auxiliary tool for PCa risk stratification. Further studies with larger cohorts are planned to confirm these findings.
Authors: Pestova K; Shan J; Van Den Eeden SK; et al.
BMC Cancer. 2018 01 02;18(1):2. Epub 2018-01-02.
miRNA involvement in cell cycle regulation in colorectal cancer cases
Uncontrolled cell replication is a key component of carcinogenesis. MicroRNAs (miRNAs) regulate genes involved in checkpoints, DNA repair, and genes encoding for key proteins regulating the cell cycle. We investigated how miRNAs and mRNAs in colorectal cancer subjects interact to regulate the cell cycle. Using RNA-Seq data from 217 individuals, we analyzed differential expression (carcinoma minus normal mucosa) of 123 genes within the cell cycle pathway with differential miRNA expression, adjusting for age and sex. Multiple comparison adjustments for gene/miRNA associations were made at the gene level using an FDR <0.05. Differentially expressed miRNAs and mRNAs were tested for associations with colorectal cancer survival. MRNA and miRNA sequences were compared to identify seed region matches to support biological interpretation of the observed associations. Sixty-seven mRNAs were dysregulated with a fold change (FC) <0.67 or >1.50. Thirty-two mRNAs were associated with 48 miRNAs; 102 of 290 total associations had identified seed matches; of these, ten had negative beta coefficients. Hsa-miR-15a-5p and hsa-miR-20b-5p were associated with colorectal cancer survival with an FDR <0.05 (HR 0.86 95% CI 0.79, 0.94; HR 0.83 95% CI 0.75, 0.91 respectively). Our findings suggest that miRNAs impact mRNA translation at multiple levels within the cell cycle.
Authors: Mullany LE; Herrick JS; Sakoda LC; Samowitz W; Stevens JR; Wolff RK; Slattery ML
Genes Cancer. 2018 Jan;9(1-2):53-65.
An Unexpected Finding During Colonoscopy: Pinworms.
Authors: Kidambi, Trilokesh D TD; Lee, Jeffrey K JK
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018 Jan ;16(1):e4. Epub --.
Change in longitudinal trends in sleep quality and duration following breast cancer diagnosis: results from the Women’s Health Initiative
Breast cancer survivors frequently report sleep problems, but little research has studied sleep patterns longitudinally. We examined trends in sleep quality and duration up to 15 years before and 20 years after a diagnosis of breast cancer, over time among postmenopausal women participating in the Women’s Health Initiative (WHI). We included 12,098 participants who developed invasive breast cancer after study enrollment. A linear mixed-effects model was used to determine whether the time trend in sleep quality, as measured by the WHI Insomnia Rating Scale (WHIIRS), a measure of perceived insomnia symptoms from the past 4 weeks, changed following a cancer diagnosis. To examine sleep duration, we fit a logistic regression model with random effects for both short (<6 h) and long (≥9 h) sleep. In addition, we studied the association between depressive symptoms and changes in WHIIRS and sleep duration. There was a significantly slower increase in the trend of WHIIRS after diagnosis (β = 0.06; p = 0.03), but there were non-significant increases in the trend of the probability of short or long sleep after diagnosis. The probability of depressive symptoms significantly decreased, though the decrease was more pronounced after diagnosis (p < 0.01). Trends in WHIIRS worsened at a relatively slower rate following diagnosis and lower depression rates may explain the slower worsening in WHIIRS. Our findings suggest that over a long period of time, breast cancer diagnosis does not adversely affect sleep quality and duration in postmenopausal women compared to sleep pre-diagnosis, yet both sleep quality and duration continue to worsen over time.
Authors: Beverly CM; Naughton MJ; Pennell ML; Foraker RE; Young G; Hale L; Feliciano EMC; Pan K; Crane TE; Danhauer SC; Paskett ED
NPJ Breast Cancer. 2018;4:15. Epub 2018-06-29.
Being Present: A single-arm feasibility study of audio-based mindfulness meditation for colorectal cancer patients and caregivers
A metastatic cancer diagnosis is associated with high levels of distress in patients and caregivers. Mindfulness interventions can reduce distress and improve quality of life in cancer patients. However, standard mindfulness training relies on in-person instruction, which is often not practical for either patients receiving chemotherapy or their caregivers. In the Being Present single arm pilot study, we designed and tested an 8-week audio-based mindfulness meditation program for patients with metastatic colorectal cancer receiving chemotherapy with or without a participating caregiver. The study accrued 33 of 74 (45%) eligible patients consenting together with 20 family caregivers (53 participants total) within nine months. Forty-one participants were evaluable (77%); 10 of 12 cases of attrition were attributable to hospitalization or death. Median participant age was 51 (range 21-78 years); 38% were men. Baseline levels of distress were similar in patients and caregivers. The top reasons for participation cited in pre-intervention interviews were to increase relaxation/calm, improve mood/emotions, and reduce stress/anxiety. In measures of adherence, 59% of responses to weekly texts asking: “Have you practiced today?” were “Yes” and 59% of interviewees reported practicing >50% of the time. Compared to baseline, post-intervention surveys demonstrated significantly reduced distress (p = 0.01) and anxiety (p = 0.03); as well as increased non-reactivity (p<0.01), and feeling at peace (p<0.01). Post-intervention qualitative interviews, where 71% of participants reported benefit, were consistent with quantitative findings. In the interviews, participants spontaneously described reduced stress/anxiety and increased relaxation/calm. Benefits appeared to be accentuated in patient-caregiver pairs as compared to unpaired patients. Seventy-nine percent of participants reported plans for continued practice after study completion. We conclude that the Being Present audio-based mindfulness meditation program is of interest to, feasible, and acceptable for patients with metastatic colorectal cancer and caregivers, with initial evidence of efficacy. These results will guide plans for a follow-up study. ClinicalTrials.gov NCT02423720.
Authors: Atreya CE; Kubo A; Borno HT; Rosenthal B; Campanella M; Rettger JP; Joseph G; Allen IE; Venook AP; Altschuler A; Dhruva A
PLoS ONE. 2018;13(7):e0199423. Epub 2018-07-23.
Prevalence of Parkinson’s disease across North America
Estimates of the prevalence of Parkinson’s disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson’s disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.
Authors: Marras C; Van Den Eeden SK; Parkinson’s Foundation P4 Group; et al.
NPJ Parkinsons Dis. 2018;4:21. Epub 2018-07-10.
The MAPK-Signaling Pathway in Colorectal Cancer: Dysregulated Genes and Their Association With MicroRNAs
Mitogen-activated protein kinase (MAPK) pathways regulate many cellular functions including cell proliferation and apoptosis. We examined associations of differential gene and microRNA (miRNA) expression between carcinoma and paired normal mucosa for 241 genes in the KEGG-identified MAPK-signaling pathway among 217 colorectal cancer (CRC) cases. Gene expression data (RNA-Seq) and miRNA expression data (Agilent Human miRNA Microarray V19.0; Agilent Technologies Inc., Santa Clara, CA, USA) were analyzed. We first identified genes most strongly associated with CRC using a fold change (FC) of >1.50 or <0.67) that were statistically significant after adjustment for multiple comparisons. We then determined miRNAs associated with dysregulated genes and through miRNA:mRNA (messenger RNA) seed region matches discerned genes with a greater likelihood of having a direct biological association. Ninety-nine genes had a meaningful FC for all CRC, microsatellite unstable-specific tumors, or microsatellite stable-specific tumors. Thirteen dysregulated genes were associated with miRNAs, totaling 68 miRNA:mRNA associations. Thirteen of the miRNA:mRNA associations had seed region matches where the differential expression between the miRNA and mRNA was inversely related suggesting a direct association as a result of their binding. Several direct associations, upstream of ERK1/ERK2, JNK, and p38, were found for PDGFRA with 7 miRNAs; RASGRP3 and PRKCB with miR-203a; and TGFBR1 with miR-6071 and miR-2117. Other associations between miRNAs and mRNAs are most likely indirect, resulting from feedback and feed forward loops. Our results suggest that miRNAs may alter MAPK signaling through direct binding with key genes in this pathway. We encourage others to validate results in targeted CRC experiments that can help solidify important therapeutic targets.
Authors: Slattery ML; Mullany LE; Sakoda LC; Wolff RK; Samowitz WS; Herrick JS
Cancer Inform. 2018;17:1176935118766522. Epub 2018-03-26.
Associations between ACE-Inhibitors, Angiotensin Receptor Blockers, and Lean Body Mass in Community Dwelling Older Women
Studies suggest that ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) may preserve skeletal muscle with aging. We evaluated longitudinal differences in lean body mass (LBM) among women diagnosed with hypertension and classified as ACE-I/ARB users and nonusers among Women’s Health Initiative participants that received dual energy X-ray absorptiometry scans to estimate body composition (n=10,635) at baseline and at years 3 and 6 of follow-up. Of those, 2642 were treated for hypertension at baseline. Multivariate linear regression models, adjusted for relevant demographics, behaviors, and medications, assessed ACE-I/ARB use/nonuse and LBM associations at baseline, as well as change in LBM over 3 and 6 years. Although BMI did not differ by ACE-I/ARB use, LBM (%) was significantly higher in ACE-I/ARB users versus nonusers at baseline (52.2% versus 51.3%, resp., p=0.001). There was no association between ACE-I/ARB usage and change in LBM over time. Reasons for higher LBM with ACE-I/ARB use cross sectionally, but not longitundinally, are unclear and may reflect a threshold effect of these medications on LBM that is attenuated over time. Nevertheless, ACE-I/ARB use does not appear to negatively impact LBM in the long term.
Authors: Bea JW; Wassertheil-Smoller S; Wertheim BC; Klimentidis Y; Chen Z; Zaslavsky O; Manini TM; Womack CR; Kroenke CH; LaCroix AZ; Thomson CA
J Aging Res. 2018;2018:8491092. Epub 2018-02-19.
Serum cholesterol trajectories in the 10 years prior to lymphoma diagnosis
Many studies suggest a role for cholesterol in cancer development. Serum cholesterol levels have been observed to be low in newly diagnosed lymphoma cases. The objective of these analyses was to examine the time-varying relationship of cholesterol with lymphomagenesis in the 10 years prior to diagnosis by lymphoma subtype. Participants were selected from the combined membership of six National Cancer Institute-funded Cancer Research Network health plans from 1998 to 2008, excluding members with human immunodeficiency virus, cancer (except lymphoma), or organ transplants. Incident lymphoma cases within this population were ascertained and matched with up to five controls. Total serum cholesterol, high-density lipoprotein, and low-density lipoprotein were collected from plan databases. Multilevel, multivariable longitudinal models were fit after choosing the best polynomial order by deviance statistics for selected lymphoma histotypes to examine pre-diagnosis cholesterol trajectories: Hodgkin lymphoma (n = 519) and all non-Hodgkin lymphomas combined (n = 12,635) as well as six subtypes of the latter. For all categories, lymphoma cases had statistically significantly lower estimated total serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels than controls in the years prior to diagnosis/index date. Between-group differences were most pronounced 3-4 years prior to diagnosis, when cases’ cholesterol levels declined steeply. This analysis is the first to examine changes in serum cholesterol for a decade prior to lymphoma diagnosis. A drop in cholesterol levels was evident several years before diagnosis. Our results suggest that cholesterol-related pathways have an important relationship with lymphomagenesis and low cholesterol could be a preclinical lymphoma marker.
Authors: Alford SH; Habel LA; Cancer Research Network Lymphoma Study Group; et al.
Cancer Causes Control. 2018 01;29(1):143-156. Epub 2017-11-30.
The 75th Diamond Anniversary of Gastroenterology: 1943-2018
Authors: Peek RM; Corley DA
Gastroenterology. 2018 01;154(1):1-5. Epub 2017-11-09.
A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease
A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa). To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up. A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results. We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights. The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units=3.23 (95% confidence interval [CI] 1.84-5.65; p<0.001), and time to metastasis, HR/20 units=2.75 (95% CI 1.63-4.63; p<0.001). The association between GPS and both end points remained significant after adjusting for National Comprehensive Cancer Network, American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks (p<0.001). No patient with low- or intermediate-risk disease and a GPS of<20 developed metastases or PCD (n=31). In receiver operating characteristic analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to 0.84 (GPS+CAPRA; p<0.001). A limitation of the study was that patients were treated during an era when definitive treatment was standard of care with little adoption of active surveillance. GPS is a strong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease. Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and threaten his life after surgery, providing information that may help patients and their doctors decide on the best course of management of their disease.
Authors: Van Den Eeden SK; Lu R; Zhang N; Quesenberry CP; Shan J; Han JS; Tsiatis AC; Leimpeter AD; Lawrence HJ; Febbo PG; Presti JC
Eur Urol. 2018 01;73(1):129-138. Epub 2017-10-06.
Use of iDXA spine scans to evaluate total and visceral abdominal fat
Abdominal fat may be a better predictor than body mass index (BMI) for risk of metabolically-related diseases, such as diabetes, cardiovascular disease, and some cancers. We sought to validate the percent fat reported on dual energy X-ray absorptiometry (DXA) regional spine scans (spine fat fraction, SFF) against abdominal fat obtained from total body scans using the iDXA machine (General Electric, Madison, WI), as previously done on the Prodigy model. Total body scans and regional spine scans were completed on the same day (N = 50). In alignment with the Prodigy-based study, the following regions of interest (ROI) were assessed from total body scans and compared to the SFF from regional spine scans: total abdominal fat at (1) lumbar vertebrae L2-L4 and (2) L2-Iliac Crest (L2-IC); (3) total trunk fat; and (4) visceral fat in the android region. Separate linear regression models were used to predict each total body scan ROI from SFF; models were validated by bootstrapping. The sample was 84% female, a mean age of 38.5 ± 17.4 years, and mean BMI of 23.0 ± 3.8 kg/m2 . The SFF, adjusted for BMI, predicted L2-L4 and L2-IC total abdominal fat (%; Adj. R2 : 0.90) and total trunk fat (%; Adj. R2 : 0.88) well; visceral fat (%) adjusted R2 was 0.83. Linear regression models adjusted for additional participant characteristics resulted in similar adjusted R2 values. This replication of the strong correlation between SFF and abdominal fat measures on the iDXA in a new population confirms the previous Prodigy model findings and improves generalizability.
Authors: Bea JW; Hsu CH; Blew RM; Irving AP; Caan BJ; Kwan ML; Abraham I; Going SB
Am J Hum Biol. 2018 01;30(1). Epub 2017-09-08.
Decision making processes among men with low-risk prostate cancer: a survey study
To characterize decision-making processes and outcomes among men expressing early-treatment preferences for low-risk prostate cancer. We conducted telephone surveys of men newly diagnosed with low-risk prostate cancer in 2012 to 2014. We analyzed subjects who had discussed prostate cancer treatment with a clinician and expressed a treatment preference. We asked about decision-making processes, including physician discussions, prostate-cancer knowledge, decision-making styles, treatment preference, and decisional conflict. We compared the responses across treatment groups with χ2 or ANOVA. Participants (n = 761) had a median age of 62; 82% were white, 45% had a college education, and 35% had no comorbidities. Surveys were conducted at a median of 25 days (range 9-100) post diagnosis. Overall, 55% preferred active surveillance (AS), 26% preferred surgery, and 19% preferred radiotherapy. Participants reported routinely considering surgery, radiotherapy, and AS. Most were aware of their low-risk status (97%) and the option for AS (96%). However, men preferring active treatment (AT) were often unaware of treatment complications, including sexual dysfunction (23%) and urinary complications (41%). Most men (63%) wanted to make their own decision after considering the doctor’s opinion, and about 90% reported being sufficiently involved in the treatment discussion. Men preferring AS had slightly more uncertainty about their decisions than those preferring AT. Subjects were actively engaged in decision making and considered a range of treatments. However, we found knowledge gaps about treatment complications among those preferring AT and slightly more decisional uncertainty among those preferring AS, suggesting the need for early decision support.
Authors: Hoffman RM; Van Den Eeden SK; Davis KM; Lobo T; Luta G; Shan J; Aaronson D; Penson DF; Leimpeter AD; Taylor KL
Psychooncology. 2018 01;27(1):325-332. Epub 2017-07-13.
Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients: a multicenter study from the International Lung Cancer Consortium
Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide polymorphisms (SNP) are associated with overall survival among SCLC patients.Experimental Design: Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan-Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months postdiagnosis, adjusting for age, sex, race, and tumor stage.Results: Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared with those carrying AA alleles, with a HR of 1.36 [95% confidence interval (CI): 1.08-1.72, P = 0.01), but no association with survival was observed for patients carrying the AG genotype (HR = 1.04, 95% CI, 0.84-1.29, P = 0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR = 0.79; 95% CI, 0.61-1.02, P = 0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190.Conclusions: We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors. Clin Cancer Res; 23(24); 7550-7. ©2017 AACR.
Authors: Lohavanichbutr P; Amos CI; Chen C; et al.
Clin Cancer Res. 2017 Dec 15;23(24):7550-7557. Epub 2017-10-03.
Determining Risk of Barrett’s Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants
We developed comprehensive models to determine risk of Barrett’s esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors. We used pooled data from 3288 patients with BE, 2511 patients with EAC, and 2177 individuals without either (controls) from participants in the international Barrett’s and EAC consortium as well as the United Kingdom’s BE gene study and stomach and esophageal cancer study. We collected data on 23 genetic variants associated with risk for BE or EAC, and constructed a polygenic risk score (PRS) for cases and controls by summing the risk allele counts for the variants weighted by their natural log-transformed effect estimates (odds ratios) extracted from genome-wide association studies. We also collected data on demographic and lifestyle factors (age, sex, smoking, body mass index, use of nonsteroidal anti-inflammatory drugs) and symptoms of gastroesophageal reflux disease (GERD). Risk models with various combinations of non-genetic factors and the PRS were compared for their accuracy in identifying patients with BE or EAC using the area under the receiver operating characteristic curve (AUC) analysis. Individuals in the highest quartile of risk, based on genetic factors (PRS), had a 2-fold higher risk of BE (odds ratio, 2.22; 95% confidence interval, 1.89-2.60) or EAC (odds ratio, 2.46; 95% confidence interval, 2.07-2.92) than individual in the lowest quartile of risk based on PRS. Risk models developed based on only demographic or lifestyle factors or GERD symptoms identified patients with BE or EAC with AUC values ranging from 0.637 to 0.667. Combining data on demographic or lifestyle factors with data on GERD symptoms identified patients with BE with an AUC of 0.793 and patients with EAC with an AUC of 0.745. Including PRSs with these data only minimally increased the AUC values for BE (to 0.799) and EAC (to 0.754). Including the PRSs in the model developed based on non-genetic factors resulted in a net reclassification improvement for BE of 3.0% and for EAC of 5.6%. We used data from 3 large databases of patients from studies of BE or EAC to develop a risk prediction model based on genetic, clinical, and demographic/lifestyle factors. We identified a PRS that increases discrimination and net reclassification of individuals with vs without BE and EAC. However, the absolute magnitude of improvement is not sufficient to justify its clinical use.
Authors: Dong J; Corley DA; Thrift AP; et al.
Gastroenterology. 2017 Dec 13.
Applying Risk Prediction Models to Optimize Lung Cancer Screening: Current Knowledge, Challenges, and Future Directions
Risk prediction models may be useful for facilitating effective and high-quality decision-making at critical steps in the lung cancer screening process. This review provides a current overview of published lung cancer risk prediction models and their applications to lung cancer screening and highlights both challenges and strategies for improving their predictive performance and use in clinical practice. Since the 2011 publication of the National Lung Screening Trial results, numerous prediction models have been proposed to estimate the probability of developing or dying from lung cancer or the probability that a pulmonary nodule is malignant. Respective models appear to exhibit high discriminatory accuracy in identifying individuals at highest risk of lung cancer or differentiating malignant from benign pulmonary nodules. However, validation and critical comparison of the performance of these models in independent populations are limited. Little is also known about the extent to which risk prediction models are being applied in clinical practice and influencing decision-making processes and outcomes related to lung cancer screening. Current evidence is insufficient to determine which lung cancer risk prediction models are most clinically useful and how to best implement their use to optimize screening effectiveness and quality. To address these knowledge gaps, future research should be directed toward validating and enhancing existing risk prediction models for lung cancer and evaluating the application of model-based risk calculators and its corresponding impact on screening processes and outcomes.
Authors: Sakoda LC; Henderson LM; Caverly TJ; Wernli KJ; Katki HA
Curr Epidemiol Rep. 2017 Dec;4(4):307-320. Epub 2017-10-24.
Disparities in Prostate, Lung, Breast, and Colorectal Cancer Survival and Comorbidity Status among Urban American Indians and Alaskan Natives
Cancer is the second leading cause of death among American Indians and Alaskan Natives (AIAN), although cancer survival information in this population is limited, particularly among urban AIAN. In this retrospective cohort study, we compared all-cause and prostate, breast, lung, and colorectal cancer-specific mortality among AIAN (n = 582) and non-Hispanic white (NHW; n = 82,696) enrollees of Kaiser Permanente Northern California (KPNC) diagnosed with primary invasive breast, prostate, lung, or colorectal cancer from 1997 to 2015. Tumor registry and other electronic health records provided information on sociodemographic, comorbidity, tumor, clinical, and treatment characteristics. Cox regression models were used to estimate adjusted survival curves and hazard ratios (HR) with 95% confidence intervals (CI). AIAN had a significantly higher comorbidity burden compared with NHW (P < 0.05). When adjusting for patient, disease characteristics, and Charlson comorbidity scores, all-cause mortality and cancer-specific mortality were significantly higher for AIAN than NHW patients with breast cancer (HR, 1.47; 95% CI, 1.13-1.92) or with prostate cancer (HR, 1.87; 95% CI, 1.14-3.06) but not for AIAN patients with lung and colorectal cancer. Despite approximately equal access to preventive services and cancer care in this setting, we found higher mortality for AIAN than NHW with some cancers, and a greater proportion of AIAN cancer patients with multiple comorbid conditions. This study provides severely needed information on the cancer experience of the 71% of AIANs who live in urban areas and access cancer care outside of the Indian Health Services, from which the vast majority of AIAN cancer information comes. Cancer Res; 77(23); 6770-6. ©2017 AACR.
Authors: Emerson MA; Banegas MP; Chawla N; Achacoso N; Alexeeff SE; Adams AS; Habel LA
Cancer Res. 2017 12 01;77(23):6770-6776. Epub 2017-11-29.
Understanding the relation between socioeconomic position and inflammation in post-menopausal women: education, income and occupational prestige
The role of occupational prestige, a direct measure of the perceived status of job and job holder, in inflammation is unknown. To contribute to understanding the pathways by which socioeconomic position (SEP) is associated with inflammation, we aimed to estimate the direct effects of education, income and occupational prestige on C-reactive protein (CRP) and to describe the relationship between these markers and CRP. The study was based on 2026 post-menopausal women enrolled in the Women’s Health Initiative-Observational Study. Occupational prestige was determined by linking a text description of longest held occupation with a social status item from the Occupational Information Network. Path analysis was employed to estimate direct and mediated effects. The study suggests that higher levels of education, income, and occupational prestige are associated with 8% (95% CI as percentage change -12, -4), 5% [95% CI (-8, -2) and 4% (95% CI – 7, -1)] lower levels of CRP, respectively. The inverse association between education and CRP was explained by the effect of education on income and occupational prestige. The effect of occupational prestige on CRP was independent of mediators in the model. The findings indicate that education may work to influence CRP primarily through increasing income and occupational prestige and provides evidence that occupational prestige captures a unique aspect of SEP.
Authors: Pedersen JM; Budtz-Jørgensen E; De Roos A; Garcia L; Lund R; Rod NH; Kroenke C; Chan KHK; Liu S; Michael Y
Eur J Public Health. 2017 12 01;27(6):1074-1079.
Actigraphy-Derived Daily Rest-Activity Patterns and Body Mass Index in Community-Dwelling Adults
To examine associations between 24-hour rest-activity patterns and body mass index (BMI) among community-dwelling US adults. Rest-activity patterns provide a field method to study exposures related to circadian rhythms. Adults (N = 578) wore an actigraph on their nondominant wrist for 7 days. Intradaily variability and interdaily stability (IS), M10 (most active 10-hours), L5 (least active 5-hours), and relative amplitude (RA) were derived using nonparametric rhythm analysis. Mesor, acrophase, and amplitude were calculated from log-transformed count data using the parametric cosinor approach. Participants were 80% female and mean (standard deviation) age was 52 (15) years. Participants with higher BMI had lower values for magnitude, RA, IS, total sleep time (TST), and sleep efficiency. In multivariable analyses, less robust 24-hour rest-activity patterns as represented by lower RA were consistently associated with higher BMI: comparing the bottom quintile (least robust) to the top quintile (most robust 24-hour rest-activity pattern) of RA, BMI was 3-kg/m2 higher (p = .02). Associations were similar in magnitude to an hour less of TST (1-kg/m2 higher BMI) or a 10% decrease in sleep efficiency (2-kg/m2 higher BMI), and independent of age, sex, race, education, and the duration of rest and/or activity. Lower RA, reflecting both higher night activity and lower daytime activity, was associated with higher BMI. Independent of the duration of rest or activity during the day or night, 24-hour rest, and activity patterns from actigraphy provide aggregated measures of activity that associate with BMI in community-dwelling adults.
Authors: Cespedes Feliciano EM; Hipp JA; et al.
Sleep. 2017 12 01;40(12).
Methodological considerations for disentangling a risk factor’s influence on disease incidence versus postdiagnosis survival: The example of obesity and breast and colorectal cancer mortality in the Women’s Health Initiative
Often, studies modeling an exposure’s influence on time to disease-specific death from study enrollment are incorrectly interpreted as if based on time to death from disease diagnosis. We studied 151,996 postmenopausal women without breast or colorectal cancer in the Women’s Health Initiative with weight and height measured at enrollment (1993-1998). Using Cox regression models, we contrast hazard ratios (HR) from two time-scales and corresponding study subpopulations: time to cancer death after enrollment among all women and time to cancer death after diagnosis among only cancer survivors. Median follow-up from enrollment to diagnosis/censoring was 13 years for both breast (7,633 cases) and colorectal cancer (2,290 cases). Median follow-up from diagnosis to death/censoring was 7 years for breast and 5 years for colorectal cancer. In analyses of time from enrollment to death, body mass index (BMI) ≥ 35 kg/m2 versus 18.5-<25 kg/m2 was associated with higher rates of cancer mortality: HR = 1.99; 95% CI: 1.54, 2.56 for breast cancer (p trend <0.001) and HR = 1.40; 95% CI: 1.04, 1.88 for colorectal cancer (p trend = 0.05). However, in analyses of time from diagnosis to cancer death, trends indicated no significant association (for BMI ≥ 35 kg/m2 , HR = 1.25; 95% CI: 0.94, 1.67 for breast [p trend = 0.33] and HR = 1.18; 95% CI: 0.84, 1.86 for colorectal cancer [p trend = 0.39]). We conclude that a risk factor that increases disease incidence will increase disease-specific mortality. Yet, its influence on postdiagnosis survival can vary, and requires consideration of additional design and analysis issues such as selection bias. Quantitative tools allow joint modeling to compare an exposure's influence on time from enrollment to disease incidence and time from diagnosis to death.
Authors: Cespedes Feliciano EM; Ho GYF; Caan BJ; et al.
Int J Cancer. 2017 12 01;141(11):2281-2290. Epub 2017-08-31.
Impact of adenoma detection on the benefit of faecal testing vs. colonoscopy for colorectal cancer
Colonoscopy quality, as measured by adenoma detection rates, varies widely across providers and is inversely related to patients’ post-colonoscopy cancer risk. This has unknown consequences for the benefits of faecal immunochemical testing (FIT) vs. primary colonoscopy screening for colorectal cancer. Using an established microsimulation model, we predicted the lifetime colorectal cancer incidence and mortality benefits of annual FIT vs. 10-yearly colonoscopy screening at differing ADR levels (quintiles; averages 15.3-38.7%), with colonoscopy performance assumptions estimated from community-based data on physician ADRs and patients’ post-colonoscopy risk of cancer. For patients receiving FIT screening with follow-up colonoscopy by physicians from the highest ADR quintile, simulated lifetime cancer incidence and mortality were 28.8 and 5.4 per 1,000, respectively, vs. 20.6 and 4.4 for primary colonoscopy screening (risk ratios, RR = 1.40; 95% probability interval (PI), 1.19-1.71 for incidence, and RR = 1.22; 95%PI, 1.02-1.54 for mortality). With every 5% point ADR decrease, lifetime cancer incidence was predicted to increase on average 9.0% for FIT vs. 12.3% for colonoscopy, and mortality increased 9.9% vs. 13.3%. In ADR quintile 1, simulated mortality was lower for FIT than colonoscopy screening (10.1 vs. 11.8; RR = 0.85; 95%PI, 0.83-0.90), while incidences were more similar. This suggests that relative cancer incidence and mortality reductions for FIT vs. colonoscopy screening may differ by ADR, with fewer predicted deaths with colonoscopy screening in higher ADR settings and fewer deaths with annual FIT screening in lower ADR settings.
Authors: Meester RGS; Doubeni CA; Zauber AG; van Ballegooijen M; Corley DA; Lansdorp-Vogelaar I
Int J Cancer. 2017 12 01;141(11):2359-2367. Epub 2017-08-31.
Association of Systemic Inflammation and Sarcopenia With Survival in Nonmetastatic Colorectal Cancer: Results From the C SCANS Study
Systemic inflammation and sarcopenia are easily evaluated, predict mortality in many cancers, and are potentially modifiable. The combination of inflammation and sarcopenia may be able to identify patients with early-stage colorectal cancer (CRC) with poor prognosis. To examine associations of prediagnostic systemic inflammation with at-diagnosis sarcopenia, and determine whether these factors interact to predict CRC survival, adjusting for age, ethnicity, sex, body mass index, stage, and cancer site. A prospective cohort of 2470 Kaiser Permanente patients with stage I to III CRC diagnosed from 2006 through 2011. Our primary measure of inflammation was the neutrophil to lymphocyte ratio (NLR). We averaged NLR in the 24 months before diagnosis (mean count = 3 measures; mean time before diagnosis = 7 mo). The reference group was NLR of less than 3, indicating low or no inflammation. Using computed tomography scans, we calculated skeletal muscle index (muscle area at the third lumbar vertebra divided by squared height). Sarcopenia was defined as less than 52 cm2/m2 and less than 38 cm2/m2 for normal or overweight men and women, respectively, and less than 54 cm2/m2 and less than 47 cm2/m2 for obese men and women, respectively. The main outcome was death (overall or CRC related). Among 2470 patients, 1219 (49%) were female; mean (SD) age was 63 (12) years. An NLR of 3 or greater and sarcopenia were common (1133 [46%] and 1078 [44%], respectively). Over a median of 6 years of follow-up, we observed 656 deaths, 357 from CRC. Increasing NLR was associated with sarcopenia in a dose-response manner (compared with NLR < 3, odds ratio, 1.35; 95% CI, 1.10-1.67 for NLR 3 to <5; 1.47; 95% CI, 1.16-1.85 for NLR ≥ 5; P for trend < .001). An NLR of 3 or greater and sarcopenia independently predicted overall (hazard ratio [HR], 1.64; 95% CI, 1.40-1.91 and HR, 1.28; 95% CI, 1.10-1.53, respectively) and CRC-related death (HR, 1.71; 95% CI, 1.39-2.12 and HR, 1.42; 95% CI, 1.13-1.78, respectively). Patients with both sarcopenia and NLR of 3 or greater (vs neither) had double the risk of death, overall (HR, 2.12; 95% CI, 1.70-2.65) and CRC related (HR, 2.43; 95% CI, 1.79-3.29). Prediagnosis inflammation was associated with at-diagnosis sarcopenia. Sarcopenia combined with inflammation nearly doubled risk of death, suggesting that these commonly collected biomarkers could enhance prognostication. A better understanding of how the host inflammatory/immune response influences changes in skeletal muscle may open new therapeutic avenues to improve cancer outcomes.
Authors: Feliciano EMC; Kroenke CH; Kwan ML; Alexeeff S; Corley D; Caan BJ; et al.
JAMA Oncol. 2017 12 01;3(12):e172319.
Monitoring Lung Cancer Screening Utilization and Outcomes in Four Cancer Research Network Sites
Lung cancer screening registries can monitor screening outcomes and improve quality of care. To describe nascent lung cancer screening programs and share efficient data collection approaches for mandatory registry reporting in four integrated health care systems of the National Cancer Institute-funded Cancer Research Network. We documented the distinctive characteristics of lung cancer screening programs, and we provide examples of strategies to facilitate data collection and describe early challenges and possible solutions. In addition, we report preliminary data on use and outcomes of screening with low-dose computed tomography at each of the participating sites. Programs varied in approaches to confirming patient eligibility, ordering screening low-dose computed tomographic scans, and coordinating follow-up care. Most data elements were collected from structured fields in electronic health records, but sites also made use of standardized order templates, local procedure codes, identifiable hashtags in radiology reports, and natural language processing algorithms. Common challenges included incomplete documentation of tobacco smoking history, difficulty distinguishing between scans performed for screening versus diagnosis or surveillance, and variable adherence with use of standardized templates. Adherence with eligibility criteria as well as the accuracy and completeness of data collection appeared to depend at least partly on availability of personnel and other resources to support the successful implementation of screening. To maximize the effectiveness of lung cancer screening, minimize the burden of data collection, and facilitate research and quality improvement, clinical workflow and information technology should be purposefully designed to ensure that patients meet eligibility criteria and receive appropriate follow-up testing.
Authors: Gould MK; Sakoda LC; Ritzwoller DP; Simoff MJ; Neslund-Dudas CM; Kushi LH; Carter-Harris L; Feigelson HS; Minowada G; Doria-Rose VP
Ann Am Thorac Soc. 2017 Dec;14(12):1827-1835.
How do Swiss general practitioners agree with and report adhering to a top-five list of unnecessary tests and treatments? Results of a cross-sectional survey
In 2014, the ‘Smarter Medicine’ campaign released a top five list of unnecessary tests and treatments in Swiss primary care, such as imaging for acute low-back pain and long-term prescribing of proton pump inhibitors. Measure general practitioners’ (GPs) agreement with the recommendations and self-reported adherence. Cross-sectional, online survey of GPs in the ‘Swiss primary care active monitoring’ (SPAM) network, which assessed awareness of ‘Smarter Medicine’ and views on each recommendation. Questions included whether the clinical situation is common, whether the recommendation is followed, whether GPs agree with the recommendation and reasons why the recommendation would not be followed. One-hundred-and-sixty-seven of 277 GPs from the SPAM network participated (60%), of which 104 (62%) knew of ‘Smarter Medicine’, including 79% in German areas, 49% in French areas and 38% in Italian areas (P?
Authors: Selby K; Cornuz J; Cohidon C; Gaspoz JM; Senn N
Eur J Gen Pract. 2017 Nov 23:1-7.
Breast Cancer Chemoprevention in an Integrated Health Care Setting
National guidelines encourage counseling high-risk women about pharmacologic breast cancer risk reduction. We evaluated the use of integrated health care data to identify and characterize breast cancer chemoprevention use. Chemoprevention included US Food and Drug Administration-approved use of tamoxifen and raloxifene and off-label use of aromatase inhibitors (AIs). Using electronic medical and pharmacy records (EMRs) in the Kaiser Permanente Northern California health care system, we sampled cancer-free women age 35 to 69 years who used tamoxifen, raloxifene, exemestane, anastrozole, or letrozole from 2005 to 2013. Risk-benefit profiles were calculated for tamoxifen and raloxifene using published indices. The proportion of days covered was calculated from pharmacy records to assess adherence. Among 90 chemoprevention users (confirmed with EMR review from a sample of 371 women), 74% used tamoxifen, 11% used raloxifene, and 13% used an AI. For tamoxifen and raloxifene users, the risk-benefit index indicated 23% of women had insufficient evidence that benefits would outweigh risks. For all agents, adherence decreased from an average proportion of days covered of 75% at 1 year to 67% at 5 years. Automated EMR searches identified breast cancer chemoprevention users with 60% positive predictive value overall and 75% for tamoxifen after post hoc modifications. Our study contributes to an emerging picture of breast cancer chemoprevention use in real-world settings, where evidence of net benefit is not uniform and nonadherence is common. Among breast cancer chemoprevention agents, our automated selection best performed for tamoxifen use. We also identified off-label use of AIs for chemoprevention, suggesting that expansion of risk-benefit indices to include AIs is warranted.
Authors: Nichols HB; Stürmer T; Lee VS; Anderson C; Lee JS; Roh JM; Visvanathan K; Muss H; Kushi LH
JCO Clin Cancer Inform. 2017 11;1:1-12.
Association Between Weight Loss and the Risk of Cancer after Bariatric Surgery
The goal of this study was to determine whether the reduction in cancer risk after bariatric surgery is due to weight loss. A retrospective matched cohort study of patients undergoing bariatric surgery was conducted using data from a large integrated health insurance and care delivery system with five sites in four states. The study included 18,355 bariatric surgery subjects and 40,524 nonsurgical subjects matched on age, sex, BMI, site, and Elixhauser comorbidity index. Multivariable Cox proportional hazards models examined the relationship between weight loss at 1 year and incident cancer during up to 10 years of follow-up. The study identified 1,196 cases of incident cancer. The average 1-year postsurgical weight loss was 27% among patients undergoing bariatric surgery versus 1% in matched nonsurgical patients. Percent weight loss at 1 year was significantly associated with a reduced risk of any cancer in adjusted models (HR 0.897, 95% CI: 0.832-0.968, P = 0.005 for every 10% weight loss) while bariatric surgery was not a significant independent predictor of cancer incidence. Weight loss after bariatric surgery was associated with a lower risk of incident cancer. There was no apparent independent effect of the bariatric surgery itself on cancer risk that was independent of weight loss.
Authors: Schauer DP; Feigelson HS; Koebnick C; Caan B; Weinmann S; Leonard AC; Powers JD; Yenumula PR; Arterburn DE
Obesity (Silver Spring). 2017 11;25 Suppl 2:S52-S57.
Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): Rationale for Study Design
Colorectal cancer (CRC) is preventable through screening, with colonoscopy and fecal occult blood testing comprising the two most commonly used screening tests. Given the differences in complexity, risk, and cost, it is important to understand these tests’ comparative effectiveness. The CONFIRM Study is a large, pragmatic, multicenter, randomized, parallel group trial to compare screening with colonoscopy vs. the annual fecal immunochemical test (FIT) in 50,000 average risk individuals. CONFIRM examines whether screening colonoscopy will be superior to a FIT-based screening program in the prevention of CRC mortality measured over 10 years. Eligible individuals 50-75 years of age and due for CRC screening are recruited from 46 Veterans Affairs (VA) medical centers. Participants are randomized to either colonoscopy or annual FIT. Results of colonoscopy are managed as per usual care and study participants are assessed for complications. Participants testing FIT positive are referred for colonoscopy. Participants are surveyed annually to determine if they have undergone colonoscopy or been diagnosed with CRC. The primary endpoint is CRC mortality. The secondary endpoints are (1) CRC incidence (2) complications of screening colonoscopy, and (3) the association between colonoscopists’ characteristics and neoplasia detection, complications and post-colonoscopy CRC. CONFIRM leverages several key characteristics of the VA’s integrated healthcare system, including a shared medical record with national databases, electronic CRC screening reminders, and a robust national research infrastructure with experience in conducting large-scale clinical trials. When completed, CONFIRM will be the largest intervention trial conducted within the VA (ClinicalTrials.gov identifier: NCT01239082).
Authors: Dominitz JA; Allison JE; Guarino PD; et al.
Am J Gastroenterol. 2017 Nov;112(11):1736-1746. Epub 2017-10-10.
A Comparison of Fecal Immunochemical and High-Sensitivity Guaiac Tests for Colorectal Cancer Screening
Annual testing using either a high-sensitivity guaiac fecal occult blood test (HS-gFOBT) or a fecal immunochemical test (FIT) is recommended for screening average-risk people for colorectal cancer. We compared the performance characteristics of the HS-gFOBT Hemoccult II SENSA and two FITs (InSure FIT and OC FIT-CHEK) for detecting advanced colorectal neoplasia. The study included 1,006 asymptomatic patients, aged 50-75 years, who were scheduled to receive a screening colonoscopy at gastroenterology practices in the Minneapolis and Indianapolis metropolitan areas. Each participant was asked to complete all three stool tests before their colonoscopy. Each test’s performance characteristics were evaluated using the screening colonoscopic results as the reference standard. Sensitivity for detecting advanced colorectal neoplasia was highest for InSure FIT (26.3%, 95% confidence interval (CI) 15.9-40.7), followed by OC FIT-CHEK (15.1%, 95% CI 6.7-26.1) and Hemoccult II SENSA (7.4%, 95% CI 1.9-17.0). InSure FIT was statistically significantly more sensitive than both OC FIT-CHEK (absolute difference in sensitivity=11.2%, 95% CI 0.4-24.2) and Hemoccult II SENSA (difference in sensitivity=18.9%, 95% CI 10.2-32.6). Specificities were relatively high for all tests (between 96.8% and 98.6%). Our results suggest that some FITs are more sensitive than the HS-gFOBT Hemoccult II SENSA, but these results need to be confirmed in larger asymptomatic populations. Comparisons between the FITs examined in this study and other FITs are needed to determine the best tests for population screening.
Authors: Shapiro JA; Bobo JK; Church TR; Rex DK; Chovnick G; Thompson TD; Zauber AG; Lieberman D; Levin TR; Joseph DA; Nadel MR
Am J Gastroenterol. 2017 Nov;112(11):1728-1735. Epub 2017-10-10.
Colorectal Cancer Screening: Money Isn’t Everything…But it Helps!
Authors: Levin TR
Gastroenterology. 2017 11;153(5):1181-1183. Epub 2017-10-04.
The co-regulatory networks of tumor suppressor genes, oncogenes, and miRNAs in colorectal cancer
Tumor suppressor genes (TSGs) and oncogenes (OG) are involved in carcinogenesis. MiRNAs also contribute to cellular pathways leading to cancer. We use data from 217 colorectal cancer (CRC) cases to evaluate differences in TSGs and OGs expression between paired CRC and normal mucosa and evaluate how TSGs and OGs are associated with miRNAs. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were used. We focus on genes most strongly associated with CRC (fold change (FC) of ≥1.5 or ≤0.67) that were statistically significant after adjustment for multiple comparisons. Of the 74 TSGs evaluated, 22 were associated with carcinoma/normal mucosa differential expression. Ten TSGs were up-regulated (FAM123B, RB1, TP53, RUNX1, MSH2, BRCA1, BRCA2, SOX9, NPM1, and RNF43); six TSGs were down-regulated (PAX5, IZKF1, GATA3, PRDM1, TET2, and CYLD); four were associated with MSI tumors (MLH1, PTCH1, and CEBPA down-regulated and MSH6 up-regulated); and two were associated with MSS tumors (PHF6 and ASXL1 up-regulated). Thirteen of these TSGs were associated with 44 miRNAs. Twenty-seven of the 59 OGs evaluated were dysregulated: 14 down-regulated (KLF4, BCL2, SSETBP1, FGFR2, TSHR, MPL, KIT, PDGFRA, GNA11, GATA2, FGFR3, AR, CSF1R, and JAK3), seven up-regulated (DNMT1, EZH2, PTPN11, SKP2, CCND1, MET, and MYC); three down-regulated for MSI (FLT3, CARD11, and ALK); two up-regulated for MSI (IDH2 and HRAS); and one up-regulated with MSS tumors (CTNNB1). These findings suggest possible co-regulatory function between TSGs, OGs, and miRNAs, involving both direct and indirect associations that operate through feedback and feedforward loops.
Authors: Slattery ML; Herrick JS; Mullany LE; Samowitz WS; Sevens JR; Sakoda L; Wolff RK
Genes Chromosomes Cancer. 2017 11;56(11):769-787. Epub 2017-07-30.
Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery
A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions. Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC). Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well. This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.
Authors: Punglia RS; Habel LA; et al.
Breast Cancer Res Treat. 2017 Oct 28.
The PI3K/AKT Signaling Pathway: associations of miRNAs with dysregulated gene expression in colorectal cancer
The PI3K/AKT-signaling pathway is one of the most frequently activated signal-transduction pathways in cancer. We examined how dysregulated gene expression is associated with miRNA expression in this pathway in colorectal cancer (CRC). We used data from 217 CRC cases to evaluate differential pathway gene expression between paired carcinoma and normal mucosa and identify miRNAs that are associated with these genes. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were analyzed. We focused on genes most associated with CRC (fold change (FC) of >1.5 or <0.67) that were statistically significant after adjustment for multiple comparisons. Of the 304 genes evaluated, 76 had a FC of <0.67, and 57 had a FC of >1.50; 47 of these genes were associated with miRNA differential expression. There were 145 mRNA:miRNA seed-region matches of which 26 were inversely associated suggesting a greater likelihood of a direct association. Most miRNA:mRNA associations were with factors that stimulated the pathway. For instance, both IL6R and PDGFRA had inverse seed-region matches with seven miRNAs, suggesting that these miRNAs have a direct effect on these genes and may be key elements in activation of the pathway. Other miRNA:mRNA associations with similar impact on the pathway were miR-203a with ITGA4, miR-6071 with ITGAV, and miR-375 with THBS2, all genes involved in extracellular matrix function that activate PI3Ks. Gene expression in the PI3K/Akt-signaling pathway is dysregulated in CRC. MiRNAs were associated with many of these dysregulated genes either directly or in an indirect manner.
Authors: Slattery ML; Mullany LE; Sakoda LC; Wolff RK; Stevens JR; Samowitz WS; Herrick JS
Mol Carcinog. 2017 Oct 25.
Interventions to Improve Follow-up of Positive Results on Fecal Blood Tests: A Systematic Review
Fecal immunochemical testing is the most commonly used method for colorectal cancer screening worldwide. However, its effectiveness is frequently undermined by failure to obtain follow-up colonoscopy after positive test results. To evaluate interventions to improve rates of follow-up colonoscopy for adults after a positive result on a fecal test (guaiac or immunochemical). English-language studies from the Cochrane Central Register of Controlled Trials, PubMed, and Embase from database inception through June 2017. Randomized and nonrandomized studies reporting an intervention for colonoscopy follow-up of asymptomatic adults with positive fecal test results. Two reviewers independently extracted data and ranked study quality; 2 rated overall strength of evidence for each category of study type. Twenty-three studies were eligible for analysis, including 7 randomized and 16 nonrandomized studies. Three were at low risk of bias. Eleven studies described patient-level interventions (changes to invitation, provision of results or follow-up appointments, and patient navigators), 5 provider-level interventions (reminders or performance data), and 7 system-level interventions (automated referral, precolonoscopy telephone calls, patient registries, and quality improvement efforts). Moderate evidence supported patient navigators and provider reminders or performance data. Evidence for system-level interventions was low. Seventeen studies reported the proportion of test-positive patients who completed colonoscopy compared with a control population, with absolute differences of -7.4 percentage points (95% CI, -19 to 4.3 percentage points) to 25 percentage points (CI, 14 to 35 percentage points). More than half of studies were at high or very high risk of bias; heterogeneous study designs and characteristics precluded meta-analysis. Patient navigators and giving providers reminders or performance data may help improve colonoscopy rates of asymptomatic adults with positive fecal blood test results. Current evidence about useful system-level interventions is scant and insufficient. National Cancer Institute. (PROSPERO: CRD42016048286).
Authors: Selby K; Baumgartner C; Levin TR; Doubeni CA; Zauber AG; Schottinger J; Jensen CD; Lee JK; Corley DA
Ann Intern Med. 2017 Oct 17;167(8):565-575. Epub 2017-10-10.
Cardiovascular disease risk and androgen deprivation therapy in patients with localised prostate cancer: a prospective cohort study
As androgen deprivation therapy (ADT) is increasingly being used in men with localised prostate cancer, our goal was to examine the association between ADT and the risk of cardiovascular disease (CVD). We conducted a prospective cohort study using records of a large health-care system in California. The study included men with newly diagnosed localised prostate cancer (1998-2008) who initially underwent active surveillance (N=7637) and were followed through 2010. We examined 10 individual CVD outcomes. Cox proportional hazard models incorporated time-varying treatment variables and controlled for race/ethnicity, age, and tumour characteristics, recurrence risk, CVD medication use, and CVD risk factors. Of the 7637 subjects, nearly 30% were exposed to ADT. In the multivariable analyses, ADT was associated with an increased risk of heart failure (adjusted HR=1.81, 95% CI 1.40-2.32) in men without preexisting CVD. Elevated risks of arrhythmia (adjusted HR=1.44, 95% CI 1.02-2.01), and conduction disorder (adjusted HR=3.11, 95% CI 1.22, 7.91) were only observed among patients with preexisting CVD. In men with clinically localised prostate cancer who were initially under active surveillance, ADT was associated with a greater risk of heart failure in men without any preexisting CVD. We also found an increased risk of arrhythmia and conduction disorder in men with preexisting CVD. This study provides the basis for identifying high-risk men treated with ADT who might benefit from regular cardiac monitoring and lifestyle modification recommendations.
Authors: Haque R; UlcickasYood M; Xu X; Cassidy-Bushrow AE; Tsai HT; Keating NL; Van Den Eeden SK; Potosky AL
Br J Cancer. 2017 Oct 10;117(8):1233-1240. Epub 2017-08-24.
Ethnic disparities in renal cell carcinoma: An analysis of Hispanic patients in a single-payer healthcare system
To investigate differences between Hispanics and non-Hispanic whites diagnosed with and treated for renal cell carcinoma in an equal access healthcare system. We carried out a retrospective cohort study within the Kaiser Permanente healthcare system using records from renal cell carcinoma cases. Ethnicity was identified as Hispanic or non-Hispanic whites. Patient characteristics, comorbidities, tumor characteristics and treatment were compared. Overall and disease-specific survival was calculated, and a Cox proportion hazard model estimated the association of ethnicity and survival. A total of 2577 patients (2152 non-Hispanic whites, 425 Hispanic) were evaluated. Hispanics were diagnosed at a younger age (59.6 years vs 65.3 years). Clear cell renal cell carcinoma was more prevalent, whereas papillary renal cell carcinoma was less common among Hispanics. Hispanics had a lower American Joint Committee on Cancer stage (I/II vs III/IV) than non-Hispanic whites (67.4% vs 62.2%). Hispanics were found to have a greater frequency of comorbidities, such as chronic kidney disease and diabetes, but were more likely to receive surgery. The presence of metastases, nodal involvement, increased tumor size, non-surgical management, increasing age and Hispanic ethnicity were independent predictors of worse cancer-specific outcome. Within an equal access healthcare system, Hispanics seem to be diagnosed at younger ages, to have greater comorbidities and to present more frequently with clear cell renal cell carcinoma compared with non-Hispanic white patients. Despite lower stage and greater receipt of surgery, Hispanic ethnicity seems to be an independent predictor of mortality. Further work is necessary to confirm these findings.
Authors: Suarez-Sarmiento A; Yao X; Hofmann JN; Syed JS; Zhao WK; Purdue MP; Chow WH; Corley D; Shuch B
Int J Urol. 2017 10;24(10):765-770. Epub 2017-09-15.
Primary care visit use after positive fecal immunochemical test for colorectal cancer screening
For some patients, positive cancer screening test results can be a stressful experience that can affect future screening compliance and increase the use of health care services unrelated to medically indicated follow-up. Among 483,216 individuals aged 50 to 75 years who completed a fecal immunochemical test to screen for colorectal cancer at a large integrated health care setting between 2007 and 2011, the authors evaluated whether a positive test was associated with a net change in outpatient primary care visit use within the year after screening. Multivariable regression models were used to evaluate the relationship between test result group and net changes in primary care visits after fecal immunochemical testing. In the year after the fecal immunochemical test, use increased by 0.60 clinic visits for patients with true-positive results. The absolute change in visits was largest (3.00) among individuals with positive test results who were diagnosed with colorectal cancer, but significant small increases also were found for patients treated with polypectomy and who had no neoplasia (0.36) and those with a normal examination and no polypectomy performed (0.17). Groups of patients who demonstrated an increase in net visit use compared with the true-negative group included patients with true-positive results (odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.54-1.66), and positive groups with a colorectal cancer diagnosis (OR, 7.19; 95% CI, 6.12-8.44), polypectomy/no neoplasia (OR, 1.37; 95% CI, 1.27-1.48), and normal examination/no polypectomy (OR, 1.24; 95% CI, 1.18-1.30). Given the large size of outreach programs, these small changes can cumulatively generate thousands of excess visits and have a substantial impact on total health care use. Therefore, these changes should be included in colorectal cancer screening cost models and their causes investigated further. Cancer 2017;123:3744-3753. © 2017 American Cancer Society.
Authors: Hillyer GC; Jensen CD; Zhao WK; Neugut AI; Lebwohl B; Tiro JA; Kushi LH; Corley DA
Cancer. 2017 Oct 01;123(19):3744-3753. Epub 2017-06-16.
Hydrochlorothiazide use is strongly associated with risk of lip cancer
The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer. To study the association between use of hydrochlorothiazide and squamous cell carcinoma of the lip. We conducted a case-control study using Danish nationwide registry data. From the Cancer Registry (2004-2012), we identified 633 case patients with squamous cell carcinoma (SCC) of the lip and matched them to 63 067 population controls using a risk-set sampling strategy. Hydrochlorothiazide use (1995-2012) was obtained from the Prescription Registry and defined according to cumulative use. Applying conditional logistic regression, we calculated odds ratios (ORs) for SCC lip cancer associated with hydrochlorothiazide use, adjusting for predefined potential confounders obtained from demographic, prescription and patient registries. Ever-use of hydrochlorothiazide was associated with an adjusted OR for SCC lip cancer of 2.1 (95% confidence interval (CI): 1.7-2.6), increasing to 3.9 (95%CI: 3.0-4.9) for high use (≥25 000 mg). There was a clear dose-response effect (P < 0.001), with the highest cumulative dose category of hydrochlorothiazide (≥100 000 mg) presenting an OR of 7.7 (95%CI: 5.7-10.5). No association with lip cancer was seen with use of other diuretics or nondiuretic antihypertensives. Assuming causality, we estimated that 11% of the SCC lip cancer cases could be attributed to hydrochlorothiazide use. Hydrochlorothiazide use is strongly associated with an increased risk of lip cancer.
Authors: Pottegård A; Hallas J; Olesen M; Svendsen MT; Habel LA; Friedman GD; Friis S
J Intern Med. 2017 Oct;282(4):322-331. Epub 2017-06-06.
Germline variation in inflammation-related pathways and risk of Barrett’s oesophagus and oesophageal adenocarcinoma
Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett’s oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA. We used data from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207 controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling, oxidative stress, human leucocyte antigen and nuclear factor-κB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. We identified a significant signal for the COX pathway in relation to BE risk (p=0.0059, false discovery rate q=0.03), and in gene-level analyses found an association with microsomal glutathione-S-transferase 1 (MGST1); (p=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Four of these were subsequently confirmed (p<5.5×10(-5)) in a meta-analysis encompassing an independent set of 1851 BE cases and 3496 controls, and are known strong expression quantitative trait loci for MGST1. Three such variants were associated with similar elevations in OA risk. This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/OA and suggests that variants in MGST1 influence disease susceptibility.
Authors: Buas MF; Risch HA; Madeleine MM; et al.
Gut. 2017 Oct;66(10):1739-1747. Epub 2016-08-02.
Multiple Gene-Environment Interactions on the Angiogenesis Gene-Pathway Impact Rectal Cancer Risk and Survival
Characterization of gene-environment interactions (GEIs) in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We analyzed data from 747 rectal cancer cases and 956 controls from the Diet, Activity and Lifestyle as a Risk Factor for Rectal Cancer study. We applied a 3-step analysis approach: first, we searched for interactions among single nucleotide polymorphisms on the pathway genes; second, we searched for interactions among the genes, both steps using Logic regression; third, we examined the GEIs significant at the 5% level using logistic regression for cancer risk and Cox proportional hazards models for survival. Permutation-based test was used for multiple testing adjustment. We identified 8 significant GEIs associated with risk among 6 genes adjusting for multiple testing: TNF (OR = 1.85, 95% CI: 1.10, 3.11), TLR4 (OR = 2.34, 95% CI: 1.38, 3.98), and EGR2 (OR = 2.23, 95% CI: 1.04, 4.78) with smoking; IGF1R (OR = 1.69, 95% CI: 1.04, 2.72), TLR4 (OR = 2.10, 95% CI: 1.22, 3.60) and EGR2 (OR = 2.12, 95% CI: 1.01, 4.46) with alcohol; and PDGFB (OR = 1.75, 95% CI: 1.04, 2.92) and MMP1 (OR = 2.44, 95% CI: 1.24, 4.81) with protein. Five GEIs were associated with survival at the 5% significance level but not after multiple testing adjustment: CXCR1 (HR = 2.06, 95% CI: 1.13, 3.75) with smoking; and KDR (HR = 4.36, 95% CI: 1.62, 11.73), TLR2 (HR = 9.06, 95% CI: 1.14, 72.11), EGR2 (HR = 2.45, 95% CI: 1.42, 4.22), and EGFR (HR = 6.33, 95% CI: 1.95, 20.54) with protein. GEIs between angiogenesis genes and smoking, alcohol, and animal protein impact rectal cancer risk. Our results support the importance of considering the biologic hypothesis to characterize GEIs associated with cancer outcomes.
Authors: Sharafeldin N; Slattery ML; Liu Q; Franco-Villalobos C; Caan BJ; Potter JD; Yasui Y
Int J Environ Res Public Health. 2017 Sep 28;14(10). Epub 2017-09-28.
Research priorities in cancer cachexia: The University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and Sarcopenia
Cancer cachexia remains understudied and there are no standard treatments available despite the publication of an international consensus definition and the completion of several large phase III intervention trials in the past 6 years. In September 2015, The University of Rochester Cancer Center NCORP Research Base led a Symposium on Cancer Cachexia and Sarcopenia with goals of reviewing the state of the science, identifying knowledge gaps, and formulating research priorities in cancer cachexia through active discussion and consensus. Research priorities that emerged from the discussion included the implementation of morphometrics into clinical decision making, establishing specific diagnostic criteria for the stages of cachexia, expanding patient selection in intervention trials, identifying clinically meaningful trial endpoints, and the investigation of exercise as an intervention for cancer cachexia. Standardizing how we define and measure cancer cachexia, targeting its complex biologic mechanisms, enrolling patients early in their disease course, and evaluating exercise, either alone or in combination, were proposed as initiatives that may ultimately result in the improved design of cancer cachexia therapeutic trials.
Authors: Dunne RF; Cole CL; Mohile SG; et al.
Curr Opin Support Palliat Care. 2017 Sep 27.
CHILDHOOD SOCIOECONOMIC POSITION AND PUBERTAL ONSET IN A COHORT OF MULTIETHNIC GIRLS: IMPLICATIONS FOR BREAST CANCER
Background: Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with earlier age of pubertal onset, a risk factor for breast cancer, is less clear.Methods: We studied the relationship of SEP to pubertal onset in a multiethnic cohort of 1,237 girls ages 6 to 8 years at baseline. Girls in three U.S. cities were followed for 5 to 8 years with annual clinical examinations from 2004 to 2012. SEP measures were examined for associations with pubertal onset, assessed by breast budding (thelarche) and pubic hair development (adrenarche). Analyses were conducted with accelerated failure time models using a Weibull distribution, with left, right, and interval censoring.Results: Higher body mass index percentage at entry to the study and black or Hispanic race/ethnicity were the strongest predictors of age at pubertal onset. An SEP index comprising household family income, mother’s education, and home ownership was an independent predictor of thelarche in adjusted models for all girls together and for white and Latina, separately, but not black girls, and the relationship varied by study site. The SEP index was not related to adrenarche in adjusted models. Overall, girls from the lowest quintile of SEP entered puberty on average 6% earlier than girls from the highest quintile (time ratio = 0.94; 95% confidence interval 0.91-0.97) in adjusted models.Conclusions: Our results suggest that early-life SEP may influence the timing of pubertal development.Impact: Factors related to lower SEP in childhood can adversely affect early development in ways that may increase the risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1714-21. ©2017 AACR.
Authors: Hiatt RA; Stewart SL; Hoeft KS; Kushi LH; Windham GC; Biro FM; Pinney SM; Wolff MS; Teitelbaum SL; Braithwaite D
Cancer Epidemiol Biomarkers Prev. 2017 Sep 22.
Muscle mass at the time of diagnosis of nonmetastatic colon cancer and early discontinuation of chemotherapy, delays, and dose reductions on adjuvant FOLFOX: The C-SCANS study
For many chemotherapy regimens dosed based on body surface area (BSA), patients experience dose reductions or delays or discontinue treatment, thereby reducing survival. Consideration of body composition may be useful in individualizing chemotherapy dosing, but to the authors’ knowledge few studies to date have examined the association of body composition with chemotherapy tolerance in patients with colon cancer. The authors identified patients with nonmetastatic colon cancer who were diagnosed from 2006 through 2011 at Kaiser Permanente and who received leucovorin calcium/calcium folinate, 5-fluorouracil, and oxaliplatin (FOLFOX) as initial adjuvant chemotherapy (533 patients). Patients’ muscle mass was quantified using clinically acquired computed tomography scans. The authors quantified chemotherapy doses, treatment dates, and related toxicities using the electronic medical record. In logistic regression models adjusting for age, sex, and American Joint Committee on Cancer stage of disease, the authors examined associations of muscle tertiles with early treatment discontinuation (<6 cycles), treatment delay (>3 days off schedule for ≥3 times), and/or dose reduction (relative dose intensity ≤ 0.70, based on planned treatment). The average age of the patients at the time of diagnosis was 58.7 years; BSA was 1.9 m2 and body mass index was 28.7 kg/m2 . Compared with the highest sex-specific tertile of muscle mass, patients in the lowest tertile were more likely to experience toxicities and had twice the risk of adverse outcomes while receiving FOLFOX; for early discontinuation, the odds ratio (OR) was 2.34 (95% confidence interval [95% CI], 1.04-5.24; P for trend = .03), whereas the ORs were 2.24 (95% CI, 1.37-3.66; P for trend = .002) for treatment delay and 2.28 (95% CI, 1.19-4.36; P for trend = .01) for dose reduction. Lower muscle mass is associated with greater toxicity and poor chemotherapy adherence among patients receiving FOLFOX. Many chemotherapy drugs are dosed based on BSA, but treatment may be better individualized if muscle mass is considered. Cancer 2017;123:4868-77. © 2017 American Cancer Society.
Authors: Cespedes Feliciano EM; Lee VS; Prado CM; Meyerhardt JA; Alexeeff S; Kroenke CH; Xiao J; Castillo AL; Caan BJ
Cancer. 2017 Sep 07.
Age at menarche and late adolescent adiposity associated with mammographic density on processed digital mammograms in 24,840 women
Background: High mammographic density is strongly associated with increased breast cancer risk. Some, but not all, risk factors for breast cancer are also associated with higher mammographic density.Methods: The study cohort (N = 24,840) was drawn from the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California and included non-Hispanic white females ages 40 to 74 years with a full-field digital mammogram (FFDM). Percent density (PD) and dense area (DA) were measured by a radiological technologist using Cumulus. The association of age at menarche and late adolescent body mass index (BMI) with PD and DA were modeled using linear regression adjusted for confounders.Results: Age at menarche and late adolescent BMI were negatively correlated. Age at menarche was positively associated with PD (P value for trend <0.0001) and DA (P value for trend <0.0001) in fully adjusted models. Compared with the reference category of ages 12 to 13 years at menarche, menarche at age >16 years was associated with an increase in PD of 1.47% (95% CI, 0.69-2.25) and an increase in DA of 1.59 cm2 (95% CI, 0.48-2.70). Late adolescent BMI was inversely associated with PD (P < 0.0001) and DA (P < 0.0001) in fully adjusted models.Conclusions: Age at menarche and late adolescent BMI are both associated with Cumulus measures of mammographic density on processed FFDM images.Impact: Age at menarche and late adolescent BMI may act through different pathways. The long-term effects of age at menarche on cancer risk may be mediated through factors besides mammographic density. Cancer Epidemiol Biomarkers Prev; 26(9); 1450-8. ©2017 AACR.
Authors: Alexeeff SE; Habel LA; et al.
Cancer Epidemiol Biomarkers Prev. 2017 Sep;26(9):1450-1458. Epub 2017-07-11.
Genetic Ancestry Is not Associated with Breast Cancer Recurrence or Survival in U.S. Latina Women Enrolled in the Kaiser Permanente Pathways Study
Background: The U.S. Hispanic/Latino population is heterogeneous both socioculturally and by the proportion of European, Indigenous American, and African ancestry of the regions from which individuals originate. A previous study reported that genetic ancestry was associated with breast cancer survival among Latinas, independent of sociodemographic and tumor characteristics, suggesting that a genetic factor associated with ancestry may affect breast cancer survival.Methods: We evaluated the association of genetic ancestry with breast cancer outcomes among 506 Latina women with invasive breast cancer in the Pathways Study, a cohort study within Kaiser Permanente, an integrated health care delivery system. Proportional hazards models were used to assess the effect of ancestry on breast cancer recurrence (53 events), breast cancer-specific mortality (31 events) and all-cause mortality (54 events), with a mean follow-up time of 6 years.Results: Indigenous American ancestry was not associated with breast cancer recurrence [HR = 1.00 per 10% increase; 95% confidence interval (CI), 0.86-1.16], breast cancer mortality (HR = 0.95; 95% CI, 0.77-1.17), or all-cause mortality (HR = 0.93; 95% CI, 0.80-1.08). Adjustment for sociodemographic variables, tumor characteristics, and treatment did not alter the associations.Conclusions: Our results suggest that previously reported differences in breast cancer survival by genetic ancestry may be overcome by improving health care access and/or quality.Impact: Improving health care access and quality may reduce breast cancer disparities among U.S. Latinas. Cancer Epidemiol Biomarkers Prev; 26(9); 1466-9. ©2017 AACR.
Authors: Engmann NJ; Ergas IJ; Yao S; Kwan ML; Roh JM; Ambrosone CB; Kushi LH; Fejerman L
Cancer Epidemiol Biomarkers Prev. 2017 Sep;26(9):1466-1469.
Dietary sugar/starches intake and Barrett’s esophagus: a pooled analysis
Barrett’s esophagus (BE) is the key precursor lesion of esophageal adenocarcinoma, a lethal cancer that has increased rapidly in westernized countries over the past four decades. Dietary sugar intake has also been increasing over time, and may be associated with these tumors by promoting hyperinsulinemia. The study goal was to examine multiple measures of sugar/starches intake in association with BE. This pooled analysis included 472 BE cases and 492 controls from two similarly conducted case-control studies in the United States. Dietary intake data, collected by study-specific food frequency questionnaires, were harmonized across studies by linking with the University of Minnesota Nutrient Database, and pooled based on study-specific quartiles. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, race, total energy intake, study indicator, body mass index, frequency of gastro-esophageal reflux, and fruit/vegetable intake. In both studies, intake of sucrose (cases vs. controls, g/day: 36.07 vs. 33.51; 36.80 vs. 35.06, respectively) and added sugar (46.15 vs. 41.01; 44.18 vs. 40.68, respectively) were higher in cases than controls. BE risk was increased 79% and 71%, respectively, for associations comparing the fourth to the first quartile of intake of sucrose (ORQ4vs.Q1 = 1.79, 95% CI = 1.07-3.02, P trend = 0.01) and added sugar (ORQ4vs.Q1 = 1.71, 95% CI = 1.05-2.80, P trend = 0.15). Intake of sweetened desserts/beverages was associated with 71% increase in BE risk (ORQ4vs.Q1 = 1.71, 95% CI = 1.07-2.73, P trend = 0.04). Limiting dietary intake of foods and beverages that are high in added sugar, especially refined table sugar, may reduce the risk of developing BE.
Authors: Li N; Petrick JL; Steck SE; Bradshaw PT; McClain KM; Niehoff NM; Engel LS; Shaheen NJ; Corley DA; Vaughan TL; Gammon MD
Eur J Epidemiol. 2017 Sep 01.
Age at Pubertal Onset in Girls and Tobacco Smoke Exposure during Pre- and Post-natal Susceptibility Windows
Tobacco smoke contains known hormonally active chemicals and reproductive toxicants. Several studies have examined prenatal maternal smoking and offspring age at menarche, but few examined earlier pubertal markers, nor accounted for exposure during childhood. Our objective was to examine pre- and postnatal smoke exposure in relation to timing of early pubertal events. An ethnically diverse cohort of 1239 girls was enrolled at age 6-8 years old for a longitudinal study of puberty at three US sites. Girls participated in annual or semi-annual exams to measure anthropometry and Tanner breast and pubic hair stages. Prenatal and current tobacco smoke exposures, as well as covariates, were obtained from parent questionnaire. Cotinine was measured in urine collected at enrollment. Using accelerated failure time models, we calculated adjusted time ratios for age at pubertal onset (maturation stages 2 or higher) and smoke exposure. Girls with higher prenatal (≥5 cigarettes per day) or secondhand smoke exposure had earlier pubic hair development than unexposed (adjusted time ratio: 0.92 [95% CI = 0.87, 0.97] and 0.94 [95% CI = 0.90, 0.97], respectively). Including both exposures in the same model yielded similar associations. Higher urinary cotinine quartiles were associated with younger age at breast and pubic hair onset in unadjusted models, but not after adjustment. Greater prenatal and childhood secondhand smoke exposure were associated with earlier onset of pubic hair, but not breast, development. These exposures represent modifiable risk factors for early pubertal development that should be considered for addition to the extensive list of adverse effects from tobacco smoke.
Authors: Windham GC; Kushi LH; et al.
Epidemiology. 2017 Sep;28(5):719-727.
Phenol concentrations during childhood and subsequent measures of adiposity among young girls
Phenolic compounds represent a class of environmental chemicals with potentially endocrine-disrupting capabilities. We investigated longitudinal associations between childhood exposure to phenols, from both manmade and natural sources, and subsequent measures of adiposity among girls enrolled in the Breast Cancer and the Environment Research Program between 2004 and 2007. Baseline (ages 6-8 years) urinary concentrations were obtained for creatinine and phenol metabolites: enterolactone, genistein, daidzein, benzophenone-3, bisphenol A, the sum of parabens (methyl, ethyl, and propyl parabens), 2,5-dichlorophenol, and triclosan. Body mass index (weight (kg)/height (m)2), waist circumference, and percent body fat were measured at annual or semiannual examinations through 2015 (n = 1,017). Linear mixed-effects regression was used to estimate how baseline concentrations of phenols (tertile groups) were related to changes in girls’ adiposity measurements from ages 7 through 15 years. Enterolactone was inversely associated with body mass index, waist circumference, and percent body fat, while 2,5-dichlorophenol was positively associated with these measurements. A nonmonotonic association was observed for triclosan and girls’ adiposity; however, it was due to effect modification by baseline overweight status. Triclosan was positively associated with adiposity only among overweight girls. These results suggest that exposure to specific phenols during childhood may influence adiposity through adolescence.
Authors: Deierlein AL; Wolff MS; Pajak A; Pinney SM; Windham GC; Galvez MP; Rybak M; Calafat AM; Kushi LH; Biro FM; Teitelbaum SL
Am J Epidemiol. 2017 Sep 01;186(5):581-592.
Colorectal Cancer Screening Initiation After Age 50 Years in an Organized Program
Recent studies report racial disparities among individuals in organized colorectal cancer (CRC) programs; however, there is a paucity of information on CRC screening utilization by race/ethnicity among newly age-eligible adults in such programs. This was a retrospective cohort study among Kaiser Permanente Northern California enrollees who turned age 50 years between 2007 and 2012 (N=138,799) and were served by a systemwide outreach and facilitated in-reach screening program based primarily on mailed fecal immunochemical tests to screening-eligible people. Kaplan-Meier and Cox model analyses were used to estimate differences in receipt of CRC screening in 2015-2016. Cumulative probabilities of CRC screening within 1 and 2 years of subjects’ 50th birthday were 51% and 73%, respectively. Relative to non-Hispanic whites, the likelihood of completing any CRC screening was similar in blacks (hazard ratio, 0.98; 95% CI=0.96, 1.00); 5% lower in Hispanics (hazard ratio, 0.95; 95% CI=0.93, 0.96); and 13% higher in Asians (hazard ratio, 1.13; 95% CI=1.11, 1.15) in adjusted analyses. Fecal immunochemical testing was the most common screening modality, representing 86% of all screening initiations. Blacks and Hispanics had lower receipt of fecal immunochemical testing in adjusted analyses. CRC screening uptake was high among newly screening-eligible adults in an organized CRC screening program, but Hispanics were less likely to initiate screening near age 50 years than non-Hispanic whites, suggesting that cultural and other individual-level barriers not addressed within the program likely contribute. Future studies examining the influences of culturally appropriate and targeted efforts for screening initiation are needed.
Authors: Fedewa SA; Corley DA; Jensen CD; Zhao W; Goodman M; Jemal A; Ward KC; Levin TR; Doubeni CA
Am J Prev Med. 2017 Sep;53(3):335-344. Epub 2017-04-17.
Physicians’ Perceptions of Factors Influencing the Treatment Decision-Making Process for Men with Low-Risk Prostate Cancer
To assess physicians’ attitudes regarding multiple factors that may influence recommendations for active surveillance (AS) vs active treatment (AT) given the central role physicians play in the treatment decision-making process. We conducted semistructured interviews to assess factors that physicians consider important when recommending AS vs AT, as well as physicians’ perceptions of what their patients consider important in the decision. Participants included urologists (N = 11), radiation oncologists (N = 12), and primary care physicians (N = 10) from both integrated and fee-for-service healthcare settings. Across the specialties, quantitative data indicated that most physicians reported that their recommendations for AS were influenced by patients’ older age, willingness and ability to follow a surveillance protocol, anxiety, comorbidities, life expectancy, and treatment preferences. Qualitative findings highlighted physicians’ concerns about malpractice lawsuits, given the possibility of disease progression. Additionally, most physicians noted the role of the healthcare setting, suggesting that financial incentives may be associated with AT recommendations in fee-for-service settings. Finally, most physicians reported spouse or family opposition to AS due to their own anxiety or lack of understanding of AS. We found that patient and physician preferences, healthcare setting, and family or spouse factors influence physicians’ treatment recommendations for men with low-risk PCa. These were consistent themes across physician subspecialties in both an Health Maintenance Organization and in fee-for-service settings.
Authors: Davis K; Bellini P; Hagerman C; Zinar R; Leigh D; Hoffman R; Aaronson D; Van Den Eeden S; Philips G; Taylor K
Urology. 2017 09;107:86-95. Epub 2017-04-25.
Effect of depression before breast cancer diagnosis on mortality among postmenopausal women
Few previous studies investigating depression before the diagnosis of breast cancer and breast cancer-specific mortality have examined depression measured at more than 1 time point. This study investigated the effect of depression (combining depressive symptoms alone with antidepressant use) measured at 2 time points before the diagnosis of breast cancer on all-cause mortality and breast cancer-specific mortality among older postmenopausal women. A large prospective cohort, the Women’s Health Initiative, was used. The study included 3095 women with incident breast cancer who had measures of depressive symptoms and antidepressant use before their diagnosis at the baseline and at year 3. Multivariate Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) between depression at the baseline, depression at year 3, and combinations of depression at these time points and all-cause mortality and breast cancer-specific mortality. Depression at year 3 before a breast cancer diagnosis was associated with higher all-cause mortality after adjustments for multiple covariates (HR, 1.35; 95% confidence interval [CI], 1.02-1.78). There was no statistically significant association of baseline depression and all-cause mortality or breast cancer-specific mortality whether or not depression was also present at year 3. In women with late-stage (regional- or distant-stage) breast cancer, newly developed depression at year 3 was significantly associated with both all-cause mortality (HR, 2.00; 95% CI, 1.13-3.56) and breast cancer-specific mortality (HR, 2.42; 95% CI, 1.24-4.70). Women with newly developed depression before the diagnosis of breast cancer had a modestly but significantly increased risk for death from any cause and for death from breast cancer at a late stage. Cancer 2017;123:3107-15. © 2017 American Cancer Society.
Authors: Liang X; Qi L; Luo J; et al.
Cancer. 2017 Aug 15;123(16):3107-3115. Epub 2017-04-07.
The Reply
Authors: Lo Re V; Carbonari DM; Lewis JD; Roy JA; Corley DA
Am J Med. 2017 Aug;130(8):e369.
Time to Diagnostic Testing After a Positive Colorectal Cancer Screening Test
Authors: Doubeni CA; Corley DA; Levin TR
JAMA. 2017 Aug 01;318(5):483.
Vitamin D and Breast Cancer Survival-In Reply
Authors: Yao S; Ambrosone CB; Kushi LH
JAMA Oncol. 2017 08 01;3(8):1139-1140.
Statin use and risk of multiple myeloma: An analysis from the Cancer Research Network
Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US population, with an emphasis on accounting for this potential bias. We conducted a case-control study nested within 6 US integrated healthcare systems participating in the National Cancer Institute-funded Cancer Research Network. Adults aged ≥40 years who were diagnosed with multiple myeloma from 1998-2008 were identified through cancer registries (N = 2,532). For each case, five controls were matched on age, sex, health plan, and membership duration prior to diagnosis/index date. Statin prescriptions were ascertained from electronic pharmacy records. To address potential biases related to lipid levels and medication prescribing practices, multivariable marginal structural models were used to model statin use (≥6 cumulative months) and risk of multiple myeloma, with examination of multiple latency periods. Statin use 48-72 months prior to diagnosis/index date was associated with a suggestive 20-28% reduced risk of developing multiple myeloma, compared to non-users. Recent initiation of statins was not associated with myeloma risk (risk ratio range 0.90-0.99 with 0-36 months latency). Older patients had more consistent protective associations across all latency periods (risk ratio range 0.67-0.87). Our results suggest that the association between statin use and multiple myeloma risk may vary by exposure window and age. Future research is warranted to investigate the timing of statin use in relation to myeloma diagnosis.
Authors: Epstein MM; Habel LA; Johnson CC; et al.
Int J Cancer. 2017 08 01;141(3):480-487. Epub 2017-05-15.
Prognostics factors and survival in acral lentiginous melanoma
Acral lentiginous melanoma (ALM) is a rare melanoma subtype that disproportionately afflicts people of colour. ALMs have a worse prognosis than other melanoma subtypes; this has been attributed to aggressive biological behaviour, more advanced stage at presentation and possible disparities in access to health care. To examine, using comprehensive patient data and long-term follow-up information in a well-characterized cohort, how patient, tumour and clinical management variables impact overall and melanoma-specific survival. We characterized a consecutive cohort of 123 ALMs diagnosed from 1987 to 2013 and analysed predictors of overall and melanoma-specific survival for their association with survival. Univariate hazard ratios and 95% confidence intervals using Cox regression models showed that increased Breslow depth, presence of ulceration, receipt of radiation, chemo- and vaccine therapy were associated with worse melanoma-specific survival. Notably, nonwhite race/ethnicity was not associated with worse overall or melanoma-specific survival. Multivariate modelling adjusting for patient, tumour and management variables revealed Breslow depth > 2 mm and disease extent as significantly associated with poor melanoma-specific survival. Melanoma-specific mortality among patients with ALM is associated with increased tumour thickness and more advanced stage at presentation, but not with race/ethnicity. Advanced tumour features at presentation and access to care may account for less favourable survival outcomes reported among nonwhite patients.
Authors: Asgari MM; Shen L; Sokil MM; Yeh I; Jorgenson E
Br J Dermatol. 2017 Aug;177(2):428-435. Epub 2017-07-28.
Health care disparities among octogenarians and nonagenarians with stage II and III rectal cancer.
BACKGROUND: Octogenarians and nonagenarians with stage II/III rectal adenocarcinomas are underrepresented in the randomized trials that have established the standard-of-care therapy of preoperative chemoradiation followed by definitive resection (ie, chemoradiation and then surgery [CRT+S]). The purpose of this study was to evaluate the impact of therapies on overall survival (OS) for patients with stage II/III rectal cancers and determine predictors of therapy within the National Cancer Data Base (NCDB). METHODS: In the NCDB, patients who were 80 years old or older and had clinical stage II/III rectal adenocarcinoma from 2004 to 2013 were queried. Kaplan-Meier analysis, log-rank testing, logistic regression, Cox proportional hazards regression, interaction effect testing, and propensity score-matched analysis were conducted. RESULTS: The criteria were met by 2723 patients: 14.9% received no treatment, 29.7% had surgery alone, 5.0% underwent short-course radiation and then surgery (RT+S), 45.3% underwent CRT+S, and 5.1% underwent surgery and then chemoradiation (S+CRT). African American race and residence in a less educated county were associated with not receiving treatment. Male sex, older age, worsening comorbidities, and receiving no treatment or undergoing surgery alone were associated with worse OS. There was no statistical difference in OS between RT+S, S+CRT, and CRT+S. Interaction testing found that CRT+S improved OS independently of age, comorbidity status, sex, race, and tumor stage. In the propensity score-matched analysis, CRT+S was associated with improved OS in comparison with surgery alone. CONCLUSIONS: A significant portion of octogenarians and nonagenarians with stage II/III rectal adenocarcinomas do not receive treatment. African American race and living in a less educated community are associated with not receiving therapy. This series suggests that CRT+S is a reasonable strategy for elderly patients who can tolerate therapy. Cancer 2017;123:4325-36. (c) 2017 American Cancer Society.
Authors: Cassidy RJ; Switchenko JM; Cheng E; Jiang R; Jhaveri J; Patel KR; Tanenbaum DG; Russell MC; Steuer CE; Gillespie TW; McDonald MW; Landry JC
Cancer. 2017 Nov 15;123(22):4325-4336. doi: 10.1002/cncr.30896. Epub 2017 Jul 31.
Endoscopy is of low yield in the identification of gastrointestinal neoplasia in patients with dermatomyositis: A cross-sectional study.
AIM: To determine the prevalence of gastrointestinal neoplasia among dermatomyositis patients who underwent an esophagogastroduodenoscopy and/or colonoscopy.METHODS: A cross-sectional study examining the results of upper endoscopy and colonoscopy in adults with dermatomyositis at an urban, university hospital over a ten year period was performed. Chart review was performed to confirm the diagnosis of dermatomyositis. Findings on endoscopy were collected and statistical analyses stratified by age and presence of symptoms were performed. RESULTS: Among 373 adult patients identified through a code based search strategy, only 163 patients had dermatomyositis confirmed by chart review. Of the 47 patients who underwent upper endoscopy, two cases of Barrett’s esophagus without dysplasia were identified and there were no cases of malignancy. Of the 67 patients who underwent colonoscopy, no cases of malignancy were identified and an adenoma was identified in 15% of cases. No significant differences were identified in the yield of endoscopy when stratified by age or presence of symptoms. CONCLUSION: The yield of endoscopy is low in patients with dermatomyositis and is likely similar to the general population; we identified no cases of malignancy. A code based search strategy is inaccurate for the diagnosis of dermatomyositis, calling into question the results of prior population-based studies. Larger studies with rigorously validated search strategies are necessary to understand the risk of gastrointestinal malignancy in patients with dermatomyositis.
Authors: Kidambi, Trilokesh D TD; Schmajuk, Gabriela G; Gross, Andrew J AJ; Ostroff, James W JW; Terdiman, Jonathan P JP; Lee, Jeffrey K JK
World journal of gastroenterology. 2017 Jul 14;23(26):4788-4795. Epub --.
Impact of body mass index on ovarian cancer survival varies by stage
Research on the effect of body mass index (BMI) on ovarian cancer survival is inconsistent, but previous studies did not consider the possible impact of ascites, bowel obstruction, or cachexia, which commonly occur in late-stage disease. We evaluated the association of BMI, before and around the time of diagnosis, with overall and disease-specific survival in a cohort study of primary invasive epithelial ovarian cancers diagnosed from 2000 to 2013 in Kaiser Permanente Northern California (KPNC) (n=1184). Deaths were identified through December 2014, with a median follow-up of 37 months. Proportional hazards regression was used to estimate overall and ovarian cancer-specific mortality, accounting for prognostic variables including age at diagnosis, race, stage, grade, histology, comorbidities, treatment, post-treatment CA125 levels, ascites, and bowel obstruction. There was no evidence of an association between BMI and overall or ovarian cancer-specific survival. However, we found strong effect modification by stage (Pinteraction<0.01). Compared with normal prediagnosis BMI (18.5-24.9 kg m-2), for women who were obese before diagnosis (BMI⩾35 kg m-2) ovarian cancer-specific survival was lower among those diagnosed at stages I/II (hazard ratio (HR): 3.40; 95% confidence interval (CI): 1.16-9.99), but increased among those diagnosed with stage IV disease (HR: 0.58; 95% CI: 0.35-0.96). Associations were attenuated after excluding those diagnosed with cachexia (n=82) and further adjustment for ascites and bowel obstruction, with no evidence of effect modification by these factors. Associations of obesity with ovarian cancer survival may differ by stage, with decreased survival among those with localised disease and increased survival among those with late-stage disease. Stage-specific effects of obesity on survival suggest a tailored approach to improve prognosis may be appropriate.
Authors: Bandera EV; Lee VS; Qin B; Rodriguez-Rodriguez L; Powell CB; Kushi LH
Br J Cancer. 2017 Jul 11;117(2):282-289. Epub 2017-06-06.
Colorectal cancer screening: Recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer
Authors: Rex DK; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Levin TR; Lieberman D; Robertson DJ
Gastrointest Endosc. 2017 Jul;86(1):18-33. Epub 2017-06-06.
Colorectal Cancer Screening: Recommendations for Physicians and Patients From the U.S. Multi-Society Task Force on Colorectal Cancer
This document updates the colorectal cancer (CRC) screening recommendations of the U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gastroenterological Association, and The American Society for Gastrointestinal Endoscopy. CRC screening tests are ranked in 3 tiers based on performance features, costs, and practical considerations. The first-tier tests are colonoscopy every 10 years and annual fecal immunochemical test (FIT). Colonoscopy and FIT are recommended as the cornerstones of screening regardless of how screening is offered. Thus, in a sequential approach based on colonoscopy offered first, FIT should be offered to patients who decline colonoscopy. Colonoscopy and FIT are recommended as tests of choice when multiple options are presented as alternatives. A risk-stratified approach is also appropriate, with FIT screening in populations with an estimated low prevalence of advanced neoplasia and colonoscopy screening in high prevalence populations. The second-tier tests include CT colonography every 5 years, the FIT-fecal DNA test every 3 years, and flexible sigmoidoscopy every 5 to 10 years. These tests are appropriate screening tests, but each has disadvantages relative to the tier 1 tests. Because of limited evidence and current obstacles to use, capsule colonoscopy every 5 years is a third-tier test. We suggest that the Septin9 serum assay (Epigenomics, Seattle, Wash) not be used for screening. Screening should begin at age 50 years in average-risk persons, except in African Americans in whom limited evidence supports screening at 45 years. CRC incidence is rising in persons under age 50, and thorough diagnostic evaluation of young persons with suspected colorectal bleeding is recommended. Discontinuation of screening should be considered when persons up to date with screening, who have prior negative screening (particularly colonoscopy), reach age 75 or have <10 years of life expectancy. Persons without prior screening should be considered for screening up to age 85, depending on age and comorbidities. Persons with a family history of CRC or a documented advanced adenoma in a first-degree relative age <60 years or 2 first-degree relatives with these findings at any age are recommended to undergo screening by colonoscopy every 5 years, beginning 10 years before the age at diagnosis of the youngest affected relative or age 40, whichever is earlier. Persons with a single first-degree relative diagnosed at ≥60 years with CRC or an advanced adenoma can be offered average-risk screening options beginning at age 40 years.
Authors: Rex DK; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Levin TR; Lieberman D; Robertson DJ
Gastroenterology. 2017 Jul;153(1):307-323. Epub 2017-06-09.
The Troublesome Epidemiology of Barrett’s Esophagus and Esophageal Adenocarcinoma
Barrett’s esophagus and esophageal adenocarcinoma diagnoses have increased markedly in recent decades. Recent research with patients diagnosed with Barrett’s esophagus (the only known precursor for esophageal adenocarcinoma) and esophageal adenocarcinoma has identified several modifiable and nonmodifiable potential risk factors. Consistent risk factors for both disorders include increasing age, male sex, white non-Hispanic race/ethnicity, gastroesophageal reflux disease, lack of infection with Helicobacter pylori, smoking, abdominal obesity, and a Western diet. The authors present detailed discussions of these risk factors along with possible explanations for some apparent discrepancies and ideas for future study.
Authors: Schneider JL; Corley DA
Gastrointest Endosc Clin N Am. 2017 Jul;27(3):353-364.
Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer
This document updates the colorectal cancer (CRC) screening recommendations of the U.S. Multi-Society Task Force of Colorectal Cancer (MSTF), which represents the American College of Gastroenterology, the American Gastroenterological Association, and The American Society for Gastrointestinal Endoscopy. CRC screening tests are ranked in 3 tiers based on performance features, costs, and practical considerations. The first-tier tests are colonoscopy every 10 years and annual fecal immunochemical test (FIT). Colonoscopy and FIT are recommended as the cornerstones of screening regardless of how screening is offered. Thus, in a sequential approach based on colonoscopy offered first, FIT should be offered to patients who decline colonoscopy. Colonoscopy and FIT are recommended as tests of choice when multiple options are presented as alternatives. A risk-stratified approach is also appropriate, with FIT screening in populations with an estimated low prevalence of advanced neoplasia and colonoscopy screening in high prevalence populations. The second-tier tests include CT colonography every 5 years, the FIT-fecal DNA test every 3 years, and flexible sigmoidoscopy every 5 to 10 years. These tests are appropriate screening tests, but each has disadvantages relative to the tier 1 tests. Because of limited evidence and current obstacles to use, capsule colonoscopy every 5 years is a third-tier test. We suggest that the Septin9 serum assay (Epigenomics, Seattle, Wash) not be used for screening. Screening should begin at age 50 years in average-risk persons, except in African Americans in whom limited evidence supports screening at 45 years. CRC incidence is rising in persons under age 50, and thorough diagnostic evaluation of young persons with suspected colorectal bleeding is recommended. Discontinuation of screening should be considered when persons up to date with screening, who have prior negative screening (particularly colonoscopy), reach age 75 or have <10 years of life expectancy. Persons without prior screening should be considered for screening up to age 85, depending on age and comorbidities. Persons with a family history of CRC or a documented advanced adenoma in a first-degree relative age <60 years or 2 first-degree relatives with these findings at any age are recommended to undergo screening by colonoscopy every 5 years, beginning 10 years before the age at diagnosis of the youngest affected relative or age 40, whichever is earlier. Persons with a single first-degree relative diagnosed at ≥60 years with CRC or an advanced adenoma can be offered average-risk screening options beginning at age 40 years.
Authors: Rex DK; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Levin TR; Lieberman D; Robertson DJ
Am J Gastroenterol. 2017 Jul;112(7):1016-1030. Epub 2017-06-06.
Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)
Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival.Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer-specific mortality (CRCsM).Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09-1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and <30 kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity.Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker.Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008-15. ©2017 AACR.
Authors: Caan BJ; Meyerhardt JA; Kroenke CH; Alexeeff S; Xiao J; Weltzien E; Feliciano EC; Castillo AL; Quesenberry CP; Kwan ML; Prado CM
Cancer Epidemiol Biomarkers Prev. 2017 07;26(7):1008-1015. Epub 2017-05-15.
Body mass index, PAM50 subtype, recurrence and survival among patients with nonmetastatic breast cancer
Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype. This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013. Patients reported weight and height. Cox regression models were adjusted for age, menopause, race/ethnicity, stage, and chemotherapy. Over a median of 9 years (maximum, 19 years), 378 women developed recurrent disease, and 312 died from breast cancer. Overall, BMI was not associated with breast cancer recurrence or survival when controlling for subtype (eg, the hazard ratio per 5 kg/m2 of BMI was 1.05 [95% confidence interval, 0.95-1.15] for breast cancer-specific death). However, associations varied by subtype. Among women with luminal A cancers, those who had class II/III obesity, but not class I obesity or overweight, had worse outcomes. When women who had a BMI ≥35 kg/m2 were compared with those who had a BMI from 18.5 to <25 kg/m2 , the hazard ratio was 2.24 (95% confidence interval,1.22-4.11) for breast cancer-specific death and 1.24 (95% confidence interval, 1.00-1.54) for recurrence. There was no association within luminal B, basal-like or human epidermal growth factor over-expressing subtypes. Among patients who had accurately classified breast cancer subtypes based on gene expression, a BMI ≥35 kg/m2 was adversely associated with outcomes only among those who had luminal A cancers. Research is needed into whether tailoring recommendations for weight management to tumor characteristics will improve outcomes. Cancer 2017;123:2535-42. © 2017 American Cancer Society.
Authors: Cespedes Feliciano EM; Kwan ML; Kushi LH; Chen WY; Weltzien EK; Castillo AL; Sweeney C; Bernard PS; Caan BJ
Cancer. 2017 Jul 01;123(13):2535-2542. Epub 2017-03-13.
Comparison of recruitment and retention among demographic subgroups in a large diverse population study of diet
We examined the feasibility of conducting a longitudinal study of diet among diverse populations by comparing rates of response throughout recruitment and retention phases by demographic and other characteristics. Using quota sampling, participants were recruited from 3 geographically and demographically diverse integrated health systems in the United States. Overall, 12,860 adults, ages 20-70, were invited to participate via mail. Participation first required accessing the study’s website and later meeting eligibility criteria via telephone interview. Enrollees were asked to provide two 24-hour dietary recalls, either interviewer-administered or self-administered on the web, over 6 weeks. Stepped monetary incentives were provided. Rates for accessing the study website ranged from 6% to 23% (9% overall) across sites. Site differences may reflect differences in recruitment strategy or target samples. Of those accessing the website, enrollment was high (≥ 87%). Of the 1185 enrollees, 42% were non-Hispanic white, 34% were non-Hispanic black, and 24% were Hispanic. Men and minorities had lower enrollment rates than women and non-Hispanic whites, partially due to less successful telephone contact for eligibility screening. Once enrolled, 90% provided 1 recall and 80% provided both. Women had higher retention rates than men, as did older compared to younger participants. Retention rates were similar across race/ethnicity groups. While study recruitment remains challenging, once recruited most participants, regardless of race/ethnicity, completed two 24-hour dietary recalls, both interviewer-administered and self-administered on the web. This study demonstrates the feasibility of collecting multiple 24-hour recalls including less expensive automated self-administered recalls among diverse populations.
Authors: Alexander GL; Kushi LH; Thompson FE; et al.
Contemp Clin Trials Commun. 2017 Jun;6:140-146. Epub 2017-04-10.
Invited Commentary: The Contribution to the Field of Nutritional Epidemiology of the Landmark 1985 Publication by Willett et al
The semiquantitative food frequency questionnaire (FFQ) has been the primary source of dietary exposure data in epidemiology for decades. Although frequency instruments had been evaluated before the 1985 publication “Reproducibility and Validity of a Semiquantitative Food Frequency Questionnaire” by Willett et al. (Am J Epidemiol. 1985;122(1):51-65), that paper was the prototype for the development and validation of what was then a highly innovative method for collecting dietary data. This approach was adopted in nearly all subsequent cohort studies of diet and disease. The paper also catalyzed an extended scientific discourse regarding methods for validation, energy adjustment, and measurement error. It is now well established that data from FFQs and other self-reported dietary assessment instruments have both value and error and that this error should be considered in the analysis and interpretation of findings, including sensitivity analyses in which adjustment for measurement error is explored. Advances in technology make it feasible to consider collecting multiple granular short-term instruments such as recalls or records over time in addition to FFQs among all participants in large cohort studies; both provide valuable information. Without a doubt, the 1985 publication by Willett et al. provided the foundation that propelled the field of nutritional epidemiology forward, and it continues to be relevant today.
Authors: Subar AF; Kushi LH; Lerman JL; Freedman LS
Am J Epidemiol. 2017 Jun 01;185(11):1124-1129.
Patterns and reasons for switching classes of hormonal therapy among women with early-stage breast cancer
Breast cancer patients can switch hormonal therapy (HT) regimens due to treatment side effects or menopausal status change. We describe HT class switching from aromatase inhibitor (AI) to tamoxifen (TAM), and vice versa. In a cohort of 3,265 women diagnosed with hormone-receptor-positive breast cancer at Kaiser Permanente Northern California from 2005 to 2013, we analyzed prescription records, switching reasons, and treatment adherence post-switch by chart review, through 31 December 2014. There were 290 women who switched from AI to TAM (AI switchers), including 130 (45%) switchers during the first year of treatment; and 446 women who switched from TAM to AI (TAM switchers), including 120 (27%) switchers within the first year. After the switch, 136 (47%) AI switchers and 260 (58%) TAM switchers finished or remained on the planned therapy; 69 (24%) AI switchers and 99 (22%) TAM switchers discontinued therapy. AI side effects (73%), specifically joint pain/arthralgia and bone health issues, were the most common reasons for switching from AI to TAM, whereas from TAM to AI, it was menopausal status change (42%). Study findings highlight the need for better ways to control patient symptoms from HT to prevent discontinuation, and thus ensure best prognosis.
Authors: Kwan ML; Roh JM; Laurent CA; Lee J; Tang L; Hershman D; Kushi LH; Yao S
Cancer Causes Control. 2017 Jun;28(6):557-562. Epub 2017-03-27.
Feasibility of collecting tumor samples of breast cancer patients diagnosed up to 50 years ago in the Child Health and Development Studies
Environmental exposures during pregnancy may increase breast cancer risk for mothers and female offspring. Tumor tissue assays may provide insight regarding the mechanisms. This study assessed the feasibility of obtaining tumor samples and pathology reports from mothers (F0) who were enrolled in the Child Health and Development Studies during pregnancy from 1959 to 1967 and their daughters (F1) who developed breast cancer over more than 50 years of follow-up. Breast cancer cases were identified through linkage to the California Cancer Registry and self-report. Written consent was obtained from 116 F0 and 95 F1 breast cancer survivors to access their pathology reports and tumor blocks. Of those contacted, 62% consented, 13% refused and 24% did not respond. We obtained tissue samples for 57% and pathology reports for 75%, and if diagnosis was made ⩽10 years we obtained tissue samples and pathology reports for 91% and 79%, respectively. Obtaining pathology reports and tumor tissues of two generations is feasible and will support investigation of the relationship between early-life exposures and molecular tumor markers. However, we found that more recent diagnosis increased the accessibility of tumor tissue. We recommend that cohorts request consent for obtaining future tumor tissues at study enrollment and implement real-time tissue collection to enhance success of collecting tumor samples and data.
Authors: Krigbaum NY; Rubin RA; Cirillo PM; Terry MB; Habel LA; Morris C; Cohn BA
J Dev Orig Health Dis. 2017 Jun;8(3):331-336. Epub 2017-03-06.
Mortality and Androgen-Deprivation Therapy as Salvage Treatment for Biochemical Recurrence after Primary Therapy for Clinically Localized Prostate Cancer
Androgen deprivation therapy is often used as salvage treatment in men with rising prostate specific antigen after initial radical prostatectomy or radiotherapy for clinically localized prostate cancer. Given the lack of evidence from general practice, we examined the association of salvage androgen deprivation therapy with mortality in an observational cohort study. From 3 managed care organizations we assembled a retrospective cohort of all 5,804 men with newly diagnosed localized prostate cancer from 1995 to 2009 who had a prostate specific antigen increase (biochemical recurrence) after primary radical prostatectomy or radiotherapy. The main outcomes were all-cause and prostate cancer specific mortality. We used Cox proportional hazards models to estimate mortality with salvage androgen deprivation therapy as a time dependent predictor. Overall salvage androgen deprivation therapy was not associated with all-cause or prostate cancer specific mortality in the prostatectomy cohort (HR 0.97, 95% CI 0.70-1.35 or HR 1.18, 95% CI 0.68-2.07) or in the radiotherapy cohort (HR 0.84, 95% CI 0.70-1.01 or HR 1.06, 95% CI 0.80-1.40, respectively). Among men with prostate specific antigen doubling time less than 9 months after the prostate specific antigen rise, salvage androgen deprivation therapy was statistically significantly associated with a decreased risk of all-cause and prostate cancer specific mortality in the prostatectomy cohort (HR 0.35, 95% CI 0.20-0.63 and HR 0.43, 95% CI 0.21-0.91) and in the radiotherapy cohort (HR 0.62, 95% CI 0.48-0.80 and HR 0.65, 95% CI 0.47-0.90, respectively). We found no association of salvage androgen deprivation therapy with all-cause or cause specific mortality in most men with biochemical recurrence after primary radical prostatectomy or radiotherapy for clinically localized prostate cancer. Men with quickly progressed disease may derive a clinical benefit from salvage androgen deprivation therapy.
Authors: Fu AZ; Tsai HT; Haque R; Yood MU; Cassidy-Bushrow AE; Van Den Eeden SK; Keating NL; Smith MR; Zhou Y; Aaronson DS; Potosky AL
J Urol. 2017 06;197(6):1448-1454. Epub 2016-12-19.
Optimizing patient-reported outcome and risk factor reporting from cancer survivors: a randomized trial of four different survey methods among colorectal cancer survivors
The goal of this study was to determine response rates and associated costs of different survey methods among colorectal cancer (CRC) survivors. We assembled a cohort of 16,212 individuals diagnosed with CRC (2010-2014) from six health plans, and randomly selected 4000 survivors to test survey response rates across four mixed-mode survey administration protocols (in English and Spanish): arm 1, mailed survey with phone follow-up; arm 2, interactive voice response (IVR) followed by mail; arm 3; email linked to web-based survey with mail follow-up; and arm 4, email linked to web-based survey followed by IVR. Our overall response rate was 50.2%. Arm 1 had the highest response rate (59.9%), followed by arm 3 (51.9%), arm 2 (51.2%), and arm 4 (37.9%). Response rates were higher among non-Hispanic whites in all arms than other racial/ethnic groups (p < 0.001), among English (51.5%) than Spanish speakers (36.4%) (p < 0.001), and among higher (53.7%) than lower (41.4%) socioeconomic status (p < 0.001). Survey arms were roughly comparable in cost, with a difference of only 8% of total costs between the most (arm 2) and least (arm 3) expensive arms. Mailed surveys followed by phone calls achieved the highest response rate; email invitations and online surveys cost less per response. Electronic methods, even among those with email availability, may miss important populations including Hispanics, non-English speakers, and those of lower socioeconomic status. Our results demonstrate effective methods for capturing patient-reported outcomes, inform the relative benefits/disadvantages of the different methods, and identify future research directions.
Authors: Feigelson HS; McMullen CK; Madrid S; Sterrett AT; Powers JD; Blum-Barnett E; Pawloski PA; Ziegenfuss JY; Quinn VP; Arterburn DE; Corley DA
J Cancer Surviv. 2017 Jun;11(3):393-400. Epub 2017-01-13.
Providers’ Experiences with a Melanoma Web-Based Course: a Discussion on Barriers and Intentions
Primary care visits provide an opportunity for skin examinations with the potential to reduce melanoma mortality. The INFORMED (INternet curriculum FOR Melanoma Early Detection) Group developed a Web-based curriculum to improve primary care providers’ (PCPs’) skin cancer detection skills. This study details feedback obtained from participant focus groups, including the feasibility of implementing in other PCP practices. Practicing PCPs at Henry Ford Health System and Kaiser Permanente Northern California completed the curriculum. Feedback sessions were conducted with standardized questions focusing on four domains: (1) overall impressions of the curriculum, (2) recommendations for improvement, (3) current skin examination practices, and (4) suggestions for increasing skin screening by PCPs. Discussions at each site were audio recorded, transcribed verbatim, and de-identified. Providers (N = 54) had a positive impression of the Web-based curriculum, with suggestions to provide offline teaching aids and request assistance. Despite having improved confidence in diagnosing malignant lesions, many providers felt a lack of confidence in performing the screening and time constraints affected their current practices, as did institutional constraints. Providers intended to increase discussion with patients about skin cancer. The accessibility, effectiveness, and popularity of the curriculum indicate potential for implementation in the primary care setting. Participating providers noted that institutional barriers remain which must be addressed for successful dissemination and implementation.
Authors: Jiang AJ; Eide MJ; Alexander GL; Altschuler A; Asgari MM; Geller AC; Fletcher SW; Halpern AC; Weinstock MA
J Cancer Educ. 2017 Jun;32(2):272-279.
Training in the Conduct of Population-Based Multi-Site and Multi-Disciplinary Studies: the Cancer Research Network’s Scholars Program
Expanding research capacity of large research networks within health care delivery systems requires strategically training both embedded and external investigators in necessary skills for this purpose. Researchers new to these settings frequently lack the skills and specialized knowledge conducive to multi-site and multi-disciplinary research set in delivery systems. This report describes the goals and components of the Cancer Research Network (CRN) Scholars Program, a 26-month training program developed to increase the capacity for cancer research conducted within the network’s participating sites, its progression from training embedded investigators to a mix of internal and external investigators, and the content evolution of the training program. The CRN Scholars program was launched in 2007 to assist junior investigators from member sites develop independent and sustainable research programs within the CRN. Resulting from CRN’s increased emphasis on promoting external collaborations, the 2013 Scholars program began recruiting junior investigators from external institutions committed to conducting delivery system science. Based on involvement of this broader population and feedback from prior Scholar cohorts, the program has honed its focus on specific opportunities and issues encountered in conducting cancer research within health care delivery systems. Efficiency and effectiveness of working within networks is accelerated by strategic and mentored navigation of these networks. Investing in training programs specific to these settings provides the opportunity to improve multi-disciplinary and multi-institutional collaboration, particularly for early-stage investigators. Aspects of the CRN Scholars Program may help inform others considering developing similar programs to expand delivery system research or within large, multi-disciplinary research networks.
Authors: Buist DSM; Field TS; Banegas MP; Clancy HA; Doria-Rose VP; Epstein MM; Greenlee RT; McDonald S; Nichols HB; Pawloski PA; Kushi LH
J Cancer Educ. 2017 Jun;32(2):283-292.
Predictors of the multidimensional symptom experience of lung cancer patients receiving chemotherapy.
PURPOSE: Few studies have examined interindividual variability in the symptom experience of lung cancer patients. We aimed to identify the most prevalent, severe, and distressing symptoms, and risk factors associated with increased symptom burden. n METHODS: Lung cancer patients (n = 145) reported occurrence, severity, and distress for 38 symptoms on the Memorial Symptom Assessment Scale 1 week after chemotherapy. Using multidimensional subscales, risk factors for higher global distress, physical, and psychological symptoms were evaluated using simultaneous linear regression. n RESULTS: Mean age was 64.0 years and 56.6% were female. Mean Karnofsky Performance Status score was 79.1 (SD 14.6) and mean Self-Administered Comorbidity Questionnaire score was 7.3 (SD 3.9). The most distressing and prevalent symptom was fatigue. Problems with sexual interest/activity had the highest mean severity rating. Patients with lower functional status (p = 0.001) and higher comorbidity (p = 0.02) reported higher global distress. Similarly, lower functional status (p = 0.003) and higher comorbidity (p = 0.04) were associated with a higher physical symptom burden along with lower body mass index (p = 0.02). Higher psychology symptom burden was associated with lower functional status (p = 0.01), younger age (p = 0.02), non-metastatic disease (p = 0.03), higher number of prior treatments (p = 0.04), and income (p = 0.03). n CONCLUSIONS: Fatigue was the most distressing and prevalent symptom among lung cancer patients receiving chemotherapy. Lower functional status was associated with a higher burden of global distress, physical, and psychological symptoms. Younger age and non-metastatic disease were additional risk factors for increased psychological symptoms. Together, these risk factors can help clinicians identify lung cancer patients at increased need for aggressive symptom management.
Authors: Wong, Melisa L;Paul, Steven M;Cooper, Bruce A;Dunn, Laura B;Hammer, Marilyn J;Conley, Yvette P;Wright, Fay;Levine, Jon D;Walter, Louise C;Cartwright, Frances;Miaskowski, Christine
Support Care Cancer. 2017 Jun;25(6):1931-1939. doi: 10.1007/s00520-017-3593-z. Epub 2017 Feb 3.
Shared decision making in preventive care in Switzerland: From theory to action
Switzerland with its decentralized, liberal health system and its tradition of direct democracy may be an ideal place for shared decision making (SDM) to take root organically, rather than using top-down regulations seen in other countries. There are now multiple directives and programmes in place to encourage SDM, with the creation of several decision aids and specific training programs in the five Swiss medical schools. There has been an emphasis on preventive care, with the integration of patient preference into an organized colorectal cancer screening program, clear recommendations for prostate cancer screening, and inroads into the primary prevention of cardiovascular disease. Focusing on the experience of the University of Lausanne, we describe multiple approaches being taken to teaching SDM and the local development of decision aids, drawing on international experience but tailored to local needs. Efforts are being made to further involve patients in not only SDM, but also associated research and quality improvement projects.
Authors: Selby K; Auer R; Cornuz J
Z Evid Fortbild Qual Gesundhwes. 2017 Jun;123-124:91-94. doi: 10.1016/j.zefq.2017.05.008. Epub 2017 May 18.
Research Letter: Anticholinergic Drugs and the Gallbladder – A Neglected Effect?
Authors: Friedman GD; Achacoso N; Habel LA
Perm J. 2017;21.
Recommendations on surveillance and management of biallelic mismatch repair deficiency (BMMRD) syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer
Authors: Durno C; Boland CR; Cohen S; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Levin TR; Lieberman D; Robertson DJ; Rex DK
Gastrointest Endosc. 2017 May;85(5):873-882. Epub 2017-03-28.
Recommendations on Surveillance and Management of Biallelic Mismatch Repair Deficiency (BMMRD) Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer
The US Multi-Society Task Force on Colorectal Cancer, with invited experts, developed a consensus statement and recommendations to assist health care providers with appropriate management of patients with biallelic mismatch repair deficiency (BMMRD) syndrome, also called constitutional mismatch repair deficiency syndrome. This position paper outlines what is known about BMMRD, the unique genetic and clinical aspects of the disease, and reviews the current management approaches to this disorder. This article represents a starting point from which diagnostic and management decisions can undergo rigorous testing for efficacy. There is a lack of strong evidence and a requirement for further research. Nevertheless, providers need direction on how to recognize and care for BMMRD patients today. In addition to identifying areas of research, this article provides guidance for surveillance and management. The major challenge is that BMMRD is rare, limiting the ability to accumulate unbiased data and develop controlled prospective trials. The formation of effective international consortia that collaborate and share data is proposed to accelerate our understanding of this disease.
Authors: Durno C; Boland CR; Cohen S; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Levin TR; Lieberman D; Robertson DJ; Rex DK
Gastroenterology. 2017 May;152(6):1605-1614. Epub 2017-03-28.
Recommendations on Surveillance and Management of Biallelic Mismatch Repair Deficiency Syndrome: A Consensus Statement by the US Multi-society Task Force on Colorectal Cancer
Authors: Durno C; Boland CR; Cohen S; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Levin TR; Lieberman D; Robertson DJ; Rex DK
J Pediatr Gastroenterol Nutr. 2017 05;64(5):836-843.
Recommendations on Surveillance and Management of Biallelic Mismatch Repair Deficiency (BMMRD) Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer
The US Multi-Society Task Force on Colorectal Cancer, with invited experts, developed a consensus statement and recommendations to assist health care providers with appropriate management of patients with biallelic mismatch repair deficiency (BMMRD) syndrome, also called constitutional mismatch repair deficiency syndrome. This position paper outlines what is known about BMMRD, the unique genetic and clinical aspects of the disease, and reviews the current management approaches to this disorder. This article represents a starting point from which diagnostic and management decisions can undergo rigorous testing for efficacy. There is a lack of strong evidence and a requirement for further research. Nevertheless, providers need direction on how to recognize and care for BMMRD patients today. In addition to identifying areas of research, this article provides guidance for surveillance and management. The major challenge is that BMMRD is rare, limiting the ability to accumulate unbiased data and develop controlled prospective trials. The formation of effective international consortia that collaborate and share data is proposed to accelerate our understanding of this disease.
Authors: Durno C; Boland CR; Cohen S; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Levin TR; Lieberman D; Robertson DJ; Rex DK
Am J Gastroenterol. 2017 May;112(5):682-690. Epub 2017-03-28.
Weight fluctuation and cancer risk in post-menopausal women: The Women’s Health Initiative
Background: Weight cycling, defined by an intentional weight loss and subsequent regain, commonly occurs in overweight and obese women and is associated with some negative health outcomes. We examined the role of various weight-change patterns during early to mid-adulthood and associated risk of highly prevalent, obesity-related cancers (breast, endometrial, and colorectal) in postmenopausal women.Methods:A total of 80,943 postmenopausal women (age, 63.4 ± 7.4 years) in the Women’s Health Initiative Observational Study were categorized by self-reported weight change (weight stable; weight gain; lost weight; weight cycled [1-3, 4-6, 7-10, >10 times]) during early to mid-adulthood (18-50 years). Three site-specific associations were investigated using Cox proportional hazard models [age, race/ethnicity, income, education, smoking, alcohol, physical activity, hormone therapy, diet, and body mass index (BMI)].Results:A total of 7,464 (breast = 5,564; endometrial = 788; and colorectal = 1,290) incident cancer cases were identified between September 1994 and August 2014. Compared with weight stability, weight gain was significantly associated with risk of breast cancer [hazard ratio (HR), 1.11; 1.03-1.20] after adjustment for BMI. Similarly, weight cycling was significantly associated with risk of endometrial cancer (HR = 1.23; 1.01-1.49). Weight cycling “4 to 6 times” was most consistently associated with cancer risk, showing a 38% increased risk for endometrial cancer [95% confidence interval (CI), 1.08-1.76] compared with weight stable women.Conclusions:Weight gain and weight cycling were positively associated with risk of breast and endometrial cancer, respectively.Impact:These data suggest weight cycling and weight gain increase risk of prevalent cancers in postmenopausal women. Adopting ideal body-weight maintenance practices before and after weight loss should be encouraged to reduce risk of incident breast and endometrial cancers.Cancer Epidemiol Biomarkers Prev; 26(5); 779-86. ©2017 AACR.
Authors: Welti LM; Beavers DP; Caan BJ; Sangi-Haghpeykar H; Vitolins MZ; Beavers KM
Cancer Epidemiol Biomarkers Prev. 2017 May;26(5):779-786. Epub 2017-01-09.
Surveillance for One or Two Small Adenomas: Low Risk Is Really Low Risk.
The optimal timing for postpolypectomy surveillance for low-risk adenomas, defined as 1-2 small tubular adenomas, has remained a challenge for clinicians and guideline developers over the past 4 decades. From the 1970s to the 1990s, it was common practice for clinicians to recommend annual surveillance for even a small adenoma (ie, <10 mm), because of the perceived knowledge that all adenomas were premalignant. In 1993, the National Polyp Study helped to provide much needed evidence for the timing of postpolypectomy surveillance by showing there was no difference in the risk of finding an advanced adenoma at 1 and 3 years after the baseline colonoscopy versus 3 years alone. As a result, a 3-year surveillance interval after removal of any adenoma was suggested for adoption. When the first surveillance guideline was issued in 1997, the recommended follow-up interval was 5 years for patients with one small tubular adenoma. In 2003, the United States Multi-Society Task Force (USMSTF) on Colorectal Cancer and a panel of various medical specialists updated the guideline and recommended that patients with 1-2 small tubular adenomas undergo surveillance in 5 years,owing in large part to the low risk for advanced adenomas on follow-up colonoscopy 3-5 years later. In 2006, the USMSTF broadened the recommended surveillance interval to 5-10 years for patients with 1-2 small tubular adenomas. This recommendation was based mainly on the low incidence of subsequent advanced adenomas and colorectal cancer (CRC) in observational cohort studies after removal of a low-risk adenoma on the baseline examination. More recently, the USMSTF updated their 2006 surveillance guideline in 2012 again supported a surveillance interval of 5-10 years after removal of a low-risk adenoma. However, despite the evidence and decades of guideline recommendations, studies have consistently shown that clinicians are bringing back patients with low-risk adenomas for their postpolypectomy surveillance earlier than the recommended minimum of 5 years. This suggests an overuse of surveillance colonoscopy, which already accounts for >25% of colonoscopies performed annually in the United States.
Authors: Lee, Jeffrey K JK; Lieberman, David D
Gastroenterology. 2017 06 ;152(8):1819-1821. Epub 2017-04-28.
Association Between Time to Colonoscopy After a Positive Fecal Test Result and Risk of Colorectal Cancer and Cancer Stage at Diagnosis
The fecal immunochemical test (FIT) is commonly used for colorectal cancer screening and positive test results require follow-up colonoscopy. However, follow-up intervals vary, which may result in neoplastic progression. To evaluate time to colonoscopy after a positive FIT result and its association with risk of colorectal cancer and advanced-stage disease at diagnosis. Retrospective cohort study (January 1, 2010-December 31, 2014) within Kaiser Permanente Northern and Southern California. Participants were 70 124 patients aged 50 through 70 years eligible for colorectal cancer screening with a positive FIT result who had a follow-up colonoscopy. Time (days) to colonoscopy after a positive FIT result. Risk of any colorectal cancer and advanced-stage disease (defined as stage III and IV cancer). Odds ratios (ORs) and 95% CIs were adjusted for patient demographics and baseline risk factors. Of the 70 124 patients with positive FIT results (median age, 61 years [IQR, 55-67 years]; men, 52.7%), there were 2191 cases of any colorectal cancer and 601 cases of advanced-stage disease diagnosed. Compared with colonoscopy follow-up within 8 to 30 days (n = 27 176), there were no significant differences between follow-up at 2 months (n = 24 644), 3 months (n = 8666), 4 to 6 months (n = 5251), or 7 to 9 months (n = 1335) for risk of any colorectal cancer (cases per 1000 patients: 8-30 days, 30; 2 months, 28; 3 months, 31; 4-6 months, 31; and 7-9 months, 43) or advanced-stage disease (cases per 1000 patients: 8-30 days, 8; 2 months, 7; 3 months, 7; 4-6 months, 9; and 7-9 months, 13). Risks were significantly higher for examinations at 10 to 12 months (n = 748) for any colorectal cancer (OR, 1.48 [95% CI, 1.05-2.08]; 49 cases per 1000 patients) and advanced-stage disease (OR, 1.97 [95% CI, 1.14-3.42]; 19 cases per 1000 patients) and more than 12 months (n = 747) for any colorectal cancer (OR, 2.25 [95% CI, 1.89-2.68]; 76 cases per 1000 patients) and advanced-stage disease (OR, 3.22 [95% CI, 2.44-4.25]; 31 cases per 1000 patients). Among patients with a positive fecal immunochemical test result, compared with follow-up colonoscopy at 8 to 30 days, follow-up after 10 months was associated with a higher risk of colorectal cancer and more advanced-stage disease at the time of diagnosis. Further research is needed to assess whether this relationship is causal.
Authors: Corley DA; Lee JK; Quesenberry CP; Fireman BH; Levin TR; et al.
JAMA. 2017 Apr 25;317(16):1631-1641.
Community-Based Practice Variations in Topical Treatment of Actinic Keratoses
Authors: Storer M; Zhu Z; Sokil M; Ford M; Neugebauer R; Asgari MM
JAMA Dermatol. 2017 Apr 05.
Recommendations on Fecal Immunochemical Testing to Screen for Colorectal Neoplasia: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer
The use of the fecal occult blood test (FOBT) for colorectal cancer (CRC) screening is supported by randomized trials demonstrating effectiveness in cancer prevention and widely recommended by guidelines for this purpose. The fecal immunochemical test (FIT), as a direct measure of human hemoglobin in stool has a number of advantages relative to conventional FOBT and is increasingly used relative to that test. This review summarizes current evidence for FIT in colorectal neoplasia detection and the comparative effectiveness of FIT relative to other commonly used CRC screening modalities. Based on evidence, guidance statements on FIT application were developed and quality metrics for program implementation proposed.
Authors: Robertson DJ; Lee JK; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Lieberman D; Levin TR; Rex DK
Gastroenterology. 2017 Apr;152(5):1217-1237.e3. Epub 2016-10-19.
Physicians’ perspectives on the informational needs of low-risk prostate cancer patients
Despite the evidence indicating that decision aids (DA) improve informed treatment decision making for prostate cancer (PCa), physicians do not routinely recommend DAs to their patients. We conducted semi-structured interviews with urologists (n = 11), radiation oncologists (n = 12) and primary care physicians (n = 10) about their methods of educating low-risk PCa patients regarding the treatment decision, their concerns about recommending DAs, and the essential content and format considerations that need to be addressed. Physicians stressed the need for providing comprehensive patient education before the treatment decision is made and expressed concern about the current unevaluated information available on the Internet. They made recommendations for a DA that is brief, applicable to diverse populations, and that fully discloses all treatment options (including active surveillance) and their potential side effects. Echoing previous studies showing that low-risk PCa patients are making rapid and potentially uninformed treatment decisions, these results highlight the importance of providing patient education early in the decision-making process. This need may be fulfilled by a treatment DA, should physicians systematically recommend DAs to their patients. Physicians’ recommendations for the inclusion of particular content and presentation methods will be important for designing a high quality DA that will be used in clinical practice.
Authors: Hagerman CJ; Bellini PG; Davis KM; Hoffman RM; Aaronson DS; Leigh DY; Zinar RE; Penson D; Van Den Eeden S; Taylor KL
Health Educ Res. 2017 04 01;32(2):134-152.
Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency
Controversy exists regarding the safety of testosterone replacement therapy (TRT) following recent reports of an increased risk of adverse cardiovascular events. To investigate the association between TRT and cardiovascular outcomes in men with androgen deficiency. A retrospective cohort study was conducted within an integrated health care delivery system. Men at least 40 years old with evidence of androgen deficiency either by a coded diagnosis and/or a morning serum total testosterone level of less than 300 ng/dL were included. The eligibility window was January 1, 1999, to December 31, 2010, with follow-up through December 31, 2012. Any prescribed TRT given by injection, orally, or topically. The primary outcome was a composite of cardiovascular end points that included acute myocardial infarction (AMI), coronary revascularization, unstable angina, stroke, transient ischemic attack (TIA), and sudden cardiac death (SCD). Multivariable Cox proportional hazards models were used to investigate the association between TRT and cardiovascular outcomes. An inverse probability of treatment weight, propensity score methodology, was used to balance baseline characteristics. The cohorts consisted of 8808 men (19.8%) ever dispensed testosterone (ever-TRT) (mean age, 58.4 years; 1.4% with prior cardiovascular events) and 35 527 men (80.2%) never dispensed testosterone (never-TRT) (mean age, 59.8 years; 2.0% with prior cardiovascular events). Median follow was 3.2 years (interquartile range [IQR], 1.7-6.6 years) in the never-TRT group vs 4.2 (IQR, 2.1-7.8) years in the ever-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person-years in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67 (95% CI, 0.62-0.73. Similar results were seen when the outcome was restricted to combined stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0.62-0.84) and combined cardiac events (AMI, SCD, unstable angina, revascularization procedures) (HR, 0.66; 95% CI, 0.60-0.72). Among men with androgen deficiency, dispensed testosterone prescriptions were associated with a lower risk of cardiovascular outcomes over a median follow-up of 3.4 years.
Authors: Cheetham TC; An J; Jacobsen SJ; Niu F; Sidney S; Quesenberry CP; VanDenEeden SK
JAMA Intern Med. 2017 Apr 01;177(4):491-499.
Impact of social and built environment factors on body size among breast cancer survivors: the Pathways Study
Background: As social and built environment factors have been shown to be associated with physical activity, dietary patterns, and obesity in the general population, they likely also influence these health behaviors among cancer survivors and thereby impact survivorship outcomes.Methods:Enhancing the rich, individual-level survey and medical record data from 4,505 breast cancer survivors in the Pathways Study, a prospective cohort drawn from Kaiser Permanente Northern California, we geocoded baseline residential addresses and appended social and built environment data. With multinomial logistic models, we examined associations between neighborhood characteristics and body mass index and whether neighborhood factors explained racial/ethnic/nativity disparities in overweight/obesity.Results:Low neighborhood socioeconomic status, high minority composition, high traffic density, high prevalence of commuting by car, and a higher number of fast food restaurants were independently associated with higher odds of overweight or obesity. The higher odds of overweight among African Americans, U.S.-born Asian Americans/Pacific Islanders, and foreign-born Hispanics and the higher odds of obesity among African Americans and U.S.-born Hispanics, compared with non-Hispanic whites, remained significant, although somewhat attenuated, when accounting for social and built environment features.Conclusions:Addressing aspects of neighborhood environments may help breast cancer survivors maintain a healthy body weight.Impact:Further research in this area, such as incorporating data on individuals’ perceptions and use of their neighborhood environments, is needed to ultimately inform multilevel interventions that would ameliorate such disparities and improve outcomes for breast cancer survivors, regardless of their social status (e.g., race/ethnicity, socioeconomic status, nativity).Cancer Epidemiol Biomarkers Prev; 26(4); 505-15. ©2017 AACRSee all the articles in thisCEBP Focussection, “Geospatial Approaches to Cancer Control and Population Sciences.”
Authors: Shariff-Marco S; Roh JM; Ambrosone C; Gomez SL; Gomez SL; et al.
Cancer Epidemiol Biomarkers Prev. 2017 Apr;26(4):505-515. Epub 2017-02-02.
Adiposity, post-diagnosis weight change, and risk of cardiovascular events among early-stage breast cancer survivors
Little research examines whether adiposity or post-diagnosis weight changes influence Cardiovascular disease (CVD) among breast cancer patients for whom effects may differ due to treatment and recovery. We studied Stage I-III breast cancer survivors 18 to <80 years, without pre-existing CVD, diagnosed from 1997 to 2013 at Kaiser Permanente. Women reported weight at diagnosis and weight and waist circumference (WC) around 24 months post diagnosis. Using Cox models for time to incident coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, we examined at-diagnosis body mass index (BMI, n = 3109) and post-diagnosis WC (n = 1898) and weight change (n = 1903, stable, ±5 to <10-lbs or ±≥10-lbs). Mean (SD) age was 57 (11) years, and BMI was 28 (6) kg-m2. Post diagnosis, 25% of women gained and 14% lost ≥10-lbs; mean (SD) WC was 90 (15) cm. Over a median of 8.28 years, 915 women developed CVD. BMI 25-30-kg/m2 (vs. BMI < 25-kg/m2) was not associated with CVD, while BMI ≥ 35-kg/m2 increased risk by 33% (HR: 1.33; 95%CI 1.08-1.65), independent of lifestyle and tumor/treatment factors. The increased risk at BMI ≥ 35-kg/m2 attenuated with adjustment for pre-existing CVD risk factors to HR: 1.20; 95%CI 0.97-1.50. By contrast, even moderate elevations in WC increased risk of CVD, independent of pre-existing risk factors (HR: 1.93; 95%CI 1.31-2.84 comparing ≥100-cm vs. ≤80-cm). Post-diagnosis weight change had no association with CVD. Extreme adiposity and any elevation in WC increased risk of CVD among breast cancer survivors; however, changes in weight in the early post-diagnosis period were not associated with CVD. Survivors with high WC and existing CVD risk factors should be monitored.
Authors: Cespedes Feliciano EM; Kwan ML; Kushi LH; Weltzien EK; Castillo AL; Caan BJ
Breast Cancer Res Treat. 2017 04;162(3):549-557. Epub 2017-02-07.
Postdiagnosis social networks and breast cancer mortality in the After Breast Cancer Pooling Project
Large social networks have been associated with better overall survival, though not consistently with breast cancer (BC)-specific outcomes. This study evaluated associations of postdiagnosis social networks and BC outcomes in a large cohort. Women from the After Breast Cancer Pooling Project (n = 9267) provided data on social networks within approximately 2 years of their diagnosis. A social network index was derived from information about the presence of a spouse/partner, religious ties, community ties, friendship ties, and numbers of living first-degree relatives. Cox models were used to evaluate associations, and a meta-analysis was used to determine whether effect estimates differed by cohort. Stratification by demographic, social, tumor, and treatment factors was performed. There were 1448 recurrences and 1521 deaths (990 due to BC). Associations were similar in 3 of 4 cohorts. After covariate adjustments, socially isolated women (small networks) had higher risks of recurrence (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.15-1.77), BC-specific mortality (HR, 1.64; 95% CI, 1.33-2.03), and total mortality (HR, 1.69; 95% CI, 1.43-1.99) than socially integrated women; associations were stronger in those with stage I/II cancer. In the fourth cohort, there were no significant associations with BC-specific outcomes. A lack of a spouse/partner (P = .02) and community ties (P = .04) predicted higher BC-specific mortality in older white women but not in other women. However, a lack of relatives (P = .02) and friendship ties (P = .01) predicted higher BC-specific mortality in nonwhite women only. In a large pooled cohort, larger social networks were associated with better BC-specific and overall survival. Clinicians should assess social network information as a marker of prognosis because critical supports may differ with sociodemographic factors. Cancer 2017;123:1228-1237. © 2016 American Cancer Society.
Authors: Kroenke CH; Michael YL; Poole EM; Kwan ML; Nechuta S; Leas E; Caan BJ; Pierce J; Shu XO; Zheng Y; Chen WY
Cancer. 2017 Apr 01;123(7):1228-1237. Epub 2016-12-12.
In simulation modelling, there are multiple ways to effectively screen for colorectal cancer
Authors: Levin TR
Evid Based Med. 2017 04;22(2):59. Epub 2017-01-10.
The Effect of California’s Breast Density Notification Legislation on Breast Cancer Screening
Half of US states mandate women be notified if they have dense breasts on their mammogram, yet guidelines and data on supplemental screening modalities are limited. Breast density (BD) refers to the extent that breast tissue appears radiographically dense on mammograms. High BD reduces the sensitivity of screening mammography and increases breast cancer risk. The aim of this study was to determine the potential impact of California’s 2013 BD notification legislation on breast cancer screening patterns. We conducted a cohort study of women aged 40 to 74 years who were members of a large Northern California integrated health plan (approximately 3.9 million members) in 2011-2015. We calculated pre- and post-legislation rates of screening mammography and magnetic resonance imaging (MRI). We also examined whether women with dense breasts (defined as BI-RADS density c or d) had higher MRI rates than women with nondense breasts (defined as BI-RADS density a or b). After adjustment for race/ethnicity, age, body mass index, medical facility, neighborhood median income, and cancer history, there was a relative 6.6% decrease (relative risk [RR] 0.934, confidence interval [CI] 0.92-0.95) in the rate of screening mammography, largely driven by a decrease among women <50 years. While infrequent, there was a relative 16% increase (RR 1.16, CI 1.07-1.25) in the rate of screening MRI, with the greatest increase among the youngest women. In the postlegislation period, women with extremely dense breasts (BI-RADS d) had 2.77 times (CI 1.93-3.95) the odds of a MRI within 9 months of a screening mammogram compared with women with nondense breasts (BI-RADS b). In this setting, MRI rates increased in the postlegislation period. In addition, women with higher BD were more likely to have supplementary MRI. The decrease in mammography rates seen primarily among younger women may have been due to changes in national screening guidelines.
Authors: Chau SL; Alabaster A; Luikart K; Brenman LM; Habel LA
J Prim Care Community Health. 2017 Apr;8(2):55-62. Epub 2016-10-31.
Post-diagnosis social networks, and lifestyle and treatment factors in the After Breast Cancer Pooling Project
Larger social networks have been associated with better breast cancer survival. To investigate potential mediators, we evaluated associations of social network size and diversity with lifestyle and treatment factors associated with prognosis. We included 9331 women from the After Breast Cancer Pooling Project who provided data on social networks within approximately two years following diagnosis. A social network index was derived from information about the presence of a spouse or intimate partner, religious ties, community participation, friendship ties, and numbers of living relatives. Diversity was assessed as variety of ties, independent of size. We used logistic regression to evaluate associations with outcomes and evaluated whether effect estimates differed using meta-analytic techniques. Associations were similar across cohorts though analyses of smoking and alcohol included US cohorts only because of low prevalence of these behaviors in the Shanghai cohort. Socially isolated women were more likely to be obese (OR?=?1.21, 95% CI:1.03-1.42), have low physical activity (<10 MET-hours/week, OR?=?1.55, 95% CI:1.36-1.78), be current smokers (OR?=?2.77, 95% CI:2.09-3.68), and have high alcohol intake (?15 g/d, OR?=?1.23, 95% CI:1.00-1.51), compared with socially integrated women. Among node positive cases from three cohorts, socially isolated women were more likely not to receive chemotherapy (OR?=?2.10, 95% CI:1.30-3.39); associations differed in a fourth cohort. Other associations (nonsignificant) were consistent with less intensive treatment in socially isolated women. Low social network diversity was independently associated with more adverse lifestyle, but not clinical, factors. Small, less diverse social networks measured post-diagnosis were associated with more adverse lifestyle factors and less intensive cancer treatment. Copyright © 2016 John Wiley & Sons, Ltd.
Authors: Kroenke CH; Michael YL; Shu XO; Poole EM; Kwan ML; Nechuta S; Caan BJ; Pierce JP; Chen WY
Psychooncology. 2017 Apr;26(4):544-552. Epub 2016-01-08.
Oral bisphosphonates and colorectal cancer
Use of oral bisphosphonates has been associated with a decreased risk of colorectal cancer (CRC), but the association may be related to residual confounding by healthy lifestyle or body mass index (BMI). Therefore, we conducted a prospective nested case-control study within the Kaiser Permanente, Northern California health system cohort. In total, 12,505 CRC cases were individually matched to 599,534 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression models with adjustment for important covariates extracted from the database. Participants who had ever used oral bisphosphonates were less likely than non-users to be diagnosed with CRC (OR 0.82; 95% CI: 0.74, 0.89). Colon and rectum site-specific associations were similar to the overall association. A stronger inverse association for ever use of bisphosphonates was observed for men (OR 0.63; 95% CI: 0.47, 0.85), however when stratified by previous lower endoscopy, the association was only observed in the participants who did not have a previous lower endoscopy (OR 0.73 (0.64, 0.83)). In conclusion, we found that oral bisphosphonate use was associated with a decreased odds of CRC, however this association may be due to residual confounding by BMI or another confounder.
Authors: Vogtmann E; Corley DA; Almers LM; Cardwell CR; Murray LJ; Abnet CC
Sci Rep. 2017 Mar 10;7:44177. Epub 2017-03-10.
Association of Serum Level of Vitamin D at Diagnosis With Breast Cancer Survival: A Case-Cohort Analysis in the Pathways Study
There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality, yet data from prospective cohort studies are limited. To investigate a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast cancer diagnosis, to determine the association with prognosis. The Pathways Study is a prospective cohort study of breast cancer survivors established in 2006. Enrollment was completed in 2013; follow-up is ongoing. The cohort was established in Kaiser Permanente Northern California, a large integrated health care delivery system in northern California. Women with a diagnosis of incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis. The overall enrollment rate was 46% (4505 of 9820). Participants are followed for health outcomes and comorbidities at 12, 24, 48, 72, and 96 months after baseline interview. A case-cohort design was used for efficiency assay of 25OHD, selecting 1666 cohort members with serum samples and ensuring representation in the subcohort of races and clinical subtypes. The data analysis was performed from January 5, 2014, to March 15, 2015. Primary outcomes are breast cancer recurrence, second primary cancer, and death. Mean (SD) age was 58.7 (12.4) years. Serum 25OHD concentrations were lower in women with advanced-stage tumors, and the lowest in premenopausal women with triple-negative cancer. Levels were also inversely associated with hazards of disease progression and death. Compared with the lowest tertile, women with the highest tertile of 25OHD levels had superior overall survival (OS). This association remained after adjustment for clinical prognostic factors (hazard ratio [HR], 0.72; 95% CI, 0.54-0.98). Among premenopausal women, the association with OS was stronger, and there were also associations with breast cancer-specific survival and invasive disease-free survival (OS: HR, 0.45; 95% CI, 0.21-0.96; breast cancer-specific survival: HR, 0.37; 95% CI, 0.15-0.93; invasive disease-free survival: HR, 0.58; 95% CI, 0.34-1.01; all after full adjustment). Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis, most prominently among premenopausal women. Our findings from a large, well-characterized prospective cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality.
Authors: Yao S; Ergas IJ; Roh JM; Lee MM; Kushi LH; et al.
JAMA Oncol. 2017 Mar 01;3(3):351-357.
Endoscopist Fatigue Estimates and Colonoscopic Adenoma Detection in a Large Community-Based Setting
Endoscopist fatigue may impact colonoscopy quality, but prior studies conflict, and minimal data exist from community-based practices where most colonoscopies are performed. Within a large, community-based integrated healthcare system, we evaluated the associations among 4 measures of endoscopist fatigue and colonoscopic adenoma detection from 2010 to 2013. Fatigue measures included afternoon versus morning colonoscopy and the number of GI procedures performed before a given colonoscopy, including consideration of prior procedure complexity. Analyses were adjusted for potential confounders using multivariate logistic regression. We identified 126 gastroenterologists who performed 259,064 total GI procedures (median, 6 per day; range, 1-24), including 76,445 screening and surveillance colonoscopies. Compared with morning examinations, colonoscopies in the afternoon were not associated with lower adenoma detection for screening examinations, surveillance examinations, or their combination (OR for combination, .99; 95% CI, .96-1.03). The number of procedures performed before a given colonoscopy, with or without consideration of prior procedure complexity, was also not inversely associated with adenoma detection (OR for adenoma detection for colonoscopies in the fourth quartile of fatigue based on the number of prior procedures performed vs colonoscopies performed as the first procedure of the day, .99; 95% CI, .94-1.04). In a large community-based setting, adenoma detection for screening and surveillance colonoscopies were not associated with either time of day or the number of prior procedures performed by the endoscopist, within the range of procedure volumes evaluated. The lack of association persisted after accounting for prior procedure complexity.
Authors: Lee A; Jensen CD; Marks AR; Zhao WK; Doubeni CA; Zauber AG; Quinn VP; Levin TR; Corley DA
Gastrointest Endosc. 2017 Mar;85(3):601-610.e2. Epub 2016-10-01.
Racial/ethnic differences in obesity and comorbidities between safety-net- and non safety-net integrated health systems
Previous research shows that patients in integrated health systems experience fewer racial disparities compared with more traditional healthcare systems. Little is known about patterns of racial/ethnic disparities between safety-net and non safety-net integrated health systems.We evaluated racial/ethnic differences in body mass index (BMI) and the Charlson comorbidity index from 3 non safety-net- and 1 safety-net integrated health systems in a cross-sectional study. Multinomial logistic regression modeled comorbidity and BMI on race/ethnicity and health care system type adjusting for age, sex, insurance, and zip-code-level incomeThe study included 1.38 million patients. Higher proportions of safety-net versus non safety-net patients had comorbidity score of 3+ (11.1% vs. 5.0%) and BMI ?35 (27.7% vs. 15.8%). In both types of systems, blacks and Hispanics were more likely than whites to have higher BMIs. Whites were more likely than blacks or Hispanics to have higher comorbidity scores in a safety net system, but less likely to have higher scores in the non safety-nets. The odds of comorbidity score 3+ and BMI 35+ in blacks relative to whites were significantly lower in safety-net than in non safety-net settings.Racial/ethnic differences were present within both safety-net and non safety-net integrated health systems, but patterns differed. Understanding patterns of racial/ethnic differences in health outcomes in safety-net and non safety-net integrated health systems is important to tailor interventions to eliminate racial/ethnic disparities in health and health care.
Authors: Balasubramanian BA; Garcia MP; Corley DA; Doubeni CA; Haas JS; Kamineni A; Quinn VP; Wernli K; Zheng Y; Skinner CS
Medicine (Baltimore). 2017 Mar;96(11):e6326.
The Best Laid Plans: Adaptation is an Essential Part of Going From Efficacy Research to Program Implementation
Authors: Levin TR
Gastroenterology. 2017 03;152(4):693-694. Epub 2017-01-29.
Genetic Biomarker Prevalence Is Similar in Fecal Immunochemical Test Positive and Negative Colorectal Cancer Tissue
Fecal immunochemical test (FIT) screening detects most asymptomatic colorectal cancers. Combining FIT screening with stool-based genetic biomarkers increases sensitivity for cancer, but whether DNA biomarkers (biomarkers) differ for cancers detected versus missed by FIT screening has not been evaluated in a community-based population. To evaluate tissue biomarkers among Kaiser Permanente Northern California patients diagnosed with colorectal cancer within 2 years after FIT screening. FIT-negative and FIT-positive colorectal cancer patients 50-77 years of age were matched on age, sex, and cancer stage. Adequate DNA was isolated from paraffin-embedded specimens in 210 FIT-negative and 211 FIT-positive patients. Quantitative allele-specific real-time target and signal amplification assays were performed for 7 K-ras mutations and 10 aberrantly methylated DNA biomarkers (NDRG4, BMP3, SFMBT2_895, SFMBT2_896, SFMBT2_897, CHST2_7890, PDGFD, VAV3, DTX1, CHST2_7889). One or more biomarkers were found in 414 of 421 CRCs (98.3%). Biomarker expression was not associated with FIT status, with the exception of higher SFMBT2_897 expression in FIT-negative (194 of 210; 92.4%) than in FIT-positive cancers (180 of 211; 85.3%; p = 0.02). There were no consistent differences in biomarker expression by FIT status within age, sex, stage, and cancer location subgroups. The biomarkers of a currently in-use multi-target stool DNA test (K-ras, NDRG4, and BMP3) and eight newly characterized methylated biomarkers were commonly expressed in tumor tissue specimens, independent of FIT result. Additional study using stool-based testing with these new biomarkers will allow assessment of sensitivity, specificity, and clinical utility.
Authors: Levin TR; Corley DA; Berger BM; et al.
Dig Dis Sci. 2017 Mar;62(3):678-688. Epub 2017-01-02.
Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency
Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) suppress gastric acid production, which can inhibit iron absorption. However, few data exist regarding whether these medications increase the risk of clinical iron deficiency. A community-based case-control study evaluated the association between acid-suppressing medication use and the subsequent risk of iron deficiency. It contrasted 77,046 patients with new iron deficiency diagnoses (January 1999-December 2013), with 389,314 controls. Medication exposures, outcomes, and potential confounders used electronic databases. We excluded patients with pre-existing risk factors for iron deficiency. Associations were estimated using conditional logistic regression. Among cases, 2343 (3.0%) received a prior ≥2-year supply of PPIs and 1063 (1.4%) received H2RAs (without PPI use). Among controls, 3354 (0.9%) received a prior ≥2-year supply of PPIs and 2247 (0.6%) H2RAs. Both ≥2 years of PPIs (adjusted odds ratio, 2.49; 95% confidence interval, 2.35-2.64) and ≥2 years of H2RAs (odds ratio, 1.58; 95% CI, 1.46-1.71) were associated with an increased subsequent risk for iron deficiency. Among PPI users, the associations were stronger for higher daily doses (>1.5 vs <0.75 PPI pills/d; P value interaction = .004) and decreased after medication discontinuation (P-trend < .001). Some of the strongest associations were among persons taking >1.5 pills per day for at least 10 years (odds ratio, 4.27; 95% CI, 2.53-7.21). No similar strong associations were found for other commonly used prescription medications. Among patients without known risk factors for iron deficiency, gastric acid inhibitor use for ≥2 years was associated with an increased subsequent risk of iron deficiency. The risk increased with increasing potency of acid inhibition and decreased after medication discontinuation.
Authors: Lam JR; Schneider JL; Quesenberry CP; Corley DA
Gastroenterology. 2017 Mar;152(4):821-829.e1. Epub 2016-11-24.
Effect of Angiotensin System Inhibitors on Survival in Patients Receiving Chemotherapy for Advanced Non-Small-Cell Lung Cancer
Preclinical studies suggest that angiotensin system inhibitors (ASI) and bevacizumab improve tumor perfusion and chemotherapy efficacy. We performed a retrospective study to examine whether concomitant ASI use during carboplatin and paclitaxel (CP) without or with bevacizumab (CPB) was associated with improved overall survival (OS) in patients with advanced nonsquamous, non-small-cell lung cancer (NS-NSCLC). In a retrospective cohort study, adult patients diagnosed with stage IIIB or IV NS-NSCLC between 2005 and 2011 were identified from tumor registries at 1 of 4 Kaiser Permanente regions. Survival differences between those who did and did not receive ASIs concomitant with chemotherapy (CP or CPB) were assessed using propensity score-matched proportional hazard models. OS was measured from the initiation of chemotherapy until death, disenrollment, or December 31, 2012. Of the 1465 CP and 348 CPB patients included, 273 (19%) and 78 (22%), respectively, received concomitant ASI. For CP patients with and without concomitant ASI exposure, median OS was 12.0 and 8.4 months, respectively (crude hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.84). For CPB patients, the comparable median OS was 14.9 and 11.9 months, respectively (crude HR, 0.77; 95% CI, 0.57-1.02). Using propensity score-matched cohorts, the HR for concomitant ASI use was 0.73 (95% CI, 0.61-0.88) for CP patients and 0.79 (95% CI, 0.51-1.21) for CPB patients. Concomitant ASI receipt during CP or CPB therapy for NS-NSCLC was associated with improved survival, although the association was only statistically significant in the CP group.
Authors: Menter AR; Carroll NM; Sakoda LC; Delate T; Hornbrook MC; Jain RK; Kushi LH; Quinn VP; Ritzwoller DP
Clin Lung Cancer. 2017 Mar;18(2):189-197.e3. Epub 2016-08-20.
Appropriate Use of Antiemetics to Prevent Chemotherapy-Induced Nausea and Vomiting
Authors: Check DK; Basch EM
JAMA Oncol. 2017 03 01;3(3):307-309.
Achievements, challenges, and future perspectives of epidemiologic research in restless legs syndrome (RLS)
In the 20 years since the initial consensus on a common definition for restless legs syndrome (RLS), over 600 scientific reports on epidemiological aspects of RLS have been published. Most are descriptive and address important issues such as prevalence, familial patterns, comorbidities, and quality of life. While the establishment of prospective cohort studies and the use of secondary data sources are rather new to RLS research, both options significantly broaden the possibilities for analysis of disease risk factors. These two options, as well as the inclusion of a broader phenotyping of individual patients, have great potential to elucidate etiologic factors for RLS and expand knowledge about this common disorder. This article summarizes achievements in the area of RLS epidemiology, describes current challenges, and highlights future perspectives in the field.
Authors: Picchietti DL; Van Den Eeden SK; Inoue Y; Berger K
Sleep Med. 2017 Mar;31:3-9. Epub 2016-07-12.
Temporal Trends in Satellite-Derived Erythemal UVB and Implications for Ambient Sun Exposure Assessment.
Ultraviolet radiation (UVR) has been associated with various health outcomes, including skin cancers, vitamin D insufficiency, and multiple sclerosis. Measurement of UVR has been difficult, traditionally relying on subject recall. We investigated trends in satellite-derived UVB from 1978 to 2014 within the continental United States (US) to inform UVR exposure assessment and determine the potential magnitude of misclassification bias created by ignoring these trends. Monthly UVB data remotely sensed from various NASA satellites were used to investigate changes over time in the United States using linear regression with a harmonic function. Linear regression models for local geographic areas were used to make inferences across the entire study area using a global field significance test. Temporal trends were investigated across all years and separately for each satellite type due to documented differences in UVB estimation. UVB increased from 1978 to 2014 in 48% of local tests. The largest UVB increase was found in Western Nevada (0.145 kJ/m2 per five-year increment), a total 30-year increase of 0.87 kJ/m2. This largest change only represented 17% of total ambient exposure for an average January and 2% of an average July in Western Nevada. The observed trends represent cumulative UVB changes of less than a month, which are not relevant when attempting to estimate human exposure. The observation of small trends should be interpreted with caution due to measurement of satellite parameter inputs (ozone and climatological factors) that may impact derived satellite UVR nearly 20% compared to ground level sources. If the observed trends hold, satellite-derived UVB data may reasonably estimate ambient UVB exposures even for outcomes with long latency phases that predate the satellite record.
Authors: Langston, Marvin M; Dennis, Leslie L; Lynch, Charles C; Roe, Denise D; Brown, Heidi H
International journal of environmental research and public health. 2017 02 10;14(2):760-765. Epub 2017-02-10.
Human papillomavirus vaccination and subsequent cervical cancer screening in a large integrated healthcare system
Human papillomavirus vaccination may result in lowered intention to be screened for cervical cancer, potentially leading to gaps in screening coverage and avoidable cervical cancer diagnoses. The purpose of this study was to examine the association between human papillomavirus vaccination and subsequent cervical cancer screening initiation and adherence to recommended screening intervals to detect gaps in screening coverage and inform future prevention efforts. A retrospective cohort study was conducted in 2 distinct cohorts of female members of Kaiser Permanente Southern California, which is a large integrated healthcare delivery system. Papanicolaou screening initiation was evaluated in women who reached 21 years from 2010-2013. Adherence to recommended screening intervals was evaluated in women who were 25-30 years old in 2010. All women were observed to the end of 2013 for the evaluation of their screening behaviors. History of human papillomavirus vaccination and Papanicolaou screening were obtained from electronic medical records. Adherence to recommended screening intervals was measured as ≥85% vs <85% of the observed "screening up-to-date" person-time. Multivariable Cox and logistic regression models were used to examine associations between vaccination history and screening initiation and interval adherence. Demographic characteristics, gynecologic health history, healthcare use, and characteristics of women's primary care providers were included as potential confounders in the analyses. There were 27,352 and 41,328 women included in the screening initiation and screening interval adherence analyses, respectively. In comparison with unvaccinated women, adjusted hazard ratios (95% confidence intervals [CIs]) for screening initiation among women who had been vaccinated against human papillomavirus were 1.19 (95% CI, 1.11-1.28), 1.44 (95% CI, 1.34-1.53), and 1.57 (95% CI, 1.50-1.65) for 1, 2, and ≥3 doses, respectively. Adjusted odds ratios for screening interval adherence were 0.93 (95% CI, 0.83-1.04), 1.73 (95% CI, 1.52-1.97), and 2.29 (95% CI, 2.05-2.56), for 1, 2, and ≥3 doses, respectively. Women who had been vaccinated against human papillomavirus in this community-based, integrated healthcare setting were more likely to be screened for cervical cancer than were unvaccinated women. Our findings underscore the need for targeted interventions among unvaccinated women who may be disproportionally affected by cervical cancer, despite the presence of population-based screening programs.
Authors: Chao C; Silverberg MJ; Becerra TA; Corley DA; Jensen CD; Chen Q; Quinn VP
Am J Obstet Gynecol. 2017 Feb;216(2):151.e1-151.e9. Epub 2016-10-14.
Actigraphic Sleep Patterns of U.S. Hispanics: The Hispanic Community Health Study/Study of Latinos
To assess the extent to which objective sleep patterns vary among U.S. Hispanics/Latinos. We assessed objective sleep patterns in 2087 participants of the Hispanic Community Health Study/Study of Latinos from 6 Hispanic/Latino subgroups aged 18-64 years who underwent 7 days of wrist actigraphy. The age- and sex-standardized mean (SE) sleep duration was 6.82 (0.05), 6.72 (0.07), 6.61 (0.07), 6.59 (0.06), 6.57 (0.10), and 6.44 (0.09) hr among individuals of Mexican, Cuban, Dominican, Central American, Puerto Rican, and South American heritage, respectively. Sleep maintenance efficiency ranged from 89.2 (0.2)% in Mexicans to 86.5 (0.4)% in Puerto Ricans, while the sleep fragmentation index ranged from 19.7 (0.3)% in Mexicans to 24.2 (0.7)% in Puerto Ricans. In multivariable models adjusted for age, sex, season, socioeconomic status, lifestyle habits, and comorbidities, these differences persisted. There are important differences in actigraphically measured sleep across U.S. Hispanic/Latino heritages. Individuals of Mexican heritage have longer and more consolidated sleep, while those of Puerto Rican heritage have shorter and more fragmented sleep. These differences may have clinically important effects on health outcomes.
Authors: Dudley KA; Weng J; Sotres-Alvarez D; Simonelli G; Cespedes Feliciano E; Ramirez M; Ramos AR; Loredo JS; Reid KJ; Mossavar-Rahmani Y; Zee PC; Chirinos DA; Gallo LC; Wang R; Patel SR
Sleep. 2017 Feb 01;40(2).
BMI, Lifestyle Factors and Taxane-Induced Neuropathy in Breast Cancer Patients: The Pathways Study
Lifestyle factors may be associated with chemotherapy-induced peripheral neuropathy (CIPN). We examined associations between body mass index (BMI) and lifestyle factors with CIPN in the Pathways Study, a prospective cohort of women with invasive breast cancer. Analyses included 1237 women who received taxane treatment and provided data on neurotoxicity symptoms. Baseline interviews assessed BMI (normal: <25?kg/m 2 ; overweight: 25-29.9?kg/m 2 ; obese: ?30?kg/m 2 ), moderate-to-vigorous physical activity (MVPA) (low: <2.5; medium: 2.5-5; high: >5?hours/week) and fruit/vegetable intake (low: <35 servings/week; high: ?35 servings/week). Baseline and six-month interviews assessed antioxidant supplement use (nonuser, discontinued, continued user, initiator). CIPN was assessed at baseline, six months, and 24 months using the Functional Assessment of Cancer Therapy-Taxane Neurotoxicity (FACT-NTX); a 10% decrease was considered clinically meaningful. At baseline, 65.6% of patients in the sample were overweight or obese, 29.9% had low MVPA, 57.5% had low fruit/vegetable intake, and 9.5% reported antioxidant supplement use during treatment. In multivariable analyses, increased CIPN was more likely to occur in overweight (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.19 to 4.88) and obese patients (OR?=?3.21, 95% CI?=?1.52 to 7.02) compared with normal weight patients at 24 months and less likely to occur in patients with high MVPA compared with those with low MVPA at six (OR?=?0.56, 95% CI?=?0.34 to 0.94) and 24 months (OR?=?0.43, 95% CI?=?0.21 to 0.87). Compared with nonusers, patients who initiated antioxidant use during treatment were more likely to report increased CIPN at six months (OR?=?3.81, 95% CI?=?1.82 to 8.04). Obesity and low MVPA were associated with CIPN in breast cancer patients who received taxane treatment.
Authors: Greenlee H; Hershman DL; Shi Z; Kwan ML; Ergas IJ; Roh JM; Kushi LH
J Natl Cancer Inst. 2017 Feb 01;109(2):1-8.
Metabolic Phenotype and Risk of Colorectal Cancer in Normal-Weight Postmenopausal Women
The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, and few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Our aim was to compare the risk of colorectal cancer in normal-weight postmenopausal women who were characterized by either the metabolically healthy phenotype or the metabolically unhealthy phenotype. A large prospective cohort, the Women’s Health Initiative, was used. The analytic sample included 5,068 postmenopausal women with BMI 18.5 to <25 kg/m2Metabolic phenotype was defined using the Adult Treatment Panel-III definition, excluding waist circumference; therefore, women with one or none of the four components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose) were classified as metabolically healthy. Multivariable Cox proportional hazards regression was used to estimate adjusted HRs for the association between metabolic phenotype and risk of colorectal cancer. Among normal-weight women, those who were metabolically unhealthy had higher risks of colorectal cancer (HR, 1.49; 95% CI, 1.02-2.18) compared with those who were metabolically healthy. A metabolically unhealthy phenotype was associated with higher risk of colorectal cancer among normal-weight women. Normal-weight women should still be evaluated for metabolic health and appropriate steps taken to reduce their risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 155-61. ©2017 AACR.
Authors: Liang X; Margolis KL; Hendryx M; Rohan TE; Groessl EJ; Thomson CA; Kroenke CH; Simon MS; Lane D; Stefanick M; Luo J
Cancer Epidemiol Biomarkers Prev. 2017 Feb;26(2):155-161.
Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis
The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients’ demographic, lifestyle, clinical tumor characteristics, as well as bone health history. The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.
Authors: Yao S; Zhang Y; Tang L; Roh JM; Laurent CA; Hong CC; Hahn T; Lo JC; Ambrosone CB; Kushi LH; Kwan ML
Breast Cancer Res Treat. 2017 02;161(3):501-513. Epub 2016-12-03.
Physical activity induced protection against breast cancer risk associated with delayed parity
Epidemiological evidence indicates that physical activity between menarche and first pregnancy is associated with a lower risk of breast cancer among women with at least 20years between these reproductive events. The mechanism by which physical activity during this interval confers protection is unknown. This study used a novel animal model to assess potentially protective effects of physical activity on tumor development in delayed parity. Thirty-six female Sprague Dawley rats received an i.p. injection of 50mg/kg N-methyl-N-nitrosourea (MNU) at 5weeks of age. Estrogen and progesterone pellets were implanted subcutaneously 1week (early parity, EP, n=8) or 4weeks (delayed parity, DP, n=11) following MNU injection. An additional group of DP rats were progressively exercise trained (Ex+DP, n=9) on a treadmill following MNU injection for 7weeks (up to 20m/min at 15% incline for 30min). We observed the greatest tumor latency and smallest tumor burden in Ex+DP animals. Ductal hyperplasia and inflammation of non-tumor bearing mammary glands were only found in DP, and we detected a significant increase in collagen for DP and Ex+DP compared to EP. Exercise induced differential gene expression of cyclin-dependent kinase-inhibitor 1C (Cdkn1c) and urokinase-plasminogen activator (Plau) in mammary tissue of Ex+DP animals compared to DP alone. While there are delayed parity-induced changes in mammary gland collagen and gene expression levels, Ex+DP animals had longer tumor latency, smaller tumor burden, and glandular tissue resistant to ductal hyperplasia. Exercise may induce protection through beneficial regulation of gene expression profiles.
Authors: Sturgeon KM; Schweitzer A; Leonard JJ; Tobias DK; Liu Y; Cespedes Feliciano E; Malik VS; Joshi A; Rosner B; De Jonghe BC
Physiol Behav. 2017 Feb 01;169:52-58. Epub 2016-11-21.
Measurement equivalence of the Consumer Assessment of Healthcare Providers and Systems (CAHPS(�)) Medicare survey items between Whites and Asians
Asians report worse experiences with care than Whites. This could be due to true differences in care received, expectations about care, or survey response styles. We examined responses to the Consumer Assessment of Healthcare Providers and Systems (CAHPS(®)) Medicare survey items by Whites and Asians, controlling for underlying level on the CAHPS constructs. We conducted multiple group analyses to evaluate measurement equivalence of CAHPS Medicare survey data between White and Asian Medicare beneficiaries for CAHPS reporting composites (communication with personal doctor, access to care, plan customer service) and global ratings of care using pooled data from 2007 to 2011. Responses were obtained from 1,326,410 non-Hispanic Whites and 40,672 non-Hispanic Asians (hereafter referred to as Whites and Asians). The median age for Whites was 70, with 24 % 80 or older, and 70 for Asians, with 23 % 80 or older. Fifty-eight percent of Whites and 56 % of Asians were female. A model without group-specific estimates fit the data as well as a model that included 12 group-specific estimates (7 factor loadings, 3 measured variable errors, and 2 item intercepts): Comparative Fit Index = 0.947 and 0.948; root-mean-square error of approximation = 0.052 and 0.052, respectively). Differences in latent CAHPS score means between Whites and Hispanics estimated from the two models were similar, differing by 0.053 SD or less. This study provides support for measurement equivalence of the CAHPS Medicare survey composites (communication, access, customer service) and global ratings between White and Asian respondents, supporting comparisons of care experiences between the two groups.
Authors: Hays RD; Chawla N; Kent EE; Arora NK
Qual Life Res. 2017 Feb;26(2):311-318. Epub 2016-08-05.
Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer
Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa-such as genetics-can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10-8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment.
Authors: Hoffmann TJ; Sakoda LC; Habel LA; Quesenberry CP; Schaefer C; Risch N; Van Den Eeden SK; Witte JS; et al.
Nat Commun. 2017 Jan 31;8:14248. Epub 2017-01-31.
Fecal Immunochemical Test (FIT) for Colon Cancer Screening: Variable Performance with Ambient Temperature
Fecal immunochemical tests (FITs) are widely used in colorectal cancer (CRC) screening, but hemoglobin degradation, due to exposure of the collected sample to high temperatures, could reduce test sensitivity. We examined the relation of ambient temperature exposure with FIT positivity rate and sensitivity. This was a retrospective cohort study of patients 50 to 75 years in Northern California’s CRC screening program, which began mailing FIT kits annually to screen-eligible members in 2007. Primary outcomes were FIT positivity rate and sensitivity to detect CRC. Predictors were month, season, and daily ambient temperatures of test result dates based on US National Oceanic and Atmospheric Administration data. Patients (n = 472,542) completed 1,141,162 FITs. Weekly test positivity rate ranged from 2.6% to 8.0% (median, 4.4%) and varied significantly by month (June/July vs December/January rate ratio [RR] = 0.79, 95% confidence interval [CI], 0.76 to 0.83) and season. FIT sensitivity was lower in June/July (74.5%; 95% CI, 72.5 to 76.6) than January/December (78.9%; 95% CI, 77.0 to 80.7). FITs completed during high ambient temperatures had lower positivity rates and lower sensitivity. Changing kit design, specimen transportation practices, or avoiding periods of high ambient temperatures may help optimize FIT performance, but may also increase testing complexity and reduce patient adherence, requiring careful study.
Authors: Doubeni CA; Jensen CD; Fedewa SA; Quinn VP; Zauber AG; Schottinger JE; Corley DA; Levin TR
J Am Board Fam Med. 2016 11/12;29(6):672-681.
Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men
Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin. Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates. Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones. Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.
Authors: Watts EL; Habel LA; Schaefer CA; Travis RC; et al.
PLoS ONE. 2017;12(12):e0187741. Epub 2017-12-27.
Shifts in the fecal microbiota associated with adenomatous polyps
Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547). Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer. This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota. Cancer Epidemiol Biomarkers Prev; 26(1); 85-94. ©2016 AACR.
Authors: Hale VL; Levin TR; Chia N; et al.
Cancer Epidemiol Biomarkers Prev. 2017 Jan;26(1):85-94. Epub 2016-09-26.
Variation in actigraphy-estimated rest-activity patterns by demographic factors
Rest-activity patterns provide an indication of circadian rhythmicity in the free-living setting. We aimed to describe the distributions of rest-activity patterns in a sample of adults and children across demographic variables. A sample of adults (N = 590) and children (N = 58) wore an actigraph on their nondominant wrist for 7 days and nights. We generated rest-activity patterns from cosinor analysis (MESOR, acrophase and magnitude) and nonparametric circadian rhythm analysis (IS: interdaily stability; IV: intradaily variability; L5: least active 5-hour period; M10: most active 10-hour period; and RA: relative amplitude). Demographic variables included age, sex, race, education, marital status, and income. Linear mixed-effects models were used to test for demographic differences in rest-activity patterns. Adolescents, compared to younger children, had (1) later M10 midpoints (β = 1.12 hours [95% CI: 0.43, 1.18] and lower M10 activity levels; (2) later L5 midpoints (β = 1.6 hours [95% CI: 0.9, 2.3]) and lower L5 activity levels; (3) less regular rest-activity patterns (lower IS and higher IV); and 4) lower magnitudes (β = -0.95 [95% CI: -1.28, -0.63]) and relative amplitudes (β = -0.1 [95% CI: -0.14, -0.06]). Mid-to-older adults, compared to younger adults (aged 18-29 years), had (1) earlier M10 midpoints (β = -1.0 hours [95% CI: -1.6, -0.4]; (2) earlier L5 midpoints (β = -0.7 hours [95% CI: -1.2, -0.2]); and (3) more regular rest-activity patterns (higher IS and lower IV). The magnitudes and relative amplitudes were similar across the adult age categories. Sex, race and education level rest-activity differences were also observed. Rest-activity patterns vary across the lifespan, and differ by race, sex and education. Understanding population variation in these patterns provides a foundation for further elucidating the health implications of rest-activity patterns across the lifespan.
Authors: Mitchell JA; Glanz K; Kerr J; et al.
Chronobiol Int. 2017;34(8):1042-1056. Epub 2017-06-26.
Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US Multi-Society Task Force on colorectal cancer
Authors: Robertson DJ; Lee JK; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Lieberman D; Levin TR; Rex DK
Gastrointest Endosc. 2017 Jan;85(1):2-21.e3. Epub 2016-10-18.
Participation in Activities Associated With Quality of Life for Long-Term Survivors of Rectal Cancer
Cancer patients’ participation in social, recreational, and civic activities is strongly associated with quality of life (QOL), but these activities are not well integrated into cancer survivorship research or interventions. Test the hypothesis that for long-term (≥ 5 years) survivors of rectal cancer, clinical factors (type of surgery and bowel function) are associated with long-term participation in activities and that participation in activities is associated with long-term QOL. Observational study with longitudinal and cross-sectional components. Participation in activities and QOL. Tumor registry records were used to identify patients and obtain clinical data; surveys assessed participation and QOL. Using general linear models, we analyzed participation in activities in relation to type of surgery and bowel function after adjustment for potential confounders. We analyzed overall QOL relative to participation in activities after adjustment. A total of 567 rectal cancer survivors completed a mailed questionnaire. Overall response rate was 61%. The type of operation (p < 0.0001), receipt of radiation therapy (p = 0.002), and bowel function (p < 0.0001) were associated with participation in activities. Participation in activities was the strongest predictor of QOL (p < 0.0001), explaining 20% of the variance (R2) in QOL, with all other variables together accounting for another 18% of the variance. The importance of participation in activities on rectal cancer survivors' QOL is underappreciated. We recommend revising QOL instruments used in cancer care and research to include questions about participation in activities. Interventions should address maintenance of preferred activities and adoption of new, fulfilling activities.
Authors: Mcmullen C; Liu L; Bulkley JE; Hornbrook MC; Wendel C; Grant M; Altschuler A; Temple LK; Krouse RS; Herrinton L
Perm J. 2017;21.
Risk of Acute Liver Injury With Antiretroviral Therapy by Viral Hepatitis Status
The risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status. We followed a cohort of 10 083 human immunodeficiency virus (HIV)-infected persons in Kaiser Permanente Northern California (n = 2099) from 2004 to 2010 and the Veterans Aging Cohort Study (n = 7984) from 2004 to 2012. Within the first year of ART, we determined occurrence of (1) liver aminotransferases >200 U/L and (2) severe ALI (coagulopathy with hyperbilirubinemia). We used Cox regression to determine hazard ratios (HRs) with 95% confidence intervals (CIs) of endpoints among initiators of nucleos(t)ide analogue combinations, antiretroviral classes, and ART regimens, all stratified by viral hepatitis status. Liver aminotransferases >200 U/L developed in 206 (2%) persons and occurred more frequently among HIV/viral hepatitis-coinfected than HIV-monoinfected persons (116.1 vs 20.7 events/1000 person-years; P < .001). No evidence of differential risk was found between initiators of abacavir/lamivudine versus tenofovir/emtricitabine among coinfected (HR, 0.68; 95% CI, .29-1.57) or HIV-monoinfected (HR, 1.19; 95% CI, .47-2.97) groups. Coinfected patients had a higher risk of aminotransferases >200 U/L after initiation with a protease inhibitor than nonnucleoside reverse-transcriptase inhibitor (HR, 2.01; 95% CI, 1.36-2.96). Severe ALI (30 events; 0.3%) occurred more frequently in coinfected persons (15.9 vs 3.1 events/1000 person-years; P < .001) but was too uncommon to evaluate in adjusted analyses. Within the year after ART initiation, aminotransferase elevations were infrequently observed and rarely led to severe ALI. Protease inhibitor use was associated with a higher risk of aminotransferase elevations among viral hepatitis-coinfected patients.
Authors: Gowda C; Corley DA; Lo Re V; et al.
Open Forum Infect Dis. 2017 Spring;4(2):ofx012. Epub 2017-01-28.
Prognostic significance of marital status in breast cancer survival: A population-based study
Research shows that married cancer patients have lower mortality than unmarried patients but few data exist for breast cancer. We assessed total mortality associated with marital status, with attention to differences by race/ethnicity, tumor subtype, and neighborhood socioeconomic status (nSES). We included, from the population-based California Cancer Registry, women ages 18 and older with invasive breast cancer diagnosed between 2005 and 2012 with follow-up through December 2013. We estimated mortality rate ratios (MRR) and 95% confidence intervals (CI) for total mortality by nSES, race/ethnicity, and tumor subtype. Among 145,564 breast cancer cases, 42.7% were unmarried at the time of diagnosis. In multivariable-adjusted models, the MRR (95% CI) for unmarried compared to married women was 1.28 (1.24-1.32) for total mortality. Significant interactions were observed by race/ethnicity (P<0.001), tumor subtype (P<0.001), and nSES (P = 0.009). Higher MRRs were observed for non-Hispanic whites and Asians/Pacific Islanders than for blacks or Hispanics, and for HR+/HER2+ tumors than other subtypes. Assessment of interactive effect between marital status and nSES showed that unmarried women living in low SES neighborhoods had a higher risk of dying compared with married women in high SES neighborhoods (MRR = 1.60; 95% CI: 1.53-1.67). Unmarried breast cancer patients have higher total mortality than married patients; the association varies by race/ethnicity, tumor subtype, and nSES. Unmarried status should be further evaluated as a breast cancer prognostic factor. Identification of underlying causes of the marital status associations is needed to design interventions that could improve survival for unmarried breast cancer patients.
Authors: Martínez ME; Unkart JT; Tao L; Kroenke CH; Schwab R; Komenaka I; Gomez SL
PLoS ONE. 2017;12(5):e0175515. Epub 2017-05-05.
Recommendations on Fecal Immunochemical Testing to Screen for Colorectal Neoplasia: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer
The use of the fecal occult blood test (FOBT) for colorectal cancer (CRC) screening is supported by randomized trials demonstrating effectiveness in cancer prevention and widely recommended by guidelines for this purpose. The fecal immunochemical test (FIT), as a direct measure of human hemoglobin in stool has a number of advantages relative to conventional FOBT and is increasingly used relative to that test. This review summarizes current evidence for FIT in colorectal neoplasia detection and the comparative effectiveness of FIT relative to other commonly used CRC screening modalities. Based on evidence, guidance statements on FIT application were developed and quality metrics for program implementation proposed.
Authors: Robertson DJ; Lee JK; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Lieberman D; Levin TR; Rex DK
Am J Gastroenterol. 2017 Jan;112(1):37-53. Epub 2016-10-18.
Association of Weight Change after Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population
Higher body mass index (BMI) is associated with incident colorectal cancer but not consistently with colorectal cancer survival. Whether weight gain or loss is associated with colorectal cancer survival is largely unknown. We identified 2,781 patients from Kaiser Permanente Northern California diagnosed with stages I-III colorectal cancer between 2006 and 2011 with weight and height measurements within 3 months of diagnosis and approximately 18 months after diagnosis. We evaluated associations between weight change and colorectal cancer-specific and overall mortality, adjusted for sociodemographics, disease severity, and treatment. After completion of treatment and recovery from stage I-III colorectal cancer, loss of at least 10% of baseline weight was associated with significantly worse colorectal cancer-specific mortality (HR 3.20; 95% confidence interval [CI], 2.33-4.39; Ptrend< 0.0001) and overall mortality (HR 3.27; 95% CI, 2.56-4.18; Ptrend< 0.0001). For every 5% loss of baseline weight, there was a 41% increased risk of colorectal cancer-specific mortality (95% CI, 29%-56%). Weight gain was not significantly associated with colorectal cancer-specific mortality (Ptrend= 0.54) or overall mortality (Ptrend= 0.27). The associations were largely unchanged after restricting analyses to exclude patients who died within 6 months and 12 months of the second weight measurement. No significant interactions were demonstrated for weight loss or gain by gender, stage, primary tumor location, or baseline BMI. Weight loss after diagnosis was associated with worse colorectal cancer-specific mortality and overall mortality. Reverse causation does not appear to explain our findings. Understanding mechanistic underpinnings for the association of weight to worse mortality is important to improving patient outcomes. Cancer Epidemiol Biomarkers Prev; 26(1); 30-37. ©2016 AACR SEE ALL THE ARTICLES IN THIS CEBP FOCUS SECTION, "THE OBESITY PARADOX IN CANCER EVIDENCE AND NEW DIRECTIONS".
Authors: Meyerhardt JA; Kroenke CH; Prado CM; Kwan ML; Castillo A; Weltzien E; Cespedes Feliciano EM; Xiao J; Caan BJ
Cancer Epidemiol Biomarkers Prev. 2017 Jan;26(1):30-37. Epub 2016-12-16.
Next Steps in Understanding the Obesity Paradox in Cancer
Authors: Caan BJ; Kroenke CH
Cancer Epidemiol Biomarkers Prev. 2017 01;26(1):12.
Associations of urinary phthalate and phenol biomarkers with menarche in a multiethnic cohort of young girls
To study potential environmental influences on puberty in girls, we investigated urinary biomarkers in relation to age at menarche. Phenols and phthalates were measured at baseline (6-8 years of age). Menarche was ascertained over 11 years for 1051 girls with menarche and biomarkers. Hazards ratios were estimated from Cox models adjusted for race/ethnicity and caregiver education (aHR, 95% confidence intervals [CI] for 5th vs 1st quintile urinary biomarker concentrations). 2,5-Dichlorophenol was associated with earlier menarche (aHR 1.34 [1.06-1.71]); enterolactone was associated with later menarche (aHR 0.82 [0.66-1.03]), as was mono-3-carboxypropyl phthalate (MCPP) (aHR 0.73 [0.59-0.91]); the three p-trends were <0.05. Menarche differed by 4-7 months across this range. Enterolactone and MCPP associations were stronger in girls with below-median body mass index. These analytes were also associated with age at breast development in this cohort. Findings from this prospective study suggest that some childhood exposures are associated with pubertal timing.
Authors: Wolff MS; Kushi LH; Breast Cancer and Environment Research Program; et al.
Reprod Toxicol. 2017 Jan;67:56-64. Epub 2016-11-13.
Beyond Colonoscopy: The Role of Alternative Screening Tests for Colorectal Cancer in Your Practice
Authors: Levin TR
Am J Gastroenterol. 2017 01;112(1):8-10. Epub 2016-11-01.
Post-diagnosis Weight Change and Survival Following a Diagnosis of Early Stage Breast Cancer
Achieving a healthy weight is recommended for all breast cancer survivors. Previous research on postdiagnosis weight change and mortality had conflicting results. We examined whether change in body weight in the 18 months following diagnosis is associated with overall and breast cancer-specific mortality in a cohort of n = 12,590 stage I-III breast cancer patients at Kaiser Permanente using multivariable-adjusted Cox regression models. Follow-up was from the date of the postdiagnosis weight at 18 months until death or June 2015 [median follow-up (range): 3 (0-9) years]. We divided follow-up into earlier (18-54 months) and later (>54 months) postdiagnosis periods. Mean (SD) age-at-diagnosis was 59 (11) years. A total of 980 women died, 503 from breast cancer. Most women maintained weight within 5% of diagnosis body weight; weight loss and gain were equally common at 19% each. Compared with weight maintenance, large losses (≥10%) were associated with worse survival, with HRs and 95% confidence intervals (CI) for all-cause death of 2.63 (2.12-3.26) earlier and 1.60 (1.14-2.25) later in follow-up. Modest losses (>5%-<10%) were associated with worse survival earlier [1.39 (1.11-1.74)] but not later in follow-up [0.77 (0.54-1.11)]. Weight gain was not related to survival. Results were similar for breast cancer-specific death. Large postdiagnosis weight loss is associated with worse survival in both earlier and later postdiagnosis periods, independent of treatment and prognostic factors. Weight loss and gain are equally common after breast cancer, and weight loss is a consistent marker of mortality risk. Cancer Epidemiol Biomarkers Prev; 26(1); 44-50. ©2016 AACR SEE ALL THE ARTICLES IN THIS CEBP FOCUS SECTION, "THE OBESITY PARADOX IN CANCER EVIDENCE AND NEW DIRECTIONS".
Authors: Cespedes Feliciano EM; Kroenke CH; Bradshaw PT; Chen WY; Prado CM; Weltzien EK; Castillo AL; Caan BJ
Cancer Epidemiol Biomarkers Prev. 2017 Jan;26(1):44-50. Epub 2016-08-26.
Use of androgen deprivation therapy as salvage treatment after primary therapy for clinically localized prostate cancer
The optimal use of androgen deprivation therapy as salvage treatment (sADT) for men after initial prostatectomy or radiotherapy for clinically localized prostate cancer is undefined. We describe patterns of sADT use and investigate clinical and sociodemographic characteristics of insured men who received sADT versus surveillance in managed care settings. Using comprehensive electronic health records and cancer registry data from three integrated health plans, we identified all men with newly diagnosed clinically localized prostate cancer between 1995 and 2009 who received either prostatectomy (n = 16,445) or radiotherapy (n = 19,531) as their primary therapy. We defined sADT based on the timing of ADT following primary therapy and stage of cancer. We fit Cox proportional hazard models to identify sociodemographic characteristics and clinical factors associated with sADT. With a median follow-up of 6 years (range 2-15 years), 13 % of men who underwent primary prostatectomy or radiotherapy received sADT. After adjusting for selected covariates, sADT was more likely to be used in men who were older (e.g., HR 1.70, 95 % CI 1.48-1.96 or HR 1.33, 95 % CI 1.17-1.52 for age 70+ relative to age 35-59 for primary prostatectomy or radiotherapy, respectively), were African-American, had a short PSA doubling time, had a higher pre-treatment risk of progression, had more comorbidities, and received adjuvant ADT for initial disease. In men with localized prostate cancer in community practice initially treated with prostatectomy or radiotherapy, sADT after primary treatment was more frequent for men at greater risk of death from prostate cancer, consistent with practice guidelines.
Authors: Fu AZ; Tsai HT; Haque R; Ulcickas Yood M; Van Den Eeden SK; Cassidy-Bushrow AE; Zhou Y; Keating NL; Smith MR; Aaronson DS; Potosky AL
World J Urol. 2016 Dec;34(12):1611-1619. Epub 2016-04-15.
5-Alpha Reductase Inhibitors and the Risk of Prostate Cancer Mortality in Men Treated for Benign Prostatic Hyperplasia
To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.
Authors: Wallner LP; Van Den Eeden SK; Jacobsen SJ; et al.
Mayo Clin Proc. 2016 Dec;91(12):1717-1726. Epub 2016-10-27.
Trends in cancer survivors’ experience of patient-centered communication: results from the Health Information National Trends Survey (HINTS)
Two Institute of Medicine reports almost a decade apart suggest that cancer survivors often feel “lost in transition” and experience suboptimal quality of care. The six core functions of patient-centered communication: managing uncertainty, responding to emotions, making decisions, fostering healing relationships, enabling self-management, and exchanging information, represent a central aspect of survivors’ care experience that has not been systematically investigated. Nationally representative data from four administrations of the Health Information National Trends Survey (HINTS) was merged with combined replicate weights using the jackknife replication method. Linear and logistic regression models were used to assess (1) characteristics of cancer survivors (N = 1794) who report suboptimal patient-centered communication and (2) whether survivors’ patient-centered communication experience changed from 2007 to 2013. One third to one half of survivors report suboptimal patient-centered communication, particularly on core functions of providers helping manage uncertainty (48 %) and responding to emotions (49 %). In a fully adjusted linear regression model, survivors with more education (Wald F = 2.84, p = .04), without a usual source of care (Wald F = 11.59, p < .001), and in poorer health (Wald F = 9.08, p < .001) were more likely to report less patient-centered communication. Although ratings of patient-centered communication improved over time (p trend = .04), this trend did not remain significant in fully adjusted models. Despite increased attention to survivorship, many survivors continue to report suboptimal communication with their health care providers. Survivorship communication should include managing uncertainty about future risk and address survivors' emotional needs. Efforts to improve patient-centered communication should focus on survivors without a usual source of care and in poorer health.
Authors: Blanch-Hartigan D; Chawla N; Moser RP; Finney Rutten LJ; Hesse BW; Arora NK
J Cancer Surviv. 2016 Dec;10(6):1067-1077. Epub 2016-05-19.
Effects of web-based intervention on risk reduction behaviors in melanoma survivors
Melanoma is the most severe form of skin cancer, and survivors of melanoma carry increased risk of additional melanoma diagnosis. Multiple methods exist for primary and secondary prevention of melanoma in survivors. This study tested a web-based family communication intervention to improve these preventive behaviors in melanoma families. Families (a survivor, at least one first-degree relative and a parent) were randomized either to receive the intervention package or to serve as comparison families. We assessed melanoma prevention behaviors in each cohort member before and after the intervention. The intervention was a web-based multicomponent intervention focused on increasing family communication and exchange of risk information. Results indicated that, compared to comparison survivors, intervention survivors improved their skin self-examination and their sun protection behaviors significantly from before to after intervention. These data support the use of web-based interventions for behavioral changes in survivors and allow for consideration of dissemination of this successful intervention. These data have implications for interventions that can help cancer families deal with issues of risk and illness. These data indicate that survivors can benefit from exposure to a website that helps direct their future health behaviors.
Authors: Bowen DJ; Burke W; Hay JL; Meischke H; Harris JN
J Cancer Surviv. 2014 Nov 26.
Prospective Case-Control Study of Abnormal Bleeding after Outpatient Corticosteroid Injection
This study is aimed at evaluating the incidence of bleeding among women having outpatient corticosteroid injection compared to matched controls, using mailed surveys and electronic health records. Prospective survey study of women receiving outpatient corticosteroid injection for joint or back pain (cases) compared to women matched for visit, diagnosis of joint/back pain, and age, who did not receive an injection (controls). A survey was mailed 45 days following outpatient visit, inquiring about menstrual history, abnormal bleeding, and potential risk factors. The proportion of women reporting abnormal bleeding was compared between cases and controls, and stratified by menopausal status. One thousand and sixty two surveys were mailed to 531 identified cases/control pairs, and 40% response was seen from each group. Of 379 analyzable responders, 135 (36%) were premenopausal and 244 (64%) postmenopausal. Postmenopausal women who had a corticosteroid injection were more likely to report recent abnormal bleeding compared to controls (17 vs. 7%, p = 0.02), whereas rates were similar among premenopausal women (50 vs. 43%, p = 0.39). When logistic regression was performed, injection was associated with bleeding among postmenopausal women, independent of body mass index and hormone use. Corticosteroid injection is associated with increased abnormal vaginal bleeding among postmenopausal women.
Authors: Suh-Burgmann E; Liu JY
Gynecol Obstet Invest. 2016 Nov 23.
Access to Cancer Care and General Medical Care Services Among Cancer Survivors in the United States: An Analysis of 2011 Medical Expenditure Panel Survey Data
Cancer survivors require appropriate health care to manage their unique health needs. This study describes access to cancer care among cancer survivors in the United States and compares access to general medical care between cancer survivors and people who have no history of cancer. We assessed access to general medical care using the core 2011 Medical Expenditure Panel Survey (MEPS). We assessed access to cancer care using the MEPS Experiences With Cancer Survey. We used multivariable logistic regression to compare access to general medical care among 2 groups of cancer survivors (those who reported having access to all necessary cancer care [n = 1088] and those who did not [n = 70]) with self-reported access to general medical care among people who had no history of cancer (n = 22 434). Of the 1158 cancer survivors, 70 (6.0%) reported that they did not receive all necessary cancer care. Adjusted analyses found that cancer survivors who reported not receiving all necessary cancer care were also less likely to report receiving general medical care (78.0%) than cancer survivors who reported having access to necessary cancer care (87.1%) and people who had no history of cancer (87.8%). This study provides nationally representative data on the proportion of cancer survivors who have access to necessary cancer care and yields insight into factors that impede survivors’ access to both cancer care and general medical care. This study is a reference for future work on access to care.
Authors: de Moor JS; Virgo KS; Li C; Chawla N; Han X; Blanch-Hartigan D; Ekwueme DU; McNeel TS; Rodriguez JL; Yabroff KR
Public Health Rep. 2016 Nov;131(6):783-790. Epub 2016-10-27.
A GWAS of Cutaneous Squamous Cell Carcinoma-Letter
Authors: Whittemore AS; Wang W; Jorgenson E; Asgari MM
Cancer Epidemiol Biomarkers Prev. 2016 11;25(11):1534.
The Cancer Research Network: a platform for epidemiologic and health services research on cancer prevention, care, and outcomes in large, stable populations
The ability to collect data on patients for long periods prior to, during, and after a cancer diagnosis is critical for studies of cancer etiology, prevention, treatment, outcomes, and costs. We describe such data capacities within the Cancer Research Network (CRN), a cooperative agreement between the National Cancer Institute (NCI) and organized health care systems across the United States. Data were extracted from each CRN site’s virtual data warehouse using a centrally written and locally executed program. We computed the percent of patients continuously enrolled ?1, ?5, and ?10 years before cancer diagnosis in 2012-2015 (year varied by CRN site). To describe retention after diagnosis, we computed the cumulative percentages enrolled, deceased, and disenrolled each year after the diagnosis for patients diagnosed in 2000. Approximately 8 million people were enrolled in ten CRN health plans on December 31, 2014 or 2015 (year varied by CRN site). Among more than 30,000 recent cancer diagnoses, 70 % were enrolled for ?5 years and 56 % for ?10 years before diagnosis. Among 25,274 cancers diagnosed in 2000, 28 % were still enrolled in 2010, 45 % had died, and 27 % had disenrolled from CRN health systems. Health plan enrollment before cancer diagnosis was generally long in the CRN, and the proportion of patients lost to follow-up after diagnosis was low. With long enrollment histories among cancer patients pre-diagnosis and low post-diagnosis disenrollment, the CRN provides an excellent platform for epidemiologic and health services research on cancer incidence, outcomes, and costs.
Authors: Chubak J; Kushi LH; et al.
Cancer Causes Control. 2016 Nov;27(11):1315-1323. Epub 2016-09-17.
Nonsteroidal Anti-Inflammatory Drug Use is Not Associated With Reduced Risk of Barrett’s Esophagus
Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of esophageal adenocarcinoma. Epidemiological studies examining the association between NSAID use and the risk of the precursor lesion, Barrett’s esophagus, have been inconclusive. We analyzed pooled individual-level participant data from six case-control studies of Barrett’s esophagus in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON). We compared medication use from 1,474 patients with Barrett’s esophagus separately with two control groups: 2,256 population-based controls and 2,018 gastroesophageal reflux disease (GERD) controls. Study-specific odds ratio (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models and were combined using a random-effects meta-analytic model. Regular (at least once weekly) use of any NSAIDs was not associated with the risk of Barrett’s esophagus (vs. population-based controls, adjusted OR=1.00, 95% CI=0.76-1.32, I(2)=61%; vs. GERD controls, adjusted OR=0.99, 95% CI=0.82-1.19, I(2)=19%). Similar null findings were observed among individuals who took aspirin or non-aspirin NSAIDs. We also found no association with highest levels of frequency (at least daily use) and duration (?5 years) of NSAID use. There was evidence of moderate between-study heterogeneity; however, associations with NSAID use remained non-significant in “leave-one-out” sensitivity analyses. Use of NSAIDs was not associated with the risk of Barrett’s esophagus. The previously reported inverse association between NSAID use and esophageal adenocarcinoma may be through reducing the risk of neoplastic progression in patients with Barrett’s esophagus.
Authors: Thrift AP; Anderson LA; Murray LJ; Cook MB; Shaheen NJ; Rubenstein JH; El-Serag HB; Vaughan TL; Schneider JL; Whiteman DC; Corley DA
Am J Gastroenterol. 2016 Nov;111(11):1528-1535. Epub 2016-08-30.
Race/Ethnicity and Adoption of a Population Health Management Approach to Colorectal Cancer Screening in a Community-Based Healthcare System
Screening outreach programs using population health management principles offer services uniformly to all eligible persons, but racial/ethnic colorectal cancer (CRC) screening patterns in such programs are not well known. To examine the association between race/ethnicity and the receipt of CRC screening and timely follow-up of positive results before and after implementation of a screening program. Retrospective cohort study of screen-eligible individuals at the Kaiser Permanente Northern California community-based integrated healthcare delivery system (2004-2013). A total of 868,934 screen-eligible individuals 51-74 years of age at cohort entry, which included 662,872 persons in the period before program implementation (2004-2006), 654,633 during the first 3 years after implementation (2007-2009), and 665,268 in the period from 4 to 7 years (2010-2013) after program implementation. A comprehensive system-wide long-term effort to increase CRC that included leadership alignment, goal-setting, and quality assurance through a PHM approach, using mailed fecal immunochemical testing (FIT) along with offering screening at office visits. Differences over time and by race/ethnicity in up-to-date CRC screening (overall and by test type) and timely follow-up of a positive screen. Race/ethnicity categories included non-Hispanic white, non-Hispanic black, Hispanic/Latino, Asian/Pacific Islander, Native American, and multiple races. From 2004 to 2013, age/sex-adjusted CRC screening rates increased in all groups, including 35.2 to 81.1 % among whites and 35.6 to 78.0 % among blacks. Screening rates among Hispanics (33.1 to 78.3 %) and Native Americans (29.4 to 74.5 %) remained lower than those for whites both before and after program implementation. Blacks, who had slightly higher rates before program implementation (adjusted rate ratio [RR] = 1.04, 99 % CI: 1.02-1.05), had lower rates after program implementation (RR for period from 4 to 7 years = 0.97, 99 % CI: 0.96-0.97). There were also substantial improvements in timely follow-up of positive screening results. In this screening program using core PHM principles, CRC screening increased markedly in all racial/ethnic groups, but disparities persisted for some groups and developed in others, which correlated with levels of adoption of mailed FIT.
Authors: Mehta SJ; Levin TR; Corley DA; Doubeni CA; et al.
J Gen Intern Med. 2016 Nov;31(11):1323-1330. Epub 2016-07-13.
BMI, Lifestyle Factors and Taxane-Induced Neuropathy in Breast Cancer Patients: The Pathways Study.
BACKGROUND: Lifestyle factors may be associated with chemotherapy-induced peripheral neuropathy (CIPN). We examined associations between body mass index (BMI) and lifestyle factors with CIPN in the Pathways Study, a prospective cohort of women with invasive breast cancer. METHODS: Analyses included 1237 women who received taxane treatment and provided data on neurotoxicity symptoms. Baseline interviews assessed BMI (normal: <25 kg/m(2); overweight: 25-29.9 kg/m(2); obese: >/=30 kg/m(2)), moderate-to-vigorous physical activity (MVPA) (low: <2.5; medium: 2.5-5; high: >5 hours/week) and fruit/vegetable intake (low: <35 servings/week; high: >/=35 servings/week). Baseline and six-month interviews assessed antioxidant supplement use (nonuser, discontinued, continued user, initiator). CIPN was assessed at baseline, six months, and 24 months using the Functional Assessment of Cancer Therapy-Taxane Neurotoxicity (FACT-NTX); a 10% decrease was considered clinically meaningful. RESULTS: At baseline, 65.6% of patients in the sample were overweight or obese, 29.9% had low MVPA, 57.5% had low fruit/vegetable intake, and 9.5% reported antioxidant supplement use during treatment. In multivariable analyses, increased CIPN was more likely to occur in overweight (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.19 to 4.88) and obese patients (OR = 3.21, 95% CI = 1.52 to 7.02) compared with normal weight patients at 24 months and less likely to occur in patients with high MVPA compared with those with low MVPA at six (OR = 0.56, 95% CI = 0.34 to 0.94) and 24 months (OR = 0.43, 95% CI = 0.21 to 0.87). Compared with nonusers, patients who initiated antioxidant use during treatment were more likely to report increased CIPN at six months (OR = 3.81, 95% CI = 1.82 to 8.04). CONCLUSIONS: Obesity and low MVPA were associated with CIPN in breast cancer patients who received taxane treatment.
Authors: Greenlee, Heather; Hershman, Dawn L; Shi, Zaixing; Kwan, Marilyn L; Ergas, Isaac J; Roh, Janise M; Kushi, Lawrence H
J Natl Cancer Inst. 2016 Oct 28;109(2):djw206. doi: 10.1093/jnci/djw206. Print 2017 Feb.
Inhibition of Escherichia coli CTP Synthetase by NADH and Other Nicotinamides and Their Mutual Interactions with CTP and GTP
CTP synthetases catalyze the last step of pyrimidine biosynthesis and provide the sole de novo source of cytosine-containing nucleotides. As a central regulatory hub, they are regulated by ribonucleotide and enzyme concentration through ATP and UTP substrate availability, CTP product inhibition, GTP allosteric modification, and quaternary structural changes including the formation of CTP-inhibited linear polymers (filaments). Here, we demonstrate that nicotinamide redox cofactors are moderate inhibitors of Escherichia coli CTP synthetase (EcCTPS). NADH and NADPH are the most potent, and the primary inhibitory determinant is the reduced nicotinamide ring. Although nicotinamide inhibition is noncompetitive with substrates, it apparently enhances CTP product feedback inhibition and GTP allosteric regulation. Further, CTP and GTP also enhance each other’s effects, consistent with the idea that NADH, CTP, and GTP interact with a common intermediate enzyme state. A filament-blocking mutation that reduces CTP inhibitory effects also reduced inhibition by GTP but not NADH. Protein-concentration effects on GTP inhibition suggest that, like CTP, GTP preferentially binds to the filament. All three compounds display nearly linear dose-dependent inhibition, indicating a complex pattern of cooperative interactions between binding sites. The apparent synergy between inhibitors, in consideration with physiological nucleotide concentrations, points to metabolically relevant inhibition by nicotinamides, and implicates cellular redox state as a regulator of pyrimidine biosynthesis.
Authors: Habrian C; Chandrasekhara A; Shahrvini B; Hua B; Lee J; Jesinghaus R; Barry R; Gitai Z; Kollman J; Baldwin EP
Biochemistry. 2016 Oct 04;55(39):5554-5565. Epub 2016-09-19.
Racial/Ethnic Disparities in Colorectal Cancer Screening Across Healthcare Systems
Racial/ethnic disparities in colorectal cancer (CRC) screening and diagnostic testing present challenges to CRC prevention programs. Thus, it is important to understand how differences in CRC screening approaches between healthcare systems are associated with racial/ethnic disparities. This was a retrospective cohort study of patients aged 50-75 years who were members of the Population-based Research Optimizing Screening Through Personalized Regimens cohort from 2010 to 2012. Data on race/ethnicity, CRC screening, and diagnostic testing came from medical records. Data collection occurred in 2014 and analysis in 2015. Logistic regression models were used to calculate AORs and 95% CIs comparing completion of CRC screening between racial/ethnic groups. Analyses were stratified by healthcare system to assess differences between systems. There were 1,746,714 participants across four healthcare systems. Compared with non-Hispanic whites (whites), odds of completing CRC screening were lower for non-Hispanic blacks (blacks) in healthcare systems with high screening rates (AOR=0.86, 95% CI=0.84, 0.88) but similar between blacks and whites in systems with lower screening rates (AOR=1.01, 95% CI=0.93, 1.09). Compared with whites, American Indian/Alaskan Natives had lower odds of completing CRC screening across all healthcare systems (AOR=0.76, 95% CI=0.72, 0.81). Hispanics had similar odds of CRC screening (AOR=0.99, 95% CI=0.98, 1.00) and Asian/Pacific Islanders had higher odds of CRC screening (AOR=1.16, 95% CI=1.15, 1.18) versus whites. Racial/ethnic differences in CRC screening vary across healthcare systems, particularly for blacks, and may be more pronounced in systems with intensive CRC screening approaches.
Authors: Burnett-Hartman AN; Corley DA; PROSPR Consortium; et al.
Am J Prev Med. 2016 Oct;51(4):e107-15. Epub 2016-04-01.
Follow-Up of Abnormal Breast and Colorectal Cancer Screening by Race/Ethnicity
Timely follow-up of abnormal tests is critical to the effectiveness of cancer screening, but may vary by screening test, healthcare system, and sociodemographic group. Timely follow-up of abnormal mammogram and fecal occult blood testing or fecal immunochemical tests (FOBT/FIT) were compared by race/ethnicity using Population-Based Research Optimizing Screening through Personalized Regimens consortium data. Participants were women with an abnormal mammogram (aged 40-75 years) or FOBT/FIT (aged 50-75 years) in 2010-2012. Analyses were performed in 2015. Timely follow-up was defined as colonoscopy ≤3 months following positive FOBT/FIT; additional imaging or biopsy ≤3 months following Breast Imaging Reporting and Data System Category 0, 4, or 5 mammograms; or ≤9 months following Category 3 mammograms. Logistic regression was used to model receipt of timely follow-up adjusting for study site, age, year, insurance, and income. Among 166,602 mammograms, 10.7% were abnormal; among 566,781 FOBT/FITs, 4.3% were abnormal. Nearly 96% of patients with abnormal mammograms received timely follow-up versus 68% with abnormal FOBT/FIT. There was greater variability in receipt of follow-up across healthcare systems for positive FOBT/FIT than for abnormal mammograms. For mammography, black women were less likely than whites to receive timely follow-up (91.8% vs 96.0%, OR=0.71, 95% CI=0.51, 0.97). For FOBT/FIT, Hispanics were more likely than whites to receive timely follow-up than whites (70.0% vs 67.6%, OR=1.12, 95% CI=1.04, 1.21). Timely follow-up among women was more likely for abnormal mammograms than FOBT/FITs, with small variations in follow-up rates by race/ethnicity and larger variation across healthcare systems.
Authors: McCarthy AM; Corley DA; PROSPR consortium; et al.
Am J Prev Med. 2016 Oct;51(4):507-12. Epub 2016-04-28.
Genome-wide association studies in oesophageal adenocarcinoma and Barrett’s oesophagus: a large-scale meta-analysis
Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett’s oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett’s oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett’s oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett’s oesophagus and oesophageal adenocarcinoma. We did a meta-analysis of all genome-wide association studies of Barrett’s oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5?×?10(-8)). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches-including functional annotation databases and gene-based and pathway-based methods-to identify pathophysiologically relevant cellular mechanisms. Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17?159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8?×?10(-10)), MSRA (rs17749155; p=5·2?×?10(-10)), LINC00208 and BLK (rs10108511; p=2·1?×?10(-9)), KHDRBS2 (rs62423175; p=3·0?×?10(-9)), TPPP and CEP72 (rs9918259; p=3·2?×?10(-9)), TMOD1 (rs7852462; p=1·5?×?10(-8)), SATB2 (rs139606545; p=2·0?×?10(-8)), and HTR3C and ABCC5 (rs9823696; p=1·6?×?10(-8)). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6?×?10(-8)) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10(-6)) belonged to muscle cell differentiation and to mesenchyme development and differentiation. Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.
Authors: Gharahkhani P; Corley DA; Schumacher J; et al.
Lancet Oncol. 2016 Oct;17(10):1363-1373. Epub 2016-08-12.
Change in Dietary Patterns and Change in Waist Circumference and DXA Trunk Fat Among Postmenopausal Women
To examine whether changes in diet quality predict changes in central adiposity among postmenopausal women. At baseline and 3-year follow-up, Women’s Health Initiative Observational Study participants completed food frequency questionnaires, and waist circumference was measured (WC, n = 67,175). In a subset, trunk fat was measured via dual-energy X-ray absorptiometry (DXA, n = 4,254). Using multivariable linear regression, 3-year changes in dietary patterns (Healthy Eating Index-2010, Alternate Healthy Eating Index-2010, Alternate Mediterranean Diet, and Dietary Approaches to Stop Hypertension) were examined as predictors of concurrent changes in WC and, secondarily, DXA. Mean (SD) age and 3-year changes in weight and WC were 63 (7) years, 0.52 (4.26) kg, and 0.94 (6.65) cm. A 10% increase in any dietary pattern score, representing improved diet quality, was associated with 0.07 to 0.43 cm smaller increase in WC over 3 years (all P < 0.05). After adjusting for weight change, associations attenuated to 0.02 to 0.10 cm but remained statistically significant for all patterns except Alternate Mediterranean Diet. Results were similar for DXA trunk fat. Three-year improvements in diet quality are modestly protective against gain in WC and partially explained by lesser weight gain. Achieving and maintaining a healthful diet after menopause may protect against gains in central adiposity.
Authors: Cespedes Feliciano EM; Tinker L; Manson JE; Allison M; Rohan T; Zaslavsky O; Waring ME; Asao K; Garcia L; Rosal M; Neuhouser ML
Obesity (Silver Spring). 2016 Oct;24(10):2176-84. Epub 2016-08-22.
Statins and Reduced Risk of Liver Cancer: Evidence for Confounding
A negative association of statin use with liver cancer risk has been reported frequently. We added laboratory measurements, to our knowledge not included in previous investigations, to a case-control analysis of 2877 case patients and 142 850 matched control subjects enrolled in Kaiser Permanente Northern California. Addressing confounding by indication by restricting subjects to those with elevated cholesterol greatly attenuated the negative association; eg, the multivariable-adjusted odds ratio (OR) rose from 0.41 (95% confidence interval [CI] = 0.35 to 0.49) to 0.87 (95% CI = 0.55 to 1.39) for receipt of 18 or more prescriptions. Confounding by contraindication was addressed by controlling for degree of abnormality of liver function tests, alanine or aspartate transaminase, measured within one year of the elevated cholesterol and strongly related to risk. The negative association of statins disappeared for all numbers of prescriptions received, with an odds ratio of 1.21 (95% CI = 0.53 to 2.75) for 18 or more prescriptions. Findings cast doubt on the causality of the frequently observed preventive association.
Authors: Friedman GD; Achacoso N; Fireman B; Habel LA
J Natl Cancer Inst. 2016 Oct;108(10). Epub 2016-07-05.
Association Between Primary Care Visits and Colorectal Cancer Screening Outcomes in the Era of Population Health Outreach
Population outreach strategies are increasingly used to improve colorectal cancer (CRC) screening. The influence of primary care on cancer screening in this context is unknown. To assess associations between primary care provider (PCP) visits and receipt of CRC screening and colonoscopy after a positive fecal immunochemical (FIT) or fecal occult blood test (FOBT). Population-based cohort study. A total of 968,072 patients ages 50-74 years who were not up to date with CRC screening in 2011 in four integrated healthcare systems (three with screening outreach programs using FIT kits) in the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. Demographic, clinical, PCP visit, and CRC screening data were obtained from electronic health records and administrative databases. We examined associations between PCP visits in 2011 and receipt of FIT/FOBT, screening colonoscopy, or flexible sigmoidoscopy (CRC screening) in 2012 and follow-up colonoscopy within 3 months of a positive FIT/FOBT in 2012. We used multivariable logistic regression and propensity score models to adjust for confounding. Fifty-eight percent of eligible patients completed a CRC screening test in 2012, most by FIT. Those with a greater number of PCP visits had higher rates of CRC screening at all sites. Patients with ≥1 PCP visit had nearly twice the adjusted-odds of CRC screening (OR = 1.88, 95 % CI: 1.86-1.89). Overall, 79.6 % of patients with a positive FIT/FOBT completed colonoscopy within 3 months. Patients with ≥1 PCP visit had 30 % higher adjusted odds of completing colonoscopy after positive FIT/FOBT (OR = 1.30; 95 % CI: 1.22-1.40). Patients with a greater number of PCP visits had higher rates of both incident CRC screening and colonoscopy after positive FIT/FOBT, even in health systems with active population health outreach programs. In this era of virtual care and population outreach, primary care visits remain an important mechanism for engaging patients in cancer screening.
Authors: Halm EA; Beaber EF; McLerran D; Chubak J; Corley DA; Rutter CM; Doubeni CA; Haas JS; Balasubramanian BA
J Gen Intern Med. 2016 Oct;31(10):1190-7. Epub 2016-06-08.
Inverse Association Between Gluteofemoral Obesity and Risk of Barrett’s Esophagus in a Pooled Analysis
Gluteofemoral obesity (determined by measurement of subcutaneous fat in the hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces the risk of Barrett’s esophagus (BE), a premalignant lesion associated with abdominal obesity. We collected data from non-Hispanic white participants in 8 studies in the Barrett’s and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n = 1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using individual participant data and multivariable logistic regression and combined using a random-effects meta-analysis. We found an inverse relationship between hip circumference and BE (OR per 5-cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was statistically significant only among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with a decreased risk of BE. Increasing waist circumference was associated with an increased risk of BE in the mutually adjusted population-based and GERD control models. Although abdominal obesity is associated with an increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.
Authors: Kendall BJ; Corley DA; Thrift AP; et al.
Clin Gastroenterol Hepatol. 2016 Oct;14(10):1412-1419.e3. Epub 2016-06-02.
Consequences of Increasing Time to Colonoscopy Examination Following Positive Result From Fecal Colorectal Cancer Screening Test
Delays in diagnostic testing after a positive result from a screening test can undermine the benefits of colorectal cancer (CRC) screening, but there are few empirical data on the effects of such delays. We used microsimulation modeling to estimate the consequences of time to colonoscopy after a positive result from a fecal immunochemical test (FIT). We used an established microsimulation model to simulate an average-risk United States population cohort that underwent annual FIT screening (from ages 50 to 75 years), with follow-up colonoscopy examinations for individuals with positive results (cutoff, 20 μg/g) at different time points in the following 12 months. Main evaluated outcomes were CRC incidence and mortality; additional outcomes were total life-years lost and net costs of screening. For individuals who underwent diagnostic colonoscopy within 2 weeks of a positive result from an FIT, the estimated lifetime risk of CRC incidence was 35.5/1000 persons, and mortality was 7.8/1000 persons. Every month added until colonoscopy was associated with a 0.1/1000 person increase in cancer incidence risk (an increase of 0.3%/month, compared with individuals who received colonoscopies within 2 weeks) and mortality risk (increase of 1.4%/month). Among individuals who received colonoscopy examinations 12 months after a positive result from an FIT, the incidence of CRC was 27.0/1000 persons (increase of 4%, compared with 2 weeks), and mortality was 9.1/1000 persons (increase of 16%). Total years of life gained for the entire screening cohort decreased from an estimated 93.7/1000 persons with an almost immediate follow-up colonoscopy (cost savings of $208 per patient, compared with no colonoscopy) to 84.8/1000 persons with follow-up colonoscopies at 12 months (decrease of 9%; cost savings of $100/patient, compared with no colonoscopy). By using a microsimulation model of an average-risk United States screening cohort, we estimated that delays of up to 12 months after a positive result from an FIT can produce proportional losses of up to nearly 10% in overall screening benefits. These findings indicate the importance of timely follow-up colonoscopy examinations of patients with positive results from FITs.
Authors: Meester RG; Zauber AG; Doubeni CA; Jensen CD; Quinn VP; Helfand M; Dominitz JA; Levin TR; Corley DA; Lansdorp-Vogelaar I
Clin Gastroenterol Hepatol. 2016 Oct;14(10):1445-1451.e8. Epub 2016-05-19.
Use of sildenafil or other phosphodiesterase inhibitors and risk of melanoma
Phosphodiesterase 5A inhibitors (PDEIs), a common treatment for erectile dysfunction, were recently linked to an increased risk of melanoma. We conducted two parallel case-control studies, using the Danish Nationwide Health Registries (DNHR) and the Kaiser Permanente Northern California (KPNC) electronic health records. Identifying men with histologically verified melanoma (cases) matched on birth year to 10 cancer-free controls, we estimated odds ratios (OR) for melanoma associated with high use of PDEIs (?100 tablets filled), adjusting for available confounders. We identified 7045 DNHR and 2972 KPNC cases with invasive melanoma. The adjusted OR for invasive melanoma associated with high PDEI use was 1.22 (95% confidence interval (CI), 0.99-1.49) in DNHR and 0.95 (95% CI, 0.78-1.14) in KPNC. Odds ratios were highest for localised invasive melanoma in DNHR (OR, 1.21) and melanoma in situ in KPNC (OR, 1.15), and lowest for non-localised disease in both populations (ORs 0.75 and 0.61, respectively). The increased ORs were slightly attenuated upon adjustment for markers of health-care utilisation. We found little evidence for a causal association between PDEI use and risk of melanoma. The marginally increased risk of early stage disease likely resulted from more frequent health-care contacts among PDEI users.
Authors: Pottegård A; Schmidt SA; Olesen AB; Achacoso N; Van Den Eeden SK; Hallas J; Sørensen HT; Friis S; Habel LA
Br J Cancer. 2016 Sep 27;115(7):895-900. Epub 2016-08-16.
Physical activity from menarche to first pregnancy and risk of breast cancer
Breast tissue is particularly susceptible to exposures between menarche and first pregnancy, and a longer interval between these reproductive events is associated with elevated breast cancer risk. Physical activity during this time period may offset breast cancer risk, particularly for those at highest risk with longer menarche-to-first-pregnancy intervals. We used data from 65,576 parous women in the Nurses’ Health Study II free of cancer in 1989 (baseline) and recalled their leisure-time physical activity at ages 12-34 in 1997. Current activity was collected at baseline and over follow-up. Relative risks (RRs) were estimated using multivariable Cox proportional hazards regression models. Between 1989 and 2011, 2,069 invasive breast cancer cases were identified. Total recreational activity between menarche and first pregnancy was not significantly associated with the risk of breast cancer. However, physical activity between menarche and first pregnancy was associated with significantly lower breast cancer risk among women in the highest category of a menarche-to first-pregnancy interval (?20 years; RR for the highest versus the lowest quartile?=?0.73, 95% confidence interval?=?0.55-0.97; Ptrend ?=?0.045; Pinteraction ?=?0.048). This was not observed in women with a shorter interval. Physical activity between menarche and first pregnancy was associated with a lower risk of breast cancer among women with at least 20 years between these reproductive events. This may provide a modifiable factor that women can intervene on to mitigate their breast cancer risk associated with a longer interval.
Authors: Liu Y; Tobias DK; Sturgeon KM; Rosner B; Malik V; Cespedes E; Joshi AD; Eliassen AH; Colditz GA
Int J Cancer. 2016 Sep 15;139(6):1223-30. Epub 2016-05-17.
Exercise and Prognosis on the Basis of Clinicopathologic and Molecular Features in Early Stage Breast Cancer: The LACE and Pathways Studies
To investigate whether the impact of postdiagnosis exercise on breast cancer outcomes in women diagnosed with early-stage breast cancer differs on the basis of tumor clinicopathologic and molecular features. Using a prospective design, 6,211 patients with early-stage breast cancer from two large population-based cohort studies were studied. Age-adjusted and multivariable Cox regression models were performed to determine the relationship between exercise exposure (total MET-hours/week) and recurrence and breast cancer-related death for: (i) all patients (“unselected” cohort), and on the basis of (ii) classic clinicopathologic features, (iii) clinical subtypes, (iv) PAM50-based molecular intrinsic subtypes, and (v) individual PAM50 target genes. After a median follow-up of 7.2 years, in the unselected cohort (n = 6,211) increasing exercise exposure was not associated with a reduction in the risk of recurrence (adjusted Ptrend = 0.60) or breast cancer-related death (adjusted Ptrend = 0.39). On the basis of clinicopathologic features, an exercise-associated reduction in breast cancer-related death was apparent for tumors <2 cm [HR, 0.50; 95% confidence interval (CI), 0.34-0.72], well/moderately differentiated tumors (HR, 0.63; 95% CI, 0.43-0.91), and ER-positive tumors (HR, 0.72; 95% CI, 0.53-0.97). Stratification by clinical subtype indicated that the ER(+)/PR(+)/HER2(-)/low-grade clinical subtype was preferentially responsive to exercise (recurrence: adjusted HR, 0.63; 95% CI, 0.45-0.88; breast cancer-related death: adjusted HR, 0.57; 95% CI, 0.37-0.86). The impact of exercise on cancer outcomes appears to differ as a function of pathologic and molecular features in early-stage breast cancer. Cancer Res; 76(18); 5415-22. ©2016 AACR.
Authors: Jones LW; Kwan ML; Sternfeld B; Habel LA; Kroenke CH; Queensberry CP; Kushi LH; Caan BJ; et al.
Cancer Res. 2016 Sep 15;76(18):5415-22. Epub 2016-08-03.
Metabolic Dysfunction, Obesity, and Survival Among Patients With Early-Stage Colorectal Cancer
The effects of obesity and metabolic dysregulation on cancer survival are inconsistent. To identify high-risk subgroups of obese patients and to examine the joint association of metabolic syndrome (MetSyn) in combination with obesity, we categorized patients with early-stage (I to III) colorectal cancer (CRC) into four metabolic categories defined by the presence of MetSyn and/or obesity and examined associations with survival. We studied 2,446 patients diagnosed from 2006 to 2011 at Kaiser Permanente. We assumed MetSyn if patients had three or more of five components present at diagnosis: fasting glucose > 100 mg/dL or diabetes; elevated blood pressure (systolic ? 130 mm Hg, diastolic ? 85 mm Hg, or antihypertensives); HDL cholesterol < 40 mg/dL (men) or < 50 mg/dL (women); triglycerides ? 150 mg/dL or antilipids; and/or highest sex-specific quartile of visceral fat by computed tomography scan (in lieu of waist circumference). We then classified participants according to the presence (or absence) of MetSyn and obesity (BMI < 30 or ? 30 kg/m(2)) and assessed associations with overall and CRC-related survival using Cox proportional hazards models adjusted for demographic, tumor, and treatment factors and muscle mass at diagnosis. Over a median follow-up of 6 years, 601 patients died, 325 as a result of CRC. Mean (SD) age was 64 (11) years. Compared with the reference of nonobese patients without MetSyn (n = 1,225), for overall survival the hazard ratios (HR) and 95% CIs were 1.45 (1.12 to 1.82) for obese patients with MetSyn (n = 480); 1.09 (0.83 to 1.44) for the nonobese with MetSyn (n = 417), and 1.00 (0.80 to 1.26) for obese patients without MetSyn (n = 324). Obesity with MetSyn also predicted CRC-related survival: 1.49 (1.09 to 2.02). The hazard of death increased with the number of MetSyn components present, independent of obesity. Patients with early-stage CRC with obesity and MetSyn have worse survival, overall and CRC related.
Authors: Cespedes Feliciano EM; Kroenke CH; Kwan ML; Quesenberry C; Caan BJ; et al.
J Clin Oncol. 2016 Sep 6.
Association Between Complementary and Alternative Medicine Use and Breast Cancer Chemotherapy Initiation: The Breast Cancer Quality of Care (BQUAL) Study
Not all women initiate clinically indicated breast cancer adjuvant treatment. It is important for clinicians to identify women at risk for noninitiation. To determine whether complementary and alternative medicine (CAM) use is associated with decreased breast cancer chemotherapy initiation. In this multisite prospective cohort study (the Breast Cancer Quality of Care [BQUAL] study) designed to examine predictors of breast cancer treatment initiation and adherence, 685 women younger than 70 years with nonmetastatic invasive breast cancer were recruited from Columbia University Medical Center, Kaiser Permanente Northern California, and Henry Ford Health System and enrolled between May 2006 and July 31, 2010. Overall, 306 patients (45%) were clinically indicated to receive chemotherapy per National Comprehensive Cancer Network guidelines. Participants were followed for up to 12 months. Baseline interviews assessed current use of 5 CAM modalities (vitamins and/or minerals, herbs and/or botanicals, other natural products, mind-body self-practice, mind-body practitioner-based practice). CAM use definitions included any use, dietary supplement use, mind-body use, and a CAM index summing the 5 modalities. Chemotherapy initiation was assessed via self-report up to 12 months after baseline. Multivariable logistic regression models examined a priori hypotheses testing whether CAM use was associated with chemotherapy initiation, adjusting for demographic and clinical covariates, and delineating groups by age and chemotherapy indication. A cohort of 685 women younger than 70 years (mean age, 59 years; median age, 59 years) with nonmetastatic invasive breast cancer were recruited and followed for up to 12 months to examine predictors of breast cancer treatment initiation. Baseline CAM use was reported by 598 women (87%). Chemotherapy was initiated by 272 women (89%) for whom chemotherapy was indicated, compared with 135 women (36%) for whom chemotherapy was discretionary. Among women for whom chemotherapy was indicated, dietary supplement users and women with high CAM index scores were less likely than nonusers to initiate chemotherapy (odds ratio [OR], 0.16; 95% CI, 0.03-0.51; and OR per unit, 0.64; 95% CI, 0.46-0.87, respectively). Use of mind-body practices was not related to chemotherapy initiation (OR, 1.45; 95% CI, 0.57-3.59). There was no association between CAM use and chemotherapy initiation among women for whom chemotherapy was discretionary. CAM use was high among patients with early-stage breast cancer enrolled in a multisite prospective cohort study. Current dietary supplement use and higher number of CAM modalities used but not mind-body practices were associated with decreased initiation of clinically indicated chemotherapy. Oncologists should consider discussing CAM with their patients during the chemotherapy decision-making process.
Authors: Greenlee H; Kwan ML; Lee M; Hershman DL; Hershman DL; et al.
JAMA Oncol. 2016 Sep 01;2(9):1170-6.
Sociodemographic and clinical predictors of switching to active treatment among a large ethnically diverse cohort of men with low-risk prostate cancer on observational management
We determined the clinical and sociodemographic predictors of beginning active treatment in an ethnically diverse population of men with low risk prostate cancer initially on observational treatment. We retrospectively studied men diagnosed with low risk prostate cancer between 2004 and 2012 at Kaiser Permanente Northern California who did not receive any treatment within the first year of diagnosis and had at least 2 years of followup. We used Cox proportional hazards regression models to determine factors associated with time from diagnosis to active treatment. We identified 2,228 eligible men who were initially on observation, of whom 27% began active treatment during followup at a median of 2.9 years. NonHispanic black men were marginally more likely to begin active treatment than nonHispanic white men independent of baseline and followup clinical measures (HR 1.3, 95% CI 1.0-1.7). Among men who remained on observation nonHispanic black men were rebiopsied within 24 months of diagnosis at a slightly lower rate than nonHispanic white men (HR 0.70, 95% CI 0.6-1.0). Gleason grade progression (HR 3.3, 95% CI 2.7-4.1) and PSA doubling time less than 48 months (HR 2.9, 95% CI 2.3-3.7) were associated with initiation of active treatment independent of race. Sociodemographic factors such as ethnicity and education may independently influence the patient decision to pursue active treatment and serial biopsies during active surveillance. These factors are important for further studies of prostate cancer treatment decision making.
Authors: Kelly SP; Van Den Eeden SK; Hoffman RM; Aaronson DS; Lobo T; Luta G; Leimpter AD; Shan J; Potosky AL; Taylor KL
J Urol. 2016 Sep;196(3):734-40. Epub 2016-04-14.
Relationship of pre-diagnostic body mass index with survival after colorectal cancer: Stage-specific associations
Higher body mass index (BMI) is a well-established risk factor for colorectal cancer (CRC), but is inconsistently associated with CRC survival. In 6 prospective studies participating in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), 2,249 non-Hispanic white CRC cases were followed for a median 4.5 years after diagnosis, during which 777 died, 554 from CRC-related causes. Associations between prediagnosis BMI and survival (overall and CRC-specific) were evaluated using Cox regression models adjusted for age at diagnosis, sex, study and smoking status (current/former/never). The association between BMI category and CRC survival varied by cancer stage at diagnosis (I-IV) for both all-cause (p-interaction?=?0.03) and CRC-specific mortality (p-interaction?=?0.04). Compared to normal BMI (18.5-24.9 kg/m(2) ), overweight (BMI 25.0-29.9) was associated with increased mortality among those with Stage I disease, and decreased mortality among those with Stages II-IV disease. Similarly, obesity (BMI ?30) was associated with increased mortality among those with Stages I-II disease, and decreased mortality among those with Stages III-IV disease. These results suggest the relationship between BMI and survival after CRC diagnosis differs by stage at diagnosis, and may emphasize the importance of adequate metabolic reserves for colorectal cancer survival in patients with late-stage disease.
Authors: Kocarnik JM; Caan B; Kroenke CH; Newcomb PA; et al.
Int J Cancer. 2016 Sep 01;139(5):1065-72. Epub 2016-05-14.
Leukocyte telomere length in relation to the risk of Barrett’s esophagus and esophageal adenocarcinoma
Chronic inflammation and oxidative damage caused by obesity, cigarette smoking, and chronic gastroesophageal reflux disease (GERD) are major risk factors associated with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). EAC has been increasing the past few decades, and early discovery and treatment are crucial for survival. Telomere shortening due to cell division and oxidative damage may reflect the impact of chronic inflammation and could possibly be used as predictor for disease development. We examined the prevalence of shorter leukocyte telomere length (LTL) among individuals with GERD, BE, or EAC using a pooled analysis of studies from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON). Telomere length was measured in leukocyte DNA samples by Q-PCR. Participants included 1173 patients (386 with GERD, 384 with EAC, 403 with BE) and 736 population-based controls. The association of LTL (in tertiles) along the continuum of disease progression from GERD to BE to EAC was calculated using study-specific odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models adjusted for potential confounders. Shorter LTL were less prevalent among GERD patients (OR 0.57; 95% CI: 0.35-0.93), compared to population-based controls. No statistically significant increased prevalence of short/long LTL among individuals with BE or EAC was observed. In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of EAC. The findings do not suggest a relationship between LTL and BE or EAC.
Authors: Wennerström EC; Corley DA; Liao LM; et al.
Cancer Med. 2016 Sep;5(9):2657-65. Epub 2016-07-06.
Residential proximity to traffic and female pubertal development
Traffic-related air pollution (TRAP) has been linked with several adverse health outcomes, including preterm birth and low birth weight, which are both related to onset of puberty. No studies to date have investigated the association between TRAP and altered pubertal timing. Determine the association between residential proximity to traffic, as a marker of long-term TRAP exposure, and age at pubertal onset in a longitudinal study of girls. We analyzed data for 437 girls at the CYGNET study site of the Breast Cancer and Environment Research Program. TRAP exposure was assessed using several measures of residential proximity to traffic based on address at study entry. Using accelerated failure time models, we calculated time ratios (TRs) and their corresponding 95% confidence intervals (CIs) for specified traffic metrics and pubertal onset, defined as stage 2 or higher for breast or pubic hair development (respectively, B2+ and PH2+). Models were adjusted for race/ethnicity, household income, and cotinine levels. At baseline, 71% of girls lived within 150m of a major road. The median age of onset was 10.3years for B2+ and 10.9years for PH2+. Living within 150m downwind of a major road was associated with earlier onset of PH2+ (TR 0.96, 95% CI 0.93, 0.99). Girls in the highest quintile of either distance-weighted traffic density, annual average daily traffic, and/or traffic density also reached PH2+ earlier than girls in the lowest quintiles. In this first study to assess the association between residential proximity to traffic and pubertal onset we found girls with higher exposure reached one pubertal milestone several months earlier than low exposed girls, even after consideration of likely confounders. Results should be expanded in larger epidemiological studies, and with measured levels of air pollutants.
Authors: McGuinn LA; Voss RW; Laurent CA; Greenspan LC; Kushi LH; Windham GC
Environ Int. 2016 09;94:635-641. Epub 2016-07-01.
Influence of Age and Comorbidity on Colorectal Cancer Screening in the Elderly
Expert recommendations differ for colorectal cancer screening in the elderly. Recent studies suggest that healthy adults aged >75 years may benefit from screening. This study examined screening use and follow-up, and how they varied by health status within age strata, among a large cohort of elderly individuals in community settings. A population-based, longitudinal cohort study was conducted among health plan members aged 65-89 years enrolled during 2011-2012 in three integrated healthcare systems participating in the Population-Based Research Optimizing Screening through Personalized Regimens consortium. Comorbidity measurements used the Charlson index. Analyses, conducted in 2015, comprised descriptive statistics and multivariable modeling that estimated age by comorbidity-specific percentages of patients for two outcomes: colorectal cancer screening uptake and follow-up of abnormal fecal blood tests. Among 846,267 patients, 72% were up-to-date with colorectal cancer screening. Of patients with a positive fecal blood test, 65% received follow-up colonoscopy within 3 months. Likelihood of being up-to-date and receiving timely follow-up was significantly lower for patients aged ≥76 years than their younger counterparts (p<0.001). Comorbidity was less influential than age and more strongly related to timely follow-up than being up-to-date. In all age groups, considerable numbers of patients with no/low comorbidity were not up-to-date or did not receive timely follow-up. In three integrated healthcare systems, many older, relatively healthy patients were not screening up-to-date, and some relatively young, healthy patients did not receive timely follow-up. Findings suggest a need for re-evaluating age-based screening guidelines and improving screening completion among the elderly.
Authors: Klabunde CN; Corley DA; PROSPR consortium; et al.
Am J Prev Med. 2016 Sep;51(3):e67-75. Epub 2016-06-22.
Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams
Physicians and investigators have sought to determine the relationship between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and colorectal cancer (CRC) outcomes, but methodologic limitations including sampling selection bias, reverse causality, and collider bias have prevented the ability to draw definitive conclusions. To evaluate the association of BMI at the time of, and following, colorectal cancer (CRC) diagnosis with mortality in a complete population using causal diagrams. This retrospective observational study with prospectively collected data included a cohort of 3408 men and women, ages 18 to 80 years, from the Kaiser Permanente Northern California population, who were diagnosed with stage I to III CRC between 2006 and 2011 and who also had surgery. Body mass index at diagnosis and 15 months following diagnosis. Hazard ratios (HRs) for all-cause mortality and CRC-specific mortality compared with normal-weight patients, adjusted for sociodemographics, disease severity, treatment, and prediagnosis BMI. This study investigated a cohort of 3408 men and women ages 18 to 80 years diagnosed with stage I to III CRC between 2006 and 2011 who also had surgery. At-diagnosis BMI was associated with all-cause mortality in a nonlinear fashion, with patients who were underweight (BMI <18.5; HR, 2.65; 95% CI, 1.63-4.31) and patients who were class II or III obese (BMI ?35; HR, 1.33; 95% CI, 0.89-1.98) exhibiting elevated mortality risks, compared with patients who were low-normal weight (BMI 18.5 to <23). In contrast, patients who were high-normal weight (BMI 23 to <25; HR, 0.77; 95% CI, 0.56-1.06), low-overweight (BMI 25 to <28; HR, 0.75; 95% CI, 0.55-1.04), and high-overweight (BMI 28 to <30; HR, 0.52; 95% CI, 0.35-0.77) had lower mortality risks, and patients who were class I obese (BMI 30 to <35) showed no difference in risk. Spline analysis confirmed a U-shaped relationship in participants with lowest mortality at a BMI of 28. Associations with CRC-specific mortality were similar. Associations of postdiagnosis BMI and mortality were also similar, but patients who were class I obese had significantly lower all-cause and cancer-specific mortality risks. In this study, body mass index at the time of diagnosis and following diagnosis of CRC was associated with mortality risk. Though evidence shows that exercise in patients with cancer should be encouraged, findings suggest that recommendations for weight loss in the immediate postdiagnosis period among patients with CRC who are overweight may be unwarranted.
Authors: Kroenke CH; Neugebauer R; Meyerhardt J; Prado CM; Weltzien E; Kwan ML; Xiao J; Caan BJ
JAMA Oncol. 2016 Sep 01;2(9):1137-45.
Paraneoplastic syndromes (PNS) associated with Merkel cell carcinoma (MCC): A case series of 8 patients highlighting different clinical manifestations
Paraneoplastic syndromes (PNS) are commonly associated with neuroendocrine cancers, such as small cell lung cancer. We examined the association of PNS in Merkel cell carcinoma (MCC), a rare neuroendocrine skin cancer. We identified PNS associated with MCC based on chart review of a Seattle-based repository and examined the incidence of MCC-associated hyponatremia in an independent cohort within Kaiser Permanente Northern California. Eight PNS cases were identified from the Seattle repository. Three distinct PNS types were observed: cerebellar degeneration (1 case), Lambert-Eaton myasthenic syndrome (2 cases), and malignancy-associated hyponatremia (5 cases). Moreover, the incidence of severe hyponatremia (serum sodium <125 mmol/L) coincident with MCC was identified among 4.3% (9 of 211) patients with MCC in the Kaiser Permanente Northern California cohort. We did not have access to complete medical records on all patients so it was not possible to determine the prevalence of PNS in MCC. MCC can be associated with PNS similar to those found in other neuroendocrine cancers. Clinicians should be aware of these presentations as PNS often precede the identification of the underlying malignancy and usually resolve with appropriate treatment of the cancer.
Authors: Iyer JG; Parvathaneni K; Bhatia S; Tarabadkar ES; Blom A; Doumani R; McKenzie J; Asgari MM; Nghiem P
J Am Acad Dermatol. 2016 Sep;75(3):541-7. Epub 2016-05-11.
What Should Cardiologists Tell Their Patients About a Healthy Dietary Pattern?
Authors: Hu FB; Cespedes Feliciano EM
J Am Coll Cardiol. 2016 08 23;68(8):815-7.
Racial/Ethnic Disparities in Ovarian Cancer Treatment and Survival
Among ovarian cancer patients, African American (AA) women experience poorer survival compared to other race/ethnicity groups. This has been attributed to differences in access to health care. We evaluated racial/ethnic differences in chemotherapy dosing and survival in a cohort study among members of Kaiser Permanente Northern California, and thus with equivalent access to health care. Analyses included epithelial invasive ovarian cancer cases (n=793) receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent, with median follow-up of 50 months. Relative dose intensity (RDI) was computed for carboplatin and paclitaxel separately as dose administered/week divided by expected dose/week, and average RDI (ARDI) was then calculated for the regimen. Proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) after adjusting for relevant covariates. Compared to whites, AAs were more likely to have dose reduction (ARDI<85%), treatment delay, and early discontinuation. Hispanics were also more likely to have dose reduction, but less likely to have early discontinuation or treatment delay. After controlling for prognostic factors including ARDI, AA women had the worst survival. Compared to whites, adjusted HRs (95% CI) for overall mortality were 1.56 (1.01-2.39) for AA; 0.89 (0.61-1.31) for Asians; and 1.41 (0.98-2.04) for Hispanics. Findings for ovarian cancer-specific mortality were similar. Disparities in ovarian cancer treatment and survival in AA persisted among women with equal access to care. These findings warrant further evaluation of biological, personal, and social factors that may be responsible for these differences.
Authors: Bandera EV; Lee VS; Rodriguez-Rodriguez L; Powell B; Kushi LH
Clin Cancer Res. 2016 Aug 12.
Exercise and Risk of Cardiovascular Events in Women With Nonmetastatic Breast Cancer
Cardiovascular disease (CVD) is a leading cause of death among women with nonmetastatic breast cancer. Whether exercise is associated with reductions in CVD risk in patients with breast cancer with an elevated CVD risk phenotype is not known. Using a prospective design, women (n = 2,973; mean age, 57 years) diagnosed with nonmetastatic breast cancer participating in two registry-based, regional cohort studies, completed a questionnaire that assessed leisure-time recreational physical activity (metabolic equivalent task [MET]-h/wk). The primary end point was the first occurrence of any of the following: new diagnosis of coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, occurring after study enrollment. Median follow-up was 8.6 years (range, 0.2 to 14.8 years). In multivariable analysis, the incidence of cardiovascular events decreased across increasing total MET-h/wk categories (Ptrend < .001). Compared with < 2 MET-h/wk, the adjusted hazard ratio was 0.91 (95% CI, 0.76 to 1.09) for 2 to 10.9 MET-h/wk, 0.79 (95% CI, 0.66 to 0.96) for 11 to 24.5 MET-h/wk, and 0.65 (95% CI, 0.53 to 0.80) for ≥ 24.5 MET-h/wk. Similar trends were observed for the incidence of coronary artery disease and heart failure (P values < .05). Adherence to national exercise guidelines for adult patients with cancer (ie, ≥ 9 MET-h/wk) was associated with an adjusted 23% reduction in the risk of cardiovascular events in comparison with not meeting the guidelines (< 9 MET-h/wk; P < .001). The association with exercise did not differ according to age, CVD risk factors, menopausal status, or anticancer treatment. Exercise is associated with substantial, graded reductions in the incidence of cardiovascular events in women with nonmetastatic breast cancer.
Authors: Jones LW; Habel LA; Kroenke CH; Kwan ML; Quesenberry CP; Sternfeld B; Kushi LH; Caan BJ; et al.
J Clin Oncol. 2016 Aug 10;34(23):2743-9. Epub 2016-05-23.
Race/ethnicity, genetic ancestry, and breast cancer-related lymphedema in the Pathways Study
Breast cancer-related lymphedema (BCRL) is a serious chronic condition after breast cancer (BC) surgery and treatment. It is unclear if BCRL risk varies by race/ethnicity. In a multiethnic prospective cohort study of 2953 BC patients, we examined the association of self-reported BCRL status with self-reported race/ethnicity and estimated genetic ancestry. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated by multivariable Cox proportional hazards models, with follow-up starting 6 months post-BC diagnosis. Estimates were further stratified by body mass index (BMI). By 48 months of follow-up, 342 (11.6 %) women reported having BCRL. Younger age at BC diagnosis, higher BMI at baseline, and lower physical activity were associated with greater BCRL risk. African American (AA) women had a 2-fold increased risk of BCRL compared with White women (HR = 2.04; 95 % CI 1.35-3.08). African genetic ancestry was also associated with an increased risk (HR = 2.50; 95 % CI 1.43, 4.36). Both risks were attenuated but remained elevated after adjusting for known risk factors and became more pronounced when restricted to the nonobese women (adjusted HR = 2.31 for AA and HR = 3.70 for African ancestry, both p < 0.05). There was also evidence of increased BCRL risk with Hispanic ethnicity in the nonobese women. Nonobese AA women had a higher risk of BCRL than White women, which cannot be fully explained by known risk factors. This is the first large-scale, prospective study demonstrating differences in BCRL risk according to race/ethnicity as assessed by both self-report and genetic ancestry data, with a potential ancestry-obesity interaction.
Authors: Kwan ML; Ergas IJ; Quesenberry CP; Kushi LH; et al.
Breast Cancer Res Treat. 2016 08;159(1):119-29. Epub 2016-07-22.
Treatment Preferences for Active Surveillance vs. Active Treatment Among Men with Low-Risk Prostate Cancer
Due to the concerns about the overtreatment of low-risk prostate cancer, active surveillance (AS) is now a recommended alternative to the active treatments (AT) of surgery and radiotherapy. However, AS is not widely utilized, partially due to psychological and decision-making factors associated with treatment preferences. In a longitudinal cohort study, we conducted pretreatment telephone interviews (N = 1,140, 69.3% participation) with newly diagnosed, low-risk prostate cancer patients (PSA ≤ 10, Gleason ≤ 6) from Kaiser Permanente Northern California. We assessed psychological and decision-making variables, and treatment preference [AS, AT, and No Preference (NP)]. Men were 61.5 (SD, 7.3) years old, 24 days (median) after diagnosis, and 81.1% white. Treatment preferences were: 39.3% AS, 30.9% AT, and 29.7% NP. Multinomial logistic regression revealed that men preferring AS (vs. AT) were older (OR, 1.64; CI, 1.07-2.51), more educated (OR, 2.05; CI, 1.12-3.74), had greater prostate cancer knowledge (OR, 1.77; CI, 1.43-2.18) and greater awareness of having low-risk cancer (OR, 3.97; CI, 1.96-8.06), but also were less certain about their treatment preference (OR, 0.57; CI, 0.41-0.8), had greater prostate cancer anxiety (OR, 1.22; CI, 1.003-1.48), and preferred a shared treatment decision (OR, 2.34; CI, 1.37-3.99). Similarly, men preferring NP (vs. AT) were less certain about treatment preference, preferred a shared decision, and had greater knowledge. Although a substantial proportion of men preferred AS, this was associated with anxiety and uncertainty, suggesting that this may be a difficult choice. Increasing the appropriate use of AS for low-risk prostate cancer will require additional reassurance and information, and reaching men almost immediately after diagnosis while the decision-making is ongoing. Cancer Epidemiol Biomarkers Prev; 25(8); 1240-50. ©2016 AACR.
Authors: Taylor KL; Van Den Eeden SK; et al.
Cancer Epidemiol Biomarkers Prev. 2016 08;25(8):1240-50. Epub 2016-06-02.
Racial disparities in renal cell carcinoma: a single-payer healthcare experience
Significant racial disparities in survival for renal cell carcinoma (RCC) exist between white and black patients. Differences in access to care and comorbidities are possible contributors. To investigate if racial disparities persist when controlling for access to care, we analyzed data from a single-payer healthcare system. As part of a case-control study within the Kaiser Permanente Northern California system, pathologic and clinical records were obtained for RCC cases (2152 white, 293 black) diagnosed from 1998 to 2008. Patient demographics, comorbidities, tumor characteristics, and treatment status were compared. Overall survival and disease-specific survival (DSS) were calculated by the Kaplan-Meier method. A Cox proportion hazards model estimated the independent associations of race, comorbidity, and clinicopathologic variables with DSS. We found that compared to white patients, black patients were diagnosed at a younger age (median 62 vs. 66 years, P < 0.001), were more likely to have papillary RCC (15% vs. 5.2%, P < 0.001), and had similar rates of surgical treatment (78.8% vs. 77.9%, P = 0.764). On multivariate analysis, advanced American Joint Committee on Cancer (AJCC) stage, lack of surgical treatment, larger tumor size, and higher grade were predictors of worse DSS. Race was not an independent predictor of survival. Therefore, we conclude that within a single healthcare system, differences in characteristics of black and white patients with RCC persist; black patients had different comorbidities, were younger, and had decreased tumor stage. However, unlike other series, race was not an independent predictor of DSS, suggesting that survival differences in large registries may result from barriers to healthcare access and/or comorbidity rather than disease biology.
Authors: Mafolasire A; Yao X; Nawaf C; Suarez-Sarmiento A; Chow WH; Zhao W; Corley D; Hofmann JN; Purdue M; Adeniran AJ; Shuch B
Cancer Med. 2016 Aug;5(8):2101-8. Epub 2016-05-26.
Dual energy X-ray absorptiometry spine scans to determine abdominal fat in postmenopausal women
Body composition may be a better predictor of chronic disease risk than body mass index (BMI) in older populations.OBJECTIVES:We sought to validate spine fat fraction (%) from dual energy X-ray absorptiometry (DXA) spine scans as a proxy for total abdominal fat.METHODS:Total body DXA scan abdominal fat regions of interest (ROI) that have been previously validated by magnetic resonance imaging were assessed among healthy, postmenopausal women who also had antero-posterior spine scans (n = 103). ROIs were (1) lumbar vertebrae L2-L4 and (2) L2-Iliac Crest (L2-IC), manually selected by two independent raters, and (3) trunk, auto-selected by DXA software. Intra-class correlation coefficients evaluated intra and inter-rater reliability on a random subset (N = 25). Linear regression models, validated by bootstrapping, assessed the relationship between spine fat fraction (%) and total abdominal fat (%) ROIs.RESULTS:Mean age, BMI, and total body fat were 66.1 ± 4.8 y, 25.8 ± 3.8 kg/m2 and 40.0 ± 6.6%, respectively. There were no significant differences within or between raters. Linear regression models adjusted for several participant and scan characteristics were equivalent to using only BMI and spine fat fraction. The model predicted L2-L4 (Adj. R2 : 0.83) and L2-IC (Adj. R2 : 0.84) abdominal fat (%) well; the adjusted R2 for trunk fat (%) was 0.78. Model validation demonstrated minimal over-fitting (Adj. R2 : 0.82, 0.83, and 0.77 for L2-L4, L2-IC, and trunk fat, respectively).CONCLUSIONS:The strong correlation between spine fat fraction and DXA abdominal fat measures make it suitable for further development in postmenopausal chronic disease risk prediction models. Am. J. Hum. Biol. 28:918-926, 2016. © 2016Wiley Periodicals, Inc.
Authors: Bea JW; Blew RM; Going SB; Hsu CH; Lee MC; Lee VR; Caan BJ; Kwan ML; Lohman TG
Am J Hum Biol. 2016 Jul 15.
Longitudinal associations of phthalate exposures during childhood and body size measurements in young girls
Phthalates are environmental chemicals that may play a role in the development of obesity. Few studies have investigated longitudinal associations between postnatal phthalate exposures and subsequent anthropometric measurements in children. We collected data as part of The Breast Cancer and Environment Research Program at three US sites. A total of 1,239 girls, aged 6-8 years, were enrolled in 2004-2007. We categorized baseline phthalate exposures, assessed from creatinine-corrected urinary concentrations of low-molecular weight phthalate metabolites, as low, <78; medium, 78 to <194; and high, ≥194 μg/g creatinine and of high-molecular weight phthalates as low, <111; medium, 111-278; and high, ≥278 μg/g creatinine. Anthropometric measurements were collected through 2012 (n = 1,017). Linear mixed effects regression estimated how baseline low and high-molecular weight phthalate concentrations related to changes in girls' body mass index (BMI), height, and waist circumference at ages 7-13 years. Low-molecular weight phthalates were positively associated with gains in BMI and waist circumference. Predicted differences in BMI and waist circumference between girls with high versus low concentrations of low-molecular weight phthalates increased from 0.56 (95% confidence interval [CI]: -0.02, 1.1) to 1.2 kg/m (95% CI: 0.28, 2.1) and from 1.5 (95% CI: -0.38, 3.3) to 3.9 cm (95% CI: 1.3, 6.5), respectively. High-molecular weight phthalates were negatively associated with height but only among girls who were normal weight at baseline (BMI ≤ 85th percentile). Phthalates, specifically low-molecular weight phthalates, have small but detectable associations with girls' anthropometric outcomes. Low-molecular weight phthalates showed stronger associations than other types of phthalates.
Authors: Deierlein AL; Kushi LH; Breast Cancer and Environment Research Program; et al.
Epidemiology. 2016 07;27(4):492-9.
Time-Based Billing: What Primary Care in the United States Can Learn From Switzerland
Authors: Selby K; Edwards S
JAMA Intern Med. 2016 Jul 1;176(7):881-2. doi: 10.1001/jamainternmed.2016.2230.
A prospective cohort study of early discontinuation of adjuvant chemotherapy in women with breast cancer: the breast cancer quality of care study (BQUAL)
For many women with non-metastatic breast cancer, adjuvant chemotherapy prevents recurrence and extends survival. Women who discontinue chemotherapy early may reduce those benefits, but little is known about what predicts early discontinuation. We sought to determine prospectively the rate and reasons for early discontinuation of adjuvant chemotherapy in women with breast cancer. We conducted a prospective cohort study among three U.S. health care organizations. Of 1158 women with newly diagnosed non-metastatic breast cancer, 2006-2010, we analyzed 445 (38.4 %) patients who initiated standard adjuvant chemotherapy as defined by accepted guidelines. We interviewed patients at baseline and twice during treatment regarding sociodemographic/psychosocial factors and treatment decision-making and collected clinical data. They were categorized according to the number of cycles required by the chemotherapy regimen they had initiated. The outcome was early discontinuation (<80 % of planned cycles). Of patients analyzed, 392 (88.1 %) completed the prescribed therapy. The strongest predictor was receipt of a regimen entailing >4 cycles of therapy (18.1 % for longer regimens, 7.4 % for 4 cycles) (odds ratio [OR] 2.59, 95 % CI 1.32-5.08), controlling for race, age, stage, hormone receptor status, social support, optimism, spirituality, stress, and physical symptoms. Higher levels of psychological symptoms on the Memorial symptom assessment scale also increased the odds of early discontinuation (OR 1.92, 95 % CI 0.998-3.68). The large majority of patients who initiated adjuvant chemotherapy for breast cancer completed their prescribed regimens, but early discontinuation was associated with lengthier regimens and, with borderline statistical significance, for those with psychological side effects.
Authors: Neugut AI; Hillyer GC; Kushi LH; Lamerato L; Buono DL; Nathanson SD; Bovbjerg DH; Mandelblatt JS; Tsai WY; Jacobson JS; Hershman DL
Breast Cancer Res Treat. 2016 07;158(1):127-38. Epub 2016-06-10.
Associations Between Maternal Pregravid Obesity and Gestational Diabetes and the Timing of Pubarche in Daughters
We investigated whether in utero exposure to maternal pregravid obesity and/or gestational diabetes mellitus (GDM) was associated with early puberty in girls. We used data from a longitudinal study of 421 mother-daughter pairs enrolled in an integrated health services organization, Kaiser Permanente Northern California (2005-2012). Girls aged 6-8 years were followed annually through ages 12-14 years. Onset of puberty was assessed using study clinic-based Tanner staging. We examined associations of self-reported pregravid obesity and maternal GDM with timing of the daughter’s transition to pubertal maturation stage 2 or above for development of breasts and pubic hair, using accelerated failure time regression models with interval censoring to estimate time ratios and hazard ratios and corresponding 95% confidence intervals. Maternal obesity (pregravid body mass index (BMI; weight (kg)/height (m)(2)) ≥30) was associated with a daughter’s earlier transition to breast and pubic hair stage 2+ in comparison with girls whose mothers had pregravid BMI <25. These associations were attenuated and not statistically significant after adjustment for covariates. Girls whose mothers had both pregravid BMI ≥25 and GDM were at higher risk of an earlier transition to pubic hair stage 2+ than those whose mothers had neither condition (adjusted time ratio = 0.89, 95% confidence interval: 0.83, 0.96; hazard ratio = 2.97, 95% confidence interval: 1.52, 5.83). These findings suggest that exposure to maternal obesity and hyperglycemia places girls at higher risk of earlier pubarche.
Authors: Kubo A; Ferrara A; Laurent CA; Windham GC; Greenspan LC; Deardorff J; Hiatt RA; Quesenberry CP; Kushi LH
Am J Epidemiol. 2016 Jul 01;184(1):7-14. Epub 2016-06-07.
The Dawning of a New Editorial Board for Gastroenterology
Authors: Corley DA; Peek RM
Gastroenterology. 2016 07;151(1):4-8. Epub 2016-05-20.
The effect of patient and contextual characteristics on racial/ethnic disparity in breast cancer mortality
Racial/ethnic disparity in breast cancer-specific mortality in the United States is well documented. We examined whether accounting for racial/ethnic differences in the prevalence of clinical, patient, and lifestyle and contextual factors that are associated with breast cancer-specific mortality can explain this disparity. The California Breast Cancer Survivorship Consortium combined interview data from six California-based breast cancer studies with cancer registry data to create a large, racially diverse cohort of women with primary invasive breast cancer. We examined the contribution of variables in a previously reported Cox regression baseline model plus additional contextual, physical activity, body size, and comorbidity variables to the racial/ethnic disparity in breast cancer-specific mortality. The cohort comprised 12,098 women. Fifty-four percent were non-Latina Whites, 17% African Americans, 17% Latinas, and 12% Asian Americans. In a model adjusting only for age and study, breast cancer-specific HRs relative to Whites were 1.69 (95% CI, 1.46-1.96), 1.00 (0.84-1.19), and 0.52 (0.33-0.85) for African Americans, Latinas, and Asian Americans, respectively. Adjusting for baseline-model variables decreased disparity primarily by reducing the HR for African Americans to 1.13 (0.96-1.33). The most influential variables were related to disease characteristics, neighborhood socioeconomic status, and smoking status at diagnosis. Other variables had negligible impact on disparity. Although contextual, physical activity, body size, and comorbidity variables may influence breast cancer-specific mortality, they do not explain racial/ethnic mortality disparity. Other factors besides those investigated here may explain the existing racial/ethnic disparity in mortality. Cancer Epidemiol Biomarkers Prev; 25(7); 1064-72. ©2016 AACR.
Authors: Sposto R; Bernstein L; Lu Y; Wu AH; et al.
Cancer Epidemiol Biomarkers Prev. 2016 07;25(7):1064-72. Epub 2016-04-26.
Obesity, diabetes, serum glucose, and risk of primary liver cancer by birth cohort, race/ethnicity, and sex: Multiphasic health checkup study
Obesity and diabetes have been associated with liver cancer. However, recent US-based studies have suggested a lack of association between obesity and liver cancer among blacks and women. We conducted a nested case-control study within the Multiphasic Health Checkup (MHC) cohort of Kaiser Permanente Northern California (KPNC) members. Liver cancer was diagnosed using the KPNC Cancer Registry. Detailed self-administered questionnaires and a standardized examination that included measurement of height and weight and a 1-h glucose tolerance test were completed prior to diagnosis of liver cancer for cases (n=450) and matched controls (4489). Height and weight were utilized to calculate BMI (kg/m(2)) as a measure of adiposity: underweight (15-?8.5kg/m(2)), normal weight (18.5-?25kg/m(2)), overweight (25-?30kg/m(2)), and obese (?30kg/m(2)). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between BMI, diabetes, and serum glucose with subsequent incidence of liver cancer, in models that were stratified by birth cohort, race/ethnicity, and sex. Compared to normal weight individuals, obese individuals had a 2.4-fold increased risk of liver cancer (OR=2.38, 95% CI: 1.68-3.36), and overweight individuals had a 32% increased risk (OR=1.32, 95% CI: 1.03-1.70). This association did not differ when stratified by birth cohort, race/ethnicity, or sex (pint>0.05). Among blacks and women, obesity was associated with at least a 2-fold increased risk of liver cancer (OR=2.29, 95% CI: 1.22-4.28 and OR=2.00, 95% CI: 1.14-3.52, respectively). More moderate increased odds ratios were noted for diabetes (OR=1.28, 95% CI: 0.65-2.54) and serum glucose ?200mg/dL (OR=1.63, 95% CI: 0.48-5.55), although the results did not attain statistical significance. In summary, our finding of a positive association between obesity and liver cancer suggests that a higher BMI may increase the risk of liver cancer in the US, for both sexes and all race/ethnicities.
Authors: Petrick JL; Freedman ND; Demuth J; Yang B; Van Den Eeden SK; Engel LS; McGlynn KA
Cancer Epidemiol. 2016 06;42:140-6. Epub 2016-05-02.
Cancer-Related Information Seeking Among Cancer Survivors: Trends Over a Decade (2003-2013)
The demonstrated benefits of information seeking for cancer patients, coupled with increases in information availability, underscore the importance of monitoring patient information seeking experiences over time. We compared information seeking among cancer survivors to those with a family history of cancer and those with no history of cancer. We identified characteristics associated with greater information seeking among cancer survivors, key sources of cancer-related information, and changes in information source use over time. Data from five iterations of the Health Information National Trends Survey (HINTS) spanning 2003 to 2013 were merged and analyzed. Frequencies, cross-tabulations, multivariate logistic regression, and multinomial regression analyses were conducted. All data were weighted to provide representative estimates of the adult US population. Cancer information seeking was reported most frequently by cancer survivors (69.8 %). The percentage of cancer survivors who reported information seeking increased from 66.8 % in 2003 to 80.8 % in 2013. Cancer information seeking was independently associated with age, education, and income; seeking was less likely among older adults, those with less education, and those with lower incomes. Compared to respondents in 2003, those in 2005 (odds ratio (OR)?=?0.40, 95 % confidence interval (CI)?=?0.24-0.65) and 2008 (OR?=?.43, 95 % CI?=?0.26-0.70) were about half as likely to use the Internet as the first source of cancer information compared to a healthcare provider. Despite overall increases in cancer information seeking and access to health information from a variety of sources, healthcare providers remain a key source of health information for cancer survivors.
Authors: Finney Rutten LJ; Agunwamba AA; Wilson P; Chawla N; Vieux S; Blanch-Hartigan D; Arora NK; Blake K; Hesse BW
J Cancer Educ. 2016 Jun;31(2):348-57.
Air Pollution and Pulmonary Tuberculosis: A Nested Case-Control Study among Members of a Northern California Health Plan
Ecologic analyses, case-case comparisons, and animal experiments suggest positive associations between air pollution and tuberculosis. We evaluated this hypothesis in a large sample, which yielded results that are applicable to the general population. We conducted a case-control study nested within a cohort of Kaiser Permanente of Northern California members. All active pulmonary tuberculosis (TB) cases newly diagnosed between 1996 and 2010 (n = 2,309) were matched to two controls (n = 4,604) by age, sex, and race/ethnicity on the index date corresponding with the case diagnosis date. Average individual-level concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) and 10 μm (PM10) for 2 years before diagnosis/entry into the study were estimated using measurements from the California Air Resources Board monitor closest to the participant’s residence. In single-pollutant adjusted conditional logistic regression models, the pulmonary TB odds ratios (95% confidence intervals) for the highest quintile (vs. lowest) were 1.50 (95% CI: 1.15, 1.95) for CO and 1.42 (95% CI: 1.10, 1.84) for NO2. Corresponding estimates were higher among never [1.68 (95% CI: 1.26, 2.24)] than ever [1.19 (95% CI: 0.74, 1.92)] smokers for CO. In contrast, for NO2, estimates were higher among ever [1.81 (95% CI: 1.13, 2.91)] than never [1.29 (95% CI: 0.97, 1.71)] smokers. O3 was inversely associated for smokers [0.66 (95% CI: 0.43, 1.02)] and never smokers [0.65 (95% CI: 0.52, 0.81)]. No other consistent patterns were observed. In this first, to our knowledge, U.S. nested case-control study on air pollution and pulmonary TB, we observed positive associations with ambient CO and NO2, which require confirmation. Smith GS, Van Den Eeden SK, Garcia C, Shan J, Baxter R, Herring AH, Richardson DB, Van Rie A, Emch M, Gammon MD. 2016. Air pollution and pulmonary tuberculosis: a nested case-control study among members of a Northern California health plan. Environ Health Perspect 124:761-768; https://dx.doi.org/10.1289/ehp.1408166.
Authors: Smith GS; Van Den Eeden SK; Garcia C; Shan J; Baxter R; Herring AH; Richardson DB; Van Rie A; Emch M; Gammon MD
Environ Health Perspect. 2016 Jun;124(6):761-8. Epub 2016-02-09.
Reply
Authors: Lo Re V; Forde KA; Goldberg DS; Lewis JD; Carbonari DM; Reddy KR; Roy J; Sha D; Strom BL; Corley DA
Clin Gastroenterol Hepatol. 2016 06;14(6):918-919. Epub 2016-02-15.
Reproductive Risk Factors and Coronary Heart Disease in the Women’s Health Initiative Observational Study
Reproductive factors provide an early window into a woman’s coronary heart disease (CHD) risk; however, their contribution to CHD risk stratification is uncertain. In the Women’s Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ?1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C statistic, net reclassification index (or net reclassification index with risk categories of <5%, 5 to <10%, and ?10% 10-year risk of CHD), and integrated discriminatory index were assessed. Among 72?982 women (CHD events, n=4607; median follow-up,12.0 [interquartile range, 8.3-13.7] years; mean [standard deviation] age, 63.2 [7.2] years), an age-adjusted reproductive risk factor model had a C statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages, and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C statistic increased from 0.726 to 0.730; integrated discriminatory index, 0.0013; P<0.0001). Net reclassification for women with events was not improved (net reclassification index events, 0.007; P=0.18); and, for women without events, net reclassification was marginally improved (net reclassification index nonevents, 0.002; P=0.04) CONCLUSIONS: Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination, and do not materially improve net reclassification.
Authors: Parikh NI; Kroenke CH; Howard BV; et al.
Circulation. 2016 May 31;133(22):2149-58. Epub 2016-04-19.
Association between dietary inflammatory potential and breast cancer incidence and death: results from the Women’s Health Initiative
Diet modulates inflammation and inflammatory markers have been associated with cancer outcomes. In the Women’s Health Initiative, we investigated associations between a dietary inflammatory index (DII) and invasive breast cancer incidence and death. The DII was calculated from a baseline food frequency questionnaire in 122?788 postmenopausal women, enrolled from 1993 to 1998 with no prior cancer, and followed until 29 August 2014. With median follow-up of 16.02 years, there were 7495 breast cancer cases and 667 breast cancer deaths. We used Cox regression to estimate multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (95% CIs) by DII quintiles (Q) for incidence of overall breast cancer, breast cancer subtypes, and deaths from breast cancer. The lowest quintile (representing the most anti-inflammatory diet) was the reference. The DII was not associated with incidence of overall breast cancer (HRQ5vsQ1, 0.99; 95% CI, 0.91-1.07; Ptrend=0.83 for overall breast cancer). In a full cohort analysis, a higher risk of death from breast cancer was associated with consumption of more pro-inflammatory diets at baseline, after controlling for multiple potential confounders (HRQ5vsQ1, 1.33; 95% CI, 1.01-1.76; Ptrend=0.03). Future studies are needed to examine the inflammatory potential of post-diagnosis diet given the suggestion from the current study that dietary inflammatory potential before diagnosis is related to breast cancer death.
Authors: Tabung FK; Caan B; Hébert JR; et al.
Br J Cancer. 2016 May 24;114(11):1277-85. Epub 2016-04-21.
Case-control study of mammographic density and breast cancer risk using processed digital mammograms
Full-field digital mammography (FFDM) has largely replaced film-screen mammography in the US. Breast density assessed from film mammograms is strongly associated with breast cancer risk, but data are limited for processed FFDM images used for clinical care. We conducted a case-control study nested among non-Hispanic white female participants of the Research Program in Genes, Environment and Health of Kaiser Permanente Northern California who were aged 40 to 74 years and had screening mammograms acquired on Hologic FFDM machines. Cases (n = 297) were women with a first invasive breast cancer diagnosed after a screening FFDM. For each case, up to five controls (n = 1149) were selected, matched on age and year of FFDM and image batch number, and who were still under follow-up and without a history of breast cancer at the age of diagnosis of the matched case. Percent density (PD) and dense area (DA) were assessed by a radiological technologist using Cumulus. Conditional logistic regression was used to estimate odds ratios (ORs) for breast cancer associated with PD and DA, modeled continuously in standard deviation (SD) increments and categorically in quintiles, after adjusting for body mass index, parity, first-degree family history of breast cancer, breast area, and menopausal hormone use. Median intra-reader reproducibility was high with a Pearson’s r of 0.956 (range 0.902 to 0.983) for replicate PD measurements across 23 image batches. The overall mean was 20.02 (SD, 14.61) for PD and 27.63 cm(2) (18.22 cm(2)) for DA. The adjusted ORs for breast cancer associated with each SD increment were 1.70 (95 % confidence interval, 1.41-2.04) for PD, and 1.54 (1.34-1.77) for DA. The adjusted ORs for each quintile were: 1.00 (ref.), 1.49 (0.91-2.45), 2.57 (1.54-4.30), 3.22 (1.91-5.43), 4.88 (2.78-8.55) for PD, and 1.00 (ref.), 1.43 (0.85-2.40), 2.53 (1.53-4.19), 2.85 (1.73-4.69), 3.48 (2.14-5.65) for DA. PD and DA measured using Cumulus on processed FFDM images are positively associated with breast cancer risk, with similar magnitudes of association as previously reported for film-screen mammograms. Processed digital mammograms acquired for routine clinical care in a general practice setting are suitable for breast density and cancer research.
Authors: Habel LA; Lipson JA; Achacoso N; Rothstein JH; Yaffe MJ; Liang RY; Acton L; McGuire V; Whittemore AS; Rubin DL; Sieh W
Breast Cancer Res. 2016 May 21;18(1):53. Epub 2016-05-21.
Reducing Variation in the “Standard of Care” for Cancer Screening: Recommendations From the PROSPR Consortium
Authors: Corley DA; Haas JS; Kobrin S
JAMA. 2016 May 17;315(19):2067-8.
Training primary care physicians to offer their patients faecal occult blood testing and colonoscopy for colorectal cancer screening on an equal basis: a pilot intervention with before-after and parallel group surveys
Authors: Selby K; Cornuz J; Gachoud D; Bulliard JL; Nichita C; Dorta G; Ducros C; Auer R
BMJ Open. 2016 May 13;6(5):e011086. doi: 10.1136/bmjopen-2016-011086.
Identification of Susceptibility Loci for Cutaneous Squamous Cell Carcinoma
We report a genome-wide association study of cutaneous squamous cell carcinoma conducted among non-Hispanic white members of the Kaiser Permanente Northern California health care system. The study includes a genome-wide screen of 61,457 members (6,891 cases and 54,566 controls) genotyped on the Affymetrix Axiom European array and a replication phase involving an independent set of 6,410 additional members (810 cases and 5,600 controls). Combined analysis of screening and replication phases identified 10 loci containing single-nucleotide polymorphisms (SNPs) with P-values < 5 × 10(-8). Six loci contain genes in the pigmentation pathway; SNPs at these loci appear to modulate squamous cell carcinoma risk independently of the pigmentation phenotypes. Another locus contains HLA class II genes studied in relation to elevated squamous cell carcinoma risk following immunosuppression. SNPs at the remaining three loci include an intronic SNP in FOXP1 at locus 3p13, an intergenic SNP at 3q28 near TP63, and an intergenic SNP at 9p22 near BNC2. These findings provide insights into the genetic factors accounting for inherited squamous cell carcinoma susceptibility.
Authors: Asgari MM; Wang W; Ioannidis NM; Itnyre J; Hoffmann T; Jorgenson E; Whittemore AS
J Invest Dermatol. 2016 May;136(5):930-7. Epub 2016-01-29.
Psychosocial factors related to non-persistence with adjuvant endocrine therapy among women with breast cancer: the Breast Cancer Quality of Care Study (BQUAL)
Non-adherence to adjuvant endocrine therapy (ET) for breast cancer (BC) is common. Our goal was to determine the associations between psychosocial factors and ET non-persistence. We recruited women with BC receiving care in an integrated healthcare system between 2006 and 2010. Using a subset of patients treated with ET, we investigated factors related to ET non-persistence (discontinuation) based on pharmacy records (≥90 days gap). Serial interviews were conducted at baseline and every 6 months. The Functional Assessment of Cancer Therapy (FACT), Medical Outcomes Survey, Treatment Satisfaction Questionnaire (TSQM), Impact of Events Scale (IES), Interpersonal Processes of Care measure, and Decision-making beliefs and concerns were measured. Multivariate models assessed factors associated with non-persistence. Of the 523 women in our final cohort who initiated ET and had a subsequent evaluation, 94 (18 %) were non-persistent over a 2-year follow-up. The cohort was primarily white (74.4 %), stage 1 (60.6 %), and on an aromatase inhibitor (68.1 %). Women in the highest income category had a lower odds of being non-persistent (OR 0.43, 95 % CI 0.23-0.81). Quality of life and attitudes toward ET at baseline were associated with non-persistence. At follow-up, the FACT, TSQM, and IES were associated with non-persistence (p < 0.001). Most women continued ET. Women who reported a better attitude toward ET, better quality of life, and more treatment satisfaction, were less likely to be non-persistent and those who reported intrusive/avoidant thoughts were more likely to be non-persistent. Interventions to enhance the psychosocial well-being of patients should be evaluated to increase adherence.
Authors: Hershman DL; Kushi LH; Neugut AI; et al.
Breast Cancer Res Treat. 2016 May;157(1):133-43. Epub 2016-04-16.
Colorectal Cancer Health Disparities and the Role of US Law and Health Policy
Authors: Doubeni CA; Corley DA; Zauber AG
Gastroenterology. 2016 05;150(5):1052-5. Epub 2016-03-24.
Identification of Associations Between Prescribed Medications and Cancer: A Nationwide Screening Study
We present a systematic screening for identifying associations between prescribed drugs and cancer risk using the high quality Danish nationwide health registries. We identified all patients (cases) with incident cancer in Denmark during 2000-2012 (n=278,485) and matched each case to 10 controls. Complete prescription histories since 1995 were extracted. Applying a two-phased case-control approach, we first identified drug classes or single drugs associated with an increased or decreased risk of 99 different cancer types, and further evaluated potential associations by examining specificity and dose-response patterns. 22,125 drug-cancer pairs underwent evaluation in the first phase. Of 4561 initial signals (i.e., drug-cancer associations), 3541 (78%) failed to meet requirements for dose-response patterns and specificity, leaving 1020 eligible signals. Of these, 510 signals involved the use of single drugs, and 33% (166 signals) and 67% (344 signals) suggested a reduced or an increased cancer risk, respectively. While a large proportion of the signals were attributable to the underlying conditions being treated, our algorithm successfully identified well-established associations, as well as several new signals that deserve further investigation. Our results provide the basis for future targeted studies of single associations to capture novel carcinogenic or chemopreventive effects of prescription drugs.
Authors: Pottegård A; Friis S; Christensen Rd; Habel LA; Gagne JJ; Hallas J
EBioMedicine. 2016 May;7:73-9. Epub 2016-03-14.
Time for integrating clinical, lifestyle and molecular data to predict drug responses – Authors’ reply
Authors: Pottegård A; Friis S; Christensen Rd; Habel LA; Gagne JJ; Hallas J
EBioMedicine. 2016 05;7:11. Epub 2016-03-18.
Breast cancer multigene testing trends and impact on chemotherapy use
A 21-gene test that predicts recurrence risk among women with hormone receptor positive (HR+), localized breast cancer was nationally recommended in 2007, but we know little about its subsequent impact. We evaluated: a) patient characteristics associated with test use, b) correlations between Recurrence Score (RS) and chemotherapy, and c) whether test introduction was associated with a reduction in chemotherapy use. Retrospective cohort study. The Kaiser Permanente Northern California tumor registry and electronic health records from 2005 to 2012 were used to identify HR+, human epidermal growth factor receptor 2 negative, node-negative cancers. Analyses used logistic regression with propensity score matching and 2-level logistic regression. Of the 7004 patients who met guidelines for testing, 22% were tested and 26% had chemotherapy. Test use was more likely in younger women (for ages 40-49 years vs 50-64 years: odds ratio [OR], 1.22; 95% CI, 1.04-1.44), in women with tumors sized 1.0 to 2.0 cm versus > 2 cm (OR, 1.20; 95% CI, 1.03-1.40), and in women from higher-income neighborhoods (for each $10,000 increase in area median income: OR, 1.05; 95% CI, 1.03-1.07). Among patients with low RS, 8% had chemotherapy versus 72% among patients with high RS (P < .01). In propensity score-matched analyses, testing was associated with an absolute reduction of 6.2% in the proportion of women receiving chemotherapy (95% CI, 2.9%-9.5%); the 2-level model showed a similar but nonsignificant (P = .14) association. The 21-gene test is used in a minority of eligible patients in this integrated plan. Its use appears to be associated with a modest decrease in overall chemotherapy use.
Authors: Ray GT; Mandelblatt J; Habel LA; Ramsey S; Kushi LH; Li Y; Lieu TA
Am J Manag Care. 2016 May 01;22(5):e153-60. Epub 2016-05-01.
Thyroid Hormones and Timing of Pubertal Onset in a Longitudinal Cohort of Females, Northern California, 2006-11
Pubertal timing is regulated by a complex interplay of hormones. Few studies have evaluated the role of thyroid hormones in pubertal onset. We investigated the associations between blood concentrations of free and total thyroxine (FT4, TT4), free triiodothyronine, and thyroid stimulating hormone and pubertal onset among females. Participants included 323 Kaiser Permanente Northern California members followed at annual intervals during 2004-11, who provided a blood sample during the first 3 years of the study. Thyroid hormone concentrations were measured in serum in the first blood specimen available for each participant. Pubertal onset was defined as Tanner stage ?2 for breast (thelarche) and pubic hair (pubarche) development. Associations between thyroid hormones and pubertal onset were assessed by multivariable logistic regression and Cox proportional hazards modelling. At blood draw, participants were age 6.5-10.1 (median 7.7) years, 10% had reached thelarche, and 12% had reached pubarche. Participants were followed 0-5 years after blood draw (median 4). At most recent clinical visit, participants were age 6.7-14.7 (median 12.3) years, 92% had reached thelarche, and 89% had reached pubarche. No associations were identified between having reached thelarche or pubarche at time of blood draw and thyroid hormones. Examined longitudinally, higher concentrations of pre-pubertal FT4 and TT4 were associated with earlier pubarche (adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.06, 1.86; per ng/dL and aHR 1.07, 95% CI 1.02, 1.12; per ?g/dL respectively). Higher pre-pubertal concentrations of FT4 and TT4 are associated with earlier pubarche.
Authors: Wilken JA; Greenspan LC; Kushi LH; Voss RW; Windham GC
Paediatr Perinat Epidemiol. 2016 May;30(3):285-93. Epub 2016-02-05.
A pooled analysis of post-diagnosis lifestyle factors in association with late estrogen-receptor positive breast cancer prognosis
Lifestyle factors have been well studied in relation to breast cancer prognosis overall; however, associations of lifestyle and late outcomes (>5 years after diagnosis) have been much less studied, and no studies have focused on estrogen receptor-positive (ER+) breast cancer survivors, who may have high risk of late recurrence and mortality. We utilized a large prospective pooling study to evaluate the associations of lifestyle factors with late recurrence and all-cause mortality among 6,295 5-year ER+ Stage I-III breast cancer survivors. Pooled and harmonized data were available on clinical factors and lifestyle factors (pre- to post-diagnosis weight change, body mass index (BMI) (kg/m(2)), recreational physical activity, alcohol intake and smoking history), measured on average 2.1 years after diagnosis. Updated information for weight only was available. Study heterogeneity was evaluated by the Q-statistic. Multivariable Cox regression models were stratified by study. Adjusting for clinical factors and potential confounders, ? 10% weight gain and obesity (BMI, 30-34.99 and ? 35) were associated with increased risk of late recurrence (hazard ratios (95% confidence intervals): 1.24 (1.00-1.53), 1.40 (1.05-1.86) and 1.41 (1.02-1.93), respectively). Daily alcohol intake was associated with late recurrence, 1.28 (1.01-1.62). Physical activity was inversely associated with late all-cause mortality (0.81 (0.71-0.93) and 0.71 (0.61-0.82) for 4.9 to <17.4 and ? 17.4 metabolic equivalent-hr/week). A U-shaped association was observed for late all-cause mortality and BMI using updated weight (1.42 (1.15-1.74) and 1.40 (1.09-1.81), <21.5 and ? 35, respectively). Smoking was associated with increased risk of late outcomes. In this large prospective pooling project, modifiable lifestyle factors were associated with late outcomes among long-term ER+ breast cancer survivors.
Authors: Nechuta S; Chen WY; Cai H; Poole EM; Kwan ML; Flatt SW; Patterson RE; Pierce JP; Caan BJ; Ou Shu X
Int J Cancer. 2016 May 1;138(9):2088-97. Epub 2015-12-09.
Neighborhood deprivation, race/ethnicity, and urinary metal concentrations among young girls in California
Although metals can adversely impact children’s health, the distribution of exposures to many metals, particularly among vulnerable subpopulations, is not well characterized. We sought to determine whether neighborhood deprivation was associated with urinary concentrations of thirteen metals and whether observed relationships varied by race/ethnicity. We obtained neighborhood characteristics from the 2005-2009 American Community Survey. Demographic information and urine samples from 400 healthy young girls in Northern California were obtained during a clinical visit. Urine samples were analyzed for metals using inductively-coupled plasma-mass spectrometry and levels were corrected for creatinine. We ran analysis of variance and generalized linear regression models to estimate associations of urinary metal concentrations with neighborhood deprivation and race/ethnicity and stratified multivariable models to evaluate possible interactions among predictors on metals concentrations. Urinary concentrations of three metals (barium, lead, antimony) varied significantly across neighborhood deprivation quartiles, and four (barium, lead, antimony, tin) varied across race/ethnicity groups. In models adjusted for family income and cotinine, both race/ethnicity (F3,224=4.34, p=0.01) and neighborhood deprivation (F3,224=4.32, p=0.01) were associated with antimony concentrations, but neither were associated with lead, barium, or tin, concentrations. Examining neighborhood deprivation within race/ethnicity groups, barium levels (pinteraction<0.01) decreased with neighborhood deprivation among Hispanic girls (ptrend<0.001) and lead levels (pinteraction=0.06) increased with neighborhood deprivation among Asian girls (ptrend=0.04). Our results indicate that children's vulnerability to some metals varies by neighborhood deprivation quartile and race/ethnicity. These differential distributions of exposures may contribute to environmental health disparities later in life.
Authors: Gonzales FA; Jones RR; Deardorff J; Windham GC; Hiatt RA; Kushi LH
Environ Int. 2016 May;91:29-39. Epub 2016-02-22.
A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ? 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.
Authors: Travis RC; Hamdy FC; Schenk JM; Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group; et al.
Cancer Res. 2016 04 15;76(8):2288-300. Epub 2016-02-26.
Pre-diagnostic Sleep Duration and Sleep Quality in Relation to Subsequent Cancer Survival
Poor sleep quality and short sleep duration have been associated with elevated risk for several cancer types; however, the relationship between sleep and cancer outcomes has not been well characterized. We assessed the association between pre-diagnostic sleep attributes and subsequent cancer survival within the Women’s Health Initiative (WHI). We identified WHI participants in whom a first primary invasive cancer had been diagnosed during follow-up (n = 21,230). Participants provided information on sleep characteristics at enrollment. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between these pre-diagnostic sleep characteristics and cancer-specific survival for all cancers combined and separately for common cancers. Analyses were adjusted for age, study arm, cancer site, marital status, income, smoking, physical activity, and time to diagnosis. No individual pre-diagnostic sleep characteristics were found to be significantly associated with cancer survival in analyses of all cancer sites combined; however, women who reported short sleep duration (? 6 h sleep/night) combined with frequent snoring (? 5 nights/w experienced significantly poorer cancer-specific survival than those who reported 7-8 h of sleep/night and no snoring (HR = 1.32, 95% CI: 1.14-1.54). Short sleep duration (HR = 1.46, 95% CI: 1.07-1.99) and frequent snoring (HR = 1.34, 95% CI: 0.98-1.85) were each associated with poorer breast cancer survival; those reporting short sleep combined with frequent snoring combined had substantially poorer breast cancer survival than those reporting neither (HR = 2.14, 95% CI: 1.47-3.13). Short sleep duration combined with frequent snoring reported prior to cancer diagnosis may influence subsequent cancer survival, particularly breast cancer survival.
Authors: Phipps AI; Ochs-Balcom H; Watson NF; et al.
J Clin Sleep Med. 2016 Apr 15;12(4):495-503. Epub 2016-04-15.
Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening: A Retrospective Cohort Study
The fecal immunochemical test (FIT) is a common method for colorectal cancer (CRC) screening, yet its acceptability and performance over several rounds of annual testing are largely unknown. To assess FIT performance characteristics over 4 rounds of annual screening. Retrospective cohort study. Kaiser Permanente Northern and Southern California. 323 349 health plan members aged 50 to 70 years on their FIT mailing date in 2007 or 2008 who completed the first round of FIT and were followed for up to 4 screening rounds. Screening participation, FIT positivity (?20 µg of hemoglobin/g), positive predictive values for adenoma and CRC, and FIT sensitivity for detecting CRC obtained from Kaiser Permanente electronic databases and cancer registries. Of the patients invited for screening, 48.2% participated in round 1. Of those who remained eligible, 75.3% to 86.1% participated in subsequent rounds. Median follow-up was 4.0 years, and 32% of round 1 participants crossed over to endoscopy over 4 screening rounds-7.0% due to a positive FIT result. The FIT positivity rate (5.0%) and positive predictive values (adenoma, 51.5%; CRC, 3.4%) were highest in round 1. Overall, programmatic FIT screening detected 80.4% of patients with CRC diagnosed within 1 year of testing, including 84.5% in round 1 and 73.4% to 78.0% in subsequent rounds. Screening detection, rather than long-term cancer prevention, was evaluated. Annual FIT screening was associated with high sensitivity for CRC, with high adherence to annual follow-up screening among initial participants. The findings indicate that annual programmatic FIT screening is feasible and effective for population-level CRC screening. National Institutes of Health.
Authors: Jensen CD; Corley DA; Lee JK; Quesenberry CP; Levin TR; Mysliwiec PA; et al.
Ann Intern Med. 2016 Apr 5;164(7):456-63. Epub 2016-01-26.
Effectiveness of bisphosphonate use and risk of contralateral breast cancer and recurrence in women with early-stage breast cancer treated with tamoxifen
The effectiveness of bisphosphonates (BP) in reducing risk of second breast cancer and recurrence in observational studies has been minimally studied. We examined the association of oral BP use on risk of contralateral breast cancer (CBC) and recurrence in 16,781 women diagnosed with early-stage breast cancer from 1996 to 2007, treated with tamoxifen, and followed through December 31, 2009 at Kaiser Permanente Northern California (KPNC, n = 8857) and Southern California (KPSC, n = 7924). Sociodemographic, clinical, and pharmacy information were extracted from electronic medical records and cancer registries. CBC was identified from cancer registries, and recurrences from electronic health records and chart reviews. Multivariate Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) treating BP use and hormonal therapy as time-varying variables. After mean 6.4 years of follow-up, 494 (3.0 %) women developed CBC. BP use post-breast cancer diagnosis (>93 % alendronate) ranged from 14.5 to 24.9 % at both study sites. Overall, there was no association of BP use with reduced risk of CBC (ever use, HR = 0.96; 95 % CI 0.67-1.38 and continuous use, HR = 1.03; 95 % CI 0.88, 1.20). Similar null associations were observed for recurrence (ever use, HR = 0.98; 95 % CI 0.82, 1.17 and continuous use, HR = 1.00; 95 % CI 0.92, 1.09). Associations varied somewhat by site yet confidence intervals overlapped. BP use was not associated with reduced risk of recurrence or new primary disease among women diagnosed with early breast cancer and treated with tamoxifen.
Authors: Kwan ML; Shi JM; Habel LA; Song J; Chung JW; Avila CC; Schottinger JE; Cheetham TC; Fletcher SW; Haque R
Breast Cancer Res Treat. 2016 Apr;156(2):379-89. Epub 2016-03-22.
RE: Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis
Authors: Bradshaw PT; Nichols HB; Caan BJ
J Natl Cancer Inst. 2016 Apr;108(4). Epub 2016-03-01.
How Context Matters: A Dissemination and Implementation Primer for Global Oncologists
Authors: Koczwara B; Birken SA; Perry CK; Cragun D; Zullig LL; Ginossar T; Nodora J; Chawla N; Ramanadhan S; Kerner J; Brownson RC
J Glob Oncol. 2016 Apr;2(2):51-55. Epub 2016-01-20.
Thyroid Antagonists (Perchlorate, Thiocyanate, and Nitrate) and Childhood Growth in a Longitudinal Study of U.S. Girls
Perchlorate, thiocyanate, and nitrate are sodium/iodide symporter (NIS) inhibitors that block iodide uptake into the thyroid, thus affecting thyroid function. Thyroid dysfunction can adversely affect somatic growth and development in children. To our knowledge, no studies have examined effects of NIS inhibitors on body size measures. We investigated associations between NIS inhibitors and childhood growth in 940 girls from the Puberty Study of the Breast Cancer and Environment Research Program. Urine samples collected from girls 6-8 years of age at enrollment (2004-2007) from New York City, greater Cincinnati, Ohio, and the Bay Area in California were analyzed for NIS inhibitors and creatinine (C). The longitudinal association between NIS inhibitors and anthropometric measures [height, waist circumference, and body mass index (BMI)] during at least three visits was examined using mixed effects linear models, adjusted for race and site. Compared with girls in the low-exposure group (3.6, 626, and 500 mg/gC, median perchlorate, thiocyanate, and nitrate, respectively) girls with the highest NIS inhibitor exposure (9.6, 2,343, and 955 mg/gC, median perchlorate, thiocyanate, and nitrate, respectively) had slower growth in waist circumference and BMI but not height. Significant differences in the predicted mean waist circumference and BMI between the low- and high-exposure groups were observed beginning at 11 years of age. Higher NIS inhibitor exposure biomarkers were associated with reductions in waist circumference and BMI. These findings underscore the need to assess exposure to NIS inhibitors with respect to their influence on childhood growth. Mervish NA, Pajak A, Teitelbaum SL, Pinney SM, Windham GC, Kushi LH, Biro FM, Valentin-Blasini L, Blount BC, Wolff MS, for the Breast Cancer and Environment Research Project (BCERP). 2016. Thyroid antagonists (perchlorate, thiocyanate, and nitrate) and childhood growth in a longitudinal study of U.S. girls. Environ Health Perspect 124:542-549;?https://dx.doi.org/10.1289/ehp.1409309.
Authors: Mervish NA; Pajak A; Teitelbaum SL; Pinney SM; Windham GC; Kushi LH; Biro FM; Valentin-Blasini L; Blount BC; Wolff MS; Breast Cancer and Environment Research Project (BCERP)
Environ Health Perspect. 2016 Apr;124(4):542-9. Epub 2015-07-07.
Variation in Screening Abnormality Rates and Follow-Up of Breast, Cervical and Colorectal Cancer Screening within the PROSPR Consortium
Primary care providers and health systems have prominent roles in guiding effective cancer screening. To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests. Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40-75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50-75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21-65 years). Breast, colorectal, or cervical cancer screening. Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up. There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7 % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5-10.3 %; colorectal, 3.0-4.8 %; cervical, 6.3-9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2-95.8 %; colorectal, 43.4-52.0 %; cervical, 29.6-61.4 %). Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities.
Authors: Tosteson AN; Corley DA; PROSPR consortium; et al.
J Gen Intern Med. 2016 Apr;31(4):372-9.
Association between sleeping difficulty and type 2 diabetes in women
Sleeping difficulty has been associated with type 2 diabetes in some prior studies. Whether the observed associations are independent of health behaviours, other cardiovascular risk factors or other sleep disorders is unclear. We analysed data from 133,353 women without diabetes, cardiovascular disease and cancer at baseline in the Nurses’ Health Study (NHS, 2000-2010) and the NHSII (2001-2011). Sleeping difficulty was assessed as having difficulty falling or staying asleep ‘all of the time’ or ‘most of the time’ at baseline (2000 in NHS and 2001 in NHSII). We documented 6,407 incident cases of type 2 diabetes during up to 10 years of follow-up. After adjustment for lifestyle factors at baseline, comparing women with and without sleeping difficulty, the multivariate-adjusted HR (95% CI) for type 2 diabetes was 1.45 (95% CI 1.33, 1.58), which changed to 1.22 (95% CI 1.12, 1.34) after further adjustment for hypertension, depression and BMI based on the updated repeated measurements. Women who reported all four sleep conditions (sleeping difficulty, frequent snoring, sleep duration ?6 h and sleep apnoea in NHS or rotating shift work in NHSII) had more than a fourfold increased likelihood of type 2 diabetes (HR 4.17, 95% CI 2.93, 5.91). Sleeping difficulty was significantly associated with type 2 diabetes. This association was partially explained by associations with hypertension, BMI and depression symptoms, and was particularly strong when combined with other sleep disorders. Our findings highlight the importance of sleep disturbance in the development and prevention of type 2 diabetes.
Authors: Li Y; Gao X; Winkelman JW; Cespedes EM; Jackson CL; Walters AS; Schernhammer E; Redline S; Hu FB
Diabetologia. 2016 Apr;59(4):719-27. Epub 2016-01-28.
Comparison of Self-Reported Sleep Duration With Actigraphy: Results From the Hispanic Community Health Study/Study of Latinos Sueño Ancillary Study.
Most studies of sleep and health outcomes rely on self-reported sleep duration, although correlation with objective measures is poor. In this study, we defined sociodemographic and sleep characteristics associated with misreporting and assessed whether accounting for these factors better explains variation in objective sleep duration among 2,086 participants in the Hispanic Community Health Study/Study of Latinos who completed more than 5 nights of wrist actigraphy and reported habitual bed/wake times from 2010 to 2013. Using linear regression, we examined self-report as a predictor of actigraphy-assessed sleep duration. Mean amount of time spent asleep was 7.85 (standard deviation, 1.12) hours by self-report and 6.74 (standard deviation, 1.02) hours by actigraphy; correlation between them was 0.43. For each additional hour of self-reported sleep, actigraphy time spent asleep increased by 20 minutes (95% confidence interval: 19, 22). Correlations between self-reported and actigraphy-assessed time spent asleep were lower with male sex, younger age, sleep efficiency
Authors: Cespedes, Elizabeth M EM; Hu, Frank B FB; Redline, Susan S; Rosner, Bernard B; Alcantara, Carmela C; Cai, Jianwen J; Hall, Martica H MH; Loredo, Jose S JS; Mossavar-Rahmani, Yasmin Y; Ramos, Alberto R AR; Reid, Kathryn J KJ; Shah, Neomi A NA; Sotres-Alvarez, Daniela D; Zee, Phyllis C PC; Wang, Rui R; Patel, Sanjay R SR
American journal of epidemiology. 2016 Mar 15;183(6):561-73. Epub 2016-03-02.
Colorectal cancer screening: 80% by 2018. Colonoscopists simply cannot do it alone
Authors: Levin TR
Gastrointest Endosc. 2016 Mar;83(3):552-4.
Colonoscopy Surveillance After Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer
The US Multi-Society Task Force has developed updated recommendations to guide health care providers with the surveillance of patients after colorectal cancer (CRC) resection with curative intent. This document is based on a critical review of the literature regarding the role of colonoscopy, flexible sigmoidoscopy, endoscopic ultrasound, fecal testing and CT colonography in this setting. The document addresses the effect of surveillance, with focus on colonoscopy, on patient survival after CRC resection, the appropriate use and timing of colonoscopy for perioperative clearing and for postoperative prevention of metachronous CRC, specific considerations for the detection of local recurrence in the case of rectal cancer, as well as the place of CT colonography and fecal tests in post-CRC surveillance.
Authors: Kahi CJ; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Lieberman D; Levin TR; Robertson DJ; Rex DK; United States Multi-Society Task Force on Colorectal Cancer
Gastroenterology. 2016 Mar;150(3):758-768.e11. Epub 2016-02-10.
Colonoscopy surveillance after colorectal cancer resection: recommendations of the US multi-society task force on colorectal cancer
Authors: Kahi CJ; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Lieberman D; Levin TR; Robertson DJ; Rex DK
Gastrointest Endosc. 2016 Mar;83(3):489-98.e10. Epub 2016-01-21.
Polymorphisms in genes in the androgen pathway and risk of Barrett’s esophagus and esophageal adenocarcinoma
The strong male predominance in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p?=?0.002) and in males (p?=?0.003), but not in females separately (p?=?0.3). This association was found in tobacco smokers (p?=?0.003) and in BE patients without reflux (p?=?0.004), but not in nonsmokers (p?=?0.2) or those with reflux (p?=?0.036). SNPs within JMJD1C were associated with risk of EAC in females (p?=?0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.
Authors: Ek WE; Corley DA; Lagergren J; et al.
Int J Cancer. 2016 Mar 1;138(5):1146-52. Epub 2015-10-05.
Validation of self-reported comorbidity status of breast cancer patients with medical records: the California Breast Cancer Survivorship Consortium (CBCSC)
To compare information from self-report and electronic medical records for four common comorbidities (diabetes, hypertension, myocardial infarction, and other heart diseases). We pooled data from two multiethnic studies (one case-control and one survivor cohort) enrolling 1,936 women diagnosed with breast cancer, who were members of Kaiser Permanente Northern California. Concordance varied by comorbidity; kappa values ranged from 0.50 for other heart diseases to 0.87 for diabetes. Sensitivities for comorbidities from self-report versus medical record were similar for racial/ethnic minorities and non-Hispanic Whites, and did not vary by age, neighborhood socioeconomic status, or education. Women with a longer history of comorbidity or who took medications for the comorbidity were more likely to report the condition. Hazard ratios for all-cause mortality were not consistently affected by source of comorbidity information; the hazard ratio was lower for diabetes, but higher for the other comorbidities when medical record versus self-report was used. Model fit was better when the medical record versus self-reported data were used. Comorbidities are increasingly recognized to influence the survival of patients with breast or other cancers. Potential effects of misclassification of comorbidity status should be considered in the interpretation of research results.
Authors: Vigen C; John EM; Lee VS; Wu AH; et al.
Cancer Causes Control. 2016 Mar;27(3):391-401. Epub 2016-01-21.
Colonoscopy Surveillance after Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer
The US Multi-Society Task Force has developed updated recommendations to guide health care providers with the surveillance of patients after colorectal cancer (CRC) resection with curative intent. This document is based on a critical review of the literature regarding the role of colonoscopy, flexible sigmoidoscopy, endoscopic ultrasound, fecal testing and CT colonography in this setting. The document addresses the effect of surveillance, with focus on colonoscopy, on patient survival after CRC resection, the appropriate use and timing of colonoscopy for perioperative clearing and for postoperative prevention of metachronous CRC, specific considerations for the detection of local recurrence in the case of rectal cancer, as well as the place of CT colonography and fecal tests in post-CRC surveillance.
Authors: Kahi CJ; Boland CR; Dominitz JA; Giardiello FM; Johnson DA; Kaltenbach T; Lieberman D; Levin TR; Robertson DJ; Rex DK
Am J Gastroenterol. 2016 Mar;111(3):337-46; quiz 347. Epub 2016-02-12.
Enhancing Breast Cancer Recurrence Algorithms Through Selective Use of Medical Record Data
The utility of data-based algorithms in research has been questioned because of errors in identification of cancer recurrences. We adapted previously published breast cancer recurrence algorithms, selectively using medical record (MR) data to improve classification. We evaluated second breast cancer event (SBCE) and recurrence-specific algorithms previously published by Chubak and colleagues in 1535 women from the Life After Cancer Epidemiology (LACE) and 225 women from the Women’s Health Initiative cohorts and compared classification statistics to published values. We also sought to improve classification with minimal MR examination. We selected pairs of algorithms-one with high sensitivity/high positive predictive value (PPV) and another with high specificity/high PPV-using MR information to resolve discrepancies between algorithms, properly classifying events based on review; we called this “triangulation.” Finally, in LACE, we compared associations between breast cancer survival risk factors and recurrence using MR data, single Chubak algorithms, and triangulation. The SBCE algorithms performed well in identifying SBCE and recurrences. Recurrence-specific algorithms performed more poorly than published except for the high-specificity/high-PPV algorithm, which performed well. The triangulation method (sensitivity = 81.3%, specificity = 99.7%, PPV = 98.1%, NPV = 96.5%) improved recurrence classification over two single algorithms (sensitivity = 57.1%, specificity = 95.5%, PPV = 71.3%, NPV = 91.9%; and sensitivity = 74.6%, specificity = 97.3%, PPV = 84.7%, NPV = 95.1%), with 10.6% MR review. Triangulation performed well in survival risk factor analyses vs analyses using MR-identified recurrences. Use of multiple recurrence algorithms in administrative data, in combination with selective examination of MR data, may improve recurrence data quality and reduce research costs.
Authors: Kroenke CH; Chubak J; Johnson L; Castillo A; Weltzien E; Caan BJ
J Natl Cancer Inst. 2016 Mar;108(3). Epub 2015-11-18.
Tamoxifen and Antidepressant Drug Interaction in a Cohort of 16 887 Breast Cancer Survivors
Controversy persists about whether certain antidepressants reduce tamoxifen’s effectiveness on lowering breast cancer recurrence. We investigated whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer. We examined 16 887 breast cancer survivors (TNM stages 0-II) diagnosed between 1996 and 2007 and treated with tamoxifen in two California health plans. Women were followed-up through December 31, 2009, for subsequent breast cancer. The main exposure was the percent of days of overlap when both tamoxifen and an antidepressant (paroxetine, fluoxetine, other selective serotonin reuptake inhibitors, tricyclics, and other classes) were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models with time-varying medication variables. Of the 16 887 women, half (n = 8099) used antidepressants and 2946 women developed subsequent breast cancer during the 14-year study period. We did not find a statistically significant increased risk of subsequent breast cancer in women who concurrently used paroxetine and tamoxifen. For 25%, 50%, and 75% increases in percent overlap days between paroxetine and tamoxifen, hazard ratios were 1.06 (95% CI = 0.98 to 1.14, P = .09), 1.13 (95% CI = 0.98 to 1.30, P = .09), and 1.20 (95% CI = 0.97 to 1.49, P = .09), respectively, in the first year of tamoxifen treatment but were not statistically significant. Hazard ratios decreased to 0.94 (95% CI = 0.81 to 1.10, P = .46), 0.89 (95% CI = 0.66 to 1.20, P = .46), and 0.85 (95% CI = 0.54 to 1.32, P = .46) by the fifth year (all non-statistically significantly). Absolute subsequent breast cancer rates were similar among women who used paroxetine concomitantly with tamoxifen vs tamoxifen-only users. For the other antidepressants, we again found no such associations. Using the comprehensive electronic health records of insured patients, we did not observe an increased risk of subsequent breast cancer in women who concurrently used tamoxifen and antidepressants, including paroxetine.
Authors: Haque R; Shi J; Schottinger JE; Ahmed SA; Cheetham TC; Chung J; Avila C; Kleinman K; Habel LA; Fletcher SW; Kwan ML
J Natl Cancer Inst. 2016 Mar;108(3). Epub 2015-12-01.
Factors Influencing Variation in Physician Adenoma Detection Rates: a Theory-Based Approach for Performance Improvement
Interventions to improve physician adenoma detection rates for colonoscopy have generally not been successful, and there are little data on the factors contributing to variation that may be appropriate targets for intervention. We sought to identify factors that may influence variation in detection rates by using theory-based tools for understanding behavior. We separately studied gastroenterologists and endoscopy nurses at 3 Kaiser Permanente Northern California medical centers to identify potentially modifiable factors relevant to physician adenoma detection rate variability by using structured group interviews (focus groups) and theory-based tools for understanding behavior and eliciting behavior change: the Capability, Opportunity, and Motivation behavior model; the Theoretical Domains Framework; and the Behavior Change Wheel. Nine factors potentially associated with adenoma detection rate variability were identified, including 6 related to capability (uncertainty about which types of polyps to remove, style of endoscopy team leadership, compromised ability to focus during an examination due to distractions, examination technique during withdrawal, difficulty detecting certain types of adenomas, and examiner fatigue and pain), 2 related to opportunity (perceived pressure due to the number of examinations expected per shift and social pressure to finish examinations before scheduled breaks or the end of a shift), and 1 related to motivation (valuing a meticulous examination as the top priority). Examples of potential intervention strategies are provided. By using theory-based tools, this study identified several novel and potentially modifiable factors relating to capability, opportunity, and motivation that may contribute to adenoma detection rate variability and be appropriate targets for future intervention trials.
Authors: Atkins L; Hunkeler EM; Jensen CD; Michie S; Lee JK; Doubeni CA; Zauber AG; Levin TR; Quinn VP; Corley DA
Gastrointest Endosc. 2016 Mar;83(3):617-26.e2. Epub 2015-09-11.
Oral Azole Antifungal Medications and Risk of Acute Liver Injury, Overall and by Chronic Liver Disease Status
Reports on associations between azole antifungal medications and acute liver injury are inconsistent and have not been based on liver-related laboratory tests. We evaluated incidence rates of acute liver injury associated with oral azole antifungals. We conducted a cohort study among Kaiser Permanente Northern California members who initiated an oral azole antifungal in an outpatient setting during 2004-2010. We determined development of: (1) liver aminotransferases >200 U/L, (2) severe acute liver injury (coagulopathy with hyperbilirubinemia), and (3) acute liver failure. We calculated incidence rates of endpoints. Cox regression was used to determine whether chronic liver disease was a risk factor for outcomes. Among 195,334 azole initiators (178,879 fluconazole; 14,296 ketoconazole; 1653 itraconazole; 478 voriconazole; 28 posaconazole), incidence rates (events/1000 person-years [95% confidence intervals (CIs)]) of liver aminotransferases >200 U/L were similarly low with fluconazole (13.0 [11.4-14.6]), ketoconazole (19.3 [13.8-26.3]), and itraconazole (24.5 [10.6-48.2]). Rates were higher with voriconazole (181.9 [112.6-278.0]) and posaconazole (191.1 [23.1-690.4]), but comparable. Severe acute liver injury was uncommon with fluconazole (2.0 [1.4-2.7]), ketoconazole (2.9 [1.1-6.3]), and itraconazole (0.0 [0.0-11.2]), but more frequent with voriconazole (16.7 [2.0-60.2]) and posaconazole (93.4 [2.4-520.6]). One patient developed acute liver failure due to ketoconazole. Pre-existing chronic liver disease increased risks of aminotransferases >200 U/L (hazard ratio 4.68 [95% CI, 3.68-5.94]) and severe acute liver injury (hazard ratio 5.62 [95% CI, 2.56-12.35]). Rates of acute liver injury were similarly low for fluconazole, ketoconazole, and itraconazole. Events were more common among voriconazole and posaconazole users but were comparable. Pre-existing chronic liver disease increased risk of azole-induced liver injury.
Authors: Lo Re V; Corley DA; et al.
Am J Med. 2016 Mar;129(3):283-91.e5. Epub 2015-11-17.
The Value of Ultrasound Monitoring of Adnexal Masses for Early Detection of Ovarian Cancer
Although ultrasound has so far been found to be ineffective as a screening tool for ovarian cancer, it is commonly used as a means of evaluating or following ovarian or adnexal masses once they are detected. We review the use of serial ultrasound for the management of adnexal masses and propose an approach to monitoring based on an understanding of the overall risk of cancer among the population in question and an assessment of how the potential benefit of monitoring compares with potential risk. In our approach, masses that are symptomatic, large (>10?cm), associated with an elevated CA 125 level or overt signs of malignancy, or that are determined to have a worrisome appearance by stringent ultrasound criteria should be evaluated surgically. Women with masses that have none of these characteristics should be offered monitoring. Short-term initial ultrasound monitoring carries significant potential benefit in terms of aiding detection of early malignancy and avoidance of unnecessary surgery. However, if a mass remains stable but persistent, the potential benefit of ongoing monitoring wanes with time, whereas the potential harms, in terms of patient anxiety, cost, and the risk of incidental findings and unnecessary surgery increase. Therefore, monitoring of stable lesions should be limited in duration in order to limit potential harms from overtreatment and overdiagnosis.
Authors: Suh-Burgmann E; Kinney W
Front Oncol. 2016;6:25. Epub 2016-02-10.
Time to Colonoscopy after Positive Fecal Blood Test in Four U.S. Health Care Systems
To reduce colorectal cancer mortality, positive fecal blood tests must be followed by colonoscopy. We identified 62,384 individuals ages 50 to 89 years with a positive fecal blood test between January 1, 2011 and December 31, 2012 in four health care systems within the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We estimated the probability of follow-up colonoscopy and 95% confidence intervals (CI) using the Kaplan-Meier method. Overall differences in cumulative incidence of follow-up across health care systems were assessed with the log-rank test. HRs and 95% CIs were estimated from multivariate Cox proportional hazards models. Most patients who received a colonoscopy did so within 6 months of their positive fecal blood test, although follow-up rates varied across health care systems (P <0.001). Median days to colonoscopy ranged from 41 (95% CI, 40-41) to 174 (95% CI, 123-343); percent followed-up by 12 months ranged from 58.1% (95% CI, 51.6%-63.7%) to 83.8% (95% CI, 83.4%-84.3%) and differences across health care systems were also observed at 1, 2, 3, and 6 months. Increasing age and comorbidity score were associated with lower follow-up rates. Individual characteristics and health care system were associated with colonoscopy after positive fecal blood tests. Patterns were consistent across health care systems, but proportions of patients receiving follow-up varied. These findings suggest that there is room to improve follow-up of positive colorectal cancer screening tests. Understanding the timing of colonoscopy after positive fecal blood tests and characteristics associated with lack of follow-up may inform future efforts to improve follow-up.
Authors: Chubak J; Corley DA; Levin TR; PROSPR consortium; et al.
Cancer Epidemiol Biomarkers Prev. 2016 Feb;25(2):344-50.
Ten-year incidence of colorectal cancer following a negative screening sigmoidoscopy: an update from the Colorectal Cancer Prevention (CoCaP) programme
To examine the rates of colorectal cancer (CRC) following a negative screening sigmoidoscopy. Cohort study. An integrated healthcare delivery organisation in California, USA. 72,483 men and women aged 50?years and above who had a negative screening sigmoidoscopy between 1994 and 1996. Those at elevated risk of CRC due to inflammatory bowel disease, prior polyps or CRC, or a strong family history of CRC were excluded. Incidence rates of distal and proximal CRC. Standardised Incidence Ratios were used to compare annual incidence rates of distal and proximal CRC in the cohort to expected rates based on Surveillance, Epidemiology, and End Results data. Additionally, rate ratios (RR) and rate differences (RD) comparing the incidence rate of distal CRC in years 6+ postscreening with that in years 1-5 were calculated. Incidence rates of distal CRC were lower than those in the San Francisco Bay area population at large during each of the first 10?years postsigmoidoscopy screening. However, the incidence of distal CRC rose steadily, from 3 per 100,000 in the first year of follow-up to 40 per 100,000 in the 10th year. During the second half of follow-up, the rate of distal CRC was twice as high as in the first half (RR 2 .08, 95% CI 1.38 to 3.16; RD 14 per 100,000 person-years, 95% CI 6 to 22). Though still below population levels, the incidence of CRC during years 6-10 following a negative sigmoiodoscopy is appreciably higher than during the first 5?years.
Authors: Doria-Rose VP; Levin TR; Palitz A; Conell C; Weiss NS
Gut. 2016 Feb;65(2):271-7. Epub 2014-12-15.
Bridging the Gap: Determinants of Undiagnosed or Untreated Urinary Incontinence in Women
More than a third of middle-aged or older women suffer from urinary incontinence, but less than half undergo evaluation or treatment for this burdensome condition. With national organizations now including an assessment of incontinence as a quality performance measure, providers and health care organizations have a growing incentive to identify and engage these women who are undiagnosed and untreated. We sought to identify clinical and sociodemographic determinants of patient-provider discussion and treatment of incontinence among ethnically diverse, community-dwelling women. We conducted an observational cohort study from 2003 through 2012 of 969 women aged 40 years and older enrolled in a Northern California integrated health care delivery system who reported at least weekly incontinence. Clinical severity, type, treatment, and discussion of incontinence were assessed by structured questionnaires. Multivariable regression evaluated predictors of discussion and treatment. Mean age of the 969 participants was 59.9 (±9.7) years, and 55% were racial/ethnic minorities (171 black, 233 Latina, 133 Asian or Native American). Fifty-five percent reported discussing their incontinence with a health care provider, 36% within 1 year of symptom onset, and with only 3% indicating that their provider initiated the discussion. More than half (52%) reported being at least moderately bothered by their incontinence. Of these women, 324 (65%) discussed their incontinence with a clinician, with 200 (40%) doing so within 1 year of symptom onset. In a multivariable analysis, women were less likely to have discussed their incontinence if they had a household income < $30,000/y vs ? $120,000/y (adjusted odds ratio [AOR], 0.49, 95% confidence interval [CI], 0.28-0.86) or were diabetic (AOR, 0.71, 95% CI, 0.51-0.99). They were more likely to have discussed incontinence if they had clinically severe incontinence (AOR, 3.09, 95% CI, 1.89-5.07), depression (AOR, 1.71, 95% CI, 1.20-2.44), pelvic organ prolapse (AOR, 1.98, 95% CI, 1.13-3.46), or arthritis (AOR, 1.44, 95% CI, 1.06-1.95). Among the subset of women reporting at least moderate subjective bother from incontinence, black race (AOR, 0.45, 95% CI, 0.25-0.81, vs white race) and income < $30,000/y (AOR, 0.37, 95% CI, 0.17-0.81, vs ? $120,000/y) were associated with a reduced likelihood of discussing incontinence. Those with clinically severe incontinence (AOR, 2.93, 95% CI, 1.53-5.61, vs low to moderate incontinence by the Sandvik scale) were more likely to discuss it with a clinician. Even in an integrated health care system, lower income was associated with decreased rates of patient-provider discussion of incontinence among women with at least weekly incontinence. Despite being at increased risk of incontinence, diabetic women were also less likely to have discussed incontinence or received care. Findings provide support for systematic screening of women to overcome barriers to evaluation and treatment.
Authors: Duralde ER; Walter LC; Van Den Eeden SK; Nakagawa S; Subak LL; Brown JS; Thom DH; Huang AJ
Am J Obstet Gynecol. 2016 Feb;214(2):266.e1-9. Epub 2015-09-05.
Characteristics of second breast events among women treated with breast-conserving surgery for DCIS in the community
We examined the clinical/pathologic features of ipsilateral second breast cancers (IP-SBCs) following breast-conserving surgery (BCS) for DCIS among community-treated patients and ascertained the degree of correlation between the features of index DCIS and IP-SBC events. From a Cancer Research Network cohort of DCIS patients diagnosed 1990-2001 and treated with BCS, we identified women who subsequently developed an ipsilateral DCIS or invasive breast cancer. All index DCIS tumors underwent expert pathology review. Pathologic characteristics of IP-SBCs were abstracted from available medical records. Logistic regression was used to examine associations between pathologic characteristics and identify factors associated with invasive versus non-invasive IP-SBC. Of 1969 DCIS patients, 182 developed an IP-SBC within a median of 38 months (range 6-160). IP-SBCs were slightly more commonly non-invasive (53 %) versus invasive (47 %). Of invasive IP-SBCs, 31 % were high grade, 67 % were <20 mm, 74 % were estrogen receptor positive, 7 % were HER2 positive, and 16 % were node positive. Of non-invasive IP-SBCs, 33 % were high grade. Comparing index DCIS and IP-SBC specimens, there was moderate-high correlation for HR status and grade. Among patients with IP-SBCs, those who were younger and whose index DCIS tumors were HR negative had shorter intervals (within 3 years) between index and IP-SBC diagnoses. No index DCIS feature was statistically significantly associated with an IP-SBC that was invasive versus non-invasive. Understanding the characteristics of SBCs and identifying correlations between these and index DCIS events could influence treatment choices for DCIS, and may help patients and providers develop treatment paradigms for SBCs.
Authors: Hassett MJ; Jiang W; Habel LA; Nekhlyudov L; Achacoso N; Acton L; Schnitt SJ; Schrag D; Punglia RS
Breast Cancer Res Treat. 2016 Feb;155(3):541-9. Epub 2016-Feb-03.
Impact of very low physical activity, BMI, and comorbidities on mortality among breast cancer survivors
The purpose of this study was to examine post-diagnosis BMI, very low physical activity, and comorbidities, as predictors of breast cancer-specific and all-cause mortality. Data from three female US breast cancer survivor cohorts were harmonized in the After Breast Cancer Pooling Project (n = 9513). Delayed entry Cox proportional hazards models were used to examine the impact of three post-diagnosis lifestyle factors: body mass index (BMI), select comorbidities (diabetes only, hypertension only, or both), and very low physical activity (defined as physical activity <1.5 MET h/week) in individual models and together in multivariate models for breast cancer and all-cause mortality. For breast cancer mortality, the individual lifestyle models demonstrated a significant association with very low physical activity but not with the selected comorbidities or BMI. In the model that included all three lifestyle variables, very low physical activity was associated with a 22 % increased risk of breast cancer mortality (HR 1.22, 95 % CI 1.05, 1.42). For all-cause mortality, the three individual models demonstrated significant associations for all three lifestyle predictors. In the combined model, the strength and significance of the association of comorbidities (both hypertension and diabetes versus neither: HR 2.16, 95 % CI 1.79, 2.60) and very low physical activity (HR 1.35, 95 % CI 1.22, 1.51) remained unchanged, but the association with obesity was completely attenuated. These data indicate that after active treatment, very low physical activity, consistent with a sedentary lifestyle (and comorbidities for all-cause mortality), may account for the increased risk of mortality, with higher BMI, that is seen in other studies.
Authors: Nelson SH; Marinac CR; Patterson RE; Nechuta SJ; Flatt SW; Caan BJ; Kwan ML; Poole EM; Chen WY; Shu XO; Pierce JP
Breast Cancer Res Treat. 2016 Feb;155(3):551-7. Epub 2016-Feb-10.
Impact of Body Weight and Body Composition on Ovarian Cancer Prognosis
Measures of body weight and anthropometrics such as body mass index (BMI) are commonly used to assess nutritional status in clinical conditions including cancer. Extensive research has evaluated associations between body weight and prognosis in ovarian cancer patients, yet little is known about the potential impact of body composition (fat mass (FM) and fat-free mass (FFM)) in these patients. Thus, the purpose of this publication was to review the literature (using PubMed and EMBASE) evaluating the impact of body weight and particularly body composition on surgical complications, morbidity, chemotherapy dosing and toxicity (as predictors of prognosis), and survival in ovarian cancer patients. Body weight is rarely associated with intra-operative complications, but obesity predicts higher rates of venous thromboembolism and wound complications post-operatively in ovarian cancer patients. Low levels of FM and FFM are superior predictors of length of hospital stay compared to measures of body weight alone, but the role of body composition on other surgical morbidities is unknown. Obesity complicates chemotherapy dosing due to altered pharmacokinetics, imprecise dosing strategies, and wide variability in FM and FFM. Measurement of body composition has the potential to reduce toxicity if the results are incorporated into chemotherapy dosing calculations. Some findings suggest that excess body weight adversely affects survival, while others find no such association. Limited studies indicate that FM is a better predictor of survival than body weight in ovarian cancer patients, but the direction of this relationship has not been determined. In conclusion, body composition as an indicator of nutritional status is a better prognostic tool than body weight or BMI alone in ovarian cancer patients.
Authors: Purcell SA; Elliott SA; Kroenke CH; Sawyer MB; Prado CM
Curr Oncol Rep. 2016 Feb;18(2):8.
Who Gets to Decide?
Authors: Smith-Bindman R; Kwan ML; Miglioretti DL
Radiology. 2016 Feb;278(2):635-6.
Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.
Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.
Authors: Sutcliffe, Siobhan S; Nevin, Remington L RL; Pakpahan, Ratna R; Elliott, Debra J DJ; Langston, Marvin E ME; De Marzo, Angelo M AM; Gaydos, Charlotte A CA; Isaacs, William B WB; Nelson, William G WG; Sokoll, Lori J LJ; Walsh, Patrick C PC; Zenilman, Jonathan M JM; Cersovsky, Steven B SB; Platz, Elizabeth A EA
International journal of cancer. 2016 May 01;138(9):2221-30. Epub 2016-01-21.
Financial Hardship Associated With Cancer in the United States: Findings From a Population-Based Sample of Adult Cancer Survivors
To estimate the prevalence of financial hardship associated with cancer in the United States and identify characteristics of cancer survivors associated with financial hardship. We identified 1,202 adult cancer survivors diagnosed or treated at ? 18 years of age from the 2011 Medical Expenditure Panel Survey Experiences With Cancer questionnaire. Material financial hardship was measured by ever (1) borrowing money or going into debt, (2) filing for bankruptcy, (3) being unable to cover one’s share of medical care costs, or (4) making other financial sacrifices because of cancer, its treatment, and lasting effects of treatment. Psychological financial hardship was measured as ever worrying about paying large medical bills. We examined factors associated with any material or psychological financial hardship using separate multivariable logistic regression models stratified by age group (18 to 64 and ? 65 years). Material financial hardship was more common in cancer survivors age 18 to 64 years than in those ? 65 years of age (28.4% v 13.8%; P < .001), as was psychological financial hardship (31.9% v 14.7%, P < .001). In adjusted analyses, cancer survivors age 18 to 64 years who were younger, female, nonwhite, and treated more recently and who had changed employment because of cancer were significantly more likely to report any material financial hardship. Cancer survivors who were uninsured, had lower family income, and were treated more recently were more likely to report psychological financial hardship. Among cancer survivors ? 65 years of age, those who were younger were more likely to report any financial hardship. Cancer survivors, especially the working-age population, commonly experience material and psychological financial hardship.
Authors: Yabroff KR; Chawla N; Ekwueme DU; et al.
J Clin Oncol. 2016 Jan 20;34(3):259-67. Epub 2015-12-07.
CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk
Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT. We included 10?835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test. The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52-0.72), P=4.8 × 10(-9)). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52-0.78), P=1.2 × 10(-5) (alpha threshold=3.1 × 10(-4)). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively. Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis.
Authors: Garcia-Albeniz X; Chanock SJ; Chang-Claude J; et al.
Br J Cancer. 2016 Jan 19;114(2):221-9. Epub 2016-01-14.
Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy
In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk of thromboembolic events (TEEs), with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this retrospective cohort study of older patients with CLL or MM identified from the Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed rates of clinically serious TEEs in 2724 new users of IVIg and a propensity-matched comparison group of 8035 nonusers. For the primary end point, arterial TEE, we observed a transient increased risk of TEE during the day of an IVIg infusion and the day afterward (hazard ration = 3.40; 95% confidence interval [CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment cycle. When considered in terms of absolute risk averaged over a 1-year treatment period, the increase in risk attributable to IVIg was estimated to be 0.7% (95% CI: -0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end point. A statistically nonsignificant risk increase of 0.3% (95% CI: -0.4%, 1.5%) compared with a baseline risk of 1.1% was observed for the venous TEE end point. Further research is needed to establish the generalizability of these results to patients receiving higher doses of IVIg for other indications.
Authors: Ammann EM; Jones MP; Link BK; Carnahan RM; Winiecki SK; Torner JC; McDowell BD; Fireman BH; Chrischilles EA
Blood. 2016 Jan 14;127(2):200-7. Epub 2015-10-06.
Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants
Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s).
Authors: Du M; Carlson CS; Peters U; et al.
PLoS ONE. 2016;11(7):e0157521. Epub 2016-07-05.
Psychosocial Clusters and their Associations with Well-Being and Health: An Empirical Strategy for Identifying Psychosocial Predictors Most Relevant to Racially/Ethnically Diverse Women’s Health
Strategies for identifying the most relevant psychosocial predictors in studies of racial/ethnic minority women’s health are limited because they largely exclude cultural influences and they assume that psychosocial predictors are independent. This paper proposes and tests an empirical solution. Hierarchical cluster analysis, conducted with data from 140,652 Women’s Health Initiative participants, identified clusters among individual psychosocial predictors. Multivariable analyses tested associations between clusters and health outcomes. A Social Cluster and a Stress Cluster were identified. The Social Cluster was positively associated with well-being and inversely associated with chronic disease index, and the Stress Cluster was inversely associated with well-being and positively associated with chronic disease index. As hypothesized, the magnitude of association between clusters and outcomes differed by race/ethnicity. By identifying psychosocial clusters and their associations with health, we have taken an important step toward understanding how individual psychosocial predictors interrelate and how empirically formed Stress and Social clusters relate to health outcomes. This study has also demonstrated important insight about differences in associations between these psychosocial clusters and health among racial/ethnic minorities. These differences could signal the best pathways for intervention modification and tailoring.
Authors: Jabson JM; Bowen D; Weinberg J; Kroenke C; Luo J; Messina C; Shumaker S; Tindle HA
Clin Med Insights Womens Health. 2016;9(Suppl 1):31-40. Epub 2016-06-06.
Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients
Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n?=?455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p?=?0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p?
Authors: Mansh M; Asgari MM; Arron ST; et al.
Am J Transplant. 2016 Jan;16(1):262-70. Epub 2015-Sep-03.
Ghrelin and Leptin Have a Complex Relationship with Risk of Barrett’s Esophagus
Abdominal obesity is a risk factor for Barrett’s esophagus independent of GERD symptoms, but little is understood about the biological mechanisms between obesity and the carcinogenic pathway of esophageal adenocarcinoma. To evaluate whether ghrelin and leptin may partially explain the association between obesity and Barrett’s esophagus. We conducted a case-control study using patients with a new diagnosis of Barrett’s esophagus (cases) and two control groups frequency matched to cases for age, gender, and geographic region: (1) patients with gastroesophageal reflux disease (GERD) and (2) a sample of the general population. We generated odds ratios using logistic regressions to evaluate quartiles of serum ghrelin or serum leptin, adjusting for known risk factors for Barrett’s esophagus. We evaluated potential interaction variables using cross products and ran stratified analyses to generate stratum-specific odds ratios. A total of 886 participants were included in the analysis. Higher ghrelin concentrations were associated with an increased risk of Barrett’s esophagus, when compared to the population controls, but not the GERD controls. Ghrelin concentrations were not associated with the frequency of GERD symptoms, but ghrelin’s relationship with Barrett’s esophagus varied significantly with the frequency of GERD symptoms. Leptin concentrations were positively associated with at least weekly GERD symptoms among the population controls and were inversely associated with Barrett’s esophagus only among the GERD controls. Adjusting for waist circumference did not change the main associations. Higher levels of ghrelin were associated with an increased risk of Barrett’s esophagus among the general population. In contrast, leptin was positively associated with frequent GERD symptoms, but inversely associated with the risk of Barrett’s esophagus among the GERD controls.
Authors: Thomas SJ; Almers L; Schneider J; Graham JE; Havel PJ; Corley DA
Dig Dis Sci. 2016 Jan;61(1):70-9. Epub 2015-09-22.
RE: Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741
Authors: Kwan ML; Quesenberry CP; Caan BJ
J Natl Cancer Inst. 2016 Jan;108(1).
What makes a “good” colonoscopy quality indicator?
Authors: Lee JK; Corley DA
Gastrointest Endosc. 2016 Jan;83(1):179-81.
Long-term changes in sleep duration, energy balance and risk of type 2 diabetes
Baseline sleep duration has a U-shaped relationship with type 2 diabetes, but little research examines the associated changes. We examined long-term changes in sleep duration and concomitant changes in diet, physical activity, weight and subsequent diabetes. The cohort includes 59,031 women aged 55-83 years in the Nurses’ Health Study without diabetes in 2000. Change in sleep duration is the difference between self-reported 24 h sleep duration in 1986 and 2000. Diet, physical activity and covariates were updated every 2-4 years. Self-reported diabetes was confirmed via validated questionnaires. Cox regression models were adjusted for 1986 sleep duration and 1986 values of diabetes risk factors, including BMI, and subsequently for change in covariates from 1986 to 2000. We documented 3,513 incident diabetes cases through to 2012. Compared with no change, decreases in sleep duration were adversely associated with changes in diet quality and physical activity, while increases were associated with greater weight gain. After adjustment for 1986 covariates, HRs (95% CI) for ? -2, > -2 to < 0, > 0 to < 2 and ? 2 h/day changes in sleep duration (vs no change) were 1.09 (0.93, 1.28), 1.10 (1.001, 1.12), 1.09 (1.00, 1.18) and 1.30 (1.14, 1.46), respectively. Additional adjustment for diet and physical activity did not appreciably alter the results. Increases in sleep duration ? 2 h/day remained adversely associated with diabetes (HR [95% CI]: 1.15 [1.01, 1.30]) after adjustment for change in covariates, including BMI. Increases in sleep duration among middle-aged and older women were modestly associated with risk of diabetes; changes in diet, physical activity and BMI did not explain associations.
Authors: Cespedes EM; Bhupathiraju SN; Li Y; Rosner B; Redline S; Hu FB
Diabetologia. 2016 Jan;59(1):101-9. Epub 2015-Nov-02.
Risk of gastric cancer, gastrointestinal cancers and other cancers: a comparison of treatment with pantoprazole and other proton pump inhibitors
Proton pump inhibitors (PPIs) have been shown to be carcinogenic in rodent studies. As part of a long-term post-marketing surveillance study requested by the US Food and Drug Administration, to compare incidence rates of gastric and other cancers after sustained exposures to pantoprazole, a long-acting PPI, compared with other shorter acting PPIs. We conducted a cohort study within the membership of the Kaiser Permanente Northern California healthcare system and compared rates of gastric and other cancers among pantoprazole users and users of other PPI medications. The Cox proportional hazards model was used to adjust for potential confounders such as sex, age, receipt of treatment for Helicobacter pylori, cumulative PPI dose, total years PPI treatment and year of index date. The study was developed in consultation with, and approved by, the FDA. A total of 61 684 persons with at least a 240-day supply of medication (34 178 pantoprazole and 27 686 other PPIs) were followed up for a total of 547 020 person-years (274 700 vs. 272 321 person-years, respectively). The primary analyses demonstrated comparable risks between the pantoprazole and other PPI groups for gastric cancer [hazard ratio (HR) = 0.68, 95% CI 0.24-1.93); colorectal, liver, pancreatic, or small bowel cancers (HR = 0.95, 95% CI 0.65-1.40) or any cancer (HR = 1.06, 95% CI 0.93-1.21). We found no evidence that pantoprazole, a longer acting PPI, compared with shorter-acting agents, conferred an excess risk of gastric cancer, other gastrointestinal cancers or all cancers for pantoprazole compared with other shorter-acting PPIs.
Authors: Schneider JL; Kolitsopoulos F; Corley DA
Aliment Pharmacol Ther. 2016 Jan;43(1):73-82. Epub 2015-11-06.
Common Genetic Variation and Survival after Colorectal Cancer Diagnosis: A Genome-Wide Analysis
Genome-wide association studies have identified several germline single nucleotide polymorphisms (SNPs) significantly associated with colorectal cancer (CRC) incidence. Common germline genetic variation may also be related to CRC survival. We used a discovery-based approach to identify SNPs related to survival outcomes after CRC diagnosis. Genome-wide genotyping arrays were conducted for 3494 individuals with invasive CRC enrolled in six prospective cohort studies (median study-specific follow-up = 4.2-8.1 years). In pooled analyses, we used Cox regression to assess SNP-specific associations with CRC-specific and overall survival, with additional analyses stratified by stage at diagnosis. Top findings were followed-up in independent studies. A P value threshold of P < 5×10(-8) in analyses combining discovery and follow-up studies was required for genome-wide significance. Among individuals with distant-metastatic CRC, several SNPs at 6p12.1, nearest the ELOVL5 gene, were statistically significantly associated with poorer survival, with the strongest associations noted for rs209489 [hazard ratio (HR) = 1.8, P = 7.6×10(-10) and HR = 1.8, P = 3.7×10(-9) for CRC-specific and overall survival, respectively). No SNPs were statistically significantly associated with survival among all cases combined or in cases without distant-metastases. SNPs in 6p12.1/ELOVL5 were associated with survival outcomes in individuals with distant-metastatic CRC, and merit further follow-up for functional significance. Findings from this genome-wide association study highlight the potential importance of genetic variation in CRC prognosis and provide clues to genomic regions of potential interest.
Authors: Phipps AI; Caan BJ; Newcomb PA; et al.
Carcinogenesis. 2016 Jan;37(1):87-95. Epub 2015-11-19.
Pioglitazone Use and Risk of Bladder Cancer–Reply
Authors: Ferrara A; Lewis JD; Habel LA
JAMA. 2015 Dec 15;314(23):2568-9.
Adiponectin may modify the risk of Barrett’s esophagus in patients with gastroesophageal reflux disease
Abdominal obesity and increasing body mass index are risk factors for esophageal adenocarcinoma and its main precursor, Barrett’s esophagus; however, there are no known biological mechanisms for these associations or regarding why only some patients with gastroesophageal reflux disease develop Barrett’s esophagus. We evaluated the association between Barrett’s esophagus and multimers of an adipose-associated hormone, adiponectin. We conducted a case-control study evaluating the associations between adiponectin (total, high-molecular-weight, and low-/medium-molecular-weight) and Barrett’s esophagus within the Kaiser Permanente Northern California population. Patients with a new diagnosis of Barrett’s esophagus (cases) were matched to patients with gastroesophageal reflux disease (GERD) without Barrett’s esophagus and to population controls. Complete serologic and epidemiologic data were available for 284 cases, 294 GERD controls, and 285 population controls. Increasing adiponectin levels were a risk factor for Barrett’s esophagus among patients with GERD (total adiponectin fourth vs first quartile odds ratio [OR], 1.96; 95% confidence interval [CI], 1.17-3.27; high-molecular-weight adiponectin OR, 1.65; 95% CI, 1.00-2.73; low-/medium-molecular-weight adiponectin OR, 2.18; 95% CI, 1.33-3.56), but not compared with population controls. The associations were significantly stronger among patients reporting frequent GERD symptoms and among smokers (P values interaction < .01). Adiponectin levels are associated positively with the risk of Barrett's esophagus among patients with GERD and among smokers, but not among population controls without GERD symptoms. Higher adiponectin concentrations either independently may contribute to the aberrant healing of esophageal injury into Barrett's esophagus or be a marker for other factors.
Authors: Almers LM; Graham JE; Havel PJ; Corley DA
Clin Gastroenterol Hepatol. 2015 Dec;13(13):2256-64.e1-3. Epub 2015-01-26.
Risk Prediction for Local Breast Cancer Recurrence Among Women with DCIS Treated in a Community Practice: A Nested, Case-Control Study
Various patient, treatment, and pathologic factors have been associated with an increased risk of local recurrence (LR) following breast-conserving therapy (BCT) for ductal carcinoma in situ (DCIS). However, the strength and importance of individual factors has varied; whether combining factors improves prediction, particularly in community practice, is uncertain. In a large, population-based cohort of women with DCIS treated with BCT in three community-based practices, we assessed the validity of the Memorial Sloan-Kettering Cancer Center (MSKCC) DCIS nomogram, which combines clinical, pathologic, and treatment features to predict LR. We reviewed slides of patients with unilateral DCIS treated with BCT. Regression methods were used to estimate risks of LR. The MSKCC DCIS nomogram was applied to the study population to compare the nomogram-predicted and observed LR at 5 and 10 years. The 495 patients in our study were grouped into quartiles and octiles to compare observed and nomogram-predicted LR. The 5-year absolute risk of recurrence for lowest and highest quartiles was 4.8 and 33.1 % (95 % CI 3.1-6.4 and 24.2-40.9, respectively; p < 0.0001). The overall correlation between 10-year nomogram-predicted recurrences and observed recurrences was 0.95. Compared with observed 10-year LR rates, the risk estimates provided by the nomogram showed good correlation, and reasonable discrimination with a c-statistic of 0.68. The MSKCC DCIS nomogram provided good prediction of the 5- and 10-year LR when applied to a population of patients with DCIS treated with BCT in a community-based practice. This nomogram, therefore, is a useful treatment decision aid for patients with DCIS.
Authors: Collins LC; Achacoso N; Haque R; Nekhlyudov L; Quesenberry CP; Schnitt SJ; Habel LA; Fletcher SW
Ann Surg Oncol. 2015 Dec;22 Suppl 3:S502-8. Epub 2015-Jun-10.
Intersection of Race/Ethnicity and Socioeconomic Status in Mortality After Breast Cancer
We investigated social disparities in breast cancer (BC) mortality, leveraging data from the California Breast Cancer Survivorship Consortium. The associations of race/ethnicity, education, and neighborhood SES (nSES) with all-cause and BC-specific mortality were assessed among 9372 women with BC (diagnosed 1993-2007 in California with follow-up through 2010) from four racial/ethnic groups [African American, Asian American, Latina, and non-Latina (NL) White] using Cox proportional hazards models. Compared to NL White women with high-education/high-nSES, higher all-cause mortality was observed among NL White women with high-education/low-nSES [hazard ratio (HR) (95 % confidence interval) 1.24 (1.08-1.43)], and African American women with low-nSES, regardless of education [high education HR 1.24 (1.03-1.49); low-education HR 1.19 (0.99-1.44)]. Latina women with low-education/high-nSES had lower all-cause mortality [HR 0.70 (0.54-0.90)] and non-significant lower mortality was observed for Asian American women, regardless of their education and nSES. Similar patterns were seen for BC-specific mortality. Individual- and neighborhood-level measures of SES interact with race/ethnicity to impact mortality after BC diagnosis. Considering the joint impacts of these social factors may offer insights to understanding inequalities by multiple social determinants of health.
Authors: Shariff-Marco S; Kwan ML; Gomez SL; et al.
J Community Health. 2015 Dec;40(6):1287-99.
Risk of Acute Liver Failure in Patients with Drug-Induced Liver Injury: Evaluation of Hy’s Law and a New Prognostic Model
Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy’s Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample. We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania. Hy’s Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval [CI], 0.76-0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71-0.99) and a specificity value of 0.76 (95% CI, 0.75-0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52-1.00) in the validation analysis. Hy’s Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and total bilirubin level that identifies patients at increased risk for ALF with high sensitivity.
Authors: Lo Re V; Corley DA; et al.
Clin Gastroenterol Hepatol. 2015 Dec;13(13):2360-8. Epub 2015-06-27.
Physical Activity and Risk of Male Breast Cancer
The association between leisure-time physical activity (LTPA) and male breast cancer risk is unclear. In the Male Breast Cancer Pooling Project, with 449 cases and 13,855 matched controls, we used logistic regression with study stratification to generate adjusted ORs and 95% confidence intervals (CI) for LTPA tertiles and male breast cancer risk. Compared with low LTPA, medium and high LTPA were not associated with male breast cancer risk (OR, 1.01; 95% CI, 0.79-1.29; 0.90, 0.69-1.18, respectively). In joint-effects analyses, compared with the referent of high body mass index (BMI; ?25 kg/m(2))/low LTPA, neither medium nor high PA was associated with risk among high BMI men, but normal BMI men (<25 kg/m(2)) with low or medium LTPA were at a nonsignificant ?16% reduced risk and those with high LTPA were at a 27% reduced risk (OR, 0.73; 95% CI, 0.50-1.07). Physical activity alone may not confer protection against male breast cancer risk.
Authors: Arem H; Johnson K; Weiderpass E; Matthews CE; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Dec;24(12):1898-901. Epub 2015-Sep-24.
Development and Use of a Traditional Mexican Diet Score in Relation to Systemic Inflammation and Insulin Resistance among Women of Mexican Descent
Women of Mexican descent are disproportionally affected by obesity, systemic inflammation, and insulin resistance (IR). Available approaches used to give scores to dietary patterns relative to dietary guidelines may not effectively capture traditional diets of Mexicans, who comprise the largest immigrant group in the United States. We characterized an a priori traditional Mexican diet (MexD) score high in corn tortillas, beans, soups, Mexican mixed dishes (e.g., tamales), fruits, vegetables, full-fat milk, and Mexican cheeses and low in refined grains and added sugars and evaluated the association of the MexD score with systemic inflammation and IR in 493 postmenopausal participants in the Women’s Health Initiative (WHI) who are of Mexican ethnic descent. The MexD score was developed from the baseline (1993-1998) WHI food frequency questionnaire, which included Hispanic foods and was available in Spanish. Body mass index (BMI) was computed from baseline measured weight and height, and ethnicity was self-reported. Outcome variables were high sensitivity C-reactive protein (hsCRP), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride concentrations measured at follow-up (2012-2013). Multivariable linear and logistic regression models were used to test the associations of the MexD score with systemic inflammation and IR. The mean ± SD MexD score was 5.8 ± 2.1 (12 maximum points) and was positively associated with intakes of carbohydrates, vegetable protein, and dietary fiber and inversely associated with intakes of added sugars and total fat (P < 0.01). Women with high compared with low MexD scores, consistent with a more-traditional Mexican diet, had 23% and 15% lower serum hsCRP (P < 0.05) and insulin concentrations, respectively (P < 0.05). Baseline BMI modified these associations such that lower MexD scores were associated with higher insulin and HOMA-IR in overweight/obese women (P-interaction <0.05). These findings suggest that greater adherence to a traditional Mexican diet could help reduce the future risk of systemic inflammation and IR in women of Mexican descent.
Authors: Santiago-Torres M; Tinker LF; Allison MA; Breymeyer KL; Garcia L; Kroenke CH; Lampe JW; Shikany JM; Van Horn L; Neuhouser ML
J Nutr. 2015 Dec;145(12):2732-40. Epub 2015-10-21.
Observational methods to assess the effectiveness of screening colonoscopy in reducing right colon cancer mortality risk: SCOLAR
Screening colonoscopy’s effectiveness in reducing risk of death from right colon cancers remains unclear. Methodological challenges of existing observational studies addressing this issue motivated the design of ‘Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults (SCOLAR)’. SCOLAR is a nested case-control study based on two large integrated health systems. This affords access to a large, well-defined historical cohort linked to integrated data on cancer outcomes, patient eligibility, test indications and important confounders. We found electronic data adequate for excluding ineligible patients (except family history), but not the detailed information needed for test indication assignment. The lessons of SCOLAR’s design and implementation may be useful for future studies seeking to evaluate the effectiveness of screening tests in community settings.
Authors: Goodman M; Fletcher RH; Doria-Rose VP; Jensen CD; Zebrowski AM; Becerra TA; Quinn VP; Zauber AG; Corley DA; Doubeni CA
J Comp Eff Res. 2015 Nov;4(6):541-51. Epub 2015-07-23.
Quality Indicators for the Management of Barrett’s Esophagus, Dysplasia and Esophageal Adenocarcinoma: International Consensus Recommendations from AGA Symposium
The development of and adherence to quality indicators in gastroenterology, as in all of medicine, is increasing in importance to ensure that patients receive consistent high-quality care. In addition, government-based and private insurers will be expecting documentation of the parameters by which we measure quality, which will likely affect reimbursements. Barrett’s esophagus remains a particularly important disease entity for which we should maintain up-to-date guidelines, given its commonality, potentially lethal outcomes, and controversies regarding screening and surveillance. To achieve this goal, a relatively large group of international experts was assembled and, using the modified Delphi method, evaluated the validity of multiple candidate quality indicators for the diagnosis and management of Barrett’s esophagus. Several candidate quality indicators achieved >80% agreement. These statements are intended to serve as a consensus on candidate quality indicators for those who treat patients with Barrett’s esophagus.
Authors: Sharma P; Corley D; Wang K; et al.
Gastroenterology. 2015 Nov;149(6):1599-606. Epub 2015-08-19.
Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk
Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett’s esophagus. We examined the associations between risks of EA and Barrett’s esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett’s esophagus) case patients from the Barrett’s and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn. After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett’s esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed. Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett’s esophagus. To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett’s esophagus.
Authors: Lee E; Corley DA; Wu AH; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Nov;24(11):1801-3. Epub 2015-09-12.
METFORMIN USE AND RISK OF COLORECTAL ADENOMA AFTER POLYPECTOMY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Existing literature suggests that metformin, the most commonly used biguanide, may lower colorectal cancer risk. Because most colorectal cancers originate in precancerous adenomas, we examined whether metformin use lowered colorectal adenoma risk after polypectomy in patients with type-2 diabetes. Retrospective cohort study of 40- to 89-year-old Kaiser Permanente Northern California patients who had type 2 diabetes, and ?1 adenoma detected at baseline colonoscopy during 2000 to 2009 and a repeat colonoscopy 1 to 10 years from baseline adenoma diagnosis through 2012. Cox models evaluated the association between metformin use during follow-up and subsequent adenoma diagnoses, controlling for age, race/ethnicity, sex, body mass index, and repeat examination indication. Study included 2,412 patients followed for a median of 4.5 years; cumulatively, 1,117 (46%) patients had ?1 adenoma at repeat colonoscopy. Compared with patients not receiving diabetes medications (n = 1,578), metformin-only use (n = 457) was associated with lower adenoma recurrence risk [adjusted HR, 0.76; 95% confidence interval (CI), 0.65-0.89], and the association was stronger with increasing total metformin dose [quartile (Q) 1: HR, 0.90; 95% CI, 0.72-1.12; Q2: HR, 0.89; 95% CI, 0.70-1.12; Q3: HR, 0.80; 95% CI, 0.63-1.01; Q4: HR, 0.50; 95% CI, 0.42-0.60, Ptrend < 0.001]. Findings were unchanged in sensitivity analyses, including evaluating only outcomes during the 3- to 10-year period from baseline. Our study suggests a potential benefit of metformin use in lowering the risk of subsequent adenomas after polypectomy in patients with type 2 diabetes. Metformin may lower colorectal cancer risk by reducing the formation of precancerous lesions, reinforcing the potential additional benefits of its use.
Authors: Marks AR; Pietrofesa RA; Jensen CD; Zebrowski A; Corley DA; Doubeni CA
Cancer Epidemiol Biomarkers Prev. 2015 Nov;24(11):1692-8. Epub 2015-09-16.
A newly identified susceptibility locus near FOXP1 modifies the association of gastroesophageal reflux with Barrett’s esophagus
Important risk factors for esophageal adenocarcinoma and its precursor, Barrett’s esophagus, include gastroesophageal reflux disease, obesity, and cigarette smoking. Recently, genome-wide association studies have identified seven germline single-nucleotide polymorphisms (SNP) that are associated with risk of Barrett’s esophagus and esophageal adenocarcinoma. Whether these genetic susceptibility loci modify previously identified exposure-disease associations is unclear. We analyzed exposure and genotype data from the BEACON Consortium discovery phase GWAS, which included 1,516 esophageal adenocarcinoma case patients, 2,416 Barrett’s esophagus case patients, and 2,187 control participants. We examined the seven newly identified susceptibility SNPs for interactions with body mass index, smoking status, and report of weekly heartburn or reflux. Logistic regression models were used to estimate ORs for these risk factors stratified by SNP genotype, separately for Barrett’s esophagus and esophageal adenocarcinoma. The odds ratio for Barrett’s esophagus associated with at least weekly heartburn or reflux varied significantly with the presence of at least one minor allele of rs2687201 (nominal P = 0.0005, FDR = 0.042). ORs (95% CIs) for weekly heartburn or reflux among participants with 0, 1, or 2 minor alleles of rs2687201 were 6.17 (4.91-7.56), 3.56 (2.85-4.44), and 3.97 (2.47-6.37), respectively. No statistically significant interactions were observed for smoking status and body mass index. Reflux symptoms are more strongly associated with Barrett’s esophagus risk among persons homozygous for the major allele of rs2687201, which lies approximately 75 kb downstream of the transcription factor gene FOXP1. The novel gene-exposure interaction discovered in this study provides new insights into the etiology of esophageal adenocarcinoma.
Authors: Dai JY; Corley DA; Vaughan TL; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Nov;24(11):1739-47. Epub 2015-09-16.
Environmental phenols and pubertal development in girls
Environmental exposures to many phenols are documented worldwide and exposures can be quite high (>1 ?M of urine metabolites). Phenols have a range of hormonal activity, but knowledge of effects on child reproductive development is limited, coming mostly from cross-sectional studies. We undertook a prospective study of pubertal development among 1239 girls recruited at three U.S. sites when they were 6-8 years old and were followed annually for 7 years to determine age at first breast or pubic hair development. Ten phenols were measured in urine collected at enrollment (benzophenone-3, enterolactone, bisphenol A, three parabens (methyl-, ethyl-, propyl-), 2,5-dichlorophenol, triclosan, genistein, daidzein). We used multivariable adjusted Cox proportional hazards ratios (HR (95% confidence intervals)) and Kaplan-Meier survival analyses to estimate relative risk of earlier or later age at puberty associated with phenol exposures. For enterolactone and benzophenone-3, girls experienced breast development 5-6 months later, adjusted HR 0.79 (0.64-0.98) and HR 0.80 (0.65-0.98) respectively for the 5th vs 1st quintiles of urinary biomarkers (?g/g-creatinine). Earlier breast development was seen for triclosan and 2,5-dichlorophenol: 4-9 months sooner for 5th vs 1st quintiles of urinary concentrations (HR 1.17 (0.96-1.43) and HR 1.37 (1.09-1.72), respectively). Association of breast development with enterolactone, but not the other three phenols, was mediated by body size. These phenols may be antiadipogens (benzophenone-3 and enterolactone) or thyroid agonists (triclosan and 2,5-dichlorophenol), and their ubiquity and relatively high levels in children would benefit from further investigation to confirm these findings and to establish whether there are certain windows of susceptibility during which exposure can affect pubertal development.
Authors: Wolff MS; Kushi LH; Breast Cancer and Environment Research Program; et al.
Environ Int. 2015 Nov;84:174-80. Epub 2015-08-31.
Brominated Flame Retardants and Other Persistent Organohalogenated Compounds in Relation to Timing of Puberty in a Longitudinal Study of Girls
Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program. Our goal was to examine persistent organic pollutants (POPs) in relation to pubertal onset. Ethnically diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and lipids. Tanner stages [breast (B) and pubic hair (PH)], and body mass index (BMI) were measured at up to seven annual clinic visits. Using accelerated failure time models, we calculated time ratios (TRs) for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1-4), adjusting for confounders (race/ethnicity, site, caregiver education, and income). We also calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling. Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related to chemical serum concentrations; but after adjustment for confounders, only the associations with B2+, not PH2+, were statistically significant. Longitudinally, the age at pubertal transition was consistently older with greater chemical concentrations; for example: adjusted TR for B2+ and Q4 for ?PBDE = 1.05; 95% CI: 1.02, 1.08, for ?PCB = 1.05; 95% CI: 1.01, 1.08, and for ?OCP = 1.10; 95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than least exposed, and with similar effect estimates for PH2+. Adjusting for BMI attenuated associations for PCBs and OCPs but not for PBDEs. This first longitudinal study of puberty in girls with serum POPs measurements (to our knowledge) reveals a delay in onset with higher concentrations.
Authors: Windham GC; Pinney SM; Voss RW; Sjödin A; Biro FM; Greenspan LC; Stewart S; Hiatt RA; Kushi LH
Environ Health Perspect. 2015 Oct;123(10):1046-52. Epub 2015-05-08.
Cancer survivors’ receipt of treatment summaries and implications for patient-centered communication and quality of care
The Institute of Medicine recommends cancer survivors completing treatment be provided with a treatment summary to facilitate delivery of patient-centered survivorship care. However, the relationship between treatment summary receipt and patient-centered communication (PCC) and overall quality of care (QOC) are not well understood. Cancer survivors responding to the Health Information National Trends Survey reported treatment summary receipt, QOC, and experiences of six core functions of PCC. Multivariable logistic regression assessed the relationship between treatment summary receipt and PCC. The prevalence of survivors’ treatment summary receipt and demographic/clinical characteristics predictive of treatment summary receipt were also assessed. Of 359 respondents with a cancer history, 34.5% reported receiving a treatment summary. Greater treatment burden was associated with increased treatment summary receipt. Treatment summary receipt was associated with higher QOC and more PCC, both overall and for five of the six PCC functions. The receipt of cancer treatment summaries may improve PCC and QOC for survivors. The positive relationship between treatment summary receipt and survivors’ PCC experience substantiates continued efforts to provide treatment summaries to survivors transitioning from active treatment to survivorship care. Future research should characterize mechanisms by which treatment summary provision may enhance PCC.
Authors: Blanch-Hartigan D; Chawla N; Beckjord EI; Forsythe LP; de Moor JS; Hesse BW; Arora NK
Patient Educ Couns. 2015 Oct;98(10):1274-9. Epub 2015-06-17.
Multiple primary melanomas among 16,570 patients with melanoma diagnosed at Kaiser Permanente Northern California, 1996 to 2011
Published rates of cutaneous multiple primary melanoma (MPM) vary widely. We examined incidence of and risk factors associated with MPMs among Kaiser Permanente Northern California members. We estimated MPM incidence among 16,570 patients with melanoma from 1996 through 2011. We compared characteristics between patients with MPMs and single primary melanomas and estimated crude and adjusted hazard ratios of MPMs using Cox models. In all, 15,448 patients had a single melanoma and 1122 had MPMs. Patients with MPMs were older and more often male, non-Hispanic white, and partnered. Subsequent primary melanomas were diagnosed after a mean of 3.83 (SD 3.61, median 2.82) years and were more likely in situ and thinner than initial tumors. The risk of a subsequent melanoma decreased from 2% in the first year after diagnosis to a stable approximately 1% rate through 15 years of follow-up. We lacked data on some known melanoma risk factors and had small numbers of non-white patients and certain tumor subtypes. The risk of MPMs, although highest in the first year after diagnosis, remains stable thereafter. Those at highest risk of MPMs are older, male, white, and partnered. Clinicians should be aware of the rate of MPMs and recognize high-risk subgroups.
Authors: Moore MM; Geller AC; Warton EM; Schwalbe J; Asgari MM
J Am Acad Dermatol. 2015 Oct;73(4):630-6. Epub 2015-08-19.
Leukocyte Telomere Length and Risks of Incident Coronary Heart Disease and Mortality in a Racially Diverse Population of Postmenopausal Women
Telomeres are regions at the ends of chromosomes that maintain chromosomal structural integrity and genomic stability. In studies of mainly older, white populations, shorter leukocyte telomere length (LTL) is associated with cardiometabolic risk factors and increased risks of mortality and coronary heart disease (CHD). On average, African Americans (AfAm) have longer LTL than whites, but the LTL-CHD relationship in AfAm is unknown. We investigated the relationship of LTL with CHD and mortality among AfAm. Using a case-cohort design, 1525 postmenopausal women (667 AfAm and 858 whites) from the Women’s Health Initiative had LTL measured in baseline blood samples by Southern blotting. CHD or mortality hazards ratios were estimated using race-stratified and risk factor-adjusted Cox proportional hazards models. There were 367 incident CHD (226 mortality) events in whites, whereas AfAm experienced 269 incident CHD (216 mortality) events during median follow-up of 13 years. Shorter LTL was associated with older age, current smoking, and white race/ethnicity. In whites, each 1 kilobase decrease in LTL was associated with 50% increased hazard of CHD, hazard ratio=1.50 (95% confidence interval, 1.08-2.10), P=0.017. There was no association between CHD and LTL in AfAm. White women with shorter LTL had higher risks of mortality. In contrast, shorter LTL was weakly associated with decreased mortality hazard in AfAm. As one of the largest prospective studies of LTL associations with incident CHD and mortality in a racially diverse sample, our study suggests differences in LTL associations with CHD and mortality between white and AfAm postmenopausal women.
Authors: Carty CL; Kooperberg C; Liu J; Herndon M; Assimes T; Hou L; Kroenke CH; LaCroix AZ; Kimura M; Aviv A; Reiner AP
Arterioscler Thromb Vasc Biol. 2015 Oct;35(10):2225-31. Epub 2015-08-06.
Potential harms outweigh benefits of indefinite monitoring of stable adnexal masses
The management of women with asymptomatic adnexal masses should aim to balance potential benefit with potential harm. While masses with highly worrisome features or other signs of malignancy should be referred for surgery, the vast majority of masses have an indeterminate or benign appearance and are candidates for observation. Evidence supports the use of initial short-term serial ultrasound in distinguishing between benign and malignant masses. However, benefit from prolonged, potentially life-long monitoring of stable masses has not been demonstrated. Since the goal of monitoring an adnexal mass is to observe for worrisome growth or increasing complexity as an indicator of malignancy, if the mass remains stable, the likelihood of malignancy and therefore, the potential benefit of observation wanes with time. The recognition that Type 2 high grade serous cancers, which are responsible for the majority of deaths from ovarian cancer, arise from fallopian tube rather than ovarian precursors, further diminishes the likelihood that monitoring a stable ovarian mass will lead to early diagnosis of high grade disease. While some Type 1 cancers may develop from ovarian precursors, the available data suggest that any measurable benefit of monitoring known lesions for detection of these cancers is realized within the first year of observation. The argument in favor of indefinite, potentially life-long monitoring of stable masses also fails to adequately account for the risks of perpetual imaging, which include the risk of incidental findings, an increased likelihood of unnecessary surgery, patient anxiety and cost. It is not always better to order a test than not order a test. Given the absence of evidence of benefit, observation of stable small adnexal masses should be limited in duration in order to minimize potential harms.
Authors: Suh-Burgmann E; Kinney W
Am J Obstet Gynecol. 2015 Dec;213(6):816.e1-4. Epub 2015-09-09.
Use of Bevacizumab in Community Settings: Toxicity Profile and Risk of Hospitalization in Patients With Advanced Non-Small-Cell Lung Cancer
Little is known regarding toxicities and hospitalizations in community-based settings for patients with advanced non-small-cell lung cancer (NSCLC) who received commonly prescribed carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) chemotherapy. Patients with stages IIIB-IV NSCLC age ? 21 years diagnosed between 2005 and 2010 who received first-line CP or CPB were identified at four health maintenance organizations (N = 1,109). Using patient and tumor characteristics and hospital and ambulatory encounters from automated data in the 180 days after chemotherapy initiation, the association between CP and CPB and toxicities and hospitalizations were evaluated with ?(2) tests and propensity score-adjusted regression models. Patients who received CPB were significantly younger and had significantly more bleeding, proteinuria, and GI perforation events (all P < .05). For these patients, the unadjusted odds ratio associated with the likelihood of having a hospitalization was 0.46 (95% CI, 0.32 to 0.67). As shown by multivariable and propensity score-adjusted models, patients who received CPB were less likely to have been hospitalized (odds ratio, 0.48; 95% CI, 0.32 to 0.71) and had fewer total hospitalizations (rate ratio, 0.62; 95% CI, 0.47 to 0.82) and hospital days (rate ratio, 0.53; 95% CI, 0.47 to 0.60) than patients who received CP. Consistent with earlier randomized clinical trials, significantly more toxicity events were identified in patients treated with CPB. However, both unadjusted and adjusted models showed that patients who received CPB were less likely than patients who received CP to experience a hospital-related event after the initiation of chemotherapy. Findings here confirm the need for adherence to clinical recommendations for judicious use of CPB, but provide reassurance regarding the relative risk for hospitalizations.
Authors: Carroll NM; Delate T; Menter A; Hornbrook MC; Kushi L; Aiello Bowles EJ; Loggers ET; Ritzwoller DP
J Oncol Pract. 2015 Sep;11(5):356-62. Epub 2015-06-09.
Impact of Chemotherapy Dosing on Ovarian Cancer Survival According to Body Mass Index
Optimal chemotherapy dosing in obese patients remains uncertain, with variation in practice. Dose reduction strategies are often used to avoid chemotoxicity, but recent American Society of Clinical Oncology guidelines recommend full dose. To evaluate the impact of body mass index (BMI) on chemotherapy dosing and of dose reduction on ovarian cancer survival. Cohort study in Kaiser Permanente Northern California (KPNC) health care setting of patients with primary invasive epithelial ovarian cancers diagnosed from January 2000 through March 2013. Analyses focused on 806 patients receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent. Overall and ovarian cancer-specific mortality. Deaths were identified through the KPNC Mortality Linkage System, with median follow-up of 52.5 months. Hazard ratios (HRs) and 95% CIs were estimated from proportional hazards regression, accounting for prognostic variables including age at diagnosis, race, stage, grade, histologic type, chemotoxic effects, comorbidities, cancer antigen 125 levels, and BMI at diagnosis. The strongest predictor of dose reduction was a high BMI. Compared with normal-weight women, obese class III women received 38% and 45% lower doses in milligrams per kilogram of body weight of paclitaxel and carboplatin, respectively (P?
Authors: Bandera EV; Lee VS; Rodriguez-Rodriguez L; Powell CB; Kushi LH
JAMA Oncol. 2015 Sep;1(6):737-45.
Leukoplakia, oral cavity cancer risk, and cancer survival in the U.S. elderly
Screening for oral leukoplakia, an oral cavity cancer (OCC) precursor, could lead to earlier detection of OCC. However, the progression rate from leukoplakia to OCC and the benefits of leukoplakia screening for improving OCC outcomes are currently unclear. We conducted a case-cohort study of U.S. adults ages ?65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linkage. We identified leukoplakia diagnoses through Medicare claims, and OCC diagnoses through SEER cancer registries. Weighted Cox regression was used to estimate leukoplakia associations with OCC incidence, and the absolute OCC risk following leukoplakia diagnosis was calculated. Among OCC cases, we compared OCC stage and OCC survival between cases with a prior leukoplakia diagnosis versus those without prior leukoplakia. Among 470,266 individuals in the SEER-Medicare subcohort, 1,526 (0.3%) had a leukoplakia diagnosis. Among people with leukoplakia, the cumulative OCC incidence was 0.7% at 3 months and 2.5% at 5 years. OCC risk was most increased <3 months after leukoplakia diagnosis (HR, 115), likely representing the diagnosis of prevalent cancers. Nonetheless, risk remained substantially increased in subsequent follow-up [HR ? 3 months, 24; 95% confidence interval (CI), 22-27; HR ? 12 months, 22, 95% CI, 20-25]. Among OCC cases (N = 8,927), those with prior leukoplakia were less likely to be diagnosed at regional/distant stage (OR, 0.36; 95% CI, 0.30-0.43), and had lower mortality (HR, 0.74; 95% CI, 0.65-0.84) when compared with OCC cases without a prior leukoplakia. Individuals with leukoplakia have substantially elevated risk of OCC. Lower stage and better survival after OCC diagnosis suggest that leukoplakia identification can lead to earlier OCC detection and reduced mortality.
Authors: Yanik EL; Katki HA; Silverberg MJ; Manos MM; Engels EA; Chaturvedi AK
Cancer Prev Res (Phila). 2015 Sep;8(9):857-63. Epub 2015-07-09.
A Candidate-Pathway Approach to Identify Gene-Environment Interactions: Analyses of Colon Cancer Risk and Survival
Genetic association studies have traditionally focused on associations between individual single nucleotide polymorphisms (SNPs) and disease. Standard analysis ignores interactions between multiple SNPs and environmental exposures explaining a small portion of disease heritability: the often-cited issue of “missing heritability.” We present a novel three-step analytic framework for modeling gene-environment interactions (GEIs) between an angiogenesis candidate-gene pathway and three lifestyle exposures (dietary protein, smoking, and alcohol consumption) on colon cancer risk and survival. Logic regression was used to summarize the gene-pathway effects, and GEIs were modeled using logistic regression and Cox proportional hazards models. We analyzed data from 1541 colon cancer case patients and 1934 control subjects in the Diet, Activity and Lifestyle as a Risk Factor for Colon Cancer Study. We identified five statistically significant GEIs for colon cancer risk. For risk interaction, odds ratios (ORINT) and 95% confidence intervals (CIs) were FLT1(rs678714) and BMP4(rs17563) and smoking (ORINT = 1.64, 95% CI = 1.11 to 2.41 and ORINT = 1.60, 95% CI = 1.10 to 2.32, respectively); FLT1(rs2387632 OR rs9513070) and protein intake (ORINT = 1.69, 95% CI = 1.03 to 2.77); KDR(rs6838752) and TLR2(rs3804099) and alcohol (ORINT = 1.53, 95% CI = 1.10 to 2.13 and ORINT = 1.59, 95% CI = 1.05 to 2.38, respectively). Three GEIs between TNF, BMP1, and BMPR2 genes and the three exposures were statistically significant at the 5% level in relation to colon cancer survival but not after multiple-testing adjustment. Adopting a comprehensive biologically informed candidate-pathway approach identified GEI effects on colon cancer. Findings may have important implications for public health and personalized medicine targeting prevention and therapeutic strategies. Findings from this study need to be validated in other studies.
Authors: Sharafeldin N; Slattery ML; Liu Q; Franco-Villalobos C; Caan BJ; Potter JD; Yasui Y
J Natl Cancer Inst. 2015 Sep;107(9). Epub 2015-06-13.
Trends in Basal Cell Carcinoma Incidence and Identification of High-Risk Subgroups, 1998-2012
The incidence of basal cell carcinomas (BCCs) is increasing globally, but incidence rates in the United States are difficult to quantify because BCCs are not reportable tumors. To estimate annual BCC incidence rates by age, sex, and race/ethnicity to identify demographically distinct high-risk subgroups and to assess changes in rates over time. In this retrospective cohort study (January 1, 1998, through December 31, 2012), we studied 147?093 patients with BCC from Kaiser Permanente Northern California, a large, integrated health care provision system, identified using a previously validated BCC registry. We estimated annual BCC incidence rates by age, sex, and race/ethnicity and assessed changes in rates over time. The BCC incidence rates were standardized to the age, sex, and race/ethnicity distribution of the 2010 US Census population. In models adjusting for age, sex, and race, male patients had higher rates than female patients (incidence rate ratio [IRR], 1.65; 95% CI, 1.60-1.70). Persons 65 through 79 years of age and those 80 years and older had higher rates than persons 40 through 64 years of age (IRR, 2.96; 95% CI, 2.86-3.06; and IRR, 5.14; 95% CI, 4.94-5.35, respectively). Whites had higher rates than multiracial persons (IRR, 1.96; 95% CI, 1.80-2.13), Hispanics (IRR, 8.56; 95% CI, 7.79-9.41), Asians (IRR, 33.13; 95% CI, 27.84-39.42), and blacks (IRR, 72.98; 95% CI, 49.21-108.22). We estimate that BCCs occur in?approximately 2 million Americans annually. Our findings provide an updated estimate of the incidence of BCCs, highlight the changing epidemiologic findings, and better identify demographically distinct high-risk subgroups.
Authors: Asgari MM; Moffet HH; Ray GT; Quesenberry CP
JAMA Dermatol. 2015 Sep;151(9):976-81.
Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs)
Little is known about the use of sirolimus for primary prevention of cutaneous squamous cell carcinoma (SCC) among solid organ transplant recipients (SOTRs). We examined the association between sirolimus exposure and incident SCC risk among SOTRs within Kaiser Permanente Northern California. Using a retrospective cohort of all Kaiser Permanente Northern California members given a diagnosis of SOTR from 2000 through 2010, we evaluated incident posttransplantation SCC risk in relation to sirolimus exposure. Sirolimus use was determined from electronic pharmacy records, and incident posttransplantation SCCs were identified from health plan electronic pathology records. We used extended Cox regression to examine the independent association between receipt of sirolimus and risk of SCC. Among 3539 SOTRs, 488 were exposed to sirolimus and 47 developed an incident SCC. SCC risk was not associated with ever use of sirolimus (adjusted hazard ratio 1.18, 95% confidence interval 0.84-1.16) or cumulative duration of sirolimus exposure (adjusted hazard ratio 2.75, 95% confidence interval 0.84-9.04, comparing long-term users with nonusers). No information was available for some known SCC risk factors, such as skin type and sun exposure. Among a large cohort of SOTRs, sirolimus exposure was not associated with a reduction in incident posttransplantation SCC risk.
Authors: Asgari MM; Arron ST; Warton EM; Quesenberry CP; Weisshaar D
J Am Acad Dermatol. 2015 Sep;73(3):444-50. Epub 2015-06-30.
Faecal immunochemical tests versus guaiac faecal occult blood tests: what clinicians and colorectal cancer screening programme organisers need to know.
Although colorectal cancer (CRC) is a common cause of cancer-related death, it is fortunately amenable to screening with faecal tests for occult blood and endoscopic tests. Despite the evidence for the efficacy of guaiac-based faecal occult blood tests (gFOBT), they have not been popular with primary care providers in many jurisdictions, in part because of poor sensitivity for advanced colorectal neoplasms (advanced adenomas and CRC). In order to address this issue, high sensitivity gFOBT have been recommended, however, these tests are limited by a reduction in specificity compared with the traditional gFOBT. Where colonoscopy is available, some providers have opted to recommend screening colonoscopy to their patients instead of faecal testing, as they believe it to be a better test. Newer methods for detecting occult human blood in faeces have been developed. These tests, called faecal immunochemical tests (FIT), are immunoassays specific for human haemoglobin. FIT hold considerable promise over the traditional guaiac methods including improved analytical and clinical sensitivity for CRC, better detection of advanced adenomas, and greater screenee participation. In addition, the quantitative FIT are more flexible than gFOBT as a numerical result is reported, allowing customisation of the positivity threshold. When compared with endoscopy, FIT are less sensitive for the detection of advanced colorectal neoplasms when only one time testing is applied to a screening population; however, this is offset by improved participation in a programme of annual or biennial screens and a better safety profile. This review will describe how gFOBT and FIT work and will present the evidence that supports the use of FIT over gFOBT, including the cost-effectiveness of FIT relative to gFOBT. Finally, specific issues related to FIT implementation will be discussed, particularly with respect to organised CRC screening programmes.
Authors: Tinmouth J; Lansdorp-Vogelaar I; Allison JE.
Gut. 2015 Aug;64(8):1327-37
A large multi-ethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences
A genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified locus 6q25.3 that replicated in PEGASUS (N = 7,539) and the Multiethnic Cohort (N = 4,679) with an overall P = 1.0 × 10(-19) (OR, 1.18). Across the 6q25.3 locus, rs4646284 exhibited the strongest association with expression of SLC22A1 (P = 1.3 × 10(-23)) and SLC22A3 (P = 3.2 × 10(-52)). At the known 19q13.33 locus, rs2659124 (P = 1.3 × 10(-13); OR, 1.18) nominally replicated in PEGASUS. A risk score of 105 known risk SNPs was strongly associated with prostate cancer (P < 1.0 × 10(-8)). Comparing the highest to lowest risk score deciles, the OR was 6.22 for non-Hispanic whites, 5.82 for Latinos, 3.77 for African-Americans, and 3.38 for East Asians. In non-Hispanic whites, the 105 risk SNPs explained approximately 7.6% of disease heritability. The entire GWAS array explained approximately 33.4% of heritability, with a 4.3-fold enrichment within DNaseI hypersensitivity sites (P = 0.004). Taken together, our findings of independent risk variants, ethnic variation in existing SNP replication, and remaining unexplained heritability have important implications for further clarifying the genetic risk of prostate cancer. Our findings also suggest that there may be much promise in evaluating understudied variation, such as indels and ethnically diverse populations.
Authors: Hoffmann TJ; Van Den Eeden SK; Sakoda LC; Habel LA; Quesenberry CP; Schaefer C; Witte JS; et al.
Cancer Discov. 2015 Aug;5(8):878-91. Epub 2015-06-01.
The Impact of DNA Input Amount and DNA source on the Performance of Whole-Exome Sequencing in Cancer Epidemiology
Whole-exome sequencing (WES) has recently emerged as an appealing approach to systematically study coding variants. However, the requirement for a large amount of high-quality DNA poses a barrier that may limit its application in large cancer epidemiologic studies. We evaluated the performance of WES with low input amount and saliva DNA as an alternative source material. Five breast cancer patients were randomly selected from the Pathways Study. From each patient, four samples, including 3 ?g, 1 ?g, and 0.2 ?g blood DNA and 1 ?g saliva DNA, were aliquoted for library preparation using the Agilent SureSelect Kit and sequencing using Illumina HiSeq2500. Quality metrics of sequencing and variant calling, as well as concordance of variant calls from the whole exome and 21 known breast cancer genes, were assessed by input amount and DNA source. There was little difference by input amount or DNA source on the quality of sequencing and variant calling. The concordance rate was about 98% for single-nucleotide variant calls and 83% to 86% for short insertion/deletion calls. For the 21 known breast cancer genes, WES based on low input amount and saliva DNA identified the same set variants in samples from a same patient. Low DNA input amount, as well as saliva DNA, can be used to generate WES data of satisfactory quality. Our findings support the expansion of WES applications in cancer epidemiologic studies where only low DNA amount or saliva samples are available.
Authors: Zhu Q; Kwan ML; Ergas IJ; Kushi LH; Yao S; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Aug;24(8):1207-13. Epub 2015-05-19.
Contribution of the Neighborhood Environment and Obesity to Breast Cancer Survival: The California Breast Cancer Survivorship Consortium
Little is known about neighborhood attributes that may influence opportunities for healthy eating and physical activity in relation to breast cancer mortality. We used data from the California Breast Cancer Survivorship Consortium and the California Neighborhoods Data System (CNDS) to examine the neighborhood environment, body mass index, and mortality after breast cancer. We studied 8,995 African American, Asian American, Latina, and non-Latina white women with breast cancer. Residential addresses were linked to the CNDS to characterize neighborhoods. We used multinomial logistic regression to evaluate the associations between neighborhood factors and obesity and Cox proportional hazards regression to examine associations between neighborhood factors and mortality. For Latinas, obesity was associated with more neighborhood crowding [quartile 4 (Q4) vs. Q1: OR, 3.24; 95% confidence interval (CI), 1.50-7.00]; breast cancer-specific mortality was inversely associated with neighborhood businesses (Q4 vs. Q1: HR, 0.46; 95% CI, 0.25-0.85) and positively associated with multifamily housing (Q3 vs. Q1: HR, 1.98; 95% CI, 1.20-3.26). For non-Latina whites, lower neighborhood socioeconomic status (SES) was associated with obesity [quintile 1 (Q1) vs. Q5: OR, 2.52; 95% CI, 1.31-4.84], breast cancer-specific (Q1 vs. Q5: HR, 2.75; 95% CI, 1.47-5.12), and all-cause (Q1 vs. Q5: HR, 1.75; 95% CI, 1.17-2.62) mortality. For Asian Americans, no associations were seen. For African Americans, lower neighborhood SES was associated with lower mortality in a nonlinear fashion. Attributes of the neighborhood environment were associated with obesity and mortality following breast cancer diagnosis, but these associations differed across racial/ethnic groups.
Authors: Cheng I; Kwan ML; Keegan TH; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Aug;24(8):1282-90. Epub 2015-06-10.
Overweight, Obesity, and Postmenopausal Invasive Breast Cancer Risk: A Secondary Analysis of the Women’s Health Initiative Randomized Clinical Trials
More than two-thirds of US women are overweight or obese, placing them at increased risk for postmenopausal breast cancer. To investigate in this secondary analysis the associations of overweight and obesity with risk of postmenopausal invasive breast cancer after extended follow-up in the Women’s Health Initiative (WHI) clinical trials. The WHI clinical trial protocol incorporated measured height and weight, baseline and annual or biennial mammography, and adjudicated breast cancer end points in 67?142 postmenopausal women ages 50 to 79 years at 40 US clinical centers. The women were enrolled from 1993 to 1998 with a median of 13 years of follow-up through 2010; 3388 invasive breast cancers were observed. Height and weight were measured at baseline, and weight was measured annually thereafter. Data were collected on demographic characteristics, personal and family medical history, and personal habits (smoking, physical activity). Women underwent annual or biennial mammograms. Breast cancers were verified by medical records reviewed by physician adjudicators. Women who were overweight and obese had an increased invasive breast cancer risk vs women of normal weight. Risk was greatest for obesity grade 2?plus?3 (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, >35.0) (hazard ratio [HR] for invasive breast cancer, 1.58; 95% CI, 1.40-1.79). A BMI of 35.0 or higher was strongly associated with risk for estrogen receptor-positive and progesterone receptor-positive breast cancers (HR, 1.86; 95% CI, 1.60-2.17) but was not associated with estrogen receptor-negative cancers. Obesity grade 2?plus?3 was also associated with advanced disease, including larger tumor size (HR, 2.12; 95% CI, 1.67-2.69; P?=?.02), positive lymph nodes (HR, 1.89; 95% CI, 1.46-2.45; P?=?.06), regional and/or distant stage (HR, 1.94; 95% CI, 1.52-2.47; P?=?.05), and deaths after breast cancer (HR, 2.11; 95% CI, 1.57-2.84; P?
Authors: Neuhouser ML; Caan BJ; Anderson GL; et al.
JAMA Oncol. 2015 Aug;1(5):611-21.
Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes
Studies suggest pioglitazone use may increase risk of cancers. To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed 193,099 persons aged 40 years or older in 1997-2002 until December 2012; 464 case patients and 464 matched controls were surveyed about additional confounders. A cohort analysis of 10 additional cancers included 236,507 persons aged 40 years or older in 1997-2005 and followed until June 2012. Cohorts were from Kaiser Permanente Northern California. Ever use, duration, cumulative dose, and time since initiation of pioglitazone as time dependent. Incident cancer, including bladder, prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma. Among 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration, 2.8 years; range, 0.2-13.2 years) and 1261 had incident bladder cancer. Crude incidences of bladder cancer in pioglitazone users and nonusers were 89.8 and 75.9 per 100,000 person-years, respectively. Ever use of pioglitazone was not associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95% CI, 0.89-1.26). Results were similar in case-control analyses (pioglitazone use: 19.6% among case patients and 17.5% among controls; adjusted odds ratio, 1.18; 95% CI, 0.78-1.80). In adjusted analyses, there was no association with 8 of the 10 additional cancers; ever use of pioglitazone was associated with increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02-1.26) and pancreatic cancer (HR, 1.41; 95% CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100,000 person-years, respectively. No clear patterns of risk for any cancer were observed for time since initiation, duration, or dose. Pioglitazone use was not associated with a statistically significant increased risk of bladder cancer, although an increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether they are causal or are due to chance, residual confounding, or reverse causality.
Authors: Lewis JD; Habel LA; Quesenberry CP; Hedderson MM; Ehrlich SF; Van Den Eeden SK; Ferrara A; et al.
JAMA. 2015 Jul 21;314(3):265-77.
An evaluation and replication of miRNAs with disease stage and colorectal cancer-specific mortality
MicroRNAs (miRNAs) have been implicated in colorectal cancer (CRC) development and associated with prognostic indicators such as disease stage and survival. Prognostic associations are often based on few individuals and imprecise. In this study, we utilize population-based data from 1,141 CRC cases to replicate previously reported associations between 121 miRNAs and disease stage and survival. The Agilent Human miRNA Microarray V19.0 was used to generate miRNA data following a stringent quality control protocol. Assessment of survival was done using Cox Proportional Hazard models adjusting for age, disease stage and tumor molecular phenotype. Five miRNAs were associated with more advanced disease stage; hsa-miR-145-5p and hsa-miR-31-5p showed increased expression with more advanced tumor stage, while hsa-miR-200b-3p, hsa-miR-215 and hsa-miR-451a had decreased expression with more advanced tumors. Thirteen miRNAs were associated with CRC mortality among individuals diagnosed with colon cancer while 14 were associated with CRC mortality after a diagnosis with rectal cancer. Strongest associations were observed for those miRNAs that were expressed in a small subset of tumors. Most notable associations were for hsa-miR-145-3p [hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.54, 5.61], and hsa-miR-9-3p (HR 10.28, 95% CI 1.31, 80.84) with colon cancer and hsa-miR-335-5p (HR 0.17, 95% CI 0.05, 0.54) for rectal cancer. hsa-miR-374a-5p, hsa-miR-570-3p and hsa-miR-18a-5p significantly reduced the hazard of dying for all cases, regardless of tumor site. Our findings illustrate the need for a large sample to evaluate the association of miRNAs with survival and disease stage in order to determine associations by tumor site.
Authors: Slattery ML; Herrick JS; Mullany LE; Valeri N; Stevens J; Caan BJ; Samowitz W; Wolff RK
Int J Cancer. 2015 Jul 15;137(2):428-38. Epub 2014-12-16.
Does Human Papillomavirus Cause Esophageal Adenocarcinoma?
Authors: Corley D; Silverberg MJ
Clin Gastroenterol Hepatol. 2015 Jul;13(7):1369-70. Epub 2014-12-24.
Public health impact of achieving 80% colorectal cancer screening rates in the United States by 2018
The National Colorectal Cancer Roundtable, a national coalition of public, private, and voluntary organizations, has recently announced an initiative to increase colorectal cancer (CRC) screening rates in the United States to 80% by 2018. The authors evaluated the potential public health benefits of achieving this goal. The authors simulated the 1980 through 2030 United States population of individuals aged 50 to 100 years using microsimulation modeling. Test-specific historical screening rates were based on National Health Interview Survey data for 1987 through 2013. The effects of increasing screening rates from approximately 58% in 2013 to 80% in 2018 were compared to a scenario in which the screening rate remained approximately constant. The outcomes were cancer incidence and mortality rates and numbers of CRC cases and deaths during short-term follow-up (2013-2020) and extended follow-up (2013-2030). Increasing CRC screening rates to 80% by 2018 would reduce CRC incidence rates by 17% and mortality rates by 19% during short-term follow-up and by 22% and 33%, respectively, during extended follow-up. These reductions would amount to a total of 277,000 averted new cancers and 203,000 averted CRC deaths from 2013 through 2030. Achieving the goal of increasing the uptake of CRC screening in the United States to 80% by 2018 may have a considerable public health impact by averting approximately 280,000 new cancer cases and 200,000 cancer deaths within <20 years. Cancer 2015;121:2281-2285. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Authors: Meester RG; Doubeni CA; Zauber AG; Goede SL; Levin TR; Corley DA; Jemal A; Lansdorp-Vogelaar I
Cancer. 2015 Jul 1;121(13):2281-5. Epub 2015-03-12.
Identification of Stevens-Johnson syndrome and toxic epidermal necrolysis in electronic health record databases
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) carry a high mortality risk. While identifying clinical and genetic risk factors for these conditions has been hindered by their rarity, large electronic health databases hold promise for identifying large numbers of cases for study, especially with the introduction in 2008 of ICD-9 codes more specific for these conditions. The objective of this study is to estimate the validity of ICD-9 codes for ascertaining SJS/TEN in 12 collaborating research units in the USA, covering almost 60 million lives. From the electronic databases at each site, we ascertained potential cases of SJS/TEN using ICD-9 codes. At five sites, a subset of medical records was abstracted and standardized criteria applied by board-certified dermatologists to adjudicate diagnoses. Multivariate logistic regression was used to identify factors independently associated with validated SJS/TEN cases. A total of 56?591 potential cases of SJS/TEN were identified. A subset of 276 charts was selected for adjudication and 39 (of the 276) were confirmed as SJS/TEN. Patients with the ICD-9 codes introduced after 2008 were more likely to be confirmed as cases (OR 3.32; 95%CI 0.82, 13.47) than those identified in earlier years. Likelihood of case status increased with length of hospitalization. Applying the probability of case status to the 56?591 potential cases, we estimated 475-875 to be valid SJS/TEN cases. Newer ICD-9 codes, along with length of hospitalization, identified patients with a high likelihood of SJS/TEN. This is important for identification of subjects for future pharmacogenomics studies.
Authors: Davis RL; Asgari MM; Pinheiro SP; et al.
Pharmacoepidemiol Drug Saf. 2015 Jul;24(7):684-92. Epub 2015-04-24.
Mendelian randomization study of body mass index and colorectal cancer risk
High body mass index (BMI) is consistently linked to increased risk of colorectal cancer for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and colorectal cancer. We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study-identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis. Individuals carrying greater numbers of BMI-increasing alleles had higher colorectal cancer risk [per weighted allele OR, 1.31; 95% confidence interval (CI), 1.10-1.57]. Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for colorectal cancer (IV-OR per 5 kg/m(2), 1.50; 95% CI, 1.13-2.01). In the sex-specific IV analyses higher BMI was associated with higher risk of colorectal cancer among women (IV-OR per 5 kg/m(2), 1.82; 95% CI, 1.26-2.61). For men, genetically influenced BMI was not associated with colorectal cancer (IV-OR per 5 kg/m(2), 1.18; 95% CI, 0.73-1.92). High BMI was associated with increased colorectal cancer risk for women. Whether abdominal obesity, rather than overall obesity, is a more important risk factor for men requires further investigation. Overall, conventional epidemiologic and Mendelian randomization studies suggest a strong association between obesity and the risk of colorectal cancer.
Authors: Thrift AP; Ogino S; Campbell PT; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Jul;24(7):1024-31. Epub 2015-05-14.
Breastfeeding, PAM50 Tumor Subtype, and Breast Cancer Prognosis and Survival
Breastfeeding is associated with decreased breast cancer risk, yet associations with prognosis and survival by tumor subtype are largely unknown. We conducted a cohort study of 1636 women from two prospective breast cancer cohorts. Intrinsic tumor subtype (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2]-enriched, basal-like) was determined by the PAM50 gene expression assay. Breastfeeding history was obtained from participant questionnaires. Questionnaires and medical record reviews documented 383 recurrences and 290 breast cancer deaths during a median follow-up of nine years. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between breastfeeding and tumor subtype. Cox regression was used to estimate hazard ratios (HRs) for breast cancer recurrence or death. Statistical significance tests were two-sided. Breast cancer patients with basal-like tumors were less likely to have previously breastfed than those with luminal A tumors (OR = 0.56, 95% CI = 0.39 to 0.80). Among all patients, ever breastfeeding was associated with decreased risk of recurrence (HR = 0.70, 95% CI = 0.53 to 0.93), especially breastfeeding for six months or more (HR = 0.63, 95% CI = 0.46 to 0.87, P trend = .01). Similar associations were observed for breast cancer death. Among women with luminal A subtype, ever breastfeeding was associated with decreased risks of recurrence (HR = 0.52, 95% CI = 0.31 to 0.89) and breast cancer death (HR = 0.52, 95% CI = 0.29 to 0.93), yet no statistically significant associations were observed among the other subtypes. Effects appeared to be limited to tumors with lower expression of proliferation genes. History of breastfeeding might affect prognosis and survival by establishing a luminal tumor environment with lower proliferative activity.
Authors: Kwan ML; Kroenke CH; Habel LA; Gunderson EP; Quesenberry CP; Kushi LH; Caan BJ; et al.
J Natl Cancer Inst. 2015 Jul;107(7). Epub 2015-04-28.
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Authors: Hofmann JN; Corley DA; Colt JS; Shuch B; Chow WH; Purdue MP
Epidemiology. 2015 Jul;26(4):e49.
Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk
Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers.
Authors: Brinton LA; Wood SN; Isaacs CJ; Cook MB; et al.
J Clin Oncol. 2015 Jun 20;33(18):2041-50. Epub 2015-05-11.
Variation in Adenoma Detection Rate and the Lifetime Benefits and Cost of Colorectal Cancer Screening: A Microsimulation Model
Colonoscopy is the most commonly used colorectal cancer screening test in the United States. Its quality, as measured by adenoma detection rates (ADRs), varies widely among physicians, with unknown consequences for the cost and benefits of screening programs. To estimate the lifetime benefits, complications, and costs of an initial colonoscopy screening program at different levels of adenoma detection. Microsimulation modeling with data from a community-based health care system on ADR variation and cancer risk among 57,588 patients examined by 136 physicians from 1998 through 2010. Using modeling, no screening was compared with screening initiation with colonoscopy according to ADR quintiles (averages 15.3%, quintile 1; 21.3%, quintile 2; 25.6%, quintile 3; 30.9%, quintile 4; and 38.7%, quintile 5) at ages 50, 60, and 70 years with appropriate surveillance of patients with adenoma. Estimated lifetime colorectal cancer incidence and mortality, number of colonoscopies, complications, and costs per 1000 patients, all discounted at 3% per year and including 95% confidence intervals from multiway probabilistic sensitivity analysis. In simulation modeling, among unscreened patients the lifetime risk of colorectal cancer incidence was 34.2 per 1000 (95% CI, 25.9-43.6) and risk of mortality was 13.4 per 1000 (95% CI, 10.0-17.6). Among screened patients, simulated lifetime incidence decreased with lower to higher ADRs (26.6; 95% CI, 20.0-34.3 for quintile 1 vs 12.5; 95% CI, 9.3-16.5 for quintile 5) as did mortality (5.7; 95% CI, 4.2-7.7 for quintile 1 vs 2.3; 95% CI, 1.7-3.1 for quintile 5). Compared with quintile 1, simulated lifetime incidence was on average 11.4% (95% CI, 10.3%-11.9%) lower for every 5 percentage-point increase of ADRs and for mortality, 12.8% (95% CI, 11.1%-13.7%) lower. Complications increased from 6.0 (95% CI, 4.0-8.5) of 2777 colonoscopies (95% CI, 2626-2943) in quintile 1 to 8.9 (95% CI, 6.1-12.0) complications of 3376 (95% CI, 3081-3681) colonoscopies in quintile 5. Estimated net screening costs were lower from quintile 1 (US $2.1 million, 95% CI, $1.8-$2.4 million) to quintile 5 (US $1.8 million, 95% CI, $1.3-$2.3 million) due to averted cancer treatment costs. Results were stable across sensitivity analyses. In this microsimulation modeling study, higher adenoma detection rates in screening colonoscopy were associated with lower lifetime risks of colorectal cancer and colorectal cancer mortality without being associated with higher overall costs. Future research is needed to assess whether increasing adenoma detection would be associated with improved patient outcomes.
Authors: Meester RG; Doubeni CA; Lansdorp-Vogelaar I; Jensen CD; van der Meulen MP; Levin TR; Quinn VP; Schottinger JE; Zauber AG; Corley DA; van Ballegooijen M
JAMA. 2015 Jun 16;313(23):2349-58.
Risk of Diabetes among Patients Receiving Primary Androgen Deprivation Therapy for Clinically Localized Prostate Cancer
Androgen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors. We conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses. Diabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38-1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction=0.008). Primary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle interventions to reduce the risk of diabetes in men receiving androgen deprivation therapy.
Authors: Tsai HT; Keating NL; Van Den Eeden SK; Haque R; Cassidy-Bushrow AE; Ulcickas Yood M; Smith MR; Potosky AL
J Urol. 2015 Jun;193(6):1956-62. Epub 2014-12-15.
Population-representative Incidence of Drug-induced Acute Liver Failure Based on an Analysis of an Integrated Healthcare System
Medications are a major cause of acute liver failure (ALF) in the United States, but no population-based studies have evaluated the incidence of ALF from drug-induced liver injury. We aimed to determine the incidence and outcomes of drug-induced ALF in an integrated health care system that approximates a population-based cohort. We performed a retrospective cohort study using data from the Kaiser Permanente Northern California (KPNC) health care system between January 1, 2004, and December 31, 2010. We included all KPNC members age 18 years and older with 6 months or more of membership and hospitalization for potential ALF. The primary outcome was drug-induced ALF (defined as coagulopathy and hepatic encephalopathy without underlying chronic liver disease), determined by hepatologists who reviewed medical records of all KPNC members with inpatient diagnostic and laboratory criteria suggesting potential ALF. Among 5,484,224 KPNC members between 2004 and 2010, 669 had inpatient diagnostic and laboratory criteria indicating potential ALF. After medical record review, 62 (9.3%) were categorized as having definite or possible ALF, and 32 (51.6%) had a drug-induced etiology (27 definite, 5 possible). Acetaminophen was implicated in 18 events (56.3%), dietary/herbal supplements in 6 events (18.8%), antimicrobials in 2 events (6.3%), and miscellaneous medications in 6 events (18.8%). One patient with acetaminophen-induced ALF died (5.6%; 0.06 events/1,000,000 person-years) compared with 3 patients with non-acetaminophen-induced ALF (21.4%; 0.18/1,000,000 person-years). Overall, 6 patients (18.8%) underwent liver transplantation, and 22 patients (68.8%) were discharged without transplantation. The incidence rates of any definite drug-induced ALF and acetaminophen-induced ALF were 1.61 events/1,000,000 person-years (95% confidence interval, 1.06-2.35) and 1.02 events/1,000,000 person-years (95% confidence interval, 0.59-1.63), respectively. Drug-induced ALF is uncommon, but over-the-counter products and dietary/herbal supplements are its most common causes.
Authors: Goldberg DS; Corley DA; Lo Re V; et al.
Gastroenterology. 2015 Jun;148(7):1353-61.e3. Epub 2015-02-28.
Cigarette smoking and pulmonary tuberculosis in northern California
A positive association between smoking and increased risk of tuberculosis disease is well documented for populations outside the USA. However, it is unclear whether smoking increases risk of tuberculosis in the USA, where both smoking prevalence and disease rates are much lower than in the countries where previous studies have been conducted. To explore the tuberculosis-smoking association in a more generalisable US population-based sample, we conducted a nested case-control study among members of Kaiser Permanente Northern California (KPNC). We identified all newly diagnosed cases of active pulmonary tuberculosis (PTB) disease between 1996 and 2010. Each of the 2380 cases were individually matched to two controls by age, gender and race/ethnicity. ORs and 95% CIs for the association between smoking status and PTB were calculated using conditional logistic regression adjusted for all matching factors. Increased PTB risk was observed among ever-smokers (OR=1.35; 95% CI 1.19 to 1.53), as well as current (OR=1.26; 95% CI 1.08 to 1.48) and past (OR=1.43; 95% CI 1.23 to 1.67) smokers, compared with never-smokers. Increased intensity and duration of smoking were also positively associated with PTB risk. Our findings among a more generalisable US population support the hypothesis that smoking increases risk of PTB, underscoring the importance of tobacco cessation and prevention programmes in eliminating tuberculosis.
Authors: Smith GS; Van Den Eeden SK; Baxter R; Shan J; Van Rie A; Herring AH; Richardson DB; Emch M; Gammon MD
J Epidemiol Community Health. 2015 Jun;69(6):568-73. Epub 2015-01-20.
BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia
Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.
Authors: Bennett C; DeCaestecker J; Jankowski J; et al.
Am J Gastroenterol. 2015 May;110(5):662-82; quiz 683. Epub 2015-04-14.
Racial/Ethnic and Socioeconomic Differences in Short-Term Breast Cancer Survival Among Women in an Integrated Health System
We examined the combined influence of race/ethnicity and neighborhood socioeconomic status (SES) on short-term survival among women with uniform access to health care and treatment. Using electronic medical records data from Kaiser Permanente Northern California linked to data from the California Cancer Registry, we included 6262 women newly diagnosed with invasive breast cancer. We analyzed survival using multivariable Cox proportional hazards regression with follow-up through 2010. After consideration of tumor stage, subtype, comorbidity, and type of treatment received, non-Hispanic White women living in low-SES neighborhoods (hazard ratio [HR]?=?1.28; 95% confidence interval [CI]?=?1.07, 1.52) and African Americans regardless of neighborhood SES (high SES: HR?=?1.44; 95% CI?=?1.01, 2.07; low SES: HR?=?1.88; 95% CI?=?1.42, 2.50) had worse overall survival than did non-Hispanic White women living in high-SES neighborhoods. Results were similar for breast cancer-specific survival, except that African Americans and non-Hispanic Whites living in high-SES neighborhoods had similar survival. Strategies to address the underlying factors that may influence treatment intensity and adherence, such as comorbidities and logistical barriers, should be targeted at low-SES non-Hispanic White and all African American patients.
Authors: Keegan TH; Kurian AW; Gali K; Tao L; Lichtensztajn DY; Hershman DL; Habel LA; Caan BJ; Gomez SL
Am J Public Health. 2015 May;105(5):938-46. Epub 2015-03-19.
Diet and Upper Gastrointestinal Malignancies
Diet is believed to modulate cancer risk and this relationship has been widely studied in the gastrointestinal tract. Observational epidemiologic studies have provided most of the evidence about the effects of diet on cancer risk because clinical trials to determine nutritional exposures are often impossible, impractical, or unaffordable. Although a few foods or nutrients are thought to protect against specific types of cancer, it seems clear that the strength and even direction of dietary associations (increasing or decreasing risk) is organ-site- and even histology-specific, along the gastrointestinal tract. Although some hypotheses are supported by a substantial body of observational data (drinking hot maté [an infusion of the herb Ilex Paraguarensis] contributes to esophageal cancer), there are not much data to support others. We discuss some highly touted hypotheses and draw interim conclusions about what is known and what could be done to improve the level of evidence. The complex nature of diet and its associations can be productively investigated with disease-specific studies. However, public health recommendations for normal-risk individuals regarding diet and gastrointestinal cancer should probably emphasize the importance of eating for overall health rather than eating specific foods to reduce risk for specific cancers.
Authors: Abnet CC; Corley DA; Freedman ND; Kamangar F
Gastroenterology. 2015 May;148(6):1234-1243.e4. Epub 2015-02-11.
Building Data Infrastructure to Evaluate and Improve Quality: PCORnet
Authors: Corley DA; Feigelson HS; Lieu TA; McGlynn EA
J Oncol Pract. 2015 May;11(3):204-6.
CDC Grand Rounds: the Future of Cancer Screening
Cancer is the second leading cause of death in the United States, with 52% of deaths caused by cancers of the lung and bronchus, female breast, uterine cervix, colon and rectum, oral cavity and pharynx, prostate, and skin (melanoma). In the 1930s, uterine cancer, including cancer of the uterine cervix, was the leading cause of cancer deaths among women in the United States. With the advent of the Papanicolaou (Pap) test in the 1950s to detect cellular level changes in the cervix, cervical cancer death rates declined significantly. Since this first cancer screening test, others have been developed that detect the presence of cancer through imaging procedures (e.g., mammography, endoscopy, and computed tomography) and laboratory tests (e.g., fecal occult blood tests).
Authors: Thomas CC; Richards TB; Plescia M; Wong FL; Ballard R; Levin TR; Calonge BN; Brawley OW; Iskander J; Centers for Disease Control and Prevention (CDC)
MMWR Morb Mortal Wkly Rep. 2015 Apr 3;64(12):324-7.
Adjusting for Patient Demographics Has Minimal Effects on Rates of Adenoma Detection in a Large, Community-based Setting
Reliable estimates of adenoma detection rates (ADRs) are needed to inform colonoscopy quality standards, yet little is known about the contributions of patient demographics to variation in ADRs. We evaluated the effects of adjusting for patient age, race/ethnicity, and family history of colorectal cancer on variations in ADRs and the relative rank order of physicians. In a retrospective cohort study, we collected data from Kaiser Permanente Northern California members who were ? 50 years old who received colonoscopies from 2006 through 2008. We evaluated ADRs (before and after adjustment for age, sex, race/ethnicity, and family history of colorectal cancer) for 102 endoscopists who performed 108,662 total colonoscopies and 20,792 screening colonoscopies. Adenomas were identified from the pathology database, and cancers were detected by using the Kaiser Permanente Northern California cancer registry. About two-thirds of examiners had unadjusted ADRs for screening exams that met gastroenterology society guidelines (>25% for men and >15% for women), although rates of detection varied widely (7.7%-61.5% for male patients and 1.7%-45.6% for female patients). Adjusting for case mix reduced the variation in detection rates (from 8-fold to 3-fold for male patients and from 27-fold to 5-fold for female patients), but the median change in physician order by detection rate was just 2 ranks, and few physicians changed quartiles of detection. For example, only 3 of 102 endoscopists moved into and 3 out of the lowest quartile of ADR. In a community-based setting, most endoscopists met the ADR standards, although there was wide variation in ADRs, which was similar to that reported from academic and referral settings. Case-mix adjustment reduced variability but had only small effects on differences in ADRs between physicians, and only a small percentage of physicians changed quartiles of detection. Adjustments to ADRs are therefore likely only needed in settings in which physicians have very different patient demographics, such as in sex or age. Moderate differences in patient demographics between physicians are unlikely to substantially change rates of adenoma detection.
Authors: Jensen CD; Levin TR; Lee JK; Fireman BH; Quesenberry CP; Corley DA; et al.
Clin Gastroenterol Hepatol. 2015 Apr;13(4):739-46. Epub 2014-10-25.
Creating a list of low-value health care activities in Swiss primary care
Authors: Selby K; Gaspoz JM; Rodondi N; Neuner-Jehle S; Perrier A; Zeller A; Cornuz J
JAMA Intern Med. 2015 Apr;175(4):640-2. doi: 10.1001/jamainternmed.2014.8111.
Longitudinal study of acculturation and BMI change among Asian American men
Cross-sectional studies examining the association between Western acculturation and BMI in Asians have been inconsistent, and studies on BMI change are lacking. This study examined the associations between indicators of acculturation (generational status, length of US residence, and age at immigration) and overweight (BMI ?25kg/m(2)) as well as 5-year BMI changes in 7,073 Chinese, Japanese, Korean, Filipino, and Vietnamese men who lived in the US and were 44-71years old at baseline of the California Men’s Health Study (2002-2003). Indicators of acculturation were reported at baseline. Repeated clinical measures of BMI were extracted from electronic health records (2005-2012). Using generalized estimating equations we found that lower generational status, shorter duration of US residence and older age at immigration were inversely associated with being overweight. However, analysis of BMI curves using linear mixed models showed that shorter length of US residence and older age at immigration were associated with larger 5-year increases in BMI. Asian immigrants who were less acculturated had larger BMI increases as they became more acculturated but had not achieved overweight status. Healthy weight interventions among Asians immigrants may be most effective when targeting weight maintenance early in the process of acculturation.
Authors: Erber Oakkar E; Stevens J; Bradshaw PT; Cai J; Perreira KM; Popkin BM; Gordon-Larsen P; Young DR; Ghai NR; Caan B; Quinn VP
Prev Med. 2015 Apr;73:15-21. Epub 2015-01-17.
Statins and breast cancer stage and mortality in the Women’s Health Initiative
To evaluate the association between statins and breast cancer stage and mortality in the Women’s Health Initiative. The study population included 128,675 postmenopausal women aged 50-79 years, out of which there were 7,883 newly diagnosed cases of in situ (19%), local (61%)-, regional (19%)- and distant (1%)-stage breast cancer and 401 deaths due to breast cancer after an average of 11.5 (SD = 3.7) years of follow-up. Stage was coded using SEER criteria and was stratified into early (in situ and local)- versus late (regional and distant)-stage disease. Information on statins and other risk factors were collected by self- and interviewer-administered questionnaires. Cause of death was based on medical record review. Multivariable-adjusted hazards ratios (HR) and 95% confidence intervals (CIs) evaluating the relationship between statin use (at baseline only and in a time-dependent manner) and diagnosis of late-stage breast cancer and breast cancer-specific mortality were computed from Cox proportional hazards analyses after adjusting for appropriate confounders. Statins were used by 10,474 women (8%) at baseline. In the multivariable-adjusted time-dependent model, use of lipophilic statins was associated with a reduction in diagnosis of late-stage breast cancer (HR 0.80, 95% CI 0.64-0.98, p = 0.035) which was also significant among women with estrogen receptor-positive disease (HR 0.72, 95% CI 0.56-0.93, p = 0.012). Breast cancer mortality was marginally lower in statin users compared with nonusers (HR 0.59, 95 % CI 0.32-1.06, p = 0.075). Prior statin use is associated with lower breast cancer stage at diagnosis.
Authors: Desai P; Kwan ML; Simon MS; et al.
Cancer Causes Control. 2015 Apr;26(4):529-39. Epub 2015-03-04.
A hybrid approach to identify subsequent breast cancer using pathology and automated health information data
Many cancer registries do not capture recurrence; thus, outcome studies have often relied on time-intensive and costly manual chart reviews. Our goal was to build an effective and efficient method to reduce the numbers of chart reviews when identifying subsequent breast cancer (BC) using pathology and electronic health records. We evaluated our methods in an independent sample. We developed methods for identifying subsequent BC (recurrence or second primary) using a cohort of 17,245 women diagnosed with early-stage BC from 2 health plans. We used a combination of information from pathology report reviews and an automated data algorithm to identify subsequent BC (for those lesions without pathologic confirmation). Test characteristics were determined for a developmental (N=175) and test (N=500) set. Sensitivity and specificity of our hybrid approach were robust [96.7% (87.6%-99.4%) and 92.1% (85.1%-96.1%), respectively] in the developmental set. In the test set, the sensitivity, specificity, and negative predictive value were also high [96.9% (88.4%-99.5%), 92.4% (89.4%-94.6%), and 99.5% (98.0%-99.0%), respectively]. The positive predictive value was lower (65.6%, 55.2%-74.8%). Chart review was required for 10.9% of the 17,245 women; 2946 (17.0%) women developed subsequent BC over a 14-year period. The date of subsequent BC identified by the algorithm was concordant with full chart reviews. We developed an efficient and effective hybrid approach that decreased the number of charts needed to be manually reviewed by approximately 90%, to determine subsequent BC occurrence and disease-free survival time.
Authors: Haque R; Shi J; Schottinger JE; Ahmed SA; Chung J; Avila C; Lee VS; Cheetham TC; Habel LA; Fletcher SW; Kwan ML
Med Care. 2015 Apr;53(4):380-5.
Family History of Skin Cancer Is Associated With Increased Risk of Cutaneous Squamous Cell Carcinoma
The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified. To examine the association between self-reported family history of skin cancer and SCC risk. Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors. Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6). Family history of skin cancer is an important independent risk factor for cutaneous SCCs.
Authors: Asgari MM; Warton EM; Whittemore AS
Dermatol Surg. 2015 Apr;41(4):481-6.
Leveraging biospecimen resources for discovery or validation of markers for early cancer detection
Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers. With this background, the Division of Cancer Control and Population Sciences (DCCPS) and the Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) held a joint workshop in August 2013. The goal was to advance early detection cancer research by considering how the infrastructure of cohort studies that already exist or are being developed might be leveraged to include appropriate blood specimens, including prediagnostic specimens, ideally collected at periodic intervals, along with clinical data about symptom status and cancer diagnosis. Three overarching recommendations emerged from the discussions: 1) facilitate sharing of existing specimens and data, 2) encourage collaboration among scientists developing biomarkers and those conducting observational cohort studies or managing healthcare systems with cohorts followed over time, and 3) conduct pilot projects that identify and address key logistic and feasibility issues regarding how appropriate specimens and clinical data might be collected at reasonable effort and cost within existing or future cohorts.
Authors: Schully SD; Kushi LH; Ransohoff DF; et al.
J Natl Cancer Inst. 2015 Apr;107(4). Epub 2015-02-16.
Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants
Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene?×?environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. Case-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent. Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. Colorectal cancer. Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74]; P?=?6.2?×?10(-28)) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P?=?4.6?×?10(-9) for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P?=?7.7?×?10(-33)) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P?=?.002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P?=?8.2?×?10(-9) for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P?=?1.9?×?10(-30)) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P?=?.76). In this genome-wide investigation of gene?×?environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies.
Authors: Nan H; Caan BJ; GECCO; et al.
JAMA. 2015 Mar 17;313(11):1133-42.
Breastfeeding Versus Formula-Feeding and Girls’ Pubertal Development
To examine the association of breastfeeding or its duration with timing of girls’ pubertal onset, and the role of BMI as a mediator in these associations. A population of 1,237 socio-economically and ethnically diverse girls, ages 6-8 years, was recruited across three geographic locations (New York City, Cincinnati, and the San Francisco Bay Area) in a prospective study of predictors of pubertal maturation. Breastfeeding practices were assessed using self-administered questionnaire/interview with the primary caregiver. Girls were seen on at least annual basis to assess breast and pubic hair development. The association of breastfeeding with pubertal timing was estimated using parametric survival analysis while adjusting for body mass index, ethnicity, birth-weight, mother’s education, mother’s menarcheal age, and family income. Compared to formula fed girls, those who were mixed-fed or predominantly breastfed showed later onset of breast development [hazard ratios 0.90 (95 % CI 0.75, 1.09) and 0.74 (95 % CI 0.59, 0.94), respectively]. Duration of breastfeeding was also directly associated with age at onset of breast development (p trend = 0.008). Associations between breastfeeding and pubic hair onset were not significant. In stratified analysis, the association of breastfeeding and later breast onset was seen in Cincinnati girls only. The association between breast feeding and pubertal onset varied by study site. More research is needed about the environments within which breastfeeding takes place in order to better understand whether infant feeding practices are a potentially modifiable risk factor that may influence age at onset of breast development and subsequent risk for disease in adulthood.
Authors: Kale A; Kushi LH; et al.
Matern Child Health J. 2015 Mar;19(3):519-27.
The association between dietary inflammatory index and risk of colorectal cancer among postmenopausal women: results from the Women’s Health Initiative
Inflammation is a process central to carcinogenesis and in particular to colorectal cancer (CRC). Previously, we developed a dietary inflammatory index (DII) from extensive literature review to assess the inflammatory potential of diet. In the current study, we utilized this novel index in the Women’s Health Initiative to prospectively evaluate its association with risk of CRC in postmenopausal women. The DII was calculated from baseline food frequency questionnaires administered to 152,536 women aged 50-79 years without CRC at baseline between 1993 and 1998 and followed through 30 September 2010. Incident CRC cases were ascertained through a central physician adjudication process. Multiple covariate-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) for colorectal, colon (proximal/distal locations), and rectal cancer risk, by DII quintiles (Q). During an average 11.3 years of follow-up, a total of 1,920 cases of CRC (1,559 colon and 361 rectal) were identified. Higher DII scores (representing a more pro-inflammatory diet) were associated with an increased incidence of CRC (HRQ5-Q1 1.22; 95 % CI 1.05, 1.43; p trend = 0.02) and colon cancer, specifically proximal colon cancer (HRQ5-Q1 1.35; 95 % CI 1.05, 1.67; p trend = 0.01) but not distal colon cancer (HRQ5-Q1 0.84; 95 % CI 0.61, 1.18; p trend = 0.63) or rectal cancer (HRQ5-Q1 1.20; 95 % CI 0.84, 1.72; p trend = 0.65). Consumption of pro-inflammatory diets is associated with an increased risk of CRC, especially cancers located in the proximal colon. The absence of a significant association for distal colon cancer and rectal cancer may be due to the small number of incident cases for these sites. Interventions that may reduce the inflammatory potential of the diet are warranted to test our findings, thus providing more information for colon cancer prevention.
Authors: Tabung FK; Caan B; Hebert JR; et al.
Cancer Causes Control. 2015 Mar;26(3):399-408. Epub 2014-12-31.
Association between high-sensitivity C-reactive protein (hsCRP) and change in mammographic density over time in the SWAN mammographic density subcohort
High mammographic density (MD) is a strong risk factor for breast cancer. Chronic inflammation may be related to breast cancer risk through a mechanism involving the percent of breast area that is dense (percent MD). Longitudinal assessments, however, are lacking and thus were constructed to evaluate the relationship between chronic inflammation and percent MD. We evaluated whether elevated (>3 mg/L) high-sensitivity C-reactive protein (hsCRP), a biomarker of inflammation, was associated with change in percent MD among 653 women aged 42-52 years at baseline in the Study of Women’s Health Across the Nation, a longitudinal study of midlife women. We used a mixed model to analyze data from an average of 4.7 mammograms per woman collected during an average follow-up of 4.9 years (SD = 1.47). Elevated hsCRP at baseline was associated with lower baseline percent MD and a significantly slower annual decline over time of percent MD in an adjusted model that did not include body mass index (BMI) (? = 0.88, 95 % CI 0.44, 1.31). This association was attenuated and nonsignificant when BMI was included in the model (? = 0.37, 95 % CI -0.09, 0.84). Elevated hsCRP levels over time (time-varying elevated hsCRP levels) were also associated with a significantly slower decline in percent MD (? = 0.62, 95 % CI 0.30, 0.94). This association was attenuated, but still significant after adjusting for baseline BMI (? = 0.40, 95 % CI 0.07, 0.73). These results suggest that inflammation may be related to slower reduction in percent MD.
Authors: Makboon K; Gold EB; Harvey DJ; Butler LM; Habel LA
Cancer Causes Control. 2015 Mar;26(3):431-42. Epub 2015-01-21.
Tobacco and Alcohol in Relation to Male Breast Cancer: An Analysis of the Male Breast Cancer Pooling Project Consortium
The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) ORs and 95% confidence intervals (CI), which were then combined using fixed-effects meta-analysis. Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one subanalysis of very high recent alcohol consumption (>60 g/day) was tentatively associated with male breast cancer (ORunexposed referent = 1.29; 95% CI, 0.97-1.71; OR>0-<7 g/day referent = 1.36; 95% CI, 1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. In this analysis of the Male Breast Cancer Pooling Project, we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.
Authors: Cook MB; Van Den Eeden SK; Brinton LA; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Mar;24(3):520-31. Epub 2014-12-16.
Development and validation of an algorithm for classifying colonoscopy indication
Accurate determination of colonoscopy indication is required for managing clinical programs and performing research; however, existing algorithms that use available electronic databases (eg, diagnostic and procedure codes) have yielded limited accuracy. To develop and validate an algorithm for classifying colonoscopy indication that uses comprehensive electronic medical data sources. We developed an algorithm for classifying colonoscopy indication by using commonly available electronic diagnostic, pathology, cancer, and laboratory test databases and validated its performance characteristics in comparison with a comprehensive review of patient medical records. We also evaluated the influence of each data source on the algorithm’s performance characteristics. Kaiser Permanente Northern California healthcare system. A total of 300 patients who underwent colonoscopy between 2007 and 2010. Colonoscopy. Algorithm’s sensitivity, specificity, and positive predictive value (PPV) for classifying screening, surveillance, and diagnostic colonoscopies. The reference standard was the indication assigned after comprehensive medical record review. For screening indications, the algorithm’s sensitivity was 88.5% (95% confidence interval [CI], 80.4%-91.7%), specificity was 91.7% (95% CI, 87.0%-95.1%), and PPV was 83.3% (95% CI, 74.7%-90.0%). For surveillance indications, the algorithm’s sensitivity was 93.4% (95% CI, 86.2%-97.5%), specificity was 92.8% (95% CI, 88.4%-95.9%), and PPV was 85.0% (95% CI, 76.5%-91.4%). The algorithm’s sensitivity, specificity, and PPV for diagnostic indications were 81.4% (95% CI, 73.0%-88.1%), 96.8% (95% CI, 93.2%-98.8%), and 93.9% (95% CI, 87.2%-97.7%), respectively. Validation was confined to a single healthcare system. An algorithm that uses commonly available modern electronic medical data sources yielded a high sensitivity, specificity, and PPV for classifying screening, surveillance, and diagnostic colonoscopy indications. This algorithm had greater accuracy than the indication listed on the colonoscopy report.
Authors: Lee JK; Jensen CD; Lee A; Doubeni CA; Zauber AG; Levin TR; Zhao WK; Corley DA
Gastrointest Endosc. 2015 Mar;81(3):575-582.e4. Epub 2015-01-08.
Colorectal cancer deaths attributable to nonuse of screening in the United States
Screening is a major contributor to colorectal cancer (CRC) mortality reductions in the United States but is underused. We estimated the fraction of CRC deaths attributable to nonuse of screening to demonstrate the potential benefits from targeted interventions. The established microsimulation screening analysis colon model was used to estimate the population attributable fraction (PAF) in people aged ?50 years. The model incorporates long-term patterns and effects of screening by age and type of screening test. PAF for 2010 was estimated using currently available data on screening uptake. PAF was also projected assuming constant future screening rates to incorporate lagged effects from past increases in screening uptake. We also computed PAF using Levin’s formula to gauge how this simpler approach differs from the model-based approach. There were an estimated 51,500 CRC deaths in 2010, about 63% (N ? 32,200) of which were attributable to nonscreening. The PAF decreases slightly to 58% in 2020. Levin’s approach yielded a considerably more conservative PAF of 46% (N ? 23,600) for 2010. Most of the current United States CRC deaths are attributable to nonscreening. This underscores the potential benefits of increasing screening uptake in the population. Traditional methods of estimating PAF underestimated screening effects compared with model-based approaches.
Authors: Meester RG; Doubeni CA; Lansdorp-Vogelaar I; Goede SL; Levin TR; Quinn VP; Ballegooijen Mv; Corley DA; Zauber AG
Ann Epidemiol. 2015 Mar;25(3):208-213.e1. Epub 2014-12-05.
Reply to E Archer and SN Blair
Authors: Hébert JR; Hurley TG; Steck SE; Miller DR; Tabung FK; Kushi LH; Frongillo EA
Adv Nutr. 2015 Mar;6(2):230-3. Epub 2015-03-13.
Day-to-Day Impact of Vaginal Aging questionnaire: a multidimensional measure of the impact of vaginal symptoms on functioning and well-being in postmenopausal women
This study aims to develop a self-report questionnaire assessing the impact of vaginal dryness, soreness, itching, irritation, and pain on functioning and well-being in postmenopausal women. Structured self-report items were developed to address the impact of vaginal symptoms on functioning and well-being based on findings from focus groups with racially/ethnically diverse, symptomatic postmenopausal women. Items were refined after cognitive interview pretesting and field-tested among symptomatic postmenopausal women enrolled in a multiethnic cohort study in California. Exploratory factor analysis (SAS PROC VARCLUS) and confirmatory factor analysis evaluated factor structure and eliminated poorly fitting items. Additional evidence of construct validity was obtained via examination of correlations with other measures of related constructs. Internal consistency and test-retest reliability were assessed using Cronbach ? and correlation coefficients, respectively. For the 745 postmenopausal women who completed the draft questionnaire, the mean (SD) age was 56.2 (8.5) years, and 66% of the respondents were racial/ethnic minorities. The refined questionnaire included four multi-item scales addressing symptom impact on (1) activities of daily living, (2) emotional well-being, (3) sexual functioning, and (4) self-concept and body image. The four-factor model provided good approximate fit (comparative fit index, 0.987; standardized root-mean-square residual, 0.038). Correlations with other measures of symptom bothersomeness, sexual function, depression, and anxiety conformed to hypotheses. Cronbach ? values ranged from 0.82 to 0.93. Intraclass coefficients ranged from 0.47 to 0.72. The Day-to-Day Impact of Vaginal Aging questionnaire is a new multidimensional self-report measure designed to facilitate evaluation of the impact of vaginal symptoms on postmenopausal women of diverse backgrounds.
Authors: Huang AJ; Gregorich SE; Kuppermann M; Nakagawa S; Van Den Eeden SK; Brown JS; Richter HE; Walter LC; Thom D; Stewart AL
Menopause. 2015 Feb;22(2):144-54.
Aspirin and Nonsteroidal Anti-Inflammatory Drug Use and the Risk of Barrett’s Esophagus
The use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of esophageal adenocarcinoma; however, it is unknown where these agents may act in the proposed pathway from normal mucosa to Barrett’s esophagus to esophageal adenocarcinoma. The aim of the study was to evaluate the association between aspirin and NSAID use and Barrett’s esophagus in a case-control study within a large community-based population. We conducted a case-control study of aspirin/NSAID use and Barrett’s esophagus within the Kaiser Permanente Northern California population. Cases had a new diagnosis of Barrett’s esophagus between October 2002 and September 2005; controls were members without a diagnosis of Barrett’s esophagus. Persons with Barrett’s esophagus were less likely to use aspirin than population controls [odds ratio (OR) 0.59, 95 % confidence interval (CI) 0.39-0.87]; a stronger association was found among cases and controls with reflux symptoms (OR 0.49, 95 % CI 0.32-0.75; p value interaction = 0.004). Similar associations were found with the use of either aspirin and/or non-aspirin NSAIDs (OR 0.53, 95 % CI 0.35-0.81), although NSAID use alone was not significantly associated with Barrett’s esophagus (OR 0.74, 95 % CI 0.47-1.16). The strength of the association was highest among persons with at least moderate-to-high total medication intake. Regular use of aspirin or NSAIDs was associated with a decreased risk of Barrett’s esophagus, particularly among persons with gastroesophageal reflux disease symptoms. These findings have implications for chemoprevention, as some of the previously described protective association between aspirin/NSAIDs and esophageal adenocarcinoma may be explained by events that occur prior to the development of Barrett’s esophagus.
Authors: Schneider JL; Zhao WK; Corley DA
Dig Dis Sci. 2015 Feb;60(2):436-43. Epub 2014-09-12.
A review of the epidemiology of Barrett’s oesophagus and oesophageal adenocarcinoma
While the incidence rates of many cancers have decreased in past decades, the incidence of oesophageal adenocarcinoma continues to increase. The only known precursor for oesophageal adenocarcinoma is Barrett’s oesophagus. Studies conducted have identified white race, male sex, GORD, cigarette smoking, obesity, and the absence of Helicobacter pylori status as risk factors for oesophageal adenocarcinoma. Other potential associations include dietary factors and the absence of non-steroidal anti-inflammatory drug use. Many individual studies have been limited by sample size and several meta-analyses have pooled data from studies to address this limitation. In this review we present a synthesis of these studies and summarize current knowledge of risk factors for both oesophageal adenocarcinoma and Barrett’s oesophagus.
Authors: Schneider JL; Corley DA
Best Pract Res Clin Gastroenterol. 2015 Feb;29(1):29-39. Epub 2014-12-03.
Diabetes and other comorbidities in breast cancer survival by race/ethnicity: The California Breast Cancer Survivorship Consortium (CBCSC)
The role of comorbidities in survival of patients with breast cancer has not been well studied, particularly in non-white populations. We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated HRs and 95% confidence intervals (CI) for overall and breast cancer-specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction. Risk of breast cancer-specific mortality increased among breast cancer cases with a history of diabetes (HR, 1.48; 95% CI, 1.18-1.87) or myocardial infarction (HR, 1.94; 95% CI, 1.27-2.97). Risk patterns were similar across race/ethnicity (non-Latina white, Latina, African American, and Asian American), body size, menopausal status, and stage at diagnosis. In subgroup analyses, risk of breast cancer-specific mortality was significantly elevated among cases with diabetes who received neither radiotherapy nor chemotherapy (HR, 2.11; 95% CI, 1.32-3.36); no increased risk was observed among those who received both treatments (HR, 1.13; 95% CI, 0.70-1.84; P(interaction) = 0.03). A similar pattern was found for myocardial infarction by radiotherapy and chemotherapy (P(interaction) = 0.09). These results may inform future treatment guidelines for patients with breast cancer with a history of diabetes or myocardial infarction. Given the growing number of breast cancer survivors worldwide, we need to better understand how comorbidities may adversely affect treatment decisions and ultimately outcome.
Authors: Wu AH; Kwan ML; Caan BJ; Vigen C; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Feb;24(2):361-8. Epub 2014-11-25.
Polymorphisms Near TBX5 and GDF7 Are Associated With Increased Risk for Barrett’s Esophagus
Barrett’s esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.
Authors: Palles C; Corley DA; Jankowski J; et al.
Gastroenterology. 2015 Feb;148(2):367-78. Epub 2014-11-05.
Caregiving Frequency and Physical Function: The Women’s Health Initiative
Informal caregiving is common for older women and can negatively affect health, but its impact on physical function remains unclear. Using inverse probability weighting methods, we quantified the association of caregiving with physical function over 6 years. Study participants were 5,649 women aged 65 years and older at baseline of the Woman’s Health Initiative Clinical Trial (multicenter recruitment, 1993-1998) with complete caregiving data and function at baseline and at least one follow-up. Caregiving was self-reported (low-frequency if ?2 times per week and high-frequency if ?3 times per week). Performance-based measures of physical function including timed walk (meters/second), grip strength (kilograms), and chair stands (number) were measured at baseline and years 1, 3, and 6. Associations and 95% confidence intervals of baseline caregiving with physical function were estimated by generalized estimating equations with inverse probability weighting by propensity and attrition scores, calculated by logistic regression of baseline health and demographic characteristics. Over follow-up, low-frequency caregivers had higher grip strength when compared with noncaregivers (mean difference = 0.63kg, confidence interval: 0.24, 1.01). There were no observed differences between high-frequency caregivers and noncaregivers on grip strength or for either caregiver group when compared with noncaregivers on walk speed or chair stands. Rates of change in physical function measures did not differ by caregiving status. Caregiving was not associated with poorer physical function in this sample of older women. Low-frequency caregiving was associated with better grip strength at baseline which persisted through follow-up. This study supports the concept that informal caregiving may not have universally negative health consequences.
Authors: Rosso AL; Lee BK; Stefanick ML; Kroenke CH; Coker LH; Woods NF; Michael YL
J Gerontol A Biol Sci Med Sci. 2015 Feb;70(2):210-5. Epub 2014-07-24.
Association Between Cannabis Use and the Risk of Bladder Cancer: Results From the California Men’s Health Study
To investigate the association of cannabis use and tobacco smoking on the incidence of bladder cancer within the California Men’s Health Study cohort. We evaluated the records of 84,170 participants in a multiethnic cohort of men aged 45-69 years. Information on demographic and lifestyle factors including smoking history and cannabis use was collected using mailed questionnaires between 2002 and 2003. We linked the study data with clinical records including cancer data from electronic health records. Overall 34,000 (41%) cohort members reported cannabis use, 47,092 (57%) reported tobacco use, 22,500 (27%) reported using both, and 23,467 (29%) used neither. Men were followed over an 11-year period and 279 (0.3%) developed incident bladder tumors. Among cannabis users, 89 (0.3%) developed bladder cancer in comparison to 190 (0.4%) men who did not report cannabis use (P < .001). After adjusting for age, race or ethnicity, and body mass index, using tobacco only was associated with an increased risk of bladder cancer (hazard regression [HR], 1.52; 95% confidence interval [CI], 1.12-2.07), whereas cannabis use only was associated with a 45% reduction in bladder cancer incidence (HR, 0.55; 95% CI, 0.31-1.00). Using both cannabis and tobacco was associated with an HR of 1.28 (95% CI, 0.91-1.80). Although a cause and effect relationship has not been established, cannabis use may be inversely associated with bladder cancer risk in this population.
Authors: Thomas AA; Wallner LP; Quinn VP; Slezak J; Van Den Eeden SK; Chien GW; Jacobsen SJ
Urology. 2015 Feb;85(2):388-92. Epub 2014-11-01.
Metformin use and lung cancer risk in patients with diabetes
Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages ?40 years, who completed a health-related survey administered between 1994 and 1996, data on prescribed diabetes medications were obtained from electronic pharmacy records. Follow-up for incident lung cancer occurred from January 1, 1997, until June 30, 2012. Using Cox regression, we estimated lung cancer risk associated with new use of metformin, along with total duration, recency, and cumulative dose (all modeled as time-dependent covariates), adjusting for potential confounding factors. During 428,557 person-years of follow-up, 747 patients were diagnosed with lung cancer. No association was found with duration, dose, or recency of metformin use and overall lung cancer risk. Among never smokers, however, ever use was inversely associated with lung cancer risk [HR, 0.57; 95% confidence interval (CI), 0.33-0.99], and risk appeared to decrease monotonically with longer use (?5 years: HR, 0.48; 95% CI, 0.21-1.09). Among current smokers, corresponding risk estimates were >1.0, although not statistically significant. Consistent with this variation in effect by smoking history, longer use was suggestively associated with lower adenocarcinoma risk (HR, 0.69; 95% CI, 0.40-1.17), but higher small cell carcinoma risk (HR, 1.82; 95% CI, 0.85-3.91). In this population, we found no evidence that metformin use affects overall lung cancer risk. The observed variation in association by smoking history and histology requires further confirmation.
Authors: Sakoda LC; Ferrara A; Achacoso NS; Peng T; Ehrlich SF; Quesenberry CP; Habel LA
Cancer Prev Res (Phila). 2015 Feb;8(2):174-9.
Reply to L. Cabel et al
Authors: Fehrenbacher L; Capra A; Habel L
J Clin Oncol. 2015 Jan 20;33(3):292-3. Epub 2014-12-15.
Imputation of the Rare HOXB13 G84E Mutation and Cancer Risk in a Large Population-Based Cohort
An efficient approach to characterizing the disease burden of rare genetic variants is to impute them into large well-phenotyped cohorts with existing genome-wide genotype data using large sequenced referenced panels. The success of this approach hinges on the accuracy of rare variant imputation, which remains controversial. For example, a recent study suggested that one cannot adequately impute the HOXB13 G84E mutation associated with prostate cancer risk (carrier frequency of 0.0034 in European ancestry participants in the 1000 Genomes Project). We show here that-by utilizing the 1000 Genomes Project data plus an enriched reference panel of mutation carriers-we were able to accurately impute the G84E mutation into a large cohort of 83,285 non-Hispanic White participants from the Kaiser Permanente Research Program on Genes, Environment and Health Genetic Epidemiology Research on Adult Health and Aging cohort. Imputation authenticity was confirmed via a novel classification and regression tree method, and then empirically validated analyzing a subset of these subjects plus an additional 1,789 men from the California Men’s Health Study specifically genotyped for the G84E mutation (r2 = 0.57, 95% CI = 0.37-0.77). We then show the value of this approach by using the imputed data to investigate the impact of the G84E mutation on age-specific prostate cancer risk and on risk of fourteen other cancers in the cohort. The age-specific risk of prostate cancer among G84E mutation carriers was higher than among non-carriers, and this difference increased with age. Risk estimates from Kaplan-Meier curves were 36.7% versus 13.6% by age 72, and 64.2% versus 24.2% by age 80, for G84E mutation carriers and non-carriers, respectively (p = 3.4×10-12). The G84E mutation was also suggestively associated with an increase in risk for the following cancer sites by approximately 50% in a pleiotropic manner: breast, non-Hodgkin’s lymphoma, kidney, bladder, melanoma, endometrium, and pancreas (p = 0.042).
Authors: Hoffmann TJ; Sakoda LC; Habel LA; Asgari MM; Corley D; Kushi LH; Quesenberry CP; Schaefer C; Van Den Eeden SK; Risch N; Witte JS; et al.
PLoS Genet. 2015 Jan;11(1):e1004930. Epub 2015-01-28.
Risk of Cardiovascular Disease Associated With a Restless Legs Syndrome Diagnosis in a Retrospective Cohort Study from Kaiser Permanente Northern California
Recent cross-sectional studies suggest that restless legs syndrome (RLS) may be associated with an increased prevalence of cardiovascular disease (CVD) comorbidity or risk factors. We evaluated whether primary or secondary RLS was associated with an increased risk of incident cardiovascular disease in a retrospective cohort study within Kaiser Permanente Northern California (KPNC). We identified members of KPNC with primary RLS and secondary RLS between 1999 and 2008 by an algorithm that incorporated longitudinal clinical records related to the diagnosis and treatment of RLS and comorbidities. We then matched each RLS case with up to 50 individuals with no clinical records of RLS by age, sex, race/ethnicity, zip code, and membership duration. For the analyses we excluded any individual with coronary artery disease (CAD: angina, acute myocardial infarction, coronary revascularization procedure, CAD death), CVD (CAD plus stroke), and hypertension at baseline. New cardiovascular events were determined from clinical records. Follow-up ended at an outcome event, disenrollment from KPNC, or death, whichever occurred earliest. There were over 473,358 person-y of follow-up in this cohort analysis with a mean follow-up time of 3.91 y and range from 6 mo to 12 y. Survival analysis techniques, including survival curves and proportional hazard regression models, were used to assess the association between RLS status and CVD. There were 7,621 primary RLS and 4,507 secondary RLS cases identified and included in the study. In general, primary RLS cases were younger and had less comorbidity than secondary RLS cases. During the follow-up period, CVD was diagnosed in 478 primary RLS cohort members, CAD was diagnosed in 310, and hypertension events were identified in 1,466. Diagnosis in secondary RLS cohort members was made during the follow-up period with 451, 338, and 598 CVD, CAD, and hypertension events, respectively. Subjects with primary RLS had a similar risk of incident CVD (hazard ratio (HR) = 0.95; 95% confidence interval (CI) = 0.86-1.04) and CAD (HR = 0.99; 95% CI = 0.89-1.13) to the comparison cohort, with a slight elevation in the risk of hypertension events (HR = 1.19; 95% CI = 1.12-1.25), after multivariable adjustment. Individuals classified as secondary RLS had a significant increased risk of CVD (HR = 1.33; 95% CI = 1.21-1.46), CAD (HR = 1.40; 95% CI = 1.25-1.56), and hypertension (HR = 1.28; 95% CI = 1.18-1.40). Primary restless legs syndrome (RLS) was not associated with new-onset cardiovascular disease (CVD) or coronary artery disease (CAD) but was associated with a slight increased risk of hypertension. In contrast, secondary RLS was associated with an increased risk of CVD, CAD, and hypertension.
Authors: Van Den Eeden SK; Albers KB; Davidson JE; Kushida CA; Leimpeter AD; Nelson LM; Popat R; Tanner CM; Bibeau K; Quesenberry CP
Sleep. 2015;38(7):1009-15. Epub 2015-07-01.
Risk factors for sun exposure during spring break among college students
In order to look at college students’ behavioral practices prior to a sunny vacation (during spring break) along with their beliefs and attitudes, we recruited sororities and fraternities in the Midwestern USA to complete a self-administered questionnaire. Sorority and fraternity students were expected to have high UVR exposure due to a strong desire to tan. The questionnaire included information on sun exposure during spring break, sun-sensitivity, and tanning attitudes and behaviors. Analyses examined associations between potential risk factors for spending 16 or more hours in the sun during spring break using logistic regression while controlling for the clustering effects of sororities and fraternities. Students who tanned mildly were 1.6 times more likely than those with moderate or deep tans to spend 16+ hours in the sun during spring break, suggesting a strong desire to tan. Students who spent 16+ hours in the sun during spring break were more likely to have frequented tanning beds (odds ratio of 2.4 for 11+ times vs. =5 times) and to have used self-tanning creams (odds ratio of 2.9) between New Years and spring break. These data provide evidence that use of artificial tanning devices and self-tanning creams or sprays among college students are related to increased intermittent sun exposure (during a spring break vacation) rather than reduced exposure. Mistaken beliefs regarding a base tan as potentially beneficial need to be addressed by excellent science examining the base tan theory and translated to the public. Replacement of tanning bed use with safer sunless tanning creams may reduce some of the harmful UVR exposures. Education alone will not be sufficient to change sun seeking behavior as was seen here and in other studies.
Authors: Langston M, Lashway S, Dennis L.
In: Sun Exposure: Risk Factors, Protection Practices and Health Effects. 2015. 93-114p
Sun sensitivity and sunburns as related to cutaneous melanoma among populations of Spanish descent: a meta-analysis.
Few studies have examined sun sensitivity risk factors for cutaneous melanoma specifically in populations of Spanish descent. Previous searches were conducted in PUBMED for articles on melanoma and sun exposure through 2008. Over 300 articles were reviewed and relevant data was abstracted. These abstract forms were subsequently reviewed for studies in populations of Spanish descent. PUBMED was then examined for more recent studies of melanoma in populations of Spanish descent. Eight appropriate articles were found, which comprised 7 discrete studies. We conducted a meta-analysis of these seven studies analyzing Fitzpatrick skin type, skin color and history of sunburns. The risk of melanoma was increased for fair vs. dark skin color (OR = 2.9, 95% CI 2.0-4.1) and for skin type I & II vs. II I& IV (OR = 3.5, 95% CI of 2.0-6.1). However, when skin type was examined as an ordered categorical factor in a linear dose-response analysis, a 12-fold difference was seen between skin type I and IV. Any history of sunburn in childhood and lifetime were also associated with melanoma with ORs of 5.6 and 4.0, respectively. The magnitudes of associations seen in this population were much higher than seen in previous meta-analyses of all studies of melanoma. These results provide some evidence of discrepancies of reporting skin color in heterogeneous populations including those of Spanish descent. Future studies should provide a more accurate measure of self-reported skin color in these populations.
Authors: Dennis LK, Lashway SG, Langston ME
J Dermatol Res Ther 2015, 1:2
Treatment patterns for ductal carcinoma in situ from 2000-2010 across six integrated health plans
Considerable debate exists about the optimal treatment of ductal carcinoma in situ (DCIS). Using electronic data sources, we examined first course treatment patterns among women aged 18 years and older diagnosed with DCIS between 2000-2010 from six Kaiser Permanente (KP) regions. We calculated the proportion of patients receiving breast conserving surgery (BCS), BCS plus radiation therapy, unilateral mastectomy, bilateral mastectomy, and hormone therapy. Multinomial logistic regression was used to assess the association between patient characteristics and treatment. We included 9,437 women: 1,086 (11.5%) African-American; 1,455 (15.4%) Asian; 918 (9.7%) Hispanic; and 5,978 (63.3%) non-Hispanic white. Most cases (42.2%) received BCS plus radiation as their initial treatment. Nearly equal numbers of women received BCS without radiation (28.5%) or unilateral mastectomy (24.6%). Use of bilateral mastectomy was uncommon (4.7%), and most women (72.2%) did not receive hormone therapy has part of their first course treatment. We observed statistically significant differences in treatment patterns for DCIS by KP region and patient age. Predictably, nuclear grade and the presence of comorbidities were associated with first course treatment for DCIS. We observed statistically significant increases in BCS plus radiation therapy and bilateral mastectomy over time. Although still uncommon, the frequency of bilateral mastectomy increased from 2.7% in 2000 to 7.0% in 2010. We also observed differences in treatment by race/ethnicity. Our findings help illustrate the complex nature of DCIS treatment in the United States, and highlight the need for evidence based guidelines for DCIS care.
Authors: Feigelson HS; Carroll NM; Weinmann S; Haque R; Yu CL; Butler MG; Waitzfelder B; Wrenn MG; Capra A; McGlynn EA; Habel LA
Springerplus. 2015;4:24. Epub 2015-01-17.
Preliminary Development and Evaluation of an Algorithm to Identify Breast Cancer Chemotherapy Toxicities Using Electronic Medical Records and Administrative Data
Breast cancer chemotherapy toxicity is not well documented outside of randomized trials. We developed and conducted preliminary evaluation of an algorithm to detect grade 3 and 4 toxicities using electronic data from a large integrated managed care organization. The algorithm used administrative, pharmacy, and electronic data from outpatient, emergency room, and inpatient records of 99 women diagnosed with breast cancer from 2006 to 2009 who underwent chemotherapy. Data were abstracted for 12 months post-treatment initiation (24 months for trastuzumab recipients). An oncology nurse independently blindly reviewed records; these results were the “gold standard.” Sensitivity and specificity were calculated for overall toxicity, categories of toxicities, and toxicity by age or regimen. The algorithm was applied to an independent sample of 1,575 patients with breast cancer diagnosed during the study period to estimate prevalence rates. The overall sensitivity for detecting chemotherapy-related toxicity was 89% (95% CI, 77% to 95%). The highest sensitivity was for identification of hematologic toxicities (97%; 95% CI, 84% to 99%). There were good sensitivities for infectious toxicity, but rates dropped for GI and neurological toxicities. Specificity was high within each category (89% to 99%), but when combined to measure any toxicity, it was lower (70%; 95% CI, 57% to 81%). When applied to an independent chemotherapy sample, the algorithm estimates a 26% rate of hematologic toxicity; rates were higher among patients age ≥ 65 years versus less than 65 years. If validated in other samples and health care settings, algorithms to capture toxicity could be useful in comparative and cost-effectiveness evaluations of community practice-delivered treatment.
Authors: Mandelblatt JS; Kushi L; et al.
J Oncol Pract. 2015 Jan;11(1):e1-8. Epub 2014-08-26.
Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer
Authors: Kwan ML; Quesenberry CP; Caan BJ
J Natl Cancer Inst. 2015 Jan;108(1). Epub 2015-11-11.
Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947-2009)
Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER), which are the oldest, extend back only to the 1970s. To extend scant knowledge about the feasibility of obtaining long-term data on tumor biomarkers, we randomly selected 60 breast cancer cases (10 per decade) diagnosed between 1947-2009 among women members of the Kaiser Permanente Northern California health plan to obtain and analyze their formalin-fixed paraffin-embedded (FFPE) tumor specimens. For each tumor specimen, we created duplicate tissue microarrays for analysis. We located tumor blocks and pathology reports for 50 of the 60 cases (83%), from which we randomly sampled 5 cases per decade for biomarker analysis (n = 30). All 30 cases displayed excellent morphology and exhibited biomarkers compatible with histologic type and grade. Test-retest reliability was also excellent: 100% for ER; 97% for human epidermal growth factor receptor 2 and epidermal growth factor receptor; 93% for progesterone receptor and cytokeratin 5/6; and 90% for Ki67 and molecular phenotype; the kappa statistic was excellent (>0.9) for 4 of the 7 biomarkers, strong (0.6-0.8) for 2, and fair for only 1 (owing to low prevalence). These results indicate immunostaining for biomarkers commonly used to evaluate breast cancer biology and assign surrogate molecular phenotypes can reliably be employed on archival FFPE specimens up to 60 years old.
Authors: Krieger N; Habel LA; Waterman PD; Shabani M; Ellison-Loschmann L; Achacoso NS; Acton L; Schnitt SJ
NPJ Breast Cancer. 2015;1. Epub 2015-10-07.
Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma
Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear. Using the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n?=?97) and those with an adenoma (n?=?97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study. The concentrations of interleukin-10 (IL-10), IL-1?, IL-6, IL-17A, IL-2, IL-4, IL-7, IL-12(p70), interferon-? (IFN-?), macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-?), vascular endothelial growth factor (VEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1? (MIP-1?) were determined. Multiple logistic regression analyses were used to evaluate the association between adenoma prevalence and cytokine levels. The presence of colorectal adenomas was not associated with significant increases in the systemic levels of proinflammatory (TNF-?, IL-6, IL-1?) or T-cell polarizing (IL-12, IL-2, IL-10, IL-4, IL-17, IFN-?) cytokines. Furthermore, MCP-1 and RANTES levels were equivalent in the serum of study participants with and without adenomas. These findings suggest colorectal adenoma prevalence may not be associated with significant alterations in systemic inflammation.
Authors: Henry CJ; Sedjo RL; Rozhok A; Salstrom J; Ahnen D; Levin TR; D'Agostino R; Haffner S; DeGregori J; Byers T
BMC Cancer. 2015;15:123. Epub 2015-03-14.
Association of high obesity with PAM50 breast cancer intrinsic subtypes and gene expression
Invasive breast cancers are now commonly classified using gene expression into biologically and clinically distinct tumor subtypes. However, the role of obesity in breast tumor gene expression and intrinsic subtype is unknown. Early-stage breast cancer (BC) patients (n?=?1,676) were sampled from two prospective cohorts. The PAM50 qRT-PCR assay was used to: a) assess tumor gene expression levels for ESR1, PGR, ERBB2, and 10 proliferation genes and b) classify tumors into intrinsic subtype (Luminal A, Luminal B, Basal-like, HER2-enriched, Normal-like). Body mass index (BMI) around BC diagnosis (kg/m(2)) was categorized as: underweight (<18.5), normal (18.5-24), overweight (25-29), mildly obese (30-34), and highly obese (?35). In a cross-sectional analysis, we evaluated associations of BMI with gene expression using linear regression models, and associations of BMI with non-Luminal A intrinsic subtypes, compared with Luminal A subtype, using multinomial logistic regression. Statistical significance tests were two-sided. Highly obese women had tumors with higher expression of proliferation genes compared with normal weight women (adjusted mean difference?=?0.44; 95% CI: 0.18, 0.71), yet mildly obese (adjusted mean difference?=?0.16; 95% CI: -0.06, 0.38) and overweight (adjusted mean difference?=?0.18; 95% CI: -0.01, 0.36) women did not. This association was stronger in postmenopausal women (p for interaction?=?0.06). Being highly obese, however, was inversely associated with ESR1 expression (adjusted mean difference?=?-0.95; 95% CI: -1.47, -0.42) compared with being normal weight, whereas being mildly obese and overweight were not. In addition, women with Basal-like and Luminal B subtypes, relative to those with Luminal A subtype, were more likely to be highly obese, compared with normal-weight. ER expression may not increase correspondingly with increasing degree of obesity. Highly obese patients are more likely to have tumor subtypes associated with high proliferation and poorer prognosis.
Authors: Kwan ML; Kroenke CH; Kushi LH; Quesenberry CP; Habel LA; Caan BJ; et al.
BMC Cancer. 2015;15:278. Epub 2015-04-14.
Alcohol Intake, Beverage Choice, and Cancer: A Cohort Study in a Large Kaiser Permanente Population
The authors studied incident cancer risk from 1978 to 1985 and through follow-up in 2012 relative to light-to-moderate and heavy drinking and to the choice of alcoholic beverage in a cohort of 124,193 persons. With lifelong abstainers as referent, heavy drinking (? 3 drinks per day) was associated with increased risk of 5 cancer types: upper airway/digestive tract, lung, female breast, colorectal, and melanoma, with light-to-moderate drinking related to all but lung cancer.
Authors: Klatsky AL; Li Y; Nicole Tran H; Baer D; Udaltsova N; Armstrong MA; Friedman GD
Perm J. 2015 Spring;19(2):28-34. Epub 2015-03-01.
Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies
Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and colorectal cancer has been inconsistently reported. We used pooled individual-level data from the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. From 11 studies, 8,290 colorectal cancer cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of colorectal cancer compared with the lowest quartile [OR, 1.41; 95% confidence interval (CI), 1.29-1.55]. However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with colorectal cancer in those with a rapid/intermediate NAT2 genotype (OR, 1.38; 95% CI, 1.20-1.59) as with a slow genotype (OR, 1.43; 95% CI, 1.28-1.61; P interaction = 0.9). We found that high red meat intake was associated with increased risk of colorectal cancer only from retrospective case-control studies and not modified by NAT2 enzyme activity. Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer.
Authors: Ananthakrishnan AN; Caan BJ; Chan AT; et al.
Cancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):198-205. Epub 2014-10-23.
Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett’s Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium
The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett’s oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.
Authors: Lagergren K; Corley DA; Lagergren J; et al.
PLoS ONE. 2015;10(9):e0138738. Epub 2015-09-25.
Longitudinal study of body mass index in Asian men who immigrate to the US
Cross-sectional studies indicate that adaptation to Western norms, especially at a younger age, might explain the higher average body mass index (BMI) among Asians living in the United States (US) compared to Asians living in Asia. However, migrants differ from non-migrants in sociocultural factors that are difficult to measure and, thus, longitudinal studies on the same individuals prior to and after immigration are needed. The objective of this study was to determine differences in changes in BMI across age by residence (US or Asia) and age at immigration using longitudinal data on BMI prior to and after immigration. The California Men’s Health Study includes 1,549 foreign-born Asian men who were aged 44-71 at baseline in 2002-03. BMI at ages 30, 40, 50 and 60 was calculated using self-reported weight history and current height. Residence at each age decade and age at immigration were determined. Data were analyzed using generalized estimating equations. Ten-year BMI increases were smaller among Asians who lived in Asia prior to migrating to the US compared to those who already lived in the US. This effect was most evident be-tween ages 30-40 when Asians in Asia had a 0.69 kg/m2 (95% CI: -1.08, -0.30) smaller increase in BMI. Immigrants who moved to the US before age 40 experienced greater increases in BMI than immigrants who moved to the US at an older age. This study is the first to support the hypothesis that living in the US and younger age at immigration results in larger BMI increases in Asian men. Abstract available from the publisher.
Authors: Oakkar EE; Stevens J; Bradshaw PT; Cai J; Perreira KM; Popkin BM; Gordon-Larsen P; Young DR; Ghai NR; Caan B; Quinn VP
Asia Pac J Clin Nutr. 2015;24(4):701-9.
Oral Bisphosphonate Exposure and the Risk of Upper Gastrointestinal Cancers
The association between oral bisphosphonate use and upper gastrointestinal cancer has been controversial. Therefore, we examined the association with esophageal and gastric cancer within the Kaiser Permanente, Northern California population. A total of 1,011 cases of esophageal (squamous cell carcinoma and adenocarcinoma) and 1,923 cases of gastric adenocarcinoma (cardia, non-cardia and other) diagnosed between 1997 and 2011 from the Kaiser Permanente, Northern California cancer registry were matched to 49,886 and 93,747 controls, respectively. Oral bisphosphonate prescription fills at least one year prior to the index date were extracted. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between prospectively evaluated oral bisphosphonate use with incident esophageal and gastric cancer diagnoses with adjustment for potential confounders. After adjustment for potential confounders, no significant associations were found for esophageal squamous cell carcinoma (OR 0.88; 95% CI: 0.51, 1.52), esophageal adenocarcinoma (OR 0.68; 95% CI: 0.37, 1.24), or gastric non-cardia adenocarcinoma (OR 0.83, 95% CI: 0.59, 1.18), but we observed an adverse association with gastric cardia adenocarcinoma (OR 1.64; 95% CI: 1.07, 2.50). In conclusion, we observed no association between oral bisphosphonate use and esophageal cancer risk within a large community-based population. A significant association was detected with gastric cardia and other adenocarcinoma risk, although this needs to be replicated.
Authors: Vogtmann E; Corley DA; Almers LM; Cardwell CR; Murray LJ; Abnet CC
PLoS ONE. 2015;10(10):e0140180. Epub 2015-10-07.
Representativeness of breast cancer cases in an integrated health care delivery system
Integrated health care delivery systems, with their comprehensive and integrated electronic medical records (EMR), are well-poised to conduct research that leverages the detailed clinical data within the EMRs. However, information regarding the representativeness of these clinical populations is limited, and thus the generalizability of research findings is uncertain. Using data from the population-based California Cancer Registry, we compared age-adjusted distributions of patient and neighborhood characteristics for three groups of breast cancer patients: 1) those diagnosed within Kaiser Permanente Northern California (KPNC), 2) non-KPNC patients from NCI-designated cancer centers, and 3) those from all other hospitals. KPNC patients represented 32 % (N = 36,109); cancer center patients represented 7 % (N = 7805); and all other hospitals represented 61 % (N = 68,330) of the total breast cancer patients from this geographic area during 1996-2009. Compared with cases from all other hospitals, KPNC had slightly fewer non-Hispanic Whites (70.6 % versus 74.4 %) but more Blacks (8.1 % versus 5.0 %), slightly more patients in the 50-69 age range and fewer in the younger and older age groups, a slightly lower proportion of in situ but higher proportion of stage I disease (41.6 % versus 38.9 %), were slightly less likely to reside in the lowest (4.2 % versus 6.5 %) and highest (36.2 % versus 39.0 %) socioeconomic status neighborhoods, and more likely to live in suburban metropolitan areas and neighborhoods with more racial/ethnic minorities. Cancer center patients differed substantially from patients from KPNC and all other hospitals on all characteristics assessed. All differences were statistically significant (p
Authors: Gomez SL; Shariff-Marco S; Von Behren J; Kwan ML; Kroenke CH; Keegan TH; Reynolds P; Kushi LH
BMC Cancer. 2015;15:688. Epub 2015-10-14.
Progression and treatment of incident lower urinary tract symptoms among men in the California Men’s Health Study
To characterise the progression and treatment of lower urinary tract symptoms (LUTS) among men aged 45-69 years in the California Men’s Health Study. A total of 39,222 men, aged 45-69 years, enrolled in the Southern California Kaiser Permanente Health Plan were surveyed in 2002-2003 and again in 2006-2007. Those men who completed both surveys who did not have a diagnosis of benign prostatic hyperplasia (BPH) and were not on medication for LUTS at baseline were included in the study (N = 19,505). Among the men with no or mild symptoms at baseline, the incidence of moderate/severe LUTS (American Urological Association Symptom Index [AUASI] score ?8) and odds of progression to severe LUTS (AUASI score ?20) was estimated during 4 years of follow-up. Of the 9640 men who reported no/mild LUTS at baseline, 3993 (41%) reported moderate/severe symptoms at follow-up and experienced a 4-point change in AUASI score on average. Of these men, 351 (8.8%) had received a pharmacological treatment, eight (0.2%) had undergone a minimally invasive or surgical procedure and 3634 (91.0%) had no treatment recorded. Men who progressed to severe symptoms (AUASI score ?20; n = 165) were more likely to be on medication for BPH (odds ratio [OR] 8.09, 95% confidence interval [CI] 5.77-11.35), have a BPH diagnosis (OR 4.74, 95% CI 3.40-6.61) or have seen a urologist (OR 2.49, 95% CI 1.81-3.43) when compared with men who did not progress to severe symptoms (AUASI score <20). These data show that the majority of men who experienced progression did not have pharmacological or surgical therapy for their symptoms and, therefore, may prove to be good candidates for a self-management plan.
Authors: Wallner LP; Slezak JM; Loo RK; Quinn VP; Van Den Eeden SK; Jacobsen SJ
BJU Int. 2015 Jan;115(1):127-33. Epub 2014-08-16.
Chronic Kidney Disease and Risk of Renal Cell Carcinoma: Differences by Race
The incidence of renal cell carcinoma in the United States differs by race/ethnicity. To better understand these disparities, we conducted a nested case-control study investigating renal cell carcinoma risk factors across racial/ethnic groups within the Kaiser Permanente Northern California health care network. Our study included 3136 renal cell carcinoma cases (2152 whites, 293 blacks, 425 Hispanics, and 255 Asians) diagnosed between 1998 and 2008 and 31031 individually matched controls (21478 whites, 2836 blacks, 4147 Hispanics, and 2484 Asians). Risk of renal cell carcinoma was assessed in relation to smoking status, body mass index (BMI), hypertension, and chronic kidney disease. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, and population attributable risk (PAR) to estimate by race the proportion of cases attributable to hypertension and chronic kidney disease. The association between chronic kidney disease and renal cell carcinoma differed markedly by race (Pinteraction < 0.001), with associations observed among blacks (OR = 10.4 [95% CI = 6.0-17.9]), Asians (5.1 [2.2-11.7]), and Hispanics (2.3 [1.1-4.6]) but not whites (1.1 [0.6-1.9]). Hypertension, high BMI, and smoking were associated with renal cell carcinoma, but findings generally did not differ by race. Relative to other racial/ethnic groups, blacks had the highest proportion of renal cell carcinoma incidence attributable to hypertension and chronic kidney disease (combined, PAR = 37%; hypertension only, PAR = 27%; chronic kidney disease, PAR = 10%). Our findings suggest that hypertension and chronic kidney disease likely have contributed to the observed excess in renal cell carcinoma incidence among blacks compared with whites.
Authors: Hofmann JN; Corley DA; Zhao WK; Colt JS; Shuch B; Chow WH; Purdue MP
Epidemiology. 2015 Jan;26(1):59-67.
MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium
Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett’s esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P<0.05) of 29 SNPs with EA risk, and 25 SNPs with BE risk, were observed. None remained significant after correction for multiple comparisons (FDR q>0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.
Authors: Buas MF; Shaheen NJ; Vaughan TL; et al.
PLoS ONE. 2015;10(6):e0128617. Epub 2015-06-03.
Imputation and subset based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
Authors: Wang Z; Van Den Eeden SK; Amundadottir LT; et al.
Hum Mol Genet. 2014 Dec 15;23(24):6616-33. Epub 2014-07-15.
Genome-wide association and admixture analysis of glaucoma in the Women’s Health Initiative
We report a genome-wide association study (GWAS) and admixture analysis of glaucoma in 12 008 African-American and Hispanic women (age 50-79 years) from the Women’s Health Initiative (WHI). Although GWAS of glaucoma have been conducted on several populations, this is the first to look at glaucoma in individuals of African-American and Hispanic race/ethnicity. Prevalent and incident glaucoma was determined by self-report from study questionnaires administered at baseline (1993-1998) and annually through 2005. For African Americans, there was a total of 658 prevalent cases, 1062 incident cases and 6067 individuals who never progressed to glaucoma. For our replication cohort, we used the WHI Hispanics, including 153 prevalent cases, 336 incident cases and 2685 non-cases. We found an association of African ancestry with glaucoma incidence in African Americans (hazards ratio 1.62, 95% CI 1.023-2.56, P = 0.038) and in Hispanics (hazards ratio 3.21, 95% CI 1.32-7.80, P = 0.011). Although we found that no previously identified glaucoma SNPs replicated in either the WHI African Americans or Hispanics, a risk score combining all previously reported hits was significant in African-American prevalent cases (P = 0.0046), and was in the expected direction in the incident cases, as well as in the Hispanic incident cases. Additionally, after imputing to 1000 Genomes, two less common independent SNPs were suggestive in African Americans, but had too low of an allele frequency in Hispanics to test for replication. These results suggest the possibility of a distinct genetic architecture underlying glaucoma in individuals of African ancestry.
Authors: Hoffmann TJ; Tang H; Thornton TA; Caan B; Haan M; Millen AE; Thomas F; Risch N
Hum Mol Genet. 2014 Dec 15;23(24):6634-43. Epub 2014-07-15.
Younger pubertal age is associated with allergy and other atopic conditions in girls
Early menarche is linked to higher incidence of adult asthma, suggesting that earlier puberty may influence type 2 immune response characteristics of allergic diseases. We examined the hypothesis that timing of breast and pubic hair development, which precede menarche, is associated with increased childhood atopic conditions. Girls were enrolled at 6-8 yr of age (2004-2007) in the Breast Cancer and the Environment Research Program Puberty Study and were followed through 2011. Pubertal stages were assessed and atopic conditions were queried annually. Associations of age at pubertal stage 2 for breast or pubic hair development with atopic conditions were assessed using prevalence ratios (PR) or odds ratios (OR) and 95% confidence intervals (CI) from log-binomial regression and generalized estimating equation models, controlling for body mass index and other covariates. A total of 1055 girls with medical and pubertal stage data were included. Asthma (ever vs. never) was associated with younger pubarche (?10 vs. >10 yr, PR = 1.15, CI: 1.04-1.28 adjusted for race/ethnicity and site; PR = 1.13, CI: 1.01-1.25 further adjusted for BMI), but not thelarche. In longitudinal models, risk of developing allergies increased with younger age at pubarche (adjusted OR = 1.60, CI: 1.10-2.34; ?10 vs. >10 yr). Risks were highest among black girls with earlier pubarche (n = 248/326); for allergies, their fully adjusted OR was 2.35, CI: 1.06-5.19 for pubarche ?10 vs. >10 yr. Atopic conditions during childhood are associated with younger age at pubarche, independent of obesity, and these relationships may vary by racial/ethnic groups.
Authors: Hong CC; Pajak A; Teitelbaum SL; Vangeepuram N; Galvez M; Pinney SM; Windham G; Kushi LH; Biro FM; Wolff MS; Breast Cancer and Environment Research Program
Pediatr Allergy Immunol. 2014 Dec;25(8):773-80. Epub 2014-12-29.
Outcomes from ultrasound follow-up of small complex adnexal masses in women over 50
The discovery of a complex adnexal mass in an older woman often raises concern for cancer. We evaluate outcomes for a large population-based cohort of women older than age 50 years with a small complex adnexal mass reported on ultrasound, without elevated CA125 or other evidence of malignancy, including time to detection of malignancy and stage at diagnosis for those initially observed. Women older than age 50 years who had an ultrasound during 2007-2011 reporting a complex adnexal mass 1-6 cm in size were identified. Previous or subsequent pelvic ultrasounds were reviewed to determine when the mass was first identified and whether there was change over time. Women with concurrent elevated CA125, evidence of metastatic disease, or less than 24 months of clinical follow-up were excluded. Surgical pathology from removal and diagnoses of ovarian cancer within 24 months of follow-up were identified. Among 1363 complex masses identified, 18 cancers or borderline tumors (1.3%; 95% confidence interval, 0.8-2.1%) were found. Six cases were diagnosed among 204 women who had immediate surgery after initial ultrasound (15%), and 12 additional cases were found among 994 women with at least 1 repeat ultrasound (73%). Growth was apparent on ultrasound by 7 months for all borderline and epithelial ovarian cancers. Of the 12 cases diagnosed during follow-up, 10 were found to be stage 1 at surgery. Among isolated adnexal masses reported as complex and 1-6 cm on pelvic ultrasound in women older than 50 years, the overall risk of malignancy is low. All cases of epithelial cancer and borderline tumor demonstrated growth by 7 months of observation.
Authors: Suh-Burgmann E; Hung YY; Kinney W
Am J Obstet Gynecol. 2014 Dec;211(6):623.e1-7. Epub 2014-07-25.
Integrative post-genome-wide association analysis of CDKN2A and TP53 SNPs and risk of esophageal adenocarcinoma
Incidence of esophageal adenocarcinoma (EA) in Western countries has increased markedly in recent decades. Although several risk factors have been identified for EA and its precursor, Barrett’s esophagus (BE), including reflux, Caucasian race, male gender, obesity, and smoking, less is known about the role of inherited genetic variation. Frequent somatic mutations in the tumor suppressor genes CDKN2A and TP53 were recently reported in EA tumors, while somatic alterations at 9p (CDKN2A) and 17p (TP53) have been implicated as predictors of progression from BE to EA. Motivated by these findings, we used data from a genome-wide association study of 2515 EA cases and 3207 controls to analyze 37 germline single nucleotide polymorphisms at the CDKN2A and TP53 loci. Three CDKN2A polymorphisms were nominally associated (P < 0.05) with reduced risk of EA: rs2518720 C>T [intronic, odds ratio 0.90, P = 0.0121, q = 0.3059], rs3088440 G>A (3’UTR, odds ratio 0.84, P = 0.0186, q = 0.3059), and rs4074785 C>T (intronic, odds ratio 0.85, P = 0.0248, q = 0.3059). None of the TP53 single nucleotide polymorphisms reached nominal significance. Two of the CDKN2A variants identified were also associated with reduced risk of progression from BE to EA, when assessed in a prospective cohort of 408 BE patients: rs2518720 (hazard ratio 0.57, P = 0.0095, q = 0.0285) and rs3088440 (hazard ratio 0.34, P = 0.0368, q = 0.0552). In vitro functional studies of rs3088440, a single nucleotide polymorphism located in the seed sequence of a predicted miR-663b binding site, suggested a mechanism whereby the G>A substitution may attenuate miR-663b-mediated repression of the CDKN2A transcript. This study provides the first evidence that germline variation at the CDKN2A locus may influence EA susceptibility.
Authors: Buas MF; Corley DA; Vaughan TL; et al.
Carcinogenesis. 2014 Dec;35(12):2740-7. Epub 2014-10-03.
Cancer Incidence and Mortality during the intervention and post intervention periods of the Women’s Health Initiative Dietary Modification Trial
The Women’s Health Initiative (WHI) low-fat (20% kcal) dietary modification (DM) trial (1993-2005) demonstrated a nonsignificant reduction in breast cancer, a nominally significant reduction in ovarian cancer, and no effect on other cancers (mean 8.3 years intervention). Consent to nonintervention follow-up was 83% (n = 37,858). This analysis was designed to assess postintervention cancer risk in women randomized to the low-fat diet (40%) versus usual diet comparison (60%). Randomized, controlled low-fat diet intervention for prevention of breast and colorectal cancers conducted in 48,835 postmenopausal U.S. women, ages 50 to 79 years at 40 U.S. sites. Outcomes included total invasive cancer, breast cancer, and colorectal cancer, and cancer-specific and overall mortality. There were no intervention effects on invasive breast or colorectal cancer, other cancers, or cancer-specific or overall mortality during the postintervention period or the combined intervention and follow-up periods. For invasive breast cancer, the hazard ratios (HR) and 95% confidence interval (CI) were 0.92 (0.84-1.01) during intervention, 1.08 (0.94-1.24) during the postintervention period, and 0.97 (0.89-1.05) during cumulative follow-up. A reduced risk for estrogen receptor positive/progesterone receptor-negative tumors was demonstrated during follow-up. In women with higher baseline fat intake (quartile), point estimates of breast cancer risk were HR, 0.76 (95% CI, 0.62-0.92) during intervention versus HR, 1.11 (95% CI, 0.84-1.4) during postintervention follow-up (Pdiff = 0.03). Dietary fat intake increased postintervention in intervention women; no long-term reduction in cancer risk or mortality was shown in the WHI DM trial. Dietary advisement to reduce fat for cancer prevention after menopause generally was not supported by the WHI DM trial.
Authors: Thomson CA; Caan BJ; Prentice RL; et al.
Cancer Epidemiol Biomarkers Prev. 2014 Dec;23(12):2924-35. Epub 2014-09-25.
Importance of determining indication for colonoscopy: implications for practice and policy original
Authors: Singal AG; Gupta S; Lee J; Halm EA; Rutter CM; Corley D; Inadomi J
Clin Gastroenterol Hepatol. 2014 Dec;12(12):1958-63.e1-3.
Pre- to post-diagnosis weight change and associations with physical functional limitations in breast cancer survivors
We investigated pre- to post-diagnosis weight change and functional limitations in a cohort of breast cancer survivors. A cohort of 1,841 early-stage breast cancer survivors provided information on pre- and post-diagnosis weight and physical function on average 2 years post-diagnosis. The mean number of limitations for each BMI category and each weight change category were compared using the Wilcoxon test. Cross-sectional associations between weight change, from 1 year prior to diagnosis to 2 years post-diagnosis, and functional limitations were determined using logistic regression. Women with BMI???30 kg/m(2) had significantly higher physical limitations compared to women with BMI?
Authors: Young A; Weltzien E; Kwan M; Castillo A; Caan B; Kroenke CH
J Cancer Surviv. 2014 Dec;8(4):539-47. Epub 2014-05-08.
Neighborhood Influences on Girls’ Obesity Risk Across the Transition to Adolescence
The neighborhoods in which children live, play, and eat provide an environmental context that may influence obesity risk and ameliorate or exacerbate health disparities. The current study examines whether neighborhood characteristics predict obesity in a prospective cohort of girls. Participants were 174 girls (aged 8-10 years at baseline), a subset from the Cohort Study of Young Girls’ Nutrition, Environment, and Transitions. Trained observers completed street audits within a 0.25-mile radius around each girl’s residence. Four scales (food and service retail, recreation, walkability, and physical disorder) were created from 40 observed neighborhood features. BMI was calculated from clinically measured height and weight. Obesity was defined as BMI-for-age ? 95%. Logistic regression models using generalized estimating equations were used to examine neighborhood influences on obesity risk over 4 years of follow-up, controlling for race/ethnicity, pubertal status, and baseline BMI. Fully adjusted models also controlled for household income, parent education, and a census tract measure of neighborhood socioeconomic status. A 1-SD increase on the food and service retail scale was associated with a 2.27 (95% confidence interval, 1.42 to 3.61; P < .001) increased odds of being obese. A 1-SD increase in physical disorder was associated with a 2.41 (95% confidence interval, 1.31 to 4.44; P = .005) increased odds of being obese. Other neighborhood scales were not associated with risk for obesity. Neighborhood food and retail environment and physical disorder around a girl's home predict risk for obesity across the transition from late childhood to adolescence.
Authors: Hoyt LT; Kushi LH; Leung CW; Nickleach DC; Adler N; Laraia BA; Hiatt RA; Yen IH
Pediatrics. 2014 Nov;134(5):942-9. Epub 2014-10-13.
Obesity and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: A Mendelian Randomization Study
Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE). However, the relationships may be affected by bias and confounding. We used data from the Barrett’s and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided. The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m(2) increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses. People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses.
Authors: Thrift AP; Corley DA; Whiteman DC; et al.
J Natl Cancer Inst. 2014 Nov;106(11). Epub 2014-09-30.
Characterization and Treatment of Local Recurrence Following Breast Conservation for Ductal Carcinoma In Situ
The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences. We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182). Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09). We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.
Authors: Greenberg CC; Habel LA; Hughes ME; Nekhlyudov L; Achacoso N; Acton L; Schrag D; Jiang W; Edge S; Weeks JC; Punglia RS
Ann Surg Oncol. 2014 Nov;21(12):3766-73. Epub 2014-05-24.
Non-initiation and early discontinuation of adjuvant trastuzumab in women with localized HER2-positive breast cancer
One year of trastuzumab therapy is recommended for women with HER2-positive breast cancer ? 1.0 cm in size to increase survival and is considered for women with tumors 0.5-0.9 cm in size. We analyzed compliance with trastuzumab among women with HER2-positive breast cancer in a prospective cohort study. Of 1145 recruited patients with breast cancer, 152 were HER2-positive (13.2 %), of whom 126 had tumors ? 1.0 cm; 110/126 (87.3 %) of these initiated trastuzumab. Non-receipt was associated with older age, better prognosis tumors, and with non-receipt of adjuvant chemotherapy. Of the 110 who initiated treatment, 18 (15 %) did not complete treatment, 15 (83 %) of them because of cardiotoxicity. Of 20 women with tumors 0.5-0.9 cm, 5 (25 %) initiated trastuzumab. Compliance with trastuzumab was very high among those with HER2-positive breast cancer, as was the completion of the recommended therapy.
Authors: Neugut AI; Hillyer GC; Kushi LH; Lamerato L; Leoce N; Ambrosone CB; Bovbjerg DH; Mandelblatt JS; Hershman DL
Breast Cancer. 2014 Nov;21(6):780-5. Epub 2014-06-06.
Maternal Hyperglycemia During Pregnancy Predicts Adiposity of the Offspring
To investigate associations between maternal pregnancy hyperglycemia, gestational diabetes mellitus (GDM), and offspring adiposity. We evaluated these associations in a longitudinal study of 421 mother-daughter pairs at Kaiser Permanente Northern California. Maternal pregnancy glucose values were obtained from maternal medical records. Outcomes included three measures of girls’ adiposity, measured annually: (1) ?85th age-specific percentile for BMI; (2) percent body fat (%BF); and (3) waist-to-height ratio (WHR). Adjusting for maternal age at delivery, race/ethnicity, pregravid BMI, girl’s age, and girl’s age at onset of puberty, having a mother with GDM increased a girl’s risk of having a BMI ?85th percentile or having %BF or WHR in the highest quartile (Q4), compared with those in the lowest quintile of blood glucose (odds ratio [OR] 3.56 [95% CI 1.28-9.92]; OR 3.13 [95% CI 1.08-9.09]; and OR 2.80 [95% CI 1.00-7.84], respectively). There was a significant interaction between the presence of GDM and pregravid BMI; girls whose mothers had both risk factors had the highest odds of having a BMI ?85th percentile (OR 5.56 [95%CI 1.70-18.2]; Q4 %BF, OR 6.04 [95% CI 1.76-20.7]; and Q4 WHR, OR 3.60 [95% CI 1.35-9.58]). Similar, although weaker, associations were found in the association between hyperglycemia and offspring adiposity. Girls who were exposed to maternal GDM or hyperglycemia in utero are at higher risk of childhood adiposity; risk increases if the mother is overweight or obese. Screening and intervention for this high-risk group is warranted to slow the intergenerational transmission of obesity and its sequelae.
Authors: Kubo A; Ferrara A; Windham GC; Greenspan LC; Deardorff J; Hiatt RA; Quesenberry CP; Laurent C; Mirabedi AS; Kushi LH
Diabetes Care. 2014 Nov;37(11):2996-3002. Epub 2014-08-22.
Assessing bowel preparation quality using the mean number of adenomas per colonoscopy
The quality of the bowel preparation directly influences colonoscopy effectiveness. Quality indicators are widely employed to monitor operator performance and to gauge colonoscopy effectiveness. Some have suggested that the enumeration of the mean number of adenomas per colonoscopy (MNA) may be a more useful measure of bowel preparation quality, but evidence of the utility of this metric is limited. The relationship between bowel preparation quality and MNA was assessed. Records of adult patients, aged 50-74 years, who had undergone a screening colonoscopy in a 6 month period at a hospital-based endoscopy suite in New York City were examined. Excluded were those who were symptomatic or having a colonoscopy for surveillance. Patient and procedural characteristics and clinical findings were abstracted from the endoscopy database. Bowel preparation quality was recorded as excellent, good, fair and poor. Histology and size of polyps removed were gathered from pathology reports. MNA was calculated and incident rate ratios assessing the relationship between bowel preparation quality, MNA, and covariates was calculated using Poisson regression. A total of 2422 colonoscopies were identified; 815 (33.6%) were screening colonoscopies among average risk individuals, 50-74 years; 203 (24.9%) had ?1 adenomas; and 666 (81.7%) had excellent/good preparation quality. Overall MNA was 0.34 [standard deviation (SD) 0.68] and MNA was greater among those >60 years [incident rate ratio (IRR) 1.89, 95% confidence interval (CI) 1.48-2.42), males (IRR 1.60, 95%CI 1.26-2.04) and those with good bowel preparation (IRR 2.54, 95%CI 1.04-6.16). Among those with ?1 adenomas, MNA was 1.48 (SD 1.05) for excellent and 1.00 (SD 0.00) for poor quality preparation (p = 0.55). We found that MNA is sensitive to changes in bowel preparation with higher MNA among those with good bowel preparation compared with those with poor preparation. Our evidence suggests MNA was particularly sensitive when restricted to only those in whom adenomas were seen.
Authors: Hillyer GC; Lebwohl B; Rosenberg RM; Neugut AI; Wolf R; Basch CH; Mata J; Hernandez E; Corley DA; Shea S; Basch CE
Therap Adv Gastroenterol. 2014 Nov;7(6):238-46.
Local food environments are associated with girls’ energy, sugar-sweetened beverage and snack-food intakes
To describe availability and frequency of use of local snack-food outlets and determine whether reported use of these outlets was associated with dietary intakes. Data were cross-sectional. Availability and frequency of use of three types of local snack-food outlets were reported. Daily dietary intakes were based on the average of up to four 24 h dietary recalls. Multivariable linear regression models estimated average daily intakes of energy, sugar-sweetened beverages (SSB) and snack foods/sweets associated with use of outlets. Multi-site, observational cohort study in the USA, 2004-2006. Girls aged 6-8 years (n 1010). Weekly frequency of use of local snack-food outlets increased with number of available types of outlets. Girls with access to only one type of outlet reported consuming food/beverage items less frequently than girls with access to two or three types of outlets (P <0·001). Girls' daily energy, SSB and snack foods/sweets intakes increased with greater use of outlets. Girls who reported using outlets>1 to 3 times/week consumed 0·27 (95 % CI 0·13, 0·40) servings of SSB more daily than girls who reported no use. Girls who reported using outlets>3 times/week consumed 449·61 (95 % CI 134·93, 764·29) kJ, 0·43 (95 % CI 0·29, 0·58) servings of SSB and 0·38 (95 % CI 0·12, 0·65) servings of snack foods/sweets more daily than those who reported no use. Girls’ frequency of use of local snack-food outlets increases with the number of available types of outlets and is associated with greater daily intakes of energy and servings of SSB and snack foods/sweets.
Authors: Deierlein AL; Galvez MP; Yen IH; Pinney SM; Biro FM; Kushi LH; Teitelbaum S; Wolff MS
Public Health Nutr. 2014 Oct;17(10):2194-200. Epub 2014-05-12.
CD8+ Lymphocyte Intratumoral Infiltration as a Stage-Independent Predictor of Merkel Cell Carcinoma Survival: A Population-Based Study
Intratumoral CD8+ lymphocytes (IT-CD8s) have shown promise as a prognostic indicator for Merkel cell carcinoma (MCC). We tested whether IT-CD8s predict survival among a population-based MCC cohort. One hundred thirty-seven MCC cases that had not previously been analyzed for IT-CD8s were studied. Three-year MCC-specific survival rates were 56%, 72%, and 100% for patients with absent (n = 46), low (n = 85), and moderate or strong (n = 6) IT-CD8s, respectively. Increased IT-CD8s were associated with improved MCC-specific survival in a multivariate competing risk-regression analysis including stage, age, and sex (hazard ratio [HR] = 0.5; 95% confidence interval [CI] = 0.3-0.9). Although a similar trend was observed for overall survival, statistical significance was not reached (HR = 0.8; 95% CI = 0.6-1.0), likely because of the high rate of non-MCC deaths among older patients. This study of prospectively captured MCC cases supports the concept that cellular immunity is important in MCC outcome and that CD8+ lymphocyte infiltration adds prognostic information to conventional staging.
Authors: Paulson KG; Iyer JG; Simonson WT; Blom A; Thibodeau RM; Schmidt M; Pietromonaco S; Sokil M; Warton EM; Asgari MM; Nghiem P
Am J Clin Pathol. 2014 Oct;142(4):452-8.
Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer
Authors: Johnson DA; Levin TR; US Multi-Society Task Force on Colorectal Cancer; et al.
Am J Gastroenterol. 2014 Oct;109(10):1528-45. Epub 2014-09-16.
A multi-level model of postmenopausal breast cancer incidence
Breast cancer has a complex etiology that includes genetic, biologic, behavioral, environmental, and social factors. Etiologic factors are frequently studied in isolation with adjustment for confounding, mediating, and moderating effects of other factors. A complex systems model approach may present a more comprehensive picture of the multifactorial etiology of breast cancer. We took a transdisciplinary approach with experts from relevant fields to develop a conceptual model of the etiology of postmenopausal breast cancer. The model incorporated evidence of both the strength of association and the quality of the evidence. We operationalized this conceptual model through a mathematical simulation model with a subset of variables, namely, age, race/ethnicity, age at menarche, age at first birth, age at menopause, obesity, alcohol consumption, income, tobacco use, use of hormone therapy (HT), and BRCA1/2 genotype. In simulating incidence for California in 2000, the separate impact of individual variables was modest, but reduction in HT, increase in the age at menarche, and to a lesser extent reduction in excess BMI >30 kg/m(2) were more substantial. Complex systems models can yield new insights on the etiologic factors involved in postmenopausal breast cancer. Modification of factors at a population level may only modestly affect risk estimates, while still having an important impact on the absolute number of women affected. This novel effort highlighted the complexity of breast cancer etiology, revealed areas of challenge in the methodology of developing complex systems models, and suggested additional areas for further study.
Authors: Hiatt RA; Kushi LH; Rehkopf DH; et al.
Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2078-92. Epub 2014-07-13.
Alcohol and the Risk of Barrett’s Esophagus: A Pooled Analysis from the International BEACON Consortium
Results from studies examining the association between alcohol consumption and the risk of Barrett’s esophagus have been inconsistent. We assessed the risk of Barrett’s esophagus associated with total and beverage-specific alcohol consumption by pooling individual participant data from five case-control studies participating in the international Barrett’s and Esophageal Adenocarcinoma Consortium. For analysis, there were 1,282 population-based controls, 1,418 controls with gastroesophageal reflux disease (GERD), and 1,169 patients with Barrett’s esophagus (cases). We estimated study-specific odds ratios (ORs) and 95% confidence intervals (95% CI) using multivariable logistic regression models adjusted for age, sex, body mass index (BMI), education, smoking status, and GERD symptoms. Summary risk estimates were obtained by random-effects models. We also examined potential effect modification by sex, BMI, GERD symptoms, and cigarette smoking. For comparisons with population-based controls, although there was a borderline statistically significant inverse association between any alcohol consumption and the risk of Barrett’s esophagus (any vs. none, summary OR=0.77, 95% CI=0.60-1.00), risk did not decrease in a dose-response manner (Ptrend=0.72). Among alcohol types, wine was associated with a moderately reduced risk of Barrett’s esophagus (any vs. none, OR=0.71, 95% CI=0.52-0.98); however, there was no consistent dose-response relationship (Ptrend=0.21). We found no association with alcohol consumption when cases were compared with GERD controls. Similar associations were observed across all strata of BMI, GERD symptoms, and cigarette smoking. Consistent with findings for esophageal adenocarcinoma, we found no evidence that alcohol consumption increases the risk of Barrett’s esophagus.
Authors: Thrift AP; Cook MB; Vaughan TL; Anderson LA; Murray LJ; Whiteman DC; Shaheen NJ; Corley DA
Am J Gastroenterol. 2014 Oct;109(10):1586-94. Epub 2014-07-22.
Risk of Esophageal Adenocarcinoma Decreases with Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization
Risks for some cancers increase with height. We investigated the relationship between height and risk of esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE). We analyzed epidemiologic and genome-wide genomic data from individuals of European ancestry in the Barrett’s and Esophageal Adenocarcinoma Consortium, from 999 cases of EAC, 2061 cases of BE, and 2168 population controls. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height and risks of EAC and BE. We performed a Mendelian randomization analysis to estimate an unconfounded effect of height on EAC and BE using a genetic risk score derived from 243 genetic variants associated with height as an instrumental variable. Height was associated inversely with EAC (per 10-cm increase in height: OR, 0.70; 95% CI, 0.62-0.79 for men and OR, 0.57; 95% CI 0.40-0.80 for women) and BE (per 10-cm increase in height: OR, 0.69; 95% CI, 0.62-0.77 for men and OR, 0.61; 95% CI, 0.48-0.77 for women). The risk estimates were consistent across strata of age, education level, smoking, gastroesophageal reflux symptoms, body mass index, and weight. Mendelian randomization analysis yielded results quantitatively similar to those from the conventional epidemiologic analysis. Height is associated inversely with risks of EAC and BE. Results from the Mendelian randomization study showed that the inverse association observed did not result from confounding factors. Mechanistic studies of the effect of height on EAC and BE are warranted; height could have utility in clinical risk stratification.
Authors: Thrift AP; Corley DA; Vaughan TL; et al.
Clin Gastroenterol Hepatol. 2014 Oct;12(10):1667-76.e1. Epub 2014-02-12.
An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk. We selected 15 validated SNPs associated with risk of either Crohn’s disease, ulcerative colitis, or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a two-stage study design. We found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however, the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the effect by mutant p53. The SNP, which lies within intron 1 of the STAT3 gene, was associated with lower expression of STAT3 mRNA in TP53 wild-type, but not mutant, tumors. These data suggest that the STAT3 locus is associated with both IBD and cancer. Further understanding the function of this variant in relation to TP53 could possibly explain the role of this gene in autoimmunity and cancer. Furthermore, an analysis of this locus, specifically in a population with IBD, could help to resolve the relationship between this SNP and cancer.
Authors: Ryan BM; Caan B; Harris CC; et al.
Cancer Epidemiol. 2014 Oct;38(5):583-90. Epub 2014-08-15.
Sebotropic eruption associated with use of oral kava kava supplement
Supplement use is prevalent, and its use is increasing among older adults. Dermatologists need to be aware of the adverse cutaneous effects that can result from herbal supplement use. A 55-year-old man presented with an eruption in a sebotropic distribution after consuming kava kava for 3 weeks, which resolved after discontinuation of the supplement. This case highlights the need for clinicians to consider kava kava in the differential of sebotropic eruptions. The biology, mechanism of action, and potential systemic and cutaneous effects of kava kava are reviewed.
Authors: Huynh JC; Asgari MM; Moore MM
Clin Exp Dermatol. 2014 Oct;39(7):816-8.
Initiation of TNF inhibitor therapy and change in physiologic measures in psoriasis
Psoriasis may predispose to cardiovascular disease and diabetes. However, the role of tumor necrosis factor (TNF) inhibitor in mediating this risk is controversial. To assess this relationship, we estimated change in metabolic physiologic measures before and after initiation of TNF inhibitor therapy compared with methotrexate (MTX) therapy among psoriasis patients. We conducted a retrospective cohort study, 2007-2012, using computerized clinical data for 1274 new users of TNF inhibitor and 979 new users of MTX therapy to compare change in blood pressure, lipids, triglycerides, fasting plasma glucose and body mass index (BMI) before and after start of TNF inhibitors or MTX. The study was restricted to new users. We computed within-person change in each measure, so that each patient served as their own control. In addition, we compared TNF inhibitor patients to MTX patients, by computing the adjusted difference in their group means. In secondary analyses, we examined phototherapy as a comparator. Among starters of TNF inhibitor and MTX therapy, within-person change in physiologic measures at 6 months did not differ significantly. We observed no important or significant changes in any of the physiologic measures with initiation of TNF inhibitor compared with MTX. The same results were found in subgroup analyses focused on men, and on those with hypertension, diabetes mellitus, or obesity. The same results were observed with phototherapy, except that diastolic blood pressure declined by 0.6 mmHg within person during the 6 months after starting phototherapy (P < 0.05). The study provides no evidence for improvement of physiologic measures associated with the metabolic syndrome resulting from TNF inhibitor use for psoriasis.
Authors: Wu JJ; Liu L; Asgari MM; Curtis JR; Harrold L; Salman C; Herrinton LJ
J Eur Acad Dermatol Venereol. 2014 Oct;28(10):1380-7. Epub 2013-11-07.
Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer
Authors: Johnson DA; Levin TR; US Multi-Society Task Force on Colorectal Cancer; et al.
Gastroenterology. 2014 Oct;147(4):903-24.
Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the U.S. Multi-Society Task Force on Colorectal Cancer
Authors: Johnson DA; Levin TR; Rex DK; et al.
Gastrointest Endosc. 2014 Oct;80(4):543-62.
Risk of subsequent cutaneous squamous cell carcinoma in patients with melanoma
Patients with melanoma are at increased risk for cutaneous squamous cell carcinomas (SCCs). We sought to examine the incidence of subsequent SCC among melanoma survivors and the impact of patient and melanoma characteristics on SCC risk. Kaiser Permanente Northern California members given the diagnosis of melanoma from 2000 to 2005 (n = 6378) were followed up through 2009 for a pathology-confirmed SCC. Cox models were used to estimate SCC risk. The crude SCC incidence rate was 2.41 per 100 person-years, and was higher among males and older subjects. In adjusted models stratified by age, SCC risk was higher among males (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.22-1.67), those with history of nonmelanoma skin cancer (HR 2.56, 95% CI 2.19-2.98), and those with higher tumor sequence numbers (HR 1.35, 95% CI 1.01-1.80). SCC risk was lower among non-Hispanic whites (HR 0.39, 95% CI 0.17-0.86). SCC risk was not examined among members without melanoma. SCCs arise in approximately 12% of patients with melanoma over a 5-year period and are more common among males, whites, patients older than 60 years, those with prior reportable cancers, and those with history of nonmelanoma skin cancer. Clinicians should be vigilant for SCCs among these individuals at high risk, and counsel melanoma survivors about their increased risk for SCCs.
Authors: Asgari MM; Warton EM; Quesenberry CP; Koralek DO; Taylor M
J Am Acad Dermatol. 2014 Sep;71(3):521-8. Epub 2014-05-21.
Gene-environment interaction involving recently identified colorectal cancer susceptibility loci
Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer. Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. Data on 9,160 cases and 9,280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, postmenopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons. None of the permutation-adjusted P values reached statistical significance. The associations between recently identified genetic susceptibility loci and colorectal cancer are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors. Results suggest no evidence of strong gene-environment interactions involving the recently identified 16 susceptibility loci for colorectal cancer taken one at a time.
Authors: Kantor ED; Caan BJ; White E; et al.
Cancer Epidemiol Biomarkers Prev. 2014 Sep;23(9):1824-33. Epub 2014-07-03.
Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia
Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixed-effect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35×10(-4) was used to determine statistical significance of the associations. SNP rs7679673, ~6.3kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37×10(-5)] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.
Authors: Setiawan VW; Sakoda LC; Le Marchand L; et al.
Carcinogenesis. 2014 Sep;35(9):2068-73. Epub 2014-05-15.
Guidelines on genetic evaluation and management of Lynch syndrome: A consensus statement by the U.S. Multi-Society Task Force on Colorectal Cancer
Authors: Giardiello FM; Levin TR; American Society for Gastrointestinal Endoscopy; et al.
Gastrointest Endosc. 2014 Aug;80(2):197-220.
Comparing characteristics of melanoma cases arising in health maintenance organizations with state and national registries
Datasets from large health maintenance organizations (HMOs), particularly those with established cancer registries that report to the Surveillance, Epidemiology, and End Results program, are potentially excellent resources for studying melanoma epidemiology and outcomes. However, generalizability of the findings beyond HMO-based populations has not been well studied. We compared melanoma patient, tumor, and treatment characteristics at Kaiser Permanente Northern California and Henry Ford Healthcare Systems with those of corresponding regional, state, and national registry-reported melanoma databases. We identified all melanoma cases diagnosed at Kaiser Permanente Northern California (1996-2009) and Henry Ford Healthcare Systems (1996-2007) and ascertained patient (age, sex, race, and ethnicity), tumor (site, size, laterality, invasiveness, depth, ulceration, subtype, and stage), and treatment (surgery and radiation) variables from health system cancer registries. Registry data were obtained from Surveillance, Epidemiology, and End Results databases for the reporting period ending in November 2011. We found that melanoma cases arising in HMO settings generally have comparable patient, tumor, and treatment characteristics to regional, state, and national cases. An important difference included improved reporting of race information at HMO sites. Melanoma studies using data derived from select HMOs are potentially generalizable to local, state, and national populations, and may be better situated for studying racial-ethnic disparities.
Authors: Asgari MM; Eide MJ; Warton M; Fletcher SW
Melanoma Res. 2014 Aug;24(4):381-7.
Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3,4,5,6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.
Authors: Giardiello FM; Levin TR; Rex DK; et al.
Am J Gastroenterol. 2014 Aug;109(8):1159-79. Epub 2014-07-22.
Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; -6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; provides guidelines for screening at-risk and affected persons with Lynch syndrome; and lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.
Authors: Giardiello FM; Levin TR; Rex DK; et al.
Dis Colon Rectum. 2014 Aug;57(8):1025-48.
Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3-6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.
Authors: Giardiello FM; Levin TR; US Multi-Society Task Force on Colorectal Cancer; et al.
Gastroenterology. 2014 Aug;147(2):502-26.
Dietary predictors of urinary environmental biomarkers in young girls, BCERP, 2004-7
Exposures of children to phthalates, parabens, and bisphenol-A (BPA) are of concern because of their hormonal potential. These agents are found in a wide range of foods and packaging. We investigated whether intake of certain foods predict exposures to these chemicals in young girls. Among 1101 girls (6-8 years at enrollment) from the Breast Cancer and Environment Research Program (BCERP) study, we measured urinary exposure biomarkers for phthalates, parabens, and BPA and assessed dietary intake using 24-h recall 2-4 times. We examined the average daily servings of major and minor food groups categorized as 0 to <0.5, 0.5 to <1 and ? 1 servings per day. Items included dairy, eggs, fats, fish, fruit, single grains, meat, non-poultry meats, pasta, poultry and vegetables. Covariate-adjusted least squares geometric means and 95% confidence intervals of creatinine-corrected phthalate and phenol metabolite concentrations in urine were calculated in relation to food intake. Grains, flour and dry mixes and total fish consumption were positively associated with BPA and the sum of four di-2-ethylhexylphthalate (DEHP) urinary metabolite concentrations. Non-fresh vegetables and poultry were both positively associated with BPA and paraben urinary concentrations. Fats, oils and poultry consumption were positively associated with BPA. Whole-fat dairy consumption was associated with ?DEHP. Some foods may contribute to child exposures to certain chemicals, and this may constitute modifiable means to reduce these environmental exposures.
Authors: Mervish N; Kushi LH; BCERP; et al.
Environ Res. 2014 Aug;133:12-9. Epub 2014-06-03.
Estimating the Heritability of Colorectal Cancer
A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) associated with CRC risk. Although it has been shown that these CRC susceptibility SNPs only explain a small proportion of the genetic risk, it is not clear how much of the heritability these SNPs explain and how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we estimated the heritability of CRC under different scenarios using Genome-Wide Complex Trait Analysis in the Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases and 10 814 controls. We estimated that the heritability explained by known common CRC SNPs identified in GWAS was 0.65% (95% CI:0.3-1%; P = 1.11 × 10-16), whereas the heritability explained by all common SNPs was at least 7.42% (95% CI: 4.71-10.12%; P = 8.13 × 10(-8)), suggesting that many common variants associated with CRC risk remain to be detected. Comparing the heritability explained by the common variants with that from twin and family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In addition, our analysis showed that the gene × smoking interaction explained a significant proportion of the CRC variance (P = 1.26 × 10(-2)). In summary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified.
Authors: Jiao S; Caan BJ; Hsu L; et al.
Hum Mol Genet. 2014 Jul 15;23(14):3898-905. Epub 2014-02-21.
Multitarget stool DNA testing for colorectal-cancer screening.
To the Editor: Imperiale and colleagues evaluate the use of a single-application multitarget stool DNA test for colorectal-cancer screening and compare its performance characteristics with those of the FIT. Two important points warrant further discussion. First, the investigators used a FIT cutoff value of 100 ng of hemoglobin per milliliter of buffer (equivalent to 20 μg of hemoglobin per gram of feces)1 instead of a lower cutoff value; this may explain the decreased sensitivity of FIT (73.8%) for colorectal cancer in their study. Recently, our systematic review and meta-analysis showed that FITs with a cutoff value of less than 20 μg per gram had a sensitivity of 89% and a specificity of 91% for colorectal cancer in an asymptomatic, average-risk population.2 Second, the overall positive rate for the stool DNA test was higher (16.1%) than that of the FIT (7.0%); this was mainly due to the higher false positive rate for the stool DNA test. This finding is an important issue to consider given the unclear screening interval for stool DNA testing and the lack of colonoscopy resources across the world.
Authors: Lee, Jeffrey K JK; Terdiman, Jonathan P JP; Corley, Douglas A DA
The New England journal of medicine. 2014 07 10;371(2):186. Epub --.
Distant Invasive Breast Cancer Recurrence Risk in Human Epidermal Growth Factor Receptor 2-Positive T1a and T1b Node-Negative Localized Breast Cancer Diagnosed From 2000 to 2006: A Cohort From an Integrated Health Care Delivery System
To determine the invasive recurrence (IR) risk among patients with small, node-negative human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Among 16,975 consecutive patients with invasive breast cancer diagnosed from January 1, 2000, to December 31, 2006, in a large, integrated health care system, we identified a cohort of 234 patients with HER2-positive T1aN0M0 or T1bN0M0 (T1abN0M0) disease with a median follow-up of 5.8 years. Kaplan-Meier methods were used to estimate the percentage of patients who were free of invasive recurrence (recurrence-free interval [RFI]) at 5 years for both distant (DRFI) and local (LRFI) recurrences. Of 15 IRs, 47% were locoregional only. Among T1ab patients not treated with adjuvant trastuzumab or chemotherapy (n = 171), the 5-year invasive DRFI was 98.2% (95% CI, 94.5% to 99.4%); it was 99.0% (95% CI, 93.0% to 99.9%) for T1a patients, and 97.0% (95% CI, 88.6% to 99.2%) for T1b patients. Locoregional plus distant 5-year invasive RFI was 97.0% (95% CI, 90.9% to 99.0%) for T1a and 91.9% (95% CI, 81.5% to 96.6%) for T1b patients; it was 89.4% (95% CI, 70.6% to 96.5%) for T1b tumors reported at 1.0 cm. T1b tumors reported at 1.0 cm accounted for 24% of the T1ab cohort, 61% of the cohort total tumor volume, and 75% of distant recurrences. Invasive RFI for T1b 1.0 cm tumors was lower than that for T1a tumors: 84.5% versus 97.4% (P = .009). The distant IR risk of T1a HER2-positive breast cancer appears quite low. The distant IR risk in T1b patients, particularly those with 1.0-cm tumors, is higher. Potential risk differences for T1a and T1b, including the 1.0-cm tumors, should be considered when making treatment decisions.
Authors: Fehrenbacher L; Capra AM; Quesenberry CP; Fulton R; Shiraz P; Habel LA
J Clin Oncol. 2014 Jul 10;32(20):2151-8. Epub 2014-06-02.
The Colorectal Cancer Screening Process in Community Settings: A Conceptual Model for the Population-Based Research Optimizing Screening through Personalized Regimens Consortium
Reducing colorectal cancer mortality by promoting screening has been a national goal for two decades. The NCI’s Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium is the first federal initiative to foster coordinated, transdisciplinary research evaluating the entire cancer screening process in community settings. PROSPR is creating a central data repository to facilitate research evaluating the breast, cervical, and colorectal cancer screening process across different patient populations, provider types, and delivery systems. Data are being collected and organized at the multiple levels in which individuals are nested (e.g., healthcare systems, facilities, providers, and patients). Here, we describe a conceptual model of the colorectal cancer screening process guiding data collection and highlight critical research questions that will be addressed through pooled data. We also describe the three research centers focused on colorectal cancer screening with respect to study populations, practice settings, and screening policies. PROSPR comprehensively elucidates the complex screening process through observational study, and has potential to improve care delivery beyond the healthcare systems studied. Findings will inform intervention designs and policies to optimize colorectal cancer screening delivery and advance the Institute of Medicine’s goals of effective, efficient, coordinated, timely, and safe health care with respect to evidence-based cancer screening.
Authors: Tiro JA; Levin TR; Corley DA; Klabunde C; et al.
Cancer Epidemiol Biomarkers Prev. 2014 Jul;23(7):1147-58. Epub 2014-06-10.
Considering the Value of Dietary Assessment Data in Informing Nutrition-Related Health Policy
Dietary assessment has long been known to be challenged by measurement error. A substantial amount of literature on methods for determining the effects of error on causal inference has accumulated over the past decades. These methods have unrealized potential for improving the validity of data collected for research studies and national nutritional surveillance, primarily through the NHANES. Recently, the validity of dietary data has been called into question. Arguments against using dietary data to assess diet-health relations or to inform the nutrition policy debate are subject to flaws that fall into 2 broad areas: 1) ignorance or misunderstanding of methodologic issues; and 2) faulty logic in drawing inferences. Nine specific issues are identified in these arguments, indicating insufficient grasp of the methods used for assessing diet and designing nutritional epidemiologic studies. These include a narrow operationalization of validity, failure to properly account for sources of error, and large, unsubstantiated jumps to policy implications. Recent attacks on the inadequacy of 24-h recall-derived data from the NHANES are uninformative regarding effects on estimating risk of health outcomes and on inferences to inform the diet-related health policy debate. Despite errors, for many purposes and in many contexts, these dietary data have proven to be useful in addressing important research and policy questions. Similarly, structured instruments, such as the food frequency questionnaire, which is the mainstay of epidemiologic literature, can provide useful data when errors are measured and considered in analyses.
Authors: Hébert JR; Hurley TG; Steck SE; Miller DR; Tabung FK; Peterson KE; Kushi LH; Frongillo EA
Adv Nutr. 2014 Jul;5(4):447-55. Epub 2014-07-14.
Complications of herpes zoster in cancer patients
Cancer patients tend to have a higher incidence of herpes zoster (HZ), but little is known about their risk of HZ complications. We conducted a retrospective study of 424 newly diagnosed hematologic (HM, n = 140) and solid tumor malignancy (STM, n = 284) patients who developed HZ between January 2001 and December 2006 to measure the frequency and identify risk factors of HZ complications. Patients were adult members of Kaiser Permanente Northern California. HZ diagnosis and complications were confirmed by medical chart review. HM patients with HZ tended to have more HZ complications than STM patients (34% vs 23%, p = 0.02), largely due to more frequent non-pain complications. On multivariate analysis, older age and being male were associated with a higher risk of HZ complications in HM patients; more advanced cancer stage was associated with HZ complications in STM patients. HZ complications are frequent and can present extra disease burden in cancer patients who develop HZ.
Authors: Tran TN; Ray GT; Horberg MA; Yawn BP; Castillo AL; Saddier P; Habel LA
Scand J Infect Dis. 2014 Jul;46(7):528-32. Epub 2014-05-05.
Risk of Cardiovascular Disease Among Postmenopausal Women with Prior Pregnancy Loss: The Women’s Health Initiative
Metabolic, hormonal, and hemostatic changes associated with pregnancy loss (stillbirth and miscarriage) may contribute to the development of cardiovascular disease (CVD) in adulthood. This study evaluated prospectively the association between a history of pregnancy loss and CVD in a cohort of postmenopausal women. Postmenopausal women (77,701) were evaluated from 1993-1998. Information on baseline reproductive history, sociodemographic, and CVD risk factors were collected. The associations between 1 or 2 or more miscarriages and 1 or more stillbirths with occurrence of CVD were evaluated using multiple logistic regression. Among 77,701 women in the study sample, 23,538 (30.3%) reported a history of miscarriage; 1,670 (2.2%) reported a history of stillbirth; and 1,673 (2.2%) reported a history of both miscarriage and stillbirth. Multivariable-adjusted odds ratio (OR) for coronary heart disease (CHD) for 1 or more stillbirths was 1.27 (95% CI, 1.07-1.51) compared with no stillbirth; for women with a history of 1 miscarriage, the OR=1.19 (95% CI, 1.08-1.32); and for 2 or more miscarriages the OR=1.18 (95% CI, 1.04-1.34) compared with no miscarriage. For ischemic stroke, the multivariable odds ratio for stillbirths and miscarriages was not significant. Pregnancy loss was associated with CHD but not ischemic stroke. Women with a history of 1 or more stillbirths or 1 or more miscarriages appear to be at increased risk of future CVD and should be considered candidates for closer surveillance and/or early intervention; research is needed into better understanding the pathophysiologic mechanisms behind the increased risk of CVD associated with pregnancy loss.
Authors: Parker DR; Lu B; Sands-Lincoln M; Kroenke CH; Lee CC; O'Sullivan M; Park HL; Parikh N; Schenken RS; Eaton CB
Ann Fam Med. 2014 Jul;12(4):302-9.
Advanced Imaging Among Health Maintenance Organization Enrollees With Cancer
Fee-for-service (FFS) Medicare expenditures for advanced imaging studies (defined as computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET] scans, and nuclear medicine studies [NM]) rapidly increased in the past two decades for patients with cancer. Imaging rates are unknown for patients with cancer, whether under or over age 65 years, in health maintenance organizations (HMOs), where incentives may differ. Incident cases of breast, colorectal, lung, prostate, leukemia, and non-Hodgkin lymphoma (NHL) cancers diagnosed in 2003 and 2006 from four HMOs in the Cancer Research Network were used to determine 2-year overall mean imaging counts and average total imaging costs per HMO enrollee by cancer type for those under and over age 65. There were 44,446 incident cancer patient cases, with a median age of 75 (interquartile range, 71-81), and 454,029 imaging procedures were performed. The mean number of images per patient increased from 7.4 in 2003 to 12.9 in 2006. Rates of imaging were similar across age groups, with the exception of greater use of echocardiograms and NM studies in younger patients with breast cancer and greater use of PET among younger patients with lung cancer. Advanced imaging accounted for approximately 41% of all imaging, or approximately 85% of the $8.7 million in imaging expenditures. Costs were nearly $2,000 per HMO enrollee; costs for younger patients with NHL, leukemia, and lung cancer were nearly $1,000 more in 2003. Rates of advanced imaging appear comparable among FFS and HMO participants of any age with these six cancers.
Authors: Loggers ET; Kushi LH; Ritzwoller DP; et al.
J Oncol Pract. 2014 Jul;10(4):231-8. Epub 2014-05-20.
Association of body mass index and prostate cancer mortality
Inconsistent evidence exists on whether obesity is associated with an increased risk of prostate cancer death post-radical prostatectomy. We examined data from three large health plans to evaluate if an increased body mass index (BMI) at prostate cancer diagnosis is related to prostate cancer mortality This population-based case-control study included 751 men with prostate cancer who underwent radical prostatectomy. Cases were men who died due to prostate cancer (N=323) and matched controls (N=428). We used multivariable logistic regression models to assess the association between BMI at diagnosis and prostate cancer mortality, adjusted for Gleason score, PSA, tumour characteristics, and matching factors. Study subjects were classified into the following BMI (kg/m2) categories: healthy (18.5-24.9), overweight (25-29.9) and obese (?30). Nearly 43% of the participants had a BMI ?25 at diagnosis. A higher fraction of cases (30%) were obese compared to controls (22%). Overall, obese men had more than a 50% increase in prostate cancer mortality (adjusted odds ratio=1.50 [95% CI, 1.03-2.19]) when compared to men with healthy BMI. After stratifying by Gleason score, the odds of mortality generally rose with increasing BMI. The strongest effect was observed in the Gleason score 8+ category (2.37, 95% CI: 1.11-5.09). These associations persisted after adjusting for PSA at diagnosis and other tumour characteristics. These results suggest that BMI at diagnosis is strongly correlated with prostate cancer mortality, and that men with aggressive disease have a markedly greater odds of death if they are overweight or obese.
Authors: Haque R; Van Den Eeden SK; Wallner LP; Richert-Boe K; Kallakury B; Wang R; Weinmann S
Obes Res Clin Pract. 2014 Jul-Aug;8(4):e374-81. Epub 2013-08-06.
Phthalate exposure and pubertal development in a longitudinal study of US girls
Does phthalate exposure during early childhood alter the timing of pubertal development in girls? Urinary concentrations of high-molecular weight phthalate (high-MWP) metabolites are associated with later pubarche. Phthalates are anti-androgenic environmental agents known to alter early development, with possible effects on pubertal onset. This multi-ethnic study included 1239 girls from New York City, greater Cincinnati, and the San Francisco Bay Area who were 6-8 years old at enrollment (2004-2007) and who were followed until 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS Phthalate metabolites were measured in urine collected at enrollment from 1170 girls; concentrations ranged from <1 to >10,000 µg/l. Breast and pubic hair stages and body size were assessed one to two times annually to determine the age at transition from stage 1 to 2 for breast and pubic hair development. Associations between exposures and pubertal ages were estimated using Cox proportional hazard ratios (HR) with 95% confidence intervals (CI) and survival analyses. Associations were examined with respect to age-specific body mass-index percentile, one of the strongest predictors of pubertal onset. Urinary concentrations of high-MWP including di(2-ethylhexyl) phthalate (?DEHP) metabolites were associated with later pubic hair development during 7 years of observation. The relationship was linear and was stronger among normal-weight girls. Among normal-weight girls, age at pubic hair stage 2 (PH2) was 9.5 months older for girls in the fifth compared with the first quintile of urinary ?DEHP (medians: 510 and 59 µg/g creatinine, respectively; adjusted HR 0.70, CI 0.53-0.93, P-trend 0.005. Age at first breast development was older for fifth quintile of mono-benzyl phthalate versus first (HR 0.83, CI 0.68-1.02; P-trend 0.018). No associations were observed between low-molecular weight phthalate urinary metabolite concentrations and age at pubertal transition in adjusted analyses. While there is evidence that phthalate exposures are fairly consistent over time, the exposure measure in this study may not reflect an earlier, more susceptible window of exposure. We investigated alternative explanations that might arise from exposure misclassification or confounding. Phthalates are widespread, hormonally active pollutants that may alter pubertal timing. Whether exposures delay or accelerate pubertal development may depend on age at exposure as well as other factors such as obesity and exposures earlier in life. Whether exposures act independently or as part of real life mixtures may also change their effects on maturation from birth through childhood. This project was supported by the US National Institutes of Health, Environmental Protection Agency, New York State Empire Clinical Research Investigator Program and the Avon Foundation. L.H.K. is employed by Kaiser Permanente. The remaining authors declare they have no actual or potential competing financial interests.
Authors: Wolff MS; Teitelbaum SL; McGovern K; Windham GC; Pinney SM; Galvez M; Calafat AM; Kushi LH; Biro FM; Breast Cancer and Environment Research Program
Hum Reprod. 2014 Jul;29(7):1558-66. Epub 2014-04-29.
Effect of Host, Tumor, Diagnostic, and Treatment Variables on Outcomes in a Large Cohort With Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine-derived skin cancer with high rates of recurrence and associated mortality. Few published studies have used comprehensive patient data and long-term follow-up to examine factors that predict MCC outcomes. To characterize MCC in a large defined-population cohort and analyze predictors of disease recurrence and survival. Retrospective cohort study of 218 patients with MCC from the cancer registry of Kaiser Permanente Northern California, a large integrated health care delivery system. Patients were diagnosed as having MCC and followed up from January 1, 1995, through December 31, 2009. We examined host (age, sex, race, and immunosuppression), tumor (anatomic site, size, and extent), diagnostic (results of imaging and pathologic nodal evaluation), and treatment (surgery, radiation therapy, and chemotherapy) variables for their association with MCC outcomes. Host, tumor, diagnostic, and treatment factors. Recurrence (locoregional and distant) of MCC and patient survival (overall and MCC specific). We estimated adjusted hazard ratios (AHRs) and 95% CIs for outcomes using Cox proportional hazards regression models. After adjustment for host, tumor, diagnostic, and treatment variables, tumor extent (categorized as local, regional, and distant) remained significantly associated with all outcomes. Immunosuppression was associated with higher MCC-specific mortality (AHR, 4.9 [95% CI, 1.7-14.4]), and an unknown primary site was associated with a lower risk for distant metastasis (0.1 [0.0-0.7]) and improved survival (0.4 [0.2-0.9]). Pathological nodal evaluation was associated with a lower risk for metastasis (AHR, 0.2 [95% CI, 0.0-1.0]) and improved survival. Radiation treatment was associated with a decreased risk for locoregional recurrence (AHR, 0.3 [95% CI, 0.1-0.6]), whereas chemotherapy was not associated with any alteration in outcomes. Tumor site and extent, results of pathologic nodal evaluation, and the presence of radiation treatment were associated with MCC recurrence. Immunosuppression, tumor extent, and results of pathologic nodal evaluation were associated with MCC-specific survival, whereas chemotherapy was not associated with any outcomes. Our findings may help to inform diagnostic and therapeutic management of MCCs.
Authors: Asgari MM; Sokil MM; Warton EM; Iyer J; Paulson KG; Nghiem P
JAMA Dermatol. 2014 Jul;150(7):716-23.
Aspirin and non-aspirin NSAIDs increase risk of colonic diverticular bleeding: a systematic review and meta-analysis
Lower gastrointestinal bleeding is a frequent cause of hospitalization, particularly in the elderly, and its incidence appears to be on the rise. Colonic diverticular bleeding is the most common form of lower gastrointestinal bleeding and is responsible for 30-40 % of bleeding episodes. Risk factors associated with diverticular bleeding include obesity, hypertension, anticoagulants, diabetes mellitus, and ischemic heart disease. Recent studies have suggested a relationship between usage of non-steroidal anti-inflammatory drugs (NSAIDs) and colonic diverticular bleeding; however, most studies were small with wide confidence intervals. We identified studies by searching the PubMed and Scopus databases (from inception through 31 December 2012) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with fixed-effects and random-effects models. A total of six studies (five case-control studies and one cohort study) met inclusion criteria for analysis. Non-aspirin NSAIDs (NANSAIDs) and aspirin were associated with an increased risk of colonic diverticular bleeding (summary RR = 2.48, 95 % CI 1.86-3.31), with moderate heterogeneity among these studies (P heterogeneity = 0.11, I (2) = 44.4 %). Stratification to evaluate the heterogeneity found that both NANSAIDs (summary RR = 2.24, 95 % CI 1.63-3.09; 5 studies) and aspirin (summary RR = 1.73; 95 % CI 1.31-2.30; 3 studies) were associated with the risk of diverticular bleeding. Aspirin/NANSAIDs use was strongly and consistently associated with an increased risk of colonic diverticular bleeding. Further studies are needed to stratify individuals at risk of diverticular bleeding associated with the use of these agents.
Authors: Yuhara H; Corley DA; Nakahara F; Nakajima T; Koike J; Igarashi M; Suauki T; Mine T
J Gastroenterol. 2014 Jun;49(6):992-1000. Epub 2013-11-14.
Proteinuria testing among patients with diabetes mellitus is associated with bladder cancer diagnosis: potential for unmeasured confounding in studies of pioglitazone and bladder cancer
The observed association between pioglitazone and bladder cancer could be causal or because of bias in the design of prior studies. We hypothesize that proteinuria testing may lead to detection bias if routine test results for proteinuria lead to a full urinalysis. We reanalyzed patients with diabetes mellitus within Kaiser Permanente Northern California. Logistic and Cox regression adjusted for age, sex, race, and smoking were used to assess the association of proteinuria testing with pioglitazone use, subsequent full urinalysis, and diagnosis with bladder cancer. Patients treated with pioglitazone were more likely than others with diabetes to undergo testing for proteinuria (p?4?years exposure HR: from 1.38 to 1.28). Proteinuria testing may be a confounder in studies of pioglitazone and bladder cancer but does not fully explain the association between pioglitazone and bladder cancer in this cohort. Optimal adjustment for proteinuria testing likely requires knowledge of the test result.
Authors: Lewis JD; Habel L; Quesenberry C; Mamtani R; Peng T; Bilker WB; Hedderson M; Nessel L; Vaughn DJ; Strom BL; Ferrara A
Pharmacoepidemiol Drug Saf. 2014 Jun;23(6):636-45. Epub 2014-04-25.
Associations of Stressful Life Events and Social Strain With Incident Cardiovascular Disease in the Women’s Health Initiative
Epidemiologic studies have yielded mixed findings on the association of psychosocial stressors with cardiovascular disease (CVD) risk. In this study, we examined associations of stressful life events (SLE) and social strain with incident coronary heart disease (CHD) and stroke (overall, and for hemorrhagic and ischemic strokes) independent of sociodemographic characteristics, and we evaluated whether these relationships were explained by traditional behavioral and biological risk factors. Data from approximately 82 000 Women’s Health Initiative Observational Study participants were used for the SLE and social strain analyses, respectively. Participants were followed for events for up to 18.0 years (median, 14.0). Separate Cox proportional hazards models were generated to estimate associations of each stress measure with incident CVD. After adjusting for sociodemographic characteristics and depressive symptoms, higher SLE and social strain were associated with higher incident CHD and stroke (each P trend <0.05). Hazard ratios and 95% confidence intervals were 1.12 (1.01, 1.25) for incident CHD and 1.14 (1.01, 1.28) for incident stroke among participants reporting high versus low SLE. Findings were similar for social strain. Associations were attenuated with further adjustment for mediating behavioral and biological risk factors. Findings were similar for associations of SLE with ischemic stroke and hemorrhagic stroke, but social strain was only associated with ischemic stroke. Higher SLE and social strain were associated with higher incident CVD independent of sociodemographic factors and depressive symptoms, but not behavioral and biological risk factors.
Authors: Kershaw KN; Kroenke CH; Van Horn L; et al.
J Am Heart Assoc. 2014 Jun;3(3):e000687. Epub 2014-06-27.
Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: Differences by age, race, and tumor characteristics
Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, P Trend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3-0.9). Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Subtyping in a population-based cohort revealed distinct profiles by age and race.
Authors: Sweeney C; Kwan ML; Habel LA; Quesenberry CP; Kushi LH; Caan BJ; et al.
Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):714-24. Epub 2014-02-12.
Intrinsic subtypes from the PAM50 gene expression assay in a population-based breast cancer survivor cohort: Prognostication of short and long term outcomes
The PAM50, a gene expression assay to categorize breast tumors into intrinsic subtypes, has not been previously used to examine short- and long-term prognostication in a population-based cohort where treatment patterns and time of initial follow-up vary. In a stratified case-cohort design of 1,691 women from the LACE and Pathways breast cancer survivor cohorts, we used PAM50 to categorize tumors into Luminal A (LumA), Luminal B (LumB), HER2-enriched (HER2-E), Basal-like and Normal-like, and to examine risk of early and late recurrence and mortality by Cox proportional hazards regression. Compared with LumA, cumulative risk of recurrence and breast cancer death was higher for LumB, HER2-E, and Basal-like tumors at 2, 5, and 10 years. However, HR of breast cancer death varied over time [<5 years (early) vs. > 5 years (late)] for both Basal-like (HR, 6.23 early vs. HR, 0.63 late) and HER2-E tumors (HR, 2.97 early vs. HR, 0.73 late) but not for LumB tumors where risk was elevated consistently (HR, 2.67 early vs. HR, 1.47 late). The contrast between LumB, HER2-E, and Basal-like compared with LumA on early recurrence was stronger when subtype was defined by PAM50 than by immunohistochemistry (IHC) markers. The PAM50 categorized intrinsic subtypes in a manner that more accurately predicts recurrence and survival, especially for luminal tumors, compared with commonly used methods that rely on traditional IHC clinical markers. The PAM50 is robust for use in epidemiologic studies and should be considered when archived tumor tissues are available.
Authors: Caan BJ; Sweeney C; Habel LA; Kwan ML; Kroenke CH; Weltzien EK; Quesenberry CP; Castillo A; Factor RE; Kushi LH; Bernard PS
Cancer Epidemiol Biomarkers Prev. 2014 May;23(5):725-34. Epub 2014-02-12.
Comparative Effectiveness of Adjunctive Bevacizumab for Advanced Lung Cancer: The Cancer Research Network Experience
Bevacizumab plus carboplatin-paclitaxel (BCP) chemotherapy has Food and Drug Administration approval for advanced nonsquamous, non-small-cell lung cancer based upon improved survival in a clinical trial. However, subgroup analyses of this and other studies have suggested variable results by age and gender. Using data from four health maintenance organizations (HMOs) belonging to the Cancer Research Network, 1605 HMO nonsquamous, non-small-cell lung cancer patients aged younger than 21 years, diagnosed 2002-2010, who received carboplatin-paclitaxel (CP), with and without bevacizumab for first-line treatment of stage IIIB/IV disease were identified. Patients were categorized into three groups based on year of diagnosis and regimen during 120 days postdiagnosis: (1) diagnosed 2005-2010 and received BCP; (2) 2005-2010, CP (CP2005), and (3) 2002-2004, CP (CP2002). Survival differences between groups were estimated using Cox proportional hazard models with several propensity score adjustments for demographic, comorbidity, and tumor characteristics. Multivariable subanalyses were also estimated. Median survival was 12.3 months (interquartile range [IQR], 6.0-29.1) for BCP patients versus 8.8 months (IQR, 3.7-21.3) for CP2005 patients and 7.5 months (IQR, 3.8-15.6) for CP2002 patients. In the propensity score-adjusted models, BCP demonstrated a significant survival benefit with a hazard ratio of BCP relative to CP2005 and CP2002 patients of 0.79 (95% confidence interval [CI], 0.66-0.94) and 0.63 (95% CI, 0.52-0.75), respectively. In the multivariable-adjusted subanalyses, relative to the CP2005 cohort, the BCP hazard ratios for patients age less than 65 years, age 65 years old or older, and females were 0.78 (95% CI, 0.62-1.00), 0.74 (95% CI, 0.54-1.00), and 0.77 (95% CI, 0.58-1.00). In this community-based, comparative effectiveness analysis, we found an overall survival benefit for adults receiving BCP compared with CP.
Authors: Ritzwoller DP; Carroll NM; Delate T; Hornbrook MC; Kushi L; Bowles EJ; Loggers ET; Menter A
J Thorac Oncol. 2014 May;9(5):692-701.
Effectiveness of Primary Androgen-Deprivation Therapy for Clinically Localized Prostate Cancer
Primary androgen-deprivation therapy (PADT) is often used to treat clinically localized prostate cancer, but its effects on cause-specific and overall mortality have not been established. Given the widespread use of PADT and the potential risks of serious adverse effects, accurate mortality data are needed to inform treatment decisions. We conducted a retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans. All men were newly diagnosed with clinically localized prostate cancer. Men who were diagnosed between 1995 and 2008, were not treated with curative intent therapy, and received follow-up through December 2010 were included in the study (n = 15,170). We examined all-cause and prostate cancer-specific mortality as our main outcomes. We used Cox proportional hazards models with and without propensity score analysis. Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate-cancer-specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics. PADT was associated with decreased risk of all-cause mortality but not prostate-cancer-specific mortality. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97). We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer.
Authors: Potosky AL; Haque R; Cassidy-Bushrow AE; Ulcickas Yood M; Jiang M; Tsai HT; Luta G; Keating NL; Smith MR; Van Den Eeden SK
J Clin Oncol. 2014 May 1;32(13):1324-30. Epub 2014-03-17.
Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia
Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10(-4) was used to determine statistical significance of the associations. Two correlated SNPs–rs10090154 and rs4242382–in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.
Authors: Cheng I; Caan BJ; Peters U; et al.
Gut. 2014 May;63(5):800-7. Epub 2013-08-09.
Performance of Claims-based Algorithms for Identifying Heart Failure and Cardiomyopathy Among Patients Diagnosed With Breast Cancer
Cardiotoxicity is a known complication of certain breast cancer therapies, but rates come from clinical trials with design features that limit external validity. The ability to accurately identify cardiotoxicity from administrative data would enhance safety information. To characterize the performance of clinical coding algorithms for identification of cardiac dysfunction in a cancer population. We sampled 400 charts among 6460 women diagnosed with incident breast cancer, tumor size ? 2 cm or node positivity, treated within 8 US health care systems between 1999 and 2007. We abstracted medical records for clinical diagnoses of heart failure (HF) and cardiomyopathy (CM) or evidence of reduced left ventricular ejection fraction. We then assessed the performance of 3 different International Classification of Diseases, 9th Edition (ICD-9)-based algorithms. The HF/CM coding algorithm designed a priori to balance performance characteristics provided a sensitivity of 62% (95% confidence interval, 40%-80%), specificity of 99% (range, 97% to 99%), positive predictive value (PPV) of 69% (range, 45% to 85%), and negative predictive value (NPV) of 98% (range, 96% to 99%). When applied only to incident HF/CM (ICD-9 codes and gold standard diagnosis both occurring after breast cancer diagnosis) in patients exposed to anthracycline and/or trastuzumab therapy, the PPV was 42% (range, 14% to 76%). Claims-based algorithms have moderate sensitivity and high specificity for identifying HF/CM among patients with invasive breast cancer. As the prevalence of HF/CM among the breast cancer population is low, ICD-9 codes have high NPV but only moderate PPV. These findings suggest a significant degree of misclassification due to HF/CM overcoding versus incomplete clinical documentation of HF/CM in the medical record.
Authors: Allen LA; Habel L; Pharmacovigilance Research Group; et al.
Med Care. 2014 May;52(5):e30-8.
Television viewing, bedroom television, and sleep duration from infancy to mid-childhood.
BACKGROUND: Television and insufficient sleep are associated with poor mental and physical health. This study assessed associations of TV viewing and bedroom TV with sleep duration from infancy to midchildhood.METHOD: We studied 1864 children in Project Viva. Parents reported children’s average daily TV viewing and sleep (at 6 months and annually from 1-7 years) and the presence of a bedroom TV (annually 4-7 years). We used mixed effects models to assess associations of TV exposures with contemporaneous sleep, adjusting for child age, gender, race/ethnicity, maternal education, and income.RESULTS: Six hundred forty-three children (35%) were racial/ethnic minorities; 37% of households had incomes ≤$70 000. From 6 months to 7 years, mean (SD) sleep duration decreased from 12.2 (2.0) hours to 9.8 (0.9) hours per day; TV viewing increased from 0.9 (1.2) hours to 1.6 (1.0) hours per day. At 4 years, 17% had a bedroom TV, rising to 23% at 7 years. Each 1 hour per day increase in lifetime TV viewing was associated with 7 minutes per day (95% confidence interval [CI]: 4 to 10) shorter sleep. The association of bedroom TV varied by race/ethnicity; bedroom TV was associated with 31 minutes per day shorter sleep (95% CI: 16 to 45) among racial/ethnic minority children, but not among white, non-Hispanic children (8 fewer minutes per day [95% CI: -19 to 2]).CONCLUSIONS: More TV viewing, and, among racial/ethnic minority children, the presence of a bedroom TV, were associated with shorter sleep from infancy to midchildhood.
Authors: Cespedes, Elizabeth M EM; Gillman, Matthew W MW; Kleinman, Ken K; Rifas-Shiman, Sheryl L SL; Redline, Susan S; Taveras, Elsie M EM
Pediatrics. 2014 May ;133(5):e1163-71. Epub 2014-04-14.
Gastric acid-inhibiting medications and vitamin B12 deficiency–reply
Authors: Corley D; Lam J; Schneider J
JAMA. 2014 Apr 9;311(14):1445-6.
Adenoma detection rate and risk of colorectal cancer and death
The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas (the adenoma detection rate) is a recommended quality measure. However, little is known about the association between this rate and patients’ risks of a subsequent colorectal cancer (interval cancer) and death. Using data from an integrated health care delivery organization, we evaluated the associations between the adenoma detection rate and the risks of colorectal cancer diagnosed 6 months to 10 years after colonoscopy and of cancer-related death. With the use of Cox regression, our estimates of attributable risk were adjusted for the demographic characteristics of the patients, indications for colonoscopy, and coexisting conditions. We evaluated 314,872 colonoscopies performed by 136 gastroenterologists; the adenoma detection rates ranged from 7.4 to 52.5%. During the follow-up period, we identified 712 interval colorectal adenocarcinomas, including 255 advanced-stage cancers, and 147 deaths from interval colorectal cancer. The unadjusted risks of interval cancer according to quintiles of adenoma detection rates, from lowest to highest, were 9.8, 8.6, 8.0, 7.0, and 4.8 cases per 10,000 person-years of follow-up, respectively. Among patients of physicians with adenoma detection rates in the highest quintile, as compared with patients of physicians with detection rates in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52 (95% confidence interval [CI], 0.39 to 0.69), for advanced-stage interval cancer, 0.43 (95% CI, 0.29 to 0.64), and for fatal interval cancer, 0.38 (95% CI, 0.22 to 0.65). Each 1.0% increase in the adenoma detection rate was associated with a 3.0% decrease in the risk of cancer (hazard ratio, 0.97; 95% CI, 0.96 to 0.98). The adenoma detection rate was inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. (Funded by the Kaiser Permanente Community Benefit program and the National Cancer Institute.).
Authors: Corley DA; Lee JK; Fireman BH; Levin TR; Quesenberry CP; et al.
N Engl J Med. 2014 Apr 3;370(14):1298-306.
Multitarget Stool DNA Testing for Colorectal-Cancer Screening
An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and ?-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ?1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).
Authors: Imperiale TF; Ransohoff DF; Itzkowitz SH; Levin TR; Lavin P; Lidgard GP; Ahlquist DA; Berger BM
N Engl J Med. 2014 Apr 3;370(14):1287-97. Epub 2014-03-19.
Better postdiagnosis diet quality is associated with reduced risk of death among postmenopausal women with invasive breast cancer in the Women’s Health Initiative
Few studies have evaluated whether adherence to dietary recommendations is associated with mortality among cancer survivors. In breast cancer survivors, we examined how postdiagnosis Healthy Eating Index (HEI)-2005 scores were associated with all-cause and cause-specific mortality. Our prospective cohort study included 2,317 postmenopausal women, ages 50 to 79 years, in the Women’s Health Initiative’s Dietary Modification Trial (n = 1,205) and Observational Study (n = 1,112), who were diagnosed with invasive breast cancer and completed a food frequency questionnaire after being diagnosed. We followed women from this assessment forward. We used Cox proportional hazards models to estimate multivariate-adjusted HRs and 95% confidence intervals (CI) for death from any cause, breast cancer, and causes other than breast cancer, according to HEI-2005 quintiles. Over 9.6 years, 415 deaths occurred. After adjustment for key covariates, women consuming better quality diets had a 26% lower risk of death from any cause (HRQ4:Q1, 0.74; 95% CI, 0.55-0.99; Ptrend = 0.043) and a 42% lower risk of death from non-breast cancer causes (HRQ4:Q1, 0.58; 95% CI, 0.38-0.87; Ptrend = 0.011). HEI-2005 score was not associated with breast cancer death (HRQ4:Q1, 0.91; 95% CI, 0.60-1.40; Ptrend = 0.627). In analyses stratified by tumor estrogen receptor (ER) status, better diet quality was associated with a reduced risk of all-cause mortality among women with ER(+) tumors (n = 1,758; HRQ4:Q1, 0.55; 95% CI, 0.38-0.79; Ptrend = 0.0009). Better postdiagnosis diet quality was associated with reduced risk of death, particularly from non-breast cancer causes. Breast cancer survivors may experience improved survival by adhering to U.S. dietary guidelines.
Authors: George SM; Ballard-Barbash R; Shikany JM; Caan BJ; Freudenheim JL; Kroenke CH; Vitolins MZ; Beresford SA; Neuhouser ML
Cancer Epidemiol Biomarkers Prev. 2014 Apr;23(4):575-83. Epub 2014-02-03.
Genome-wide diet-gene interaction analyses for risk of colorectal cancer
Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.
Authors: Figueiredo JC; Caan BJ; GECCO; et al.
PLoS Genet. 2014 Apr;10(4):e1004228. Epub 2014-04-17.
Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression
To evaluate whether differences in PAM50 breast cancer (BC) intrinsic (Luminal A, Luminal B, Basal-like, and HER2-enriched) subtypes help explain the Black-White BC survival disparity. Utilizing a stratified case-cohort design, this study included 1,635 women from the Pathways and Life After Cancer Epidemiology cohorts, selecting women with tumors based upon IHC classification, recurrences, and deaths.One millimeter punches were obtained from tumor tissue, and expression of the PAM50 genes for molecular subtype was determined by RT-qPCR of extracted RNA. Cox proportional hazards models were used to analyze associations between race and BC outcomes, adjusted for PAM50 BC subtype. All tests of statistical significance were two-sided. Black women had a higher prevalence of the Basal-like BC subtype. Adjusted for potential confounding variables and disease characteristics at diagnosis, Black women had higher risks of recurrence (HR 1.65, 95 % CI 1.06-2.57) and breast cancer-specific mortality (HR 1.71, 95 % CI 1.02-2.86) than White women, but adjusting further for subtype did not attenuate survival disparities. By contrast, Hispanic women had a lower risk of recurrence (HR 0.54, 95 % CI 0.30-0.96) than Whites. Among those with the Basal-like subtype, Black women had a similar recurrence risk as women in other race groups but a higher recurrence risk for all other subtypes. Hispanic women had a lower recurrence risk within each subtype, though associations were not significant, given limited power. Although Black women had a higher risk of the Basal-like subtype, which has poor prognosis, this did not explain the Black-White BC survival disparity.
Authors: Kroenke CH; Sweeney C; Kwan ML; Quesenberry CP; Weltzien EK; Habel LA; Castillo A; Bernard PS; Factor RE; Kushi LH; Caan BJ
Breast Cancer Res Treat. 2014 Apr;144(3):689-99. Epub 2014-03-07.
Asthma and physical activity in multiracial girls from three US sites
Studies comparing physical activity levels in children with and without asthma have had mixed results. Our objective was to investigate the association between asthma diagnosis and physical activity and to examine differences in these associations by race/ethnicity, weight status and caregiver education. We investigated the association between asthma (defined as report of physician-diagnosed asthma with at least one asthma related symptom) and measures of physical and sedentary activity in a study of 6- to 8-year-old girls in the Breast Cancer and the Environment Research Project. We compared reported activity and pedometer measurements among girls with and without asthma, and examined modification of these associations by race/ethnicity, weight status and caregiver education. Girls (n?=?1182) were included with 33.5% White, 4.8% Asian, 30.6% non Hispanic Black and 30.7% Hispanic. Asthma was present in 16.2% of girls. Overall, 38% of girls reported no participation in organized recreational activities and 58% had >2?h/day of television, video game and computer time combined. Girls with asthma whose parents were less educated reported fewer pedometer steps and less non-scheduled activity than girls without asthma with similar caregiver education level. Among girls with asthma, those on a controller medication had higher levels of sedentary activity and more structured physical activity but were less likely to report high intensity physical activity. Among girls whose parents are less educated, girls with asthma may have lower physical activity levels than girls without asthma. Use of a controller medication may be related to physical and sedentary activity.
Authors: Vangeepuram N; McGovern KJ; Teitelbaum S; Galvez MP; Pinney SM; Biro FM; Kushi LH; Wolff MS
J Asthma. 2014 Mar;51(2):193-9. Epub 2013-11-15.
Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results
The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors. In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design-specific (case-control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided. Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86). Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.
Authors: Brinton LA; Van Den Eeden SK; Thomas DB; et al.
J Natl Cancer Inst. 2014 Mar;106(3):djt465. Epub 2014-02-19.
Menopausal Quality of Life: A RCT of Yoga, Exercise and Omega-3 Supplements
The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms. We conducted a 12-week 3 × 2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, 40-62 years old, were assigned randomly to yoga (n = 107), exercise (n = 106), or usual activity (n = 142) and also assigned randomly to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules. We performed the following interventions: (1) weekly 90-minute yoga classes with daily at-home practice, (2) individualized facility-based aerobic exercise training 3 times/week, and (3) 0.615 g omega-3 supplement, 3 times/day. The outcomes were assessed with the following scores: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (vasomotor symptoms, psychosocial, physical and sexual). Among 355 randomly assigned women who average age was 54.7 years, 338 women (95%) completed 12-week assessments. Mean baseline vasomotor symptoms frequency was 7.6/day, and the mean baseline total MENQOL score was 3.8 (range, 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% confidence interval, -0.6 to 0; P = .02), vasomotor symptom domain (P = .02), and sexuality domain (P = .03) scores. For women who underwent exercise and omega-3 therapy compared with control subjects, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12 weeks (P = .02). All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence-based information exists. We found that, among healthy sedentary menopausal women, yoga appears to improve menopausal quality of life; the clinical significance of our finding is uncertain because of the modest effect.
Authors: Reed SD; Caan B; Sternfeld BS; LaCroix AZ; et al.
Am J Obstet Gynecol. 2014 Mar;210(3):244.e1-11. Epub 2013-11-08.
“Everyone should be able to choose how they get around”: how Topeka, Kansas, passed a complete streets resolution.
BACKGROUND: Regular physical activity can help prevent chronic diseases, yet only half of US adults meet national physical activity guidelines. One barrier to physical activity is a lack of safe places to be active, such as bike paths and sidewalks. Complete Streets, streets designed to enable safe access for all users, can help provide safe places for activity.COMMUNITY CONTEXT: This community case study presents results from interviews with residents and policymakers of Topeka, Kansas, who played an integral role in the passage of a Complete Streets resolution in 2009. It describes community engagement processes used to include stakeholders, assess existing roads and sidewalks, and communicate with the public and decision-makers.METHODS: Key informant interviews were conducted with city council members and members of Heartland Healthy Neighborhoods in Topeka to learn how they introduced a Complete Streets resolution and the steps they took to ensure its successful passage in the City Council. Interviews were recorded, transcribed, and analyzed by using focused-coding qualitative analysis.OUTCOME: Results included lessons learned from the process of passing the Complete Streets resolution and advice from participants for other communities interested in creating Complete Streets in their communities.INTERPRETATION: Lessons learned can apply to other communities pursuing Complete Streets. Examples include clearly defining Complete Streets; educating the public, advocates, and decision-makers about Complete Streets and how this program enhances a community; building a strong and diverse network of supporters; and using stories and examples from other communities with Complete Streets to build a convincing case.
Authors: Dodson, Elizabeth A EA; Langston, Marvin M; Cardick, Lauren C LC; Johnson, Nancy N; Clayton, Paula P; Brownson, Ross C RC
Preventing chronic disease. 2014 Feb 20;11(9):E25. Epub 2014-02-20.
Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis
Performance characteristics of fecal immunochemical tests (FITs) to screen for colorectal cancer (CRC) have been inconsistent. To synthesize data about the diagnostic accuracy of FITs for CRC and identify factors affecting its performance characteristics. Online databases, including MEDLINE and EMBASE, and bibliographies of included studies from 1996 to 2013. All studies evaluating the diagnostic accuracy of FITs for CRC in asymptomatic, average-risk adults. Two reviewers independently extracted data and critiqued study quality. Nineteen eligible studies were included and meta-analyzed. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FITs for CRC were 0.79 (95% CI, 0.69 to 0.86), 0.94 (CI, 0.92 to 0.95), 13.10 (CI, 10.49 to 16.35), 0.23 (CI, 0.15 to 0.33), respectively, with an overall diagnostic accuracy of 95% (CI, 93% to 97%). There was substantial heterogeneity between studies in both the pooled sensitivity and specificity estimates. Stratifying by cutoff value for a positive test result or removal of discontinued FIT brands resulted in homogeneous sensitivity estimates. Sensitivity for CRC improved with lower assay cutoff values for a positive test result (for example, 0.89 [CI, 0.80 to 0.95] at a cutoff value less than 20 µg/g vs. 0.70 [CI, 0.55 to 0.81] at cutoff values of 20 to 50 µg/g) but with a corresponding decrease in specificity. A single-sample FIT had similar sensitivity and specificity as several samples, independent of FIT brand. Only English-language articles were included. Lack of data prevented complete subgroup analyses by FIT brand. Fecal immunochemical tests are moderately sensitive, are highly specific, and have high overall diagnostic accuracy for detecting CRC. Diagnostic performance of FITs depends on the cutoff value for a positive test result. National Institute of Diabetes and Digestive and Kidney Diseases and National Cancer Institute.
Authors: Lee JK; Liles EG; Bent S; Levin TR; Corley DA
Ann Intern Med. 2014 Feb 4;160(3):171.
Antidepressants and testicular cancer
Re-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with 4 years more follow-up and expanded study of these and other antidepressant drugs. In the Kaiser Permanente Medical Care Program in Northern California, 906 men with testicular cancer diagnosed August 1996-December 2010 were compared with 38,253 matched controls with race/ethnicity recorded regarding receipt of antidepressant drugs at least 2 years before diagnosis or control index date. Analyses emphasized duration of use and histological subgroups. With control for race/ethnicity and use of other antidepressant drugs, odds ratios (OR) and 95 % confidence intervals (CI) for associations with testicular cancer were as follows: fluoxetine 1.22 (0.88-1.71), paroxetine 1.19 (0.78-1.83), and 1.21 (0.92-1.58) for all serotonin reuptake inhibitors. There was no statistically significant association with risk of all testicular cancers or their histological subtypes for any individual drug or for tricyclics or all antidepressants combined except for citalopram with all testicular cancers 2.55 (1.43-4.52) and those of mixed histology 4.36 (1.50-12.68) and nefazodone with embryonal cancers 9.79 (1.85-51.81). These could readily be chance findings in the context of the many analyses that were performed. Duration of use was not associated with risk of the drugs and drug groups with sufficient numbers of exposed cases for analysis. We found little evidence to support a testicular carcinogenic effect of fluoxetine, paroxetine, or other antidepressant drugs, but a weakly positive association is not ruled out. The signals in prior screening may have been due to chance and/or uncontrolled confounding.
Authors: Friedman GD; Schwalbe J; Achacoso N; Meng MV; Kroenke CH; Habel LA
Cancer Causes Control. 2014 Feb;25(2):251-8. Epub 2013-11-26.
A pragmatic cluster randomized clinical trial of diabetes prevention strategies for women with gestational diabetes: design and rationale of the Gestational Diabetes’ Effects on Moms (GEM) study
Women with gestational diabetes (GDM) are at high risk of developing diabetes later in life. After a GDM diagnosis, women receive prenatal care to control their blood glucose levels via diet, physical activity and medications. Continuing such lifestyle skills into early motherhood may reduce the risk of diabetes in this high risk population. In the Gestational Diabetes’ Effects on Moms (GEM) study, we are evaluating the comparative effectiveness of diabetes prevention strategies for weight management designed for pregnant/postpartum women with GDM and delivered at the health system level. The GEM study is a pragmatic cluster randomized clinical trial of 44 medical facilities at Kaiser Permanente Northern California randomly assigned to either the intervention or usual care conditions, that includes 2,320 women with a GDM diagnosis between March 27, 2011 and March 30, 2012. A Diabetes Prevention Program-derived print/telephone lifestyle intervention of 13 telephonic sessions tailored to pregnant/postpartum women was developed. The effectiveness of this intervention added to usual care is to be compared to usual care practices alone, which includes two pages of printed lifestyle recommendations sent to postpartum women via mail. Primary outcomes include the proportion of women who reach a postpartum weight goal and total weight change. Secondary outcomes include postpartum glycemia, blood pressure, depression, percent of calories from fat, total caloric intake and physical activity levels. Data were collected through electronic medical records and surveys at baseline (soon after GDM diagnosis), 6 weeks (range 2 to 11 weeks), 6 months (range 12 to 34 weeks) and 12 months postpartum (range 35 to 64 weeks). There is a need for evidence regarding the effectiveness of lifestyle modification for the prevention of diabetes in women with GDM, as well as confirmation that a diabetes prevention program delivered at the health system level is able to successfully reach this population. Given the use of a telephonic case management model, our Diabetes Prevention Program-derived print/telephone intervention has the potential to be adopted in other settings and to inform policies to promote the prevention of diabetes among women with GDM.
Authors: Ferrara A; Hedderson MM; Brown SD; Ehrlich SF; Caan BJ; Sternfeld B; Gordon NP; Schmittdiel JA; Gunderson EP; Quesenberry CP; et al.
BMC Pregnancy Childbirth. 2014;14:21. Epub 2014-01-15.
Changes in vitamin and mineral supplement use after breast cancer diagnosis in the Pathways Study: a prospective cohort study
Vitamin and mineral supplement use after a breast cancer diagnosis is common and controversial. Dosages used and the timing of initiation and/or discontinuation of supplements have not been clearly described. We prospectively examined changes in use of 17 vitamin/mineral supplements in the first six months following breast cancer diagnosis among 2,596 members (28% non-white) of Kaiser Permanente Northern California. We used multivariable logistic regression to examine demographic, clinical, and lifestyle predictors of initiation and discontinuation. Most women used vitamin/mineral supplements before (84%) and after (82%) diagnosis, with average doses far in excess of Institute of Medicine reference intakes. Over half (60.2%) reported initiating a vitamin/mineral following diagnosis, 46.3% discontinuing a vitamin/mineral, 65.6% using a vitamin/mineral continuously, and only 7.2% not using any vitamin/mineral supplement before or after diagnosis. The most commonly initiated supplements were calcium (38.2%), vitamin D (32.01%), vitamin B6 (12.3%) and magnesium (11.31%); the most commonly discontinued supplements were multivitamins (17.14%), vitamin C (15.97%) and vitamin E (45.62%). Higher education, higher intake of fruits/vegetables, and receipt of chemotherapy were associated with initiation (p-values <0.05). Younger age and breast-conserving surgery were associated with discontinuation (p-values <0.05). In this large cohort of ethnically diverse breast cancer patients, high numbers of women used vitamin/mineral supplements in the 6 months following breast cancer diagnosis, often at high doses and in combination with other supplements. The immediate period after diagnosis is a critical time for clinicians to counsel women on supplement use.
Authors: Greenlee H; Kwan ML; Ergas IJ; Kushi LH; et al.
BMC Cancer. 2014;14:382. Epub 2014-05-29.
Social Dis (ease) of African American Males and Health
Authors: Gilbert K, Ray R, Langston M
In: Urban ills : twenty-first-century complexities of urban living in global contexts. Vol. 2. 2014; 23-26
Does KRAS Testing in Metastatic Colorectal Cancer Impact Overall Survival? A Comparative Effectiveness Study in a Population-Based Sample
Epidermal growth factor receptor (EGFR) inhibitors are approved for treating metastatic colorectal cancer (CRC); KRAS mutation testing is recommended prior to treatment. We conducted a non-inferiority analysis to examine whether KRAS testing has impacted survival in CRC patients. We included 1186 metastatic CRC cases from seven health plans. A cutpoint of July, 2008, was used to define two KRAS testing time period groups: “pre-testing” (n?=?760 cases) and “post-testing” (n?=?426 cases). Overall survival (OS) was estimated, and the difference in median OS between the groups was calculated. The lower bound of the one-sided 95% confidence interval (CI) for the difference in survival was used to test the null hypothesis of post-testing inferiority. Multivariable Cox regression models were constructed to adjust for covariates. The median unadjusted OS was 15.4 months (95% CI: 14.0-17.5) and 12.8 months (95% CI: 10.0-15.2) in the pre- and post-testing groups, respectively. The OS difference was -2.6 months with one-sided 95% lower confidence bound of -5.13 months, which was less than the non-inferiority margin (-5.0 months, unadjusted p?=?0.06), leading to a failure to reject inferiority of OS in the post-testing period. In contrast, in the adjusted analysis, OS non-inferiority was identified in the post-testing period (p?=?0.001). Sensitivity analyses using cutpoints before and after July, 2008, also met the criteria for non-inferiority. Implementation of KRAS testing did not influence CRC OS. Our data support the use of KRAS testing to guide administration of EGFR inhibitors for treatment of metastatic CRC without diminished OS.
Authors: Feigelson HS; Kushi LH; CERGEN Study Team; et al.
PLoS ONE. 2014;9(5):e94977. Epub 2014-05-01.
Obesity and Mortality After Breast Cancer by Race/Ethnicity: The California Breast Cancer Survivorship Consortium
We investigated body size and survival by race/ethnicity in 11,351 breast cancer patients diagnosed from 1993 to 2007 with follow-up through 2009 by using data from questionnaires and the California Cancer Registry. We calculated hazard ratios and 95% confidence intervals from multivariable Cox proportional hazard model-estimated associations of body size (body mass index (BMI) (weight (kg)/height (m)(2)) and waist-hip ratio (WHR)) with breast cancer-specific and all-cause mortality. Among 2,744 ascertained deaths, 1,445 were related to breast cancer. Being underweight (BMI <18.5) was associated with increased risk of breast cancer mortality compared with being normal weight in non-Latina whites (hazard ratio (HR) = 1.91, 95% confidence interval (CI): 1.14, 3.20), whereas morbid obesity (BMI ? 40) was suggestive of increased risk (HR = 1.43, 95% CI: 0.84, 2.43). In Latinas, only the morbidly obese were at high risk of death (HR = 2.26, 95% CI: 1.23, 4.15). No BMI-mortality associations were apparent in African Americans and Asian Americans. High WHR (quartile 4 vs. quartile 1) was associated with breast cancer mortality in Asian Americans (HR = 2.21, 95% CI: 1.21, 4.03; P for trend = 0.01), whereas no associations were found in African Americans, Latinas, or non-Latina whites. For all-cause mortality, even stronger BMI and WHR associations were observed. The impact of obesity and body fat distribution on breast cancer patients' risk of death may vary across racial/ethnic groups.
Authors: Kwan ML; Caan BJ; Wu AH; et al.
Am J Epidemiol. 2014 Jan 1;179(1):95-111. Epub 2013-10-09.
Stem cells guided gene therapy of cancer: New frontier in personalized and targeted therapy
Introduction: Bevacizumab was approved for treatment of advanced non-squamous, non-small cell lung cancer (NSCLC) in the US in late 2006. Information on its uptake and patient and tumor factors associated with its use is lacking. Materials and methods: This was a longitudinal, retrospective cohort study of patients with stage IIIB/IV non-squamous NSCLC aged 21 years or greater diagnosed between 2005 and 2010 at four Cancer Research Network sites. Patients were categorized as receiving first-line carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) within 120 days of diagnosis. Information on patient and tumor characteristics was obtained from queries of sites electronic tumor registries and administrative databases. Factors independently associated with CPB use were evaluated using bivariate and multivariate logistic regression analyses. Results: A total of 1109 patients with advanced NSCLC were included with 198 (17.9%) and 911 (82.1%) patients receiving CPB and CP, respectively. Bevacizumab use increased modestly during the study period, peaking in 2008 at 18.5%. In bivariate analyses, patients who received CPB were younger with less comorbidity and well to moderately differentiated tumors while patients who received CP were more likely to have had hypertension, peripheral vascular disease, and a prior hospitalization. Factors independently associated with CPB use included younger age, well/ moderately differentiated tumor grade, no prior hospitalization, and more recent study year. Conclusions: Use of bevacizumab in patients with advanced NSCLC increased rapidly then moderated. Younger patients and those with lower risks for adverse effects were more likely to receive bevacizumab.
Authors: Delate T; Won K; Carroll NM; Kushi L; Hornbrook M; Bowles EJA; Menter A; Loggers ET; Ritzwoller D
J Cancer Res Therapy. Jan 2014;2(1):1-8.
Ovarian cancer rates after hysterectomy with and without salpingo-oophorectomy
To estimate ovarian and peritoneal cancer rates after hysterectomy with and without salpingo-oophorectomy for benign conditions. All patients after hysterectomy for benign disease from 1988 to 2006 in Kaiser Permanente Northern California, an integrated health organization. Incidence rates per 100,000 person-years were calculated. Of 56,692 patients, the majority (54%) underwent hysterectomy with bilateral salpingo-oophorectomy; 7% had hysterectomy with unilateral salpingo-oophorectomy, and 39% had hysterectomy alone. There were 40 ovarian and eight peritoneal cancers diagnosed during follow-up. Median age at ovarian and peritoneal cancer diagnosis was 50 and 64 years, respectively. Age-standardized rates (per 100,000 person-years) of ovarian or peritoneal cancer were 26.7 (95% confidence interval [CI] 16-37.5) for those with hysterectomy alone, 22.8 (95% CI 0.0-46.8) for hysterectomy and unilateral salpingo-oophorectomy, and 3.9 (95% CI 1.5-6.4) for hysterectomy and bilateral salpingo-oophorectomy. Rates of ovarian cancer were 26.2 (95% CI 15.5-37) for those with hysterectomy alone, 17.5 (95% CI 0.0-39.1) for hysterectomy and unilateral salpingo-oophorectomy, and 1.7 (95% CI 0.4-3) for those with hysterectomy and bilateral salpingo-oophorectomy. Compared with women undergoing hysterectomy alone, those receiving an unilateral salpingo-oophorectomy had a hazard ratio (HR) for ovarian cancer of 0.58 (95% CI 0.18-1.9) and those undergoing bilateral salpingo-oophorectomy had an HR of 0.12 (95% CI 0.05-0.28). The removal of both ovaries decreases the incidence of ovarian and peritoneal cancers. Removal of one ovary might also decrease the incidence of ovarian cancer but warrants further investigation. II.
Authors: Chan JK; Urban R; Capra AM; Jacoby V; Osann K; Whittemore A; Habel LA
Obstet Gynecol. 2014 Jan;123(1):65-72.
Gastroesophageal Reflux in Relation to Adenocarcinomas of the Esophagus: A Pooled Analysis from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON)
Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues. Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted. Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ?20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index. This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.
Authors: Cook MB; Corley DA; Vaughan TL; et al.
PLoS ONE. 2014;9(7):e103508. Epub 2014-07-30.
Bone health history in breast cancer patients on aromatase inhibitors
A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI) users before breast cancer (BC) diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC). Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001). Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.
Authors: Kwan ML; Lo JC; Quesenberry CP; Kushi LH; Yao S; et al.
PLoS ONE. 2014;9(10):e111477. Epub 2014-10-29.
Dietary guideline adherence for gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) is the most common gastrointestinal disease, and the cost of health care and lost productivity due to GERD is extremely high. Recently described side effects of long-term acid suppression have increased the interest in nonpharmacologic methods for alleviating GERD symptoms. We aimed to examine whether GERD patients follow recommended dietary guidelines, and if adherence is associated with the severity and frequency of reflux symptoms. We conducted a population-based cross-sectional study within the Kaiser Permanente Northern California population, comparing 317 GERD patients to 182 asymptomatic population controls. All analyses adjusted for smoking and education. GERD patients, even those with moderate to severe symptoms or frequent symptoms, were as likely to consume tomato products and large portion meals as GERD-free controls and were even more likely to consume soft drinks and tea [odds ratio (OR) = 2.01 95% confidence interval (CI) 1.12-3.61; OR = 2.63 95% CI 1.24-5.59, respectively] and eat fried foods and high fat diet. The only reflux-triggering foods GERD patients were less likely to consume were citrus and alcohol [OR = 0.59; 95% CI: 0.35-0.97 for citrus; OR = 0.41 95% CI 0.19-0.87 for 1 + drink/day of alcohol]. The associations were similar when we excluded users of proton pump inhibitors. GERD patients consume many putative GERD causing foods as frequently or even more frequently than asymptomatic patients despite reporting symptoms. These findings suggest that, if dietary modification is effective in reducing GERD, substantial opportunities for nonpharmacologic interventions exist for many GERD patients.
Authors: Kubo A; Block G; Quesenberry CP; Buffler P; Corley DA
BMC Gastroenterol. 2014;14:144. Epub 2014-08-14.
Serum biomarkers of polyfluoroalkyl compound exposure in young girls in Greater Cincinnati and the San Francisco Bay Area, USA
PFC serum concentrations were measured in 6-8 year-old girls in Greater Cincinnati (GC) (N = 353) and the San Francisco Bay Area (SFBA) (N = 351). PFOA median concentration was lower in the SFBA than GC (5.8 vs. 7.3 ng/mL). In GC, 48/51 girls living in one area had PFOA concentrations above the NHANES 95th percentile for children 12-19 years (8.4 ng/mL), median 22.0 ng/mL. The duration of being breast fed was associated with higher serum PFOA at both sites and with higher PFOS, PFHxS and Me-PFOSA-AcOH concentrations in GC. Correlations of the PFC analytes with each other suggest that a source upriver from GC may have contributed to exposures through drinking water, and water treatment with granular activated carbon filtration resulted in less exposure for SWO girls compared to those in NKY. PFOA has been characterized as a drinking water contaminant, and water treatment systems effective in removing PFCs will reduce body burdens.
Authors: Pinney SM; Kushi LH; Bornschein R; et al.
Environ Pollut. 2014 Jan;184:327-34. Epub 2013-10-01.
Lifetime Cigarette Smoking and Breast Cancer Prognosis in the After Breast Cancer Pooling Project
There is controversy on whether former smokers have increased risk for breast cancer recurrence or all-cause mortality, regardless of how much they smoked. Data were from three US cohorts in the After Breast Cancer Pooling Project, with detailed information on smoking among 9975 breast cancer survivors. Smoking was assessed an average of 2 years after diagnosis. Delayed entry Cox proportional hazards models were used to examine the relationships of smoking status, cigarettes per day, years of smoking, and pack years with breast cancer prognosis. Endpoints included breast cancer recurrence (n = 1727), breast cancer mortality (n = 1059), and overall mortality (n = 1803). Compared with never smokers, former smokers with less than 20 pack-years of exposure had no increased risk of any outcome. However, former smokers with 20 to less than 34.9 pack-years of exposure had a 22% increased risk of breast cancer recurrence (hazard ratio [HR] = 1.22; 95% confidence interval [CI] = 1.01 to 1.48) and a 26% increased risk of all-cause mortality (HR = 1.26; 95% CI = 1.07 to 1.48). For former smokers with 35 or more pack-years of exposure, the probability of recurrence increased by 37% (HR = 1.37; 95% CI = 1.13 to 1.66), breast cancer mortality increased by 54% (HR = 1.54; 95% CI = 1.24 to 1.91), and all-cause mortality increased by 68% (HR = 1.68; 95% CI = 1.44 to 1.96). Current smoking increased the probability of recurrence by 41% (HR = 1.41; 95% CI = 1.16 to 1.71), increased breast cancer mortality by 60% (HR = 1.61; 95% CI = 1.28 to 2.03), and doubled the risk of all-cause mortality (HR = 2.17; 95% CI = 1.85 to 2.54). Lifetime cigarette smoking was statistically significantly associated with a poor prognosis among women diagnosed with breast cancer, dose-dependent increased risks of recurrence, and breast cancer and all-cause mortality.
Authors: Pierce JP; Patterson RE; Senger CM; Flatt SW; Caan BJ; Natarajan L; Nechuta SJ; Poole EM; Shu XO; Chen WY
J Natl Cancer Inst. 2014 Jan;106(1):djt359. Epub 2013-12-07.
Obesity and Late-Age Survival Without Major Disease or Disability in Older Women
The effect of obesity on late-age survival in women without disease or disability is unknown. To investigate whether higher baseline body mass index and waist circumference affect women’s survival to 85 years of age without major chronic disease (coronary disease, stroke, cancer, diabetes mellitus, or hip fracture) and mobility disability. Examination of 36,611 women from the Women’s Health Initiative observational study and clinical trial programs who could have reached 85 years or older if they survived to the last outcomes evaluation on September 17, 2012. Recruitment was from 40 US clinical centers from October 1993 through December 1998. Multinomial logistic regression models were used to estimate odds ratios and 95% CIs for the association of baseline body mass index and waist circumference with the outcomes, adjusting for demographic, behavioral, and health characteristics. Mutually exclusive classifications: (1) survived without major chronic disease and without mobility disability (healthy); (2) survived with 1 or more major chronic disease at baseline but without new disease or disability (prevalent diseased); (3) survived and developed 1 or more major chronic disease but not disability during study follow-up (incident diseased); (4) survived and developed mobility disability with or without disease (disabled); and (5) did not survive (died). Mean (SD) baseline age was 72.4 (3.0) years (range, 66-81 years). The distribution of women classified as healthy, prevalent diseased, incident diseased, disabled, and died was 19.0%, 14.7%, 23.2%, 18.3%, and 24.8%, respectively. Compared with healthy-weight women, underweight and obese women were more likely to die before 85 years of age. Overweight and obese women had higher risks of incident disease and mobility disability. Disability risks were striking. Relative to healthy-weight women, adjusted odds ratios (95% CIs) of mobility disability were 1.6 (1.5-1.8) for overweight women and 3.2 (2.9-3.6), 6.6 (5.4-8.1), and 6.7 (4.8-9.2) for class I, II, and III obesity, respectively. Waist circumference greater than 88 cm was also associated with higher risk of earlier death, incident disease, and mobility disability. Overall and abdominal obesity were important and potentially modifiable factors associated with dying or developing mobility disability and major chronic disease before 85 years of age in older women.
Authors: Rillamas-Sun E; Kroenke CH; Wallace RB; et al.
JAMA Intern Med. 2014 Jan;174(1):98-106.
Approaches for classifying the indications for colonoscopy using detailed clinical data
Accurate indication classification is critical for obtaining unbiased estimates of colonoscopy effectiveness and quality improvement efforts, but there is a dearth of published systematic classification approaches. The objective of this study was to evaluate the effects of data-source and adjudication on indication classification and on estimates of the effectiveness of screening colonoscopy on late-stage colorectal cancer diagnosis risk. This was an observational study in members of four U.S. health plans. Eligible persons (n = 1039) were age 55-85 and had been enrolled for 5 years or longer in their health plans during 2006-2008. Patients were selected based on late-stage colorectal cancer diagnosis in a case-control design; each case patient was matched to 1-2 controls by study site, age, sex, and health plan enrollment duration. Reasons for colonoscopies received in the 10-year period before the reference date were collected from three medical records sources (progress notes; referral notes; procedure reports) and categorized using an algorithm, with committee adjudication of some tests. We evaluated indication classification concordance before and after adjudication and used logistic regressions with the Wald Chi-square test to compare estimates of the effects of screening colonoscopy on late-stage colorectal cancer diagnosis risk for each of our data sources to the adjudicated indication. Classification agreement between each data-source and adjudication was 78.8-94.0% (weighted kappa = 0.53-0.72); the highest agreement (weighted kappa = 0.86-0.88) was when information from all data sources was considered together. The choice of data-source influenced the association between screening colonoscopy and late-stage colorectal cancer diagnosis; estimates based on progress notes were closest to those based on the adjudicated indication (% difference in regression coefficients = 2.4%, p-value = 0.98), as compared to estimates from only referral notes (% difference in coefficients = 34.9%, p-value = 0.12) or procedure reports (% difference in coefficients = 27.4%, p-value = 0.23). There was no single gold-standard source of information in medical records. The estimates of colonoscopy effectiveness from progress notes alone were the closest to estimates using adjudicated indications. Thus, the details in the medical records are necessary for accurate indication classification.
Authors: Fassil H; Adams KF; Weinmann S; Doria-Rose VP; Johnson E; Williams AE; Corley DA; Doubeni CA
BMC Cancer. 2014;14:95. Epub 2014-02-15.
Effects of physical activity and sedentary time on the risk of heart failure
Although the benefits of physical activity for risk of coronary heart disease are well established, less is known about its effects on heart failure (HF). The risk of prolonged sedentary behavior on HF is unknown. The study cohort included 82 695 men aged?45 years from the California Men’s Health Study without prevalent HF who were followed up for 10 years. Physical activity, sedentary time, and behavioral covariates were obtained from questionnaires, and clinical covariates were determined from electronic medical records. Incident HF was identified through International Classification of Diseases, Ninth Revision codes recorded in electronic records. During a mean follow-up of 7.8 years (646 989 person-years), 3473 men were diagnosed with HF. Controlling for sedentary time, sociodemographics, hypertension, diabetes mellitus, unfavorable lipid levels, body mass index, smoking, and diet, the hazard ratio (95% confidence interval [CI]) of HF in the lowest physical activity category compared with those in the highest category was 1.52 (95% CI, 1.39-1.68). Those in the medium physical activity category were also at increased risk (hazard ratio, 1.17 [95% CI, 1.06-1.29]). Controlling for the same covariates and physical activity, the hazard ratio (95% CI) of HF in the highest sedentary category compared with the lowest was 1.34 (95% CI, 1.21-1.48). Medium sedentary time also conveyed risk (hazard ratio, 1.13 [95% CI, 1.04-1.24]). Results showed similar trends across white and Hispanic subgroups, body mass index categories, baseline hypertension status, and prevalent coronary heart disease. Both physical activity and sedentary time may be appropriate intervention targets for preventing HF.
Authors: Young DR; Reynolds K; Sidell M; Brar S; Ghai NR; Sternfeld B; Jacobsen SJ; Slezak JM; Caan B; Quinn VP
Circ Heart Fail. 2014 Jan;7(1):21-7.
Methods for the design of vasomotor symptom trials: the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network
This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials. Established in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and ?-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network’s structure and governance are also discussed. The methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers.
Authors: Newton KM; Caan B; Sternfeld B; Lacroix AZ; et al.
Menopause. 2014 Jan;21(1):45-58.
Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency
IMPORTANCE: Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) suppress the production of gastric acid and thus may lead to malabsorption of vitamin B12. However, few data exist regarding the associations between long-term exposure to these medications and vitamin B12 deficiency in large population-based studies. OBJECTIVE: To study the association between use of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the United States. DESIGN, SETTING, AND PATIENTS: We evaluated the association between vitamin B12 deficiency and prior use of acid-suppressing medication using a case-control study within the Kaiser Permanente Northern California population. We compared 25,956 patients having incident diagnoses of vitamin B12 deficiency between January 1997 and June 2011 with 184,199 patients without B12 deficiency. Exposures and outcomes were ascertained via electronic pharmacy, laboratory, and diagnostic databases. MAIN OUTCOMES AND MEASURES: Risk of vitamin B12 deficiency was estimated using odds ratios (ORs) from conditional logistic regression. RESULTS: Among patients with incident diagnoses of vitamin B12 deficiency, 3120 (12.0%) were dispensed a 2 or more years’ supply of PPIs, 1087 (4.2%) were dispensed a 2 or more years’ supply of H2RAs (without any PPI use), and 21,749 (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients without vitamin B12 deficiency, 13,210 (7.2%) were dispensed a 2 or more years’ supply of PPIs, 5897 (3.2%) were dispensed a 2 or more years’ supply of H2RAs (without any PPI use), and 165,092 (89.6%) had not received prescriptions for either PPIs or H2RAs. Both a 2 or more years’ supply of PPIs (OR, 1.65 [95% CI, 1.58-1.73]) and a 2 or more years’ supply of H2RAs (OR, 1.25 [95% CI, 1.17-1.34]) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77-2.15]) than were doses less than 0.75 pills/d (OR, 1.63 [95% CI, 1.48-1.78]; P = .007 for interaction). CONCLUSIONS AND RELEVANCE: Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.
Authors: Lam JR; Schneider JL; Zhao W; Corley DA
JAMA. 2013 Dec 11;310(22):2435-42.
Cohort Study of Insulin Glargine and Risk of Breast, Prostate, and Colorectal Cancer Among Patients With Diabetes
To examine whether use of insulin glargine, compared with another long-acting insulin, is associated with risk of breast, prostate, colorectal cancer, or all cancers combined. Computerized health records from Kaiser Permanente Northern and Southern California regions starting in 2001 and ending in 2009 were used to conduct a population-based cohort study among patients with diabetes aged ?18 years. With use of Cox regression modeling, cancer risk in users of insulin glargine (n = 27,418) was compared with cancer risk in users of NPH (n = 100,757). The cohort had a median follow-up of 3.3 years during which there was a median of 1.2 years of glargine use and 1.4 years of NPH use. Among users of NPH at baseline, there was no clear increase in risk of breast, prostate, colorectal, or all cancers combined associated with switching to glargine. Among those initiating insulin, ever use or ?2 years of glargine was not associated with increased risk of prostate or colorectal cancer or all cancers combined. Among initiators, the hazard ratio (HR) for breast cancer associated with ever use of glargine was 1.3 (95% CI 1.0-1.8); the HR for breast cancer associated with use of glargine for ?2 years was 1.6 or 1.7 depending on whether glargine users had also used NPH. Results of this study should be viewed cautiously, given the relatively short duration of glargine use to date and the large number of potential associations examined.
Authors: Habel LA; Danforth KN; Quesenberry CP; Capra A; Van Den Eeden SK; Weiss NS; Ferrara A
Diabetes Care. 2013 Dec;36(12):3953-60. Epub 2013-10-29.
Oncologists’ attitudes toward KRAS testing: a multisite study
Recent discoveries promise increasingly to help oncologists individually tailor anticancer therapy to their patients’ molecular tumor characteristics. One such promising molecular diagnostic is Kirsten ras (KRAS) tumor mutation testing for metastatic colorectal cancer (mCRC) patients. In the current study, we examined how and why physicians adopt KRAS testing and how they subsequently utilize the information when discussing treatment strategies with patients. We conducted 34 semi-structured in-person or telephone interviews with oncologists from seven different health plans. Each interview was audiotaped, transcribed, and coded using qualitative research methods. Information and salient themes relating to the research questions were summarized for each interview. All of the oncologists in this study reported using the KRAS test at the time of the interview. Most appeared to have adopted the test rapidly, within 6 months of the publication of National Clinical Guidelines. Oncologists chose to administer the test at various time points, although the majority ordered the test at the time their patient was diagnosed with mCRC. While oncologists expressed a range of opinions about the KRAS test, there was a general consensus that the test was useful and provided benefits to mCRC patients. The rapid adoption and enthusiasm for KRAS suggests that these types of tests may be filling an important informational need for oncologists when making treatment decisions. Future research should focus on the informational needs of patients around this test and whether patients feel informed or confident with their physicians’ use of these tests to determine treatment access.
Authors: Harris JN; Liljestrand P; Alexander GL; Goddard KA; Kauffman T; Kolevska T; McCarty C; O'Neill S; Pawloski P; Rahm A; Williams A; Somkin CP
Cancer Med. 2013 Dec;2(6):881-8. Epub 2013-10-02.
Onset of Breast Development in a Longitudinal Cohort
There is growing evidence of pubertal maturation occurring at earlier ages, with many studies based on cross-sectional observations. This study examined age at onset of breast development (thelarche), and the impact of BMI and race/ethnicity, in the 3 puberty study sites of the Breast Cancer and the Environment Research Program, a prospective cohort of >1200 girls. Girls, 6 to 8 years at enrollment, were followed longitudinally at regular intervals from 2004 to 2011 in 3 geographic areas: the San Francisco Bay Area, Greater Cincinnati, and New York City. Sexual maturity assessment using Tanner staging was conducted by using standardized observation and palpation methods by trained and certified staff. Kaplan-Meier analyses were used to describe age at onset of breast maturation by covariates. The age at onset of breast stage 2 varied by race/ethnicity, BMI at baseline, and site. Median age at onset of breast stage 2 was 8.8, 9.3, 9.7, and 9.7 years for African American, Hispanic, white non-Hispanic, and Asian participants, respectively. Girls with greater BMI reached breast stage 2 at younger ages. Age-specific and standardized prevalence of breast maturation was contrasted to observations in 2 large cross-sectional studies conducted 10 to 20 years earlier (Pediatric Research in Office Settings and National Health and Nutrition Examination Survey III) and found to have occurred earlier among white, non-Hispanic, but not African American girls. We observed the onset of thelarche at younger ages than previously documented, with important differences associated with race/ethnicity and BMI, confirming and extending patterns seen previously. These findings are consistent with temporal changes in BMI.
Authors: Biro FM; Kushi LH; Wolff MS; et al.
Pediatrics. 2013 Dec;132(6):1019-27. Epub 2013-11-04.
A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett’s esophagus
Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett’s esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precancerous Barrett’s esophagus (n = 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226: P = 3.6 × 10(-10)) in CRTC1 (encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 × 10(-9)) in BARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201: P = 5.5 × 10(-9)) near the transcription factor FOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett’s esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma.
Authors: Levine DM; Corley DA; Vaughan TL; et al.
Nat Genet. 2013 Dec;45(12):1487-93. Epub 2013-10-13.
Sex-specific associations between body mass index, waist circumference and the risk of Barrett’s oesophagus: a pooled analysis from the international BEACON consortium
Barrett’s oesophagus is a precursor lesion of oesophageal adenocarcinoma, a cancer that, in the USA, has increased in incidence over 600% during the past 40 years. Barrett’s oesophagus and oesophageal adenocarcinoma are much more common among men than among women; this finding is unexplained and most earlier studies lacked sufficient numbers of women to evaluate sex-specific risk factors. We leveraged the power of an international consortium to assess sex-specific relationships between body mass index (BMI), abdominal circumference and Barrett’s oesophagus. Four case-control studies provided a total of 1102 cases (316 women, 786 men) and 1400 population controls (436 women, 964 men) for analysis. Study-specific estimates, generated using individual participant data, were combined using random effects meta-analysis. Waist circumference was significantly associated with Barrett’s oesophagus, even after adjustment for BMI; persons in the highest versus the lowest quartiles of waist circumference had approximately 125% and 275% increases in the odds of Barrett’s oesophagus among men and women, respectively (OR 2.24, 95% CI 1.08 to 4.65, I(2)=57; OR 3.75, 95% CI 1.47 to 9.56, I(2)=0). In contrast, there was no evidence of a significant association between BMI and the risk of Barrett’s oesophagus, with or without adjustment for waist circumference. Waist circumference, independent of BMI, was found to be a risk factor for Barrett’s oesophagus among both men and women. Future studies examining the biological mechanisms of this association will extend our knowledge regarding the pathogenesis of Barrett’s oesophagus.
Authors: Kubo A; Cook MB; Shaheen NJ; Vaughan TL; Whiteman DC; Murray L; Corley DA
Gut. 2013 Dec;62(12):1684-91.
Uncontrolled confounding in studies of screening effectiveness: an example of colonoscopy
To estimate the expected magnitude of error produced by uncontrolled confounding from health behaviours in observational medical record-based studies evaluating effectiveness of screening colonoscopy. We used data from the prospective National Institutes of Health American Association of Retired Persons (NIH-AARP) Diet and Health Study to assess the impact of health behaviour related factors (lifestyle, education, and use of non-steroidal anti-inflammatory drugs [NSAID]) on the association between colonoscopy and colorectal cancer (CRC) mortality. We first examined the difference between adjusted and unadjusted results within the cohort data, and then estimated a broader range of likely confounding errors based on the Breslow-Day approach that uses prevalence of confounders among persons with and without exposure, and the rate ratio reflecting the association between these confounders and the outcome of interest. As dietary factors and habits are often inter-correlated, we combined these variables (physical activity, body mass index, waist-to-hip ratio, alcohol consumption, and intakes of red meat, processed meat, fibre, milk, and calcium) into a “healthy lifestyle score” (HLS). The estimated error (a ratio of biased-to-true result) attributable to confounding by HLS was 0.959-0.997, indicating less than 5% departure from the true effect of colonoscopy on CRC mortality. The corresponding errors ranged from 0.970 to 0.996 for NSAID, and from 0.974 to 1.006 for education (all ?3% difference). The results for other CRC screening tests were similar. Health behaviour-related confounders, either alone or in combination, seem unlikely to strongly affect the association between colonoscopy and CRC mortality in observational studies of CRC screening.
Authors: Eldridge RC; Doubeni CA; Fletcher RH; Zauber AG; Corley DA; Doria-Rose VP; Goodman M
J Med Screen. 2013 Dec;20(4):198-207. Epub 2013-10-21.
Response
Authors: Kroenke CH; Caan BJ
J Natl Cancer Inst. 2013 Nov 20;105(22):1761-2. Epub 2013-10-10.
Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett’s Esophagus, and Gastroesophageal Reflux
Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett’s esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h(2)g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were two-sided, except in the case of variance-explained estimation where one-sided tests were used. We estimated a statistically significant genetic variance explained for BE (h(2)g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10(-9)) and for EA (h(2)g = 25 %; SE = 5%; one-sided P = 2 × 10(-7)). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10(-6)), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases.
Authors: Ek WE; Corley DA; BEACON study investigators; et al.
J Natl Cancer Inst. 2013 Nov 20;105(22):1711-8. Epub 2013-10-29.
Effects on skills and practice from a web-based skin cancer course for primary care providers
Melanoma incidence and mortality is a growing concern. Better recognition and management of skin cancer by primary care providers (PCPs) could help, but studies suggest they would benefit from additional education. Effective educational programs are needed. We developed and conducted a voluntary before-and-after evaluation of a 1- to 2-hour interactive, web-based course in skin cancer detection for practicing, board-certified PCPs (https://www.skinsight.com/info/for_professionals/dermatology-education-resources). Voluntary participants’ ability to diagnose and manage skin cancer was assessed using pretests, immediate tests, and 6-month posttests. The effect on actual practice patterns was assessed using participants’ patient panels: referrals or visits to dermatology and skin biopsies during the 6 months after the course were compared with those during the same period before the course. The mean age of the 54 participants was 50.5 years (standard deviation, 11.1); 54% were women and 52% were Asian. The mean score for appropriate diagnosis and management increased from 36.1% to 46.7% (odds ratio, 1.6; 95% confidence interval, 1.4-1.9), with greatest improvement in benign lesions, from 32.1% to 46.3% (odds ratio, 1.9; 95% confidence interval, 1.6-2.4). Dermatology referrals for suspicious lesions or new visits by participants’ patients decreased at both sites after the course (from 630 to 607 and from 726 to 266, respectively). This course improved skills in practicing PCPs. Improvement was greatest in the diagnosis and appropriate management of benign lesions and dermatology utilization decreased.
Authors: Eide MJ; Asgari MM; INFORMED (INternet course FOR Melanoma Early Detection) Group; et al.
J Am Board Fam Med. 2013 Nov-Dec;26(6):648-57.
Genetic Predictors of Circulating 25-Hydroxyvitamin D and Risk of Colorectal Cancer
Experimental evidence has demonstrated an antineoplastic role for vitamin D in the colon, and higher circulating 25-hydroxyvitamin D [25(OH)D] levels are consistently associated with a lower risk of colorectal cancer. Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified single-nucleotide polymorphisms (SNPs) from four gene regions collectively explain approximately 5% of the variance in circulating 25(OH)D. We investigated whether five polymorphisms in GC, CYP2R1, CYP24A1, and DHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with colorectal cancer risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We conducted a meta-analysis of crude and multivariate-adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs individually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS). We did not observe a statistically significant association between the 25(OH)D-associated SNPs and colorectal cancer marginally, conditionally, or as a GRS, or for colon or rectal cancer separately. Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of colorectal cancer. Additional work is warranted to investigate the complex relationship between 25(OH)D and colorectal cancer risk. There was no association observed between genetic markers of circulating 25(OH)D and colorectal cancer. These genetic markers account for a small proportion of the variance in 25(OH)D.
Authors: Hiraki LT; Caan BJ; Chan AT; et al.
Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):2037-46. Epub 2013-08-27.
Associations between ambient air pollution and prevalence of stroke and cardiovascular diseases in 33 Chinese communities
Inconsistent results have been reported that long-term exposure to ambient air pollution contributes to the increased prevalence of stroke and cardiovascular diseases (CVDs). In order to examine whether the exposure to ambient air pollution was associated with the prevalence of stroke and CVDs among people living in a heavy industrial province of northeast China, we conducted a cross-sectional study of 24,845 Chinese adults, ages 18-74 years old, from 33 communities in the 11 districts of the three Northeastern Chinese Cities during 2009. Three-year (2006-2008) average concentrations of particles with an aerodynamic diameter <= 10 mu m (PM10), sulfur dioxide (SO2), nitrogen dioxides (NO2), and Ozone (O-3) were calculated from monitoring stations in each of the 11 districts. We used two-level logistic regressions models to examine the effects of yearly variations in exposure to each pollutant, controlling for important covariates. We found significant associations between PM10 and SO2 levels and stroke prevalence after accounting for important covariates: the adjusted odds ratio for stroke increased by 1.16 (95% confidence interval [CI], 1.03-1.30) per 19 mu g m(-3) increase in PM10, and 1.14 (95%Cl, 1.01-1.29) per 20 mu g m(-3) increase in SO2, respectively. When stratified analysis by gender, these associations were significant only in men, but not in women. In conclusion, this study shows the association between long-term exposure to PM10 and SO2 and increased stroke prevalence, and the associations were more apparent in men than in women.
Atmospheric Environment. 2013 October; 77:968-973. doi: 10.1016/j.atmosenv.2013.06.034.
The California Breast Cancer Survivorship Consortium (CBCSC): prognostic factors associated with racial/ethnic differences in breast cancer survival
Racial/ethnic disparities in mortality among US breast cancer patients are well documented. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American, and Asian American women. To address this knowledge gap, the California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled interview information (e.g., demographics, family history of breast cancer, parity, smoking, alcohol consumption) from six California-based breast cancer studies and assembled corresponding cancer registry data (clinical characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and 2007. In total, 3,047 deaths (1,570 breast cancer specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Cox proportional hazards regression models were fit to data to estimate hazards ratios (HRs) and 95 % confidence intervals (CIs) for overall and breast cancer-specific mortality. Compared with non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95 % CI 0.97-1.33) for African Americans, 0.84 (95 % CI 0.70-1.00) for Latinas, and 0.60 (95 % CI 0.37-0.97) for Asian Americans after adjustment for age, tumor characteristics, and select lifestyle factors. The CBCSC represents a large and racially/ethnically diverse cohort of breast cancer patients from California. This cohort will enable analyses to jointly consider a variety of clinical, lifestyle, and contextual factors in attempting to explain the long-standing disparities in breast cancer outcomes.
Authors: Wu AH; Kwan ML; Caan BJ; Sposto R; et al.
Cancer Causes Control. 2013 Oct;24(10):1821-36. Epub 2013-07-18.
Family History of Diabetes and Pancreatic Cancer as Risk Factors for Pancreatic Cancer: The PACIFIC Study
Genetic association studies have identified more than a dozen genes associated with risk of pancreatic cancer. Given this genetic heterogeneity, family history can be useful for identifying individuals at high risk for this disease. The goal of this analysis was to evaluate associations of family history of diabetes and family history of pancreatic cancer with risk of pancreatic cancer. PACIFIC is a case-control study based on two large health plans. Cases were diagnosed with pancreatic ductal adenocarcinoma (PDA) and controls were selected from the health plan enrollment databases and frequency matched to cases. Family history data were collected using an interviewer-administered questionnaire and were available on 654 cases and 697 controls. Logistic regression was used for the association analyses. First-degree relative history of diabetes was statistically significantly associated with increased risk of PDA [OR, 1.37; 95% confidence interval (CI), 1.10-1.71]. The highest risk of PDA was observed for an offspring with diabetes (OR, 1.95; 95% CI, 1.23-3.09). In addition, history of pancreatic cancer increased risk for PDA with an OR of 2.79 (95% CI, 1.44-4.08) for any first-degree relative history of pancreatic cancer. This population-based analysis showed that family history of diabetes was associated with increased risk of PDA and confirmed previous studies showing that first-degree family history of pancreatic cancer is associated with PDA. These results support the need for ongoing studies of genetic influences on pancreatic cancer in large samples and investigations of possible pleiotropic genetic effects on diabetes and pancreatic cancer.
Authors: Austin MA; Kuo E; Van Den Eeden SK; Mandelson MT; Brentnall TA; Kamineni A; Potter JD
Cancer Epidemiol Biomarkers Prev. 2013 Oct;22(10):1913-7. Epub 2013-08-21.
Leadership and Job Readiness: Addressing Social Determinants of Health Among Ruralafrican American Men
There is increased recognition that the inequitable distribution of social determinants acts as a stressor that influences health outcomes. Men on the Move’s Leadership and Job Readiness (LJR) program was developed to improve employment opportunities and build leadership capacity for African American men living in a rural community. Pre-post questionnaires and interviews were conducted with participants to assess the immediate impact of LJR. Paired t-tests indicated that those respondents who were out of work significantly increased certain dimensions of their hope scores. Results also indicated increases in some elements of active coping and decreases in risky behavior. Using a linear regression model, increased hope was found to be a significant predictor of improvements in participants’ coping and behavior scores. Qualitative interviews showed increases in communication, job readiness and coping skills as well as an increased sense of hope and understanding among participants of their role as leaders in their community.
Authors: Baker E, Barnidge E, Langston M, Schootman M, Motton F, Rose F.
International Journal of Men's Health. 2013-9-; 12(3):245-259. doi: 10.3149/jmh.1203.245.
African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women’s Health Initiative
Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk. The Women’s Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses. Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort. African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans.
Authors: Perez MV; Hoffmann TJ; Tang H; Thornton T; Stefanick ML; Larson JC; Kooperberg C; Reiner AP; Caan B; Iribarren C; Risch N
Am Heart J. 2013 Sep;166(3):566-72.
Immunohistochemical Expression of ERG in the Molecular Epidemiology of Fatal Prostate Cancer Study
BACKGROUND: Gene fusions between the ERG transcription factor and the androgen-regulated gene TMPRSS2 occur in a subset of prostate cancers and contribute to transformation of prostatic epithelial cells. Prior reports have used fluorescence in situ hybridization (FISH) or quantitative PCR (QPCR) to determine the presence of TMPRSS2-ERG fusions or ERG expression, respectively. Recently, several groups have reported on immunohistochemistry (IHC) to measure ERG expression, which is much more readily performed in clinical practice. However, the prior studies examining ERG expression by IHC had small sample sizes or they failed to clarify the association of ERG protein expression with important clinico-pathological features or prostate cancer-specific mortality. Methods: To address these deficits, we evaluated ERG expression by IHC in 208 radical prostatectomy samples from the Kaiser Permanente Molecular Epidemiology of Fatal Prostate Cancer (MEFPC) study, a case-control study of prostate cancer-specific mortality. RESULTS: Nuclear ERG expression was seen in neoplastic prostate epithelia in 49 of the samples (23.7%). ERG expression in tumor cells was associated with higher tumor stage (OR = 2.0, 95% confidence interval 1.0-4.0, P value = 0.04). ERG immunoreactivity was positively associated with prostate cancer-specific mortality, although the confidence interval was wide (OR = 1.9, 95% confidence interval 0.88-4.0, P value = 0.10). CONCLUSIONS: Our results demonstrate that ERG protein expression is readily quantifiable with an existing commercial antibody. Evaluating ERG protein expression may improve our ability to identify the subset of more aggressive, invasive prostate cancers.
Authors: Weinmann S; Van Den Eeden SK; Haque R; Chen C; Richert-Boe K; Schwartzman J; Gao L; Berry DL; Kallakury BV; Alumkal JJ
Prostate. 2013 Sep;73(13):1371-7. Epub 2013 May 9.
Abnormal vaginal bleeding after epidural steroid injection: a paired observation cohort study
OBJECTIVE: The use of epidural steroid injections has increased dramatically, but knowledge of potential adverse effects is lacking. An association between steroid injection and subsequent abnormal vaginal bleeding has been suspected clinically, but evidence has been limited to anecdotal reports. STUDY DESIGN: Paired observational retrospective cohort study using electronic medical records from a large integrated health care system. Participants were all nonhysterectomized women who underwent epidural steroid injections in 2011. For each steroid injection, encounters for abnormal vaginal bleeding during the 60 days preceding and 60 days after the injection were compared as paired observations. For women found to have bleeding, medical records review was performed to examine menopausal status and bleeding evaluation outcomes. RESULTS: Among 8166 epidural steroid injection procedures performed on 6926 nonhysterectomized women, 201 (2.5%) procedures were followed by at least 1 outpatient visit for abnormal vaginal bleeding. Women were 2.8 times more likely to present with abnormal vaginal bleeding during the postinjection period compared with the preinjection period (P < .0001). Of the 197 women with postinjection bleeding, 137 (70%) were premenopausal and 60 (30%) were postmenopausal. Postinjection bleeding prompted endometrial biopsy evaluation in 103 (52%) cases, with benign findings for 100% of premenopausal women (59/59) and 95% of postmenopausal women (42/44). CONCLUSION: Epidural steroid injections are associated with subsequent abnormal vaginal bleeding for both premenopausal and postmenopausal women. Women undergoing epidural steroid injection should be advised of abnormal bleeding as a potential adverse effect and providers should be aware of this association when evaluating abnormal bleeding.
Authors: Suh-Burgmann E; Hung YY; Mura J
Am J Obstet Gynecol. 2013 Sep;209(3):206.e1-6. Epub 2013 Jun 28.
Health Benefits and Cost-Effectiveness of a Hybrid Screening Strategy for Colorectal Cancer
Colorectal cancer (CRC) screening guidelines recommend screening schedules for each single type of test except for concurrent sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost-effectiveness of a hybrid screening strategy that was based on a fecal immunological test (FIT) and colonoscopy. We conducted a cost-effectiveness analysis by using the Archimedes Model to evaluate the effects of different CRC screening strategies on health outcomes and costs related to CRC in a population that represents members of Kaiser Permanente Northern California. The Archimedes Model is a large-scale simulation of human physiology, diseases, interventions, and health care systems. The CRC submodel in the Archimedes Model was derived from public databases, published epidemiologic studies, and clinical trials. A hybrid screening strategy led to substantial reductions in CRC incidence and mortality, gains in quality-adjusted life years (QALYs), and reductions in costs, comparable with those of the best single-test strategies. Screening by annual FIT of patients 50-65 years old and then a single colonoscopy when they were 66 years old (FIT/COLOx1) reduced CRC incidence by 72% and gained 110 QALYs for every 1000 people during a period of 30 years, compared with no screening. Compared with annual FIT, FIT/COLOx1 gained 1400 QALYs/100,000 persons at an incremental cost of $9700/QALY gained and required 55% fewer FITs. Compared with FIT/COLOx1, colonoscopy at 10-year intervals gained 500 QALYs/100,000 at an incremental cost of $35,100/QALY gained but required 37% more colonoscopies. Over the ranges of parameters examined, the cost-effectiveness of hybrid screening strategies was slightly more sensitive to the adherence rate with colonoscopy than the adherence rate with yearly FIT. Uncertainties associated with estimates of FIT performance within a program setting and sensitivities for flat and right-sided lesions are expected to have significant impacts on the cost-effectiveness results. In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.
Authors: Dinh T; Ladabaum U; Alperin P; Caldwell C; Smith R; Levin TR
Clin Gastroenterol Hepatol. 2013 Sep;11(9):1158-66. Epub 2013-03-28.
Efficacy of Intermittent Androgen Deprivation Therapy vs Conventional Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Meta-analysis
OBJECTIVE: To compare the efficacy of intermittent androgen deprivation therapy (IADT) vs continuous androgen deprivation therapy (CADT) for the treatment of advanced prostate cancer; we performed a meta-analysis of randomized controlled trials (RCTs), assessing the risks of disease progression, all-cause, and disease-specific mortality. MATERIALS AND METHODS: We conducted a systematic search of several bibliographic systems to identify all RCTs of IADT in men with newly diagnosed metastatic or biochemical only prostate cancer. We abstracted outcome data, study characteristics, and participant demographics. We performed heterogeneity tests and calculated the summarized risk differences (RD) and risk ratios at 95% confidence intervals (CI), using inverse variance methods in random-effects approaches. RESULTS: We identified 8 RCTs (N = 4664) comparing mortality between IADT and CADT. For all men combined, we observed small but nonsignificant differences in all-cause mortality (RD = 0.02, 95% CI = -0.02, 0.06), disease-specific mortality (RD = 0.04, 95% CI = -0.01, 0.08), and disease progression (RD = -0.03, 95% CI = -0.09, 0.04). Among the prespecified subgroup with histologically confirmed, newly diagnosed metastatic disease, we found no difference in overall survival (RD = 0.00, 95% CI = -0.09, 0.09). CONCLUSION: We found no difference in overall survival, but a small increased risk in disease-specific survival for men treated with IADT relative to CADT was observed. IADT could be considered as an alternative to CADT because of better quality of life outcome. Patients should be informed of the possible risks and benefits of both therapies. More research confirming the benefits of IADT vs CADT is needed to inform treatment decisions.
Authors: Tsai HT; Penson DF; Makambi KH; Lynch JH; Van Den Eeden SK; Potosky AL
Urology. 2013 Aug;82(2):327-33.
A survey of breast cancer physicians regarding patient involvement in breast cancer treatment decisions
Shared breast cancer treatment decision-making between patients and physicians increases patient treatment satisfaction and compliance and is influenced by physician-related factors. Attitudes and behaviors about patient involvement in breast cancer treatment decisions and treatment-related communication were assessed by specialty among breast cancer physicians of women enrolled in the Breast Cancer Quality of Care Study (BQUAL). Of 275 BQUAL physicians identified, 50.0% responded to the survey. Most physicians spend 46-60 min with the patient during the initial consult visit and 51.5% report that the treatment decision is made in one visit. Oncologists spend more time with new breast cancer patients during the initial consult (p = 0.021), and find it more difficult to handle their own feelings than breast surgeons (p = <0.001). Breast surgeons and oncologists share similar attitudes and behaviors related to patient involvement in treatment decision-making, yet oncologists report more difficulty managing their own feelings during the decision-making process.
Authors: Hillyer GC; Hershman DL; Kushi LH; Lamerato L; Ambrosone CB; Bovbjerg DH; Mandelblatt JS; Rana S; Neugut AI
Breast. 2013 Aug;22(4):548-54. Epub 2012-10-27.
Impact of Endoscopic Surveillance on Mortality from Barrett’s Esophagus-Associated Esophageal Adenocarcinomas
BACKGROUND & AIMS: Although patients with Barrett’s esophagus commonly undergo endoscopic surveillance, its effectiveness in reducing mortality from esophageal/gastroesophageal junction adenocarcinomas has not been evaluated rigorously. METHODS: We performed a case-control study in a community-based setting. Among 8272 members with Barrett’s esophagus, we identified 351 esophageal adenocarcinoma: 70 in persons who had a prior diagnosis of Barrett’s esophagus (who were eligible for surveillance); 51 of these patients died, 38 as a result of the cancers (cases). Surveillance histories were contrasted with a sample of 101 living persons with Barrett’s esophagus (controls), matched for age, sex, and duration of follow-up evaluation. RESULTS: Surveillance within 3 years was not associated with a decreased risk of death from esophageal adenocarcinoma (adjusted odds ratio, 0.99; 95% confidence interval, 0.36-2.75). Fatal cases were nearly as likely to have received surveillance (55.3%) as were controls (60.4%). A Barrett’s esophagus length longer than 3 cm and prior dysplasia each were associated with subsequent mortality, but adjustment for these did not change the main findings. Although all patients should be included in evaluations of effectiveness, excluding deaths related to cancer treatment and patients who failed to complete treatment, changed the magnitude, but not the significance, of the association (odds ratio, 0.46; 95% confidence interval, 0.13-1.64). CONCLUSIONS: Endoscopic surveillance of patients with Barrett’s esophagus was not associated with a substantially decreased risk of death from esophageal adenocarcinoma. The results do not exclude a small to moderate benefit. However, if such a benefit exists, our findings indicate that it is substantially smaller than currently estimated. The effectiveness of surveillance was influenced partially by the acceptability of existing treatments and the occurrence of treatment-associated mortality.
Authors: Corley DA; Mehtani K; Quesenberry C; Zhao W; de Boer J; Weiss NS
Gastroenterology. 2013 Aug;145(2):312-9.e1. Epub 2013 May 11.
Validity of diagnostic codes and prevalence of psoriasis and psoriatic arthritis in a managed care population, 1996-2009
Few population-based studies have reported the prevalence of psoriatic disease. We validated computerized diagnoses to estimate the prevalence of psoriasis and psoriatic arthritis. We identified adults with ?1 ICD-9 diagnosis codes of 696.0 (psoriatic arthritis) or 696.1 (psoriasis) in clinical encounter data during 1996-2009 and used chart review to confirm the diagnoses in random samples of patients. We then used the best performing case-finding algorithms to estimate the point prevalence of psoriasis and psoriatic arthritis. The number of persons with a diagnosis for psoriasis (ICD-9 code 696.1) was 87?827. Chart review of a random sample of 101 cases with at least one dermatologist-rendered psoriasis code revealed a positive predictive value (PPV) of 90% (95% CI, 83-95) with sensitivity of 88% (95% CI, 80-93). Psoriatic arthritis (code 696.0) was recorded for 5187 patients, with the best performing algorithm requiring ?2 diagnoses recorded by a rheumatologist or ?1 diagnosis recorded by a rheumatologist together with ?1 psoriasis diagnoses recorded by a dermatologist; the PPV was 80% (95% CI, 70-88) with sensitivity 73% (95% CI, 63-82). Among KPNC adults, the point prevalence of psoriasis, with or without psoriatic arthritis, was 939 (95% CI, 765-1142) per 100?000, and the overall prevalence of psoriatic arthritis, with or without psoriasis, was 68 (95% CI, 54-84) per 100?000. Within an integrated health care delivery system, the use of computerized diagnoses rendered by relevant disease specialists is a valid method for identifying individuals with psoriatic disease.
Authors: Asgari MM; Wu JJ; Gelfand JM; Salman C; Curtis JR; Harrold LR; Herrinton LJ
Pharmacoepidemiol Drug Saf. 2013 Aug;22(8):842-9. Epub 2013-05-02.
Post-diagnosis Cruciferous Vegetable Consumption and Breast Cancer Outcomes: a Report from the After Breast Cancer Pooling Project
Cruciferous vegetables are a major source of glucosinolate-derived bioactive compounds such as isothiocyanates, which have been shown in animal and in vitro studies to inhibit cancer growth and progression. Few studies have investigated cruciferous vegetable intake after diagnosis and breast cancer outcomes. Using data from the After Breast Cancer Pooling Project, which includes prospective data from U.S. and Chinese breast cancer survivors, we evaluated the association of cruciferous vegetables with breast cancer outcomes. Analyses included 11,390 women diagnosed with stage I-III invasive breast cancer (1990-2006) from four cohorts. Cruciferous vegetable intake (g/day) was assessed using food frequency questionnaires (mean of 22 months postdiagnosis). Study heterogeneity was evaluated by the Q statistic; hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using delayed-entry Cox regression models stratified by study. After a median follow-up of 9.0 years, 1,725 deaths and 1,421 recurrences were documented. In pooled analyses using study-specific quartiles, cruciferous vegetable intake was not associated with breast cancer outcomes, adjusting for known clinical prognostic factors and selected lifestyle factors. HRs (95% CIs) by increasing quartiles (reference = lowest quartile) were 1.08 (0.93-1.25), 1.01 (0.87-1.18), and 1.10 (0.95-1.28) for recurrence (P(trend) = 0.34) and 1.01 (0.88-1.15), 0.97 (0.84-1.11), and 0.99 (0.86-1.13) for total mortality (P(trend) = 0.84). No associations were observed for subgroups defined by estrogen receptor status, stage, or tamoxifen therapy. Cruciferous vegetable intake at approximately two years after diagnosis was not associated with recurrence or mortality. Our results do not support an association between postdiagnosis cruciferous vegetable intake and breast cancer outcomes.
Authors: Nechuta S; Caan BJ; Chen WY; Kwan ML; Lu W; Cai H; Poole EM; Flatt SW; Zheng W; Pierce JP; Shu XO
Cancer Epidemiol Biomarkers Prev. 2013 Aug;22(8):1451-6. Epub 2013 Jun 13.
Clinical predictors and significance of postvoid residual volume in women with diabetes
To identify women with diabetes at risk of increased postvoid residual volume (PVR) and investigate the relationship of increased PVR to urinary symptoms in women with diabetes. PVR was measured by bladder ultrasonography in a cross-sectional cohort of 427 middle-aged and older women with diabetes. Participants completed questionnaires assessing urgency incontinence, stress incontinence, daytime frequency, nocturia, obstructive voiding, and diabetes-related end-organ complications: heart disease, stroke, neuropathy. Serum HbA1c and creatinine were recorded. 75% of participants had a PVR of 0-49, 13% had a PVR of 50-99, and 12% had a PVR ? 100 mL. Approximately 59% of women with a PVR < 50 mL reported at least one lower urinary tract symptom. Women with diabetes and a PVR ? 100 mL were more likely to report urgency incontinence (OR 2.18, CI 1.08-4.41) and obstructive voiding symptoms (OR 2.47, CI 1.18-5.17) than women with PVR < 50 mL. In multivariable models, poorer glycemic control was associated with an increased likelihood of PVR ? 100 mL (OR 1.30, CI 1.06-1.59 per 1.0-U increase in HbA1c). PVR volumes ? 100 mL may indicate increased risk of urgency incontinence and obstructive voiding. Glycemic control may play a role in preventing increased PVR in women with diabetes.
Authors: Appa AA; Brown JS; Creasman J; Van Den Eeden SK; Subak LL; Thom DH; Ferrara A; Huang AJ
Diabetes Res Clin Pract. 2013 Aug;101(2):164-9. Epub 2013-06-14.
Phospholipase A2G1B polymorphisms and risk of colorectal neoplasia
Pancreatic phospholipase A2, product of PLA2G1B, catalyzes the release of fatty acids from dietary phospholipids.Diet is the ultimate source of arachidonic acid in cellular phospholipids, precursor of eicosanoid signaling molecules, linked to inflammation, cell proliferation and colorectal carcinogenesis. We evaluated the association of PLA2G1B tagging single-nucleotide polymorphisms with colorectal neoplasia risk. A linkage-disequilibrium-based tagSNP algorithm (r(2)=0.90, MAF>/=4%) identified three tagSNPs. The SNPs were genotyped on the Illumina platform in three population-based, case-control studies: colon cancer (1424 cases/1780 controls); rectal cancer (583/775); colorectal adenomas (485/578). Evaluating gene-wide associations, principal-component and haplotype analysis were conducted, individual SNPs were evaluated by logistic regression. Two PLA2G1B variants were statistically significantly associated with reduced risk of rectal cancer (rs5637, 3702 G>A Ser98Ser, p-trend=0.03; rs9657930, 1593 C>T, p-trend=0.01); principal component analysis showed that genetic variation in the gene overall was statistically significantly associated with rectal cancer (p=0.02). NSAID users with the rs2070873 variant had a reduced rectal cancer risk (P-inter=0.02). Specific associations were observed with tumor subtypes (TP53/KRAS). The results suggest that genetic polymorphisms in PLA2G1B affect susceptibility to rectal cancer.
Authors: Abbenhardt C; Poole EM; Kulmacz RJ; Xiao L; Curtin K; Galbraith RL; Duggan D; Hsu L; Makar KW; Caan BJ; Koepl L; Owen RW; Scherer D; Carlson CS; Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and CCFR; Potter JD; Slattery ML; Ulrich CM
Int J Mol Epidemiol Genet. 2013 Sep 12;4(3):140-9.
Incidence and Prevalence of Juvenile Idiopathic Arthritis Among Children in a Managed Care Population, 1996-2009
Few studies based in well-defined North American populations have examined the occurrence of juvenile idiopathic arthritis (JIA), and none has been based in an ethnically diverse population. We used computerized healthcare information from the Kaiser Permanente Northern California membership to validate JIA diagnoses and estimate the incidence and prevalence of the disease in this well-characterized population. We identified children aged ? 15 years with ? 1 relevant International Classification of Diseases, 9th edition, diagnosis code of 696.0, 714, or 720 in computerized clinical encounter data during 1996-2009. In a random sample, we then reviewed the medical records to confirm the diagnosis and diagnosis date and to identify the best-performing case-finding algorithms. Finally, we used the case-finding algorithms to estimate the incidence rate and point prevalence of JIA. A diagnosis of JIA was confirmed in 69% of individuals with at least 1 relevant code. Forty-five percent were newly diagnosed during the study period. The age- and sex-standardized incidence rate of JIA per 100,000 person-years was 11.9 (95% CI 10.9-12.9). It was 16.4 (95% CI 14.6-18.1) in girls and 7.7 (95% CI 6.5-8.9) in boys. The peak incidence rate occurred in children aged 11-15 years. The prevalence of JIA per 100,000 persons was 44.7 (95% CI 39.1-50.2) on December 31, 2009. The incidence rate of JIA observed in the Kaiser Permanente population, 1996-2009, was similar to that reported in Rochester, Minnesota, USA, but 2 to 3 times higher than Canadian estimates.
Authors: Harrold LR; Salman C; Shoor S; Curtis JR; Asgari MM; Gelfand JM; Wu JJ; Herrinton LJ
J Rheumatol. 2013 Jul;40(7):1218-25. Epub 2013-04-15.
Dietary fiber and the risk of precancerous lesions and cancer of the esophagus: a systematic review and meta-analysis
Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. The aim of this systematic review was to quantify the association between dietary fiber and the risk of esophageal cancer by investigating histological subtypes of esophageal cancer and the stage at which fiber may influence the carcinogenic pathway. Systematic search strategies were used to identify relevant studies, and adjusted odds ratios (ORs) were combined using random-effects meta-analyses to assess the risk of cancer when comparing extreme categories of fiber intake. Ten relevant case-control studies were identified within the timeframe searched. Pooled estimates from eight studies of esophageal adenocarcinoma revealed a significant inverse association with the highest fiber intakes (OR 0.66; 95% confidence interval [CI] 0.44-0.98). Two studies also identified protective effects of dietary fiber against Barrett’s esophagus. Similar, though nonsignificant, associations were observed when results from five studies of fiber intake and risk of squamous cell carcinoma were combined (OR 0.61; 95%CI 0.31-1.20). Dietary fiber is associated with protective effects against esophageal carcinogenesis, most notably esophageal adenocarcinoma. Potential methods of action include modification of gastroesophageal reflux and/or weight control.
Authors: Coleman HG; Murray LJ; Hicks B; Bhat SK; Kubo A; Corley DA; Cardwell CR; Cantwell MM
Nutr Rev. 2013 Jul;71(7):474-82. Epub 2013 Apr 24.
Dietary flavonol intake is associated with age of puberty in a longitudinal cohort of girls
Lignans and flavonols are dietary phytoestrogens found at high concentrations in the Western Diet. They have potential to influence the timing of puberty. We hypothesized that greater consumption of these 2 phytoestrogens would be related to later age at pubertal onset among girls. Pubertal assessment and 24-hour diet recall data were available for 1178 girls, ages 6 to 8 years (mean 7.3 years) in the Breast Cancer and Environment Research Project Puberty Study. Lignan and flavonol intakes were mainly derived from fruit and vegetable consumption. Average consumption was 6.5 mg/d for flavonols and 0.6 mg/d for lignans. Highest flavonol consumption (>5 mg/d) was associated with later breast development (adjusted hazards ratio [HR]: 0.74, 95% CI: [0.61-0.91]) compared to 2 to 5 mg/d (adjusted HR: 0.84, 95% CI: [0.70-1.0]) and <2 mg/d (referent group; P-trend = .006). Flavonol intake was not associated with pubic hair development. Lignan intake was not associated with either breast or pubic hair development. Dietary intake was only weakly correlated with urinary enterolactone, a biomarker for lignans (RS = 0.13). Consistent with biologic properties of phytoestrogens that indicate hormonal activity, their consumption may be associated with reproductive end points, even in childhood.
Authors: Mervish NA; Gardiner EW; Galvez MP; Kushi LH; Windham GC; Biro FM; Pinney SM; Rybak ME; Teitelbaum SL; Wolff MS; BCERP
Nutr Res. 2013 Jul;33(7):534-42. Epub 2013-05-31.
Commentary: mediterranean diet and cognitive function: are we approaching clarity in this area?
Authors: Whitmer RA; Kushi LH
Epidemiology. 2013 Jul;24(4):500-2.
Can You Stop Surveillance After Radiofrequency Ablation of Barrett’s Esophagus? A Glass Half Full
Authors: Corley DA
Gastroenterology. 2013 Jul;145(1):39-42.
Employment status and quality of life in recently diagnosed breast cancer survivors
Breast cancer survivors are less likely to be employed than similar healthy women, yet effects of employment on the well being of survivors are largely unknown. In a prospective cohort study of 2013 women diagnosed from 2006 to 2011 with invasive breast cancer in Kaiser Permanente Northern California, we describe associations between hours worked per week and change in employment with quality of life (QOL) from diagnosis through active treatment. Participants completed information on employment status and QOL approximately 2 and 8 months post-diagnosis. QOL was assessed by the Functional Assessment of Cancer Therapy–Breast Cancer. Multivariable linear regression models were adjusted for potential confounders including demographic, diagnostic, and medical care factors to examine associations between employment and QOL. At baseline, overall well being was higher for women who worked at least some hours per week compared with women who were not working. Women working 1-19 h/week at baseline also had higher functional well being compared with women who were not working. There was a significant, positive association between hours worked per week and physical and social well being. At the 6-month follow-up, women working at least 20 h/week had higher physical and functional well being than those who were not working. Lower scores for physical and functional well being were observed among women who stopped working during the 6-month follow-up period. Continuing to work after a breast cancer diagnosis may be beneficial to multiple areas of QOL. Strategies to help women continue working through treatment should be explored.
Authors: Timperi AW; Ergas IJ; Rehkopf DH; Roh JM; Kwan ML; Kushi LH
Psychooncology. 2013 Jun;22(6):1411-20. Epub 2012-08-22.
Patient-physician interaction and quality of life in recently diagnosed breast cancer patients
Few studies have explored how patient-physician interactions influence patients’ quality of life (QOL). In a prospective cohort study of 1,855 women diagnosed with invasive breast cancer in the Kaiser Permanente Northern California Medical Care Program from 2006 to 2011, we examined associations between patient-physician interactions during cancer treatment and QOL, overall and by racial/ethnic group. Participants completed the interpersonal processes of care (IPC) survey at approximately 8 months post-diagnosis to assess specific domains of the patient-physician interaction during the months after cancer diagnosis. Domains included: compassion, elicited concerns, explained results, decided together, lack of clarity, discrimination due to race/ethnicity, and disrespectful office staff. The functional assessment of cancer therapy-breast cancer was completed concurrently to measure QOL. Linear regression models examined the association of IPC with QOL, first adjusting for patient covariates including age, race, clinical factors, and psychosocial measures and then for physician characteristics such as age, sex, race/ethnicity, and specialty. For all participants (n = 1,855), IPC scores suggesting greater lack of clarity, discrimination due to race/ethnicity, and disrespectful office staff in patient-physician interactions were associated with lower QOL (P< 0.01). IPC scores suggesting physicians demonstrating compassion, eliciting concerns, or explaining results were associated with higher QOL (P< 0.01). Among Whites (n = 1,306), only the associations with higher QOL remained. African Americans (n = 110) who reported higher scores on physician compassion and elicited concerns had higher QOL, whereas higher scores for disrespectful office staff had lower QOL. No associations were observed among Asians (n = 201) and Hispanics (n = 186). After further adjustment for physician factors, the associations among Whites remained, whereas those among African Americans disappeared. In the breast cancer treatment setting, characteristics of the patient-physician interaction as perceived by the patient are associated with QOL, yet were not specific to patient race/ethnicity.
Authors: Kwan ML; Tam EK; Ergas IJ; Rehkopf DH; Roh JM; Lee MM; Somkin CP; Stewart AL; Kushi LH
Breast Cancer Res Treat. 2013 Jun;139(2):581-95.
Social networks, social support mechanisms, and quality of life after breast cancer diagnosis
We examined mechanisms through which social relationships influence quality of life (QOL) in breast cancer survivors. This study included 3,139 women from the Pathways Study who were diagnosed with breast cancer from 2006 to 2011 and provided data on social networks (the presence of a spouse or intimate partner, religious/social ties, volunteering, and numbers of close friends and relatives), social support (tangible support, emotional/informational support, affection, positive social interaction), and QOL, measured by the FACT-B, approximately 2 months post diagnosis. We used logistic models to evaluate associations between social network size, social support, and lower versus higher than median QOL scores. We further stratified by stage at diagnosis and treatment. In multivariate-adjusted analyses, women who were characterized as socially isolated had significantly lower FACT-B (OR = 2.18, 95 % CI: 1.72-2.77), physical well-being (WB) (OR = 1.61, 95 % CI: 1.27-2.03), functional WB (OR = 2.08, 95 % CI: 1.65-2.63), social WB (OR = 3.46, 95 % CI: 2.73-4.39), and emotional WB (OR = 1.67, 95 % CI: 1.33-2.11) scores and higher breast cancer symptoms (OR = 1.48, 95 % CI: 1.18-1.87) compared with socially integrated women. Each social network member independently predicted higher QOL. Simultaneous adjustment for social networks and social support partially attenuated associations between social networks and QOL. The strongest mediator and type of social support that was most predictive of QOL outcomes was “positive social interaction.” However, each type of support was important depending on outcome, stage, and treatment status. Larger social networks and greater social support were related to higher QOL after a diagnosis of breast cancer. Effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status.
Authors: Kroenke CH; Kwan ML; Neugut AI; Ergas IJ; Wright JD; Caan BJ; Hershman D; Kushi LH
Breast Cancer Res Treat. 2013 Jun;139(2):515-27.
Risk factors for non-invasive and invasive local recurrence in patients with ductal carcinoma in situ
We aimed to identify clinicopathologic factors associated with local recurrence (LR) in a large population of DCIS patients treated with breast-conserving therapy between 1990-2001 in three health plans. Regression methods were used to estimate relative risks (RR) of LR. Among 2,995 patients, 325 had a LR [10.9 %; median follow-up 4.8 years (range 0.5-15.7)]. After adjusting for health plan and treatment, risk of LR was increased among women <45 years (RR = 2.1, 95 % CI 1.5-2.8), African-Americans (RR = 1.6; 95 % CI 1.1-2.1) and those with DCIS detected because of signs/symptoms (RR = 1.6; 95 % CI 1.2-2.0). After also adjusting for age and diagnosis year, pathologic features associated with increased LR were larger lesion size (RR = 2.9 for ?20 low power fields of DCIS; 95 % CI 1.6-5.6) and involved (RR = 2.9; 95 % CI 1.6-5.2), or close margins (RR = 2.4; 95 % CI 1.6-3.8). Presentation with symptoms/signs was associated with increased risk of invasive recurrence; while African-American race, larger tumor size, and involved/close tumor margins were more strongly associated with increased risk of DCIS recurrence. Our findings suggest some risk factors differ for non-invasive and invasive LRs and that most factors are only moderately associated with increased LR risk. Future research efforts should focus on non-clinicopathologic factors to identify more powerful risk factors for LR.
Authors: Collins LC; Achacoso N; Haque R; Nekhlyudov L; Fletcher SW; Quesenberry CP; Schnitt SJ; Habel LA
Breast Cancer Res Treat. 2013 Jun;139(2):453-60.
Postdiagnosis supplement use and breast cancer prognosis in the After Breast Cancer Pooling Project
Vitamin supplement use after breast cancer diagnosis is common, but little is known about long-term effects on recurrence and survival. We examined postdiagnosis supplement use and risk of death or recurrence in the After Breast Cancer Pooling Project, a consortium of four cohorts of 12,019 breast cancer survivors from the United States and China. Post-treatment supplement use (vitamins A, B, C, D, E, and multivitamins) was assessed 1-5 years postdiagnosis. Associations with risk of recurrence, breast cancer-specific mortality, or total mortality were analyzed in Cox proportional hazards models separately by cohort. Individual cohort results were combined using random effects meta-analysis. Interactions with smoking, treatment, and hormonal status were examined. In multivariate models, vitamin E was associated with a decreased risk of recurrence (RR: 0.88; 95 % CI 0.79-0.99), and vitamin C with decreased risk of death (RR: 0.81; 95 % CI 0.72-0.92). However, when supplements were mutually adjusted, all associations were attenuated. There were no statistically significant associations with breast cancer mortality. The use of antioxidant supplements (multivitamins, vitamin C, or E) was not associated with recurrence, but was associated with a 16 % decreased risk of death (95 % CI 0.72-0.99). In addition, vitamin D was associated with decreased risk of recurrence among ER positive, but not ER negative tumors (p-interaction = 0.01). In this large consortium of breast cancer survivors, post-treatment use of vitamin supplements was not associated with increased risk of recurrence or death. Post-treatment use of antioxidant supplements was associated with improved survival, but the associations with individual supplement were difficult to determine. Stratification by ER status and considering antioxidants as a group may be more clinically relevant when evaluating associations with cancer risk and mortality.
Authors: Poole EM; Shu X; Caan BJ; Flatt SW; Holmes MD; Lu W; Kwan ML; Nechuta SJ; Pierce JP; Chen WY
Breast Cancer Res Treat. 2013 Jun;139(2):529-37.
Effectiveness and Reach of the FLU-FIT Program in an Integrated Health Care System: A Multisite Randomized Trial
OBJECTIVES: We tested the effectiveness of offering home fecal immunochemical tests (FITs) during influenza vaccination clinics to increase colorectal cancer screening (CRCS). METHODS: In a clinical trial at Kaiser Permanente Northern California influenza clinics in Redwood City, Richmond, South San Francisco, Union City, and Fresno, we randomly assigned influenza clinic dates to intervention (FIT offered) or control (FIT not offered) and compared subsequent CRCS activity. RESULTS: Clinic staff provided FITs to 53.9% (1805/3351) of intervention patients aged 50 to 75 years. In the intent-to-treat analysis, 26.9% (900/3351) and 11.7% (336/2884) of intervention and control patients completed an FIT, respectively, within 90 days of vaccination (P
Authors: Potter MB; Ackerson LM; Gomez V; Walsh JM; Green LW; Levin TR; Somkin CP
Am J Public Health. 2013 Jun;103(6):1128-33. Epub 2013 Apr 18.
It’s Time for Clinicians to Reconsider Their Proscription Against the Use of Soyfoods by Breast Cancer Patients
The impact of soyfood intake on breast cancer risk has been intensely investigated. This focus can be attributed to soyfoods being uniquely rich dietary sources of isoflavones. Isoflavones are classified as both phytoestrogens and selective estrogen receptor (ER) modulators. The finding that dietary genistein, the primary soybean isoflavone, stimulates the growth of existing mammary tumors in ovariectomized athymic mice implanted with ER-positive breast cancer cells has led many oncologists to advise their patients against the use of soyfoods. However, the clinical evidence indicates that isoflavone exposure has little effect on markers of breast cancer risk. Furthermore, a pooled analysis that involved 9,514 breast cancer survivors found higher isoflavone intake was associated with a statistically significant 25% reduction in recurrence over the average 7.4-year follow-up period. Given the clinical and epidemiologic data, our position is that clinicians should allow soyfood use by patients for whom soyfoods already represent a normal part of their diet, and should not discourage other breast cancer survivors from moderate consumption.
Authors: Messina M; Caan BJ; Abrams DI; Hardy M; Maskarinec G
Oncology (Williston Park, NY). 2013 May;27(5):430-7.
High- and Low-Fat Dairy Intake, Recurrence, and Mortality After Breast Cancer Diagnosis
BACKGROUND: Dietary fat in dairy is a source of estrogenic hormones and may be related to worse breast cancer survival. We evaluated associations between high- and low-fat dairy intake, recurrence, and mortality after breast cancer diagnosis. METHODS: We included 1893 women from the Life After Cancer Epidemiology study diagnosed with early-stage invasive breast cancer from 1997 to 2000, who completed the Fred Hutchinson Cancer Research Center Food Frequency Questionnaire after diagnosis. A total of 349 women had a recurrence and 372 died during a median follow-up of 11.8 years, with 189 deaths from breast cancer. We used delayed entry Cox proportional hazards regression to evaluate associations between categories of the cumulative average of dairy fat at baseline and at follow-up 5 to 6 years later and subsequent outcomes. Tests of statistical significance were two-sided. RESULTS: In multivariable-adjusted analyses, overall dairy intake was unrelated to breast cancer-specific outcomes, although it was positively related to overall mortality. Low-fat dairy intake was unrelated to recurrence or survival. However, high-fat dairy intake was positively associated with outcomes. Compared with the reference (0 to <0.5 servings/day), those consuming larger amounts of high-fat dairy had higher breast cancer mortality (0.5 to <1.0 servings/day: hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.82 to 1.77; and >/=1.0 servings/day: HR = 1.49, 95% CI = 1.00 to 2.24, P trend = .05), higher all-cause mortality (P trend < .001), and higher non-breast cancer mortality (P trend = .007); the relationship with breast cancer recurrence was positive but not statistically significant. The higher risk appeared consistent across different types of high-fat dairy products. CONCLUSIONS: Intake of high-fat dairy, but not low-fat dairy, was related to a higher risk of mortality after breast cancer diagnosis.
Authors: Kroenke CH; Kwan ML; Sweeney C; Castillo A; Caan BJ
J Natl Cancer Inst. 2013 May 1;105(9):616-23. Epub 2013 Mar 14.
Genetic variation in the lipoxygenase pathway and risk of colorectal neoplasia
Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to generate potent inflammatory mediators and play an important role in inflammation-associated diseases. We investigated associations between colorectal cancer risk and polymorphisms in ALOX5, FLAP, ALOX12, and ALOX15, and their interactions with nonsteroidal anti-inflammatory drug (NSAID) use. We genotyped fifty tagSNPs, one candidate SNP, and two functional promoter variable nucleotide tandem repeat (VNTR) polymorphisms in three US population-based case-control studies of colon cancer (1,424 cases/1,780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). Individuals with variant genotypes of the ALOX5 VNTR had a decreased risk of rectal cancer, with the strongest association seen for individuals with one or more alleles of >5 repeats (wild type = 5, OR>5/>/=5 = 0.42, 95% CI 0.20-0.92; P = 0.01). Four SNPs in FLAP (rs17239025), ALOX12 (rs2073438), and ALOX15 (rs4796535 and rs2619112) were associated with rectal cancer risk at P
Authors: Kleinstein SE; Caan BJ; Ulrich CM; et al.
Genes Chromosomes Cancer. 2013 May;52(5):437-49. Epub 2013 Feb 12.
Meta-analysis: the risk of venous thromboembolism in patients with inflammatory bowel disease
Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a systemic disorder that predominantly affects the bowels but is also associated with venous thromboembolism (VTE). To provide a quantitative assessment of the association of IBD with venous thromboembolism risk and to explore the possible sources of heterogeneity in the current literature, a meta-analysis of case-control and cohort studies was conducted. Studies were identified by a literature search of the PubMed and Scopus databases (from inception inclusive 31 December 2012) for English language studies. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias. Eleven studies met our inclusion criteria. The summary RR for deep venous thromboembolism (DVT) and pulmonary embolism (PE) comparing subjects both with and without IBD was 2.20 (95% CI 1.83-2.65). After adjusting for obesity and smoking, summary relative risks near 2.0 were seen for venous thromboembolism in both UC and CD patients. This meta-analysis showed that inflammatory bowel disease is associated with an approximately two-fold increase in the risk of venous thromboembolism.
Authors: Yuhara H; Steinmaus C; Corley D; Koike J; Igarashi M; Suzuki T; Mine T
Aliment Pharmacol Ther. 2013 May;37(10):953-62.
Racial Disparities in Posttraumatic Stress After Diagnosis of Localized Breast Cancer; The BQUAL Study
BACKGROUND: Little is known about the development of posttraumatic stress disorder (PTSD) over time among women diagnosed with breast cancer. This study examines changes in PTSD symptoms in the first 6 months after diagnosis and assesses racial/ethnic differences in PTSD symptomatology over time. METHODS: We recruited women with newly diagnosed breast cancer, stages I to III, from three sites in the United States. Three telephone interviews were conducted: baseline at about 2 to 3 months after diagnosis, first follow-up at 4 months after diagnosis, and second follow-up at 6 months after diagnosis. We measured traumatic stress in each interview using the Impact of Events Scale; recorded sociodemographic, tumor, and treatment factors; and used generalized estimating equations and polytomous logistic regression modeling to examine the associations between variables of interest and PTSD. RESULTS: Of 1139 participants, 23% reported symptoms consistent with a diagnosis of PTSD at baseline, 16.5% at first follow-up, and 12.6% at the second follow-up. Persistent PTSD was observed among 12.1% participants, as defined by having PTSD at two consecutive interviews. Among participants without PTSD at baseline, 6.6% developed PTSD at the first follow-up interview. Younger age at diagnosis, being black (odds ratio [OR] = 1.48 vs white, 95% confidence interval [CI] =1.04 to 2.10), and being Asian (OR = 1.69 vs white, 95% CI = 1.10 to 2.59) were associated with PTSD. CONCLUSIONS: Nearly one-quarter of women newly diagnosed with breast cancer reported symptoms consistent with PTSD shortly after diagnosis, with increased risk among black and Asian women. Early identification of PTSD may present an opportunity to provide interventions to manage symptoms.
Authors: Vin-Raviv N; Hillyer GC; Hershman DL; Galea S; Leoce N; Bovbjerg DH; Kushi LH; Kroenke C; Lamerato L; Ambrosone CB; Valdimorsdottir H; Jandorf L; Mandelblatt JS; Tsai WY; Neugut AI
J Natl Cancer Inst. 2013 Apr 17;105(8):563-72. Epub 2013 Feb 21.
Recurrence of subsquamous dysplasia and carcinoma after successful endoscopic and radiofrequency ablation therapy for dysplastic Barrett’s esophagus.
Barrett’s esophagus with dysplasia is commonly treated with radiofrequency ablation (RFA). Despite its effectiveness, a concern of any ablative technique is the development of subsquamous intestinal metaplasia, which could have potential for future neoplastic progression. To date, 34 cases of subsquamous neoplasia have been described in the literature after various ablation therapies. However, only three cases of subsquamous neoplasia have been reported after successful RFA treatment of dysplastic Barrett’s esophagus. In this case series, we report on four additional cases of subsquamous neoplasia detected after successful endoscopic resection and RFA for neoplastic and dysplastic Barrett’s esophagus. All four patients were treated successfully with endoscopic resection of their recurrent subsquamous neoplastic and dysplastic lesions. This case series highlights the need for continued surveillance following successful treatment of dysplastic Barrett’s esophagus with RFA.
Authors: Lee, J K JK; Cameron, R G RG; Binmoeller, K F KF; Shah, J N JN; Shergill, A A; Garcia-Kennedy, R R; Bhat, Y M YM
Endoscopy. 2013 Jul ;45(7):571-4. Epub 2013-04-16.
Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women: The Women’s Health Initiative
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women’s Health Initiative (WHI) Observational Study (OS). METHODS: At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders. RESULTS: During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63-0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1-4 years, and >/= 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with >/= 5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55-0.94). In contrast, use of non-ASA NSAIDs and acetaminophen were not associated with melanoma risk. CONCLUSIONS: Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self-report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation.
Authors: Gamba CA; Swetter SM; Stefanick ML; Kubo J; Desai M; Spaunhurst KM; Sinha AA; Asgari MM; Sturgeon S; Tang JY
Cancer. 2013 Apr 15;119(8):1562-9. Epub 2013 Mar 11.
Gene-diet-interactions in folate-mediated one-carbon metabolism modify colon cancer risk
SCOPE: The importance of folate-mediated one-carbon metabolism (FOCM) in colorectal carcinogenesis is emphasized by observations that high dietary folate intake is associated with decreased risk of colon cancer (CC) and its precursors. Additionally, polymorphisms in FOCM-related genes have been repeatedly associated with risk, supporting a causal relationship between folate and colorectal carcinogenesis. METHODS AND RESULTS: We investigated ten candidate polymorphisms with defined or probable functional impact in eight FOCM-related genes (SHMT1, DHFR, DNMT1, MTHFD1, MTHFR, MTRR, TCN2, and TDG) in 1609 CC cases and 1974 controls for association with CC risk and for interaction with dietary factors. No polymorphism was statistically significantly associated with overall risk of CC. However, statistically significant interactions modifying CC risk were observed for DNMT1 I311V with dietary folate, methionine, vitamin B2 , and vitamin B12 intake and for MTRR I22M with dietary folate, a predefined one-carbon dietary pattern, and vitamin B6 intake. We observed statistically significant gene-diet interactions with five additional polymorphisms. CONCLUSION: Our results provide evidence that FOCM-related dietary intakes modify the association between CC risk and FOCM allelic variants. These findings add to observations showing that folate-related gene-nutrient interactions play an important role in modifying the risk of CC.
Authors: Liu AY; Scherer D; Poole E; Potter JD; Curtin K; Makar K; Slattery ML; Caan BJ; Ulrich CM
Mol Nutr Food Res. 2013 Apr;57(4):721-34. Epub 2012 Sep 7.
Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-Analysis
BACKGROUND & AIMS: Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. METHODS: We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. RESULTS: Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 x 10(-8): an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 x 10(-8)). We also found evidence for 3 additional loci with P values less than 5.0 x 10(-7): a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 x 10(-8)), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 x 10(-8)), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 x 10(-7)). CONCLUSIONS: In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to beta-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.
Authors: Peters U; Caan BJ; Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium; et al.
Gastroenterology. 2013 Apr;144(4):799-807.e24. Epub 2012 Dec 22.
Turning of COGS moves forward findings for hormonally mediated cancers
The large-scale Collaborative Oncological Gene-environment Study (COGS) presents new findings that further characterize the genetic bases of breast, ovarian and prostate cancers. We summarize and provide insights into this collection of papers from COGS and discuss the implications of the results and future directions for such efforts.
Authors: Sakoda LC; Jorgenson E; Witte JS
Nat Genet. 2013 Apr;45(4):345-8.
DNA repair genotype and lung cancer risk in the beta-carotene and retinol efficacy trial
Many carcinogens in tobacco smoke cause DNA damage, and some of that damage can be mitigated by the actions of DNA repair enzymes. In a case-control study nested within the Beta-Carotene and Retinol Efficacy Trial, a randomized chemoprevention trial in current and former heavy smokers, we examined whether lung cancer risk was associated with variation in 26 base excision repair, mismatch repair, and homologous recombination repair genes. Analyses were limited to Caucasians (744 cases, 1477 controls), and logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for individual SNPs and common haplotypes, with adjustment for matching factors. Lung cancer associations were observed (p<0.05) with SNPs in MSH5 (rs3131379, rs707938), MSH2 (rs2303428), UNG (rs246079), and PCNA (rs25406). MSH5 rs3131379 is a documented lung cancer susceptibility locus in complete linkage disequilibrium with rs3117582 in BAT3, and we observed associations similar in magnitude to those in prior studies (per A allele OR 1.37, 95% CI 1.13-1.65). UNG was associated with lung cancer risk at the gene level (p=0.02), and the A allele of rs246079 was associated with an increased risk (per A allele OR 1.15, 95% CI1.01-1.31). We observed stronger associations with UNG rs246079 among individuals who carried the risk genotypes (AG/AA) for MSH5 rs3131379 (pinteraction= 0.038). Our results provide additional evidence to suggest that the MSH5/BAT3 locus is associated with increased lung cancer risk among smokers, and that associations with other SNPs may vary depending upon MSH5/BAT3 genotype. Future studies to examine this possibility are warranted.
Authors: Doherty JA; Sakoda LC; Loomis MM; Barnett MJ; Julianto L; Thornquist MD; Neuhouser ML; Weiss NS; Goodman GE; Chen C
Int J Mol Epidemiol Genet. 2013;4(1):11-34. Epub 2013 Mar 18.
Screening colonoscopy and risk for incident late-stage colorectal cancer diagnosis in average-risk adults: a nested case-control study
BACKGROUND: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. OBJECTIVE: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). DESIGN: Nested case-control study. SETTING: Four U.S. health plans. PATIENTS: 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration. MEASUREMENTS: Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures. RESULTS: In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer. LIMITATION: The small number of screening colonoscopies affected the precision of the estimates. CONCLUSION: Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.
Authors: Doubeni CA; Corley DA; Levin TR; Weiss NS; et al.
Ann Intern Med. 2013 Mar 5;158(5 Pt 1):312-20.
Sexual transmission of HCV among monogamous heterosexual couples: The HCV partners study
The efficiency of hepatitis C virus (HCV) transmission by sexual activity remains controversial. We conducted a cross-sectional study of HCV-positive subjects and their partners to estimate the risk for HCV infection among monogamous heterosexual couples. A total of 500 anti-HCV-positive, human immunodeficiency virus-negative index subjects and their long-term heterosexual partners were studied. Couples were interviewed separately for lifetime risk factors for HCV infection, within-couple sexual practices, and sharing of personal grooming items. Blood samples were tested for anti-HCV, HCV RNA, and HCV genotype and serotype. Sequencing and phylogenetic analysis determined the relatedness of virus isolates among genotype-concordant couples. The majority of HCV-positive index subjects were non-Hispanic white, with a median age of 49 years (range, 26-79 years) and median of 15 years (range, 2-52 years) of sexual activity with their partners. Overall, HCV prevalence among partners was 4% (n=20), and nine couples had concordant genotype/serotype. Viral isolates in three couples (0.6%) were highly related, consistent with transmission of virus within the couple. Based on 8,377 person-years of follow-up, the maximum incidence rate of HCV transmission by sex was 0.07% per year (95% confidence interval, 0.01-0.13) or approximately one per 190,000 sexual contacts. No specific sexual practices were related to HCV positivity among couples. CONCLUSION: The results of this study provide quantifiable risk information for counseling long-term monogamous heterosexual couples in which one partner has chronic HCV infection. In addition to the extremely low estimated risk for HCV infection in sexual partners, the lack of association with specific sexual practices provides unambiguous and reassuring counseling messages.
Authors: Terrault NA; Dodge JL; Murphy EL; Tavis JE; Kiss A; Levin TR; Gish RG; Busch MP; Reingold AL; Alter MJ
Hepatology. 2013 Mar;57(3):881-9. Epub 2013 Feb 7.
Racial/ethnic differences in use and duration of adjuvant hormonal therapy for breast cancer in the Women’s Health Initiative
BACKGROUND: Five-year breast cancer survival rates are lower among Hispanic and African-American women than among Non-Hispanic White women. Differences in breast cancer treatment likely play a role. Adjuvant hormonal therapies increase overall survival among women with hormone receptor-positive breast cancer. METHODS: We examined racial/ethnic differences in use and duration of adjuvant hormonal therapy among 3,588 postmenopausal women enrolled in the Women’s Health Initiative (WHI) Extension Study. Women diagnosed with hormone receptor-positive localized or regional stage breast cancer after study enrollment were surveyed between September 2009 and August 2010 and asked to recall prior use and duration of adjuvant hormonal breast cancer therapy. ORs comparing self-reported use and duration with race/ethnicity (Hispanic, African-American, Asian/Pacific Islander vs. Non-Hispanic White) were estimated using multivariable-adjusted logistic regression. RESULTS: Of the 3,588 women diagnosed from 1994 to 2009; 3,039 (85%) reported any use of adjuvant hormonal therapy, and 67% of women reporting ever-use who were diagnosed before 2005 reported using adjuvant hormonal therapy for the optimal duration of 5 years or more. In adjusted analysis, no statistically significant differences in use or duration by race/ethnicity were observed. CONCLUSIONS: This study did not find significant differences in use or duration of use of adjuvant hormonal therapy by race/ethnicity. Impact: Findings should be confirmed in other population-based samples, and potential reasons for discontinuation of therapy across all racial/ethnic groups should be explored. Cancer Epidemiol Biomarkers Prev; 22(3); 365-73. (c)2012 AACR.
Authors: Livaudais JC; Lacroix A; Chlebowski RT; Li CI; Habel LA; Simon MS; Thompson B; Erwin DO; Hubbell FA; Coronado GD
Cancer Epidemiol Biomarkers Prev. 2013 Mar;22(3):365-73. Epub 2012 Dec 28.
The Road Ahead: What if Gastroenterologists Were Accountable for Preventing Colorectal Cancer?
Authors: Lee JK; Levin TR; Corley DA
Clin Gastroenterol Hepatol. 2013 Mar;11(3):204-7.
Identifying primary and recurrent cancers using a SAS-based natural language processing algorithm
OBJECTIVE: Significant limitations exist in the timely and complete identification of primary and recurrent cancers for clinical and epidemiologic research. A SAS-based coding, extraction, and nomenclature tool (SCENT) was developed to address this problem. MATERIALS AND METHODS: SCENT employs hierarchical classification rules to identify and extract information from electronic pathology reports. Reports are analyzed and coded using a dictionary of clinical concepts and associated SNOMED codes. To assess the accuracy of SCENT, validation was conducted using manual review of pathology reports from a random sample of 400 breast and 400 prostate cancer patients diagnosed at Kaiser Permanente Southern California. Trained abstractors classified the malignancy status of each report. RESULTS: Classifications of SCENT were highly concordant with those of abstractors, achieving kappa of 0.96 and 0.95 in the breast and prostate cancer groups, respectively. SCENT identified 51 of 54 new primary and 60 of 61 recurrent cancer cases across both groups, with only three false positives in 792 true benign cases. Measures of sensitivity, specificity, positive predictive value, and negative predictive value exceeded 94% in both cancer groups. DISCUSSION: Favorable validation results suggest that SCENT can be used to identify, extract, and code information from pathology report text. Consequently, SCENT has wide applicability in research and clinical care. Further assessment will be needed to validate performance with other clinical text sources, particularly those with greater linguistic variability. CONCLUSION: SCENT is proof of concept for SAS-based natural language processing applications that can be easily shared between institutions and used to support clinical and epidemiologic research.
Authors: Strauss JA; Chao CR; Kwan ML; Ahmed SA; Schottinger JE; Quinn VP
J Am Med Inform Assoc. 2013 Mar-Apr;20(2):349-55. Epub 2012 Jul 21.
Variation of Adenoma Prevalence by Age, Sex, Race, and Colon Location in a Large Population: Implications for Screening and Quality Programs
BACKGROUND & AIMS: Reliable community-based colorectal adenoma prevalence estimates are needed to inform colonoscopy quality standards and to estimate patient colorectal cancer risks; however, minimal data exist from populations with large numbers of diverse patients and examiners. METHODS: We evaluated the prevalence of adenomas detected by sex, age, race/ethnicity, and colon location among 20,792 Kaiser Permanente Northern California members >/=50 years of age who received a screening colonoscopy examination (102 gastroenterologists, 2006-2008). RESULTS: Prevalence of detected adenomas increased more rapidly with age in the proximal colon (adjusted odds ratio [OR], 2.39; 95% confidence interval [CI], 2.05-2.80; 70-74 vs 50-54 years) than in the distal colon (OR, 1.89; 95% CI, 1.63-2.19). Prevalence was higher among men vs women at all ages (OR, 1.77; 95% CI, 1.66-1.89), increasing in men from 25% to 39% at >/=70 years and in women from 15% at 50-54 years to 26% (P < .001). Proximal adenoma prevalence was higher among blacks than whites (OR, 1.26; 95% CI, 1.04-1.54), although total prevalence was similar, including persons <60 years old (OR, 1.17; 95% CI, 0.91-1.50). CONCLUSIONS: Prevalence of detected adenomas increases substantially with age and is much higher in men; proximal adenomas are more common among blacks than whites, although the total prevalence and the prevalence for ages <60 years were similar by race. These demographic differences are such that current adenoma detection guidelines may not be valid, without adjustment, for comparing providers serving different populations. The variation in prevalence and location may also have implications for the effectiveness of screening methods in different demographic groups.
Authors: Corley DA; Jensen CD; Marks AR; Zhao WK; de Boer J; Levin TR; Doubeni C; Fireman BH; Quesenberry CP
Clin Gastroenterol Hepatol. 2013 Feb;11(2):172-80. Epub 2012 Sep 14.
Interpersonal influences and attitudes about adjuvant therapy treatment decisions among non-metastatic breast cancer patients: an examination of differences by age and race/ethnicity in the BQUAL study
Patients are increasingly involved in cancer treatment decisions and yet little research has explored factors that may affect patient attitudes and beliefs about their therapeutic choices. This paper examines psychosocial factors (e.g., attitudes, social support), provider-related factors (e.g., communication, trust), and treatment considerations in a prospective study of a sample of non-metastatic breast cancer patients eligible for chemotherapy and/or hormonal therapy (BQUAL cohort). The data come from a multisite cohort study of white, black, Hispanic, and Asian non-metastatic breast cancer patients recruited in New York City, Northern California, and Detroit, Michigan. Baseline surveys were conducted over the telephone between 2006 and 2010 among a total of 1,145 women. Most participants were white (69 %), had more than a high school education (76 %), and were diagnosed with stage I disease (51 %). The majority of women reported discussing chemotherapy and hormonal therapy with their doctor (90 and 83 %, respectively); these discussions primarily took place with medical oncologists. Nearly a quarter of women reported that the treatment decision was difficult, and the majority were accompanied to the doctor (76 %) and involved a friend or family member in making the decision (54 %). Positive considerations (e.g., beliefs about treatment reducing risk of recurrence) were important in making treatment decisions. Participants preferred a shared decision-making style, but results suggested that there is room for improvement in terms of actual patient’s involvement in making the decision and provider communication, particularly among black patients. Patients 65 years and older reported fewer provider discussions of chemotherapy, poorer patient-provider communication, higher rates of being assisted by family members in making the decision, and more negative attitudes and beliefs toward treatment.
Authors: Shelton RC; Clarke Hillyer G; Hershman DL; Leoce N; Bovbjerg DH; Mandelblatt JS; Kushi LH; Lamerato L; Nathanson SD; Ambrosone CB; Neugut AI
Breast Cancer Res Treat. 2013 Feb;137(3):817-28. Epub 2012 Dec 22.
Leveraging Epidemiology and Clinical Studies of Cancer Outcomes: Recommendations and Opportunities for Translational Research
As the number of cancer survivors continues to grow, research investigating the factors that affect cancer outcomes, such as disease recurrence, risk of second malignant neoplasms, and the late effects of cancer treatments, becomes ever more important. Numerous epidemiologic studies have investigated factors that affect cancer risk, but far fewer have addressed the extent to which demographic, lifestyle, genomic, clinical, and psychosocial factors influence cancer outcomes. To identify research priorities as well as resources and infrastructure needed to advance the field of cancer outcomes and survivorship research, the National Cancer Institute sponsored a workshop titled ‘Utilizing Data from Cancer Survivor Cohorts: Understanding the Current State of Knowledge and Developing Future Research Priorities’ on November 3, 2011, in Washington, DC. This commentary highlights recent findings presented at the workshop, opportunities to leverage existing data, and recommendations for future research, data, and infrastructure needed to address high priority clinical and research questions. Multidisciplinary teams that include epidemiologists, clinicians, biostatisticians, and bioinformaticists will be essential to facilitate future cancer outcome studies focused on improving clinical care of cancer patients, identifying those at high risk of poor outcomes, and implementing effective interventions to ultimately improve the quality and duration of survival.
Authors: Elena JW; Kushi LH; Freedman AN; et al.
J Natl Cancer Inst. 2013 Jan 16;105(2):85-94. Epub 2012 Nov 28.
Impact of type 2 diabetes on lower urinary tract symptoms in men: a cohort study
BACKGROUND: Studies of the impact of type 2 diabetes on the prevalence and incidence of lower urinary tract symptoms (LUTS) among men have provided divergent results. We sought to examine this issue using two large and diverse cohorts. METHODS: This study used questionnaire and clinical data from two large multiethnic cohorts, the California Men’s Health Study (CMHS) and Research Program in Genes, Environment and Health (RPGEH). Diabetes characteristics data were derived from questionnaire and Diabetes Registry data. LUTS were measured using a standardized scale. Socioeconomic and comorbidity data were obtained by self-report. Multivariable logistic regression analysis was used to examine the association between baseline DM status and prevalence and incidence of LUTS, with adjustment for potential confounding variables. RESULTS: We found type 2 diabetes to be associated with prevalent LUTS (odds ratio (OR) = 1.32, 95% confidence interval (CI) 1.26, 1.38). The association was stronger among men with type 2 diabetes who were on active pharmaceutical treatment and had it for a longer duration. No association was observed between type 2 diabetes and new onset LUTS. CONCLUSIONS: Type 2 diabetes increases the risk of LUTS.
Authors: Van Den Eeden SK; Ferrara A; Shan J; Jacobsen SJ; Quinn VP; Haque R; Quesenberry CP
BMC Urol. 2013 Feb 20;13:12.
HOXB13:IL17BR and molecular grade index and risk of breast cancer death among patients with lymph node-negative invasive disease
Studies have shown that a two-gene ratio (HOXB13:IL17BR) and a five-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) are predictive of clinical outcomes among early-stage breast cancer patients. In an independent population of lymph node-negative breast cancer patients from a community hospital setting, we evaluated the performance of two risk classifiers that have been derived from these gene signatures combined, MGI+HOXB13:IL17BR and the Breast Cancer Index (BCI). A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 who did not receive adjuvant chemotherapy. For 191 cases (breast cancer deaths) and 417 matched controls, archived tumor tissues were available and analyzed for expression levels of the seven genes of interest and four normalization genes by RT-PCR. Logistic regression methods were used to estimate the relative risk (RR) and 10-year absolute risk of breast cancer death associated with prespecified risk categories for MGI+HOXB13:IL17BR and BCI. Both MGI+HOXB13:IL17BR and BCI classified over half of all ER-positive patients as low risk. The 10-year absolute risks of breast cancer death for ER-positive, tamoxifen-treated patients classified in the low-, intermediate-, and high-risk groups were 3.7% (95% confidence interval (CI) 1.9% to 5.4%), 5.9% (95% CI 3.0% to 8.6%), and 12.9% (95% CI 7.9% to 17.6%) by MGI+HOXB13:IL17BR and 3.5% (95% CI 1.9% to 5.1%), 7.0% (95% CI 3.8% to 10.1%), and 12.9% (95% CI 7.1% to 18.3%) by BCI. Those for ER-positive, tamoxifen-untreated patients were 5.7% (95% CI 4.0% to 7.4%), 13.8% (95% CI 8.4% to 18.9%), and 15.2% (95% CI 9.4% to 20.5%) by MGI+HOXB13:IL17BR and 5.1% (95% CI 3.6% to 6.6%), 18.6% (95% CI 10.8% to 25.7%), and 17.5% (95% CI 11.1% to 23.5%) by BCI. After adjusting for tumor size and grade, the RRs of breast cancer death comparing high- versus low-risk categories of both classifiers remained elevated but were attenuated for tamoxifen-treated and tamoxifen-untreated patients. Among ER-positive, lymph node-negative patients not treated with adjuvant chemotherapy, MGI+HOXB13:IL17BR and BCI were associated with risk of breast cancer death. Both risk classifiers appeared to provide risk information beyond standard prognostic factors.
Authors: Habel LA; Sakoda LC; Achacoso N; Ma XJ; Erlander MG; Sgroi DC; Fehrenbacher L; Greenberg D; Quesenberry CP
Breast Cancer Res. 2013;15(2):R24. Epub 2013-03-14.
KRAS Testing and Epidermal Growth Factor Receptor Inhibitor Treatment for Colorectal Cancer in Community Settings
BACKGROUND: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing. METHODS: We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care. RESULTS: Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034), comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild-type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009). CONCLUSIONS: These findings show rapid uptake and incorporation of this predictive biomarker into clinical oncology care. IMPACT: In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRCs. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the United States.
Authors: Webster J; Kushi LH; CERGEN study team; et al.
Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):91-101. Epub 2012 Nov 15.
Social networks, social support, and burden in relationships, and mortality after breast cancer diagnosis in the Life After Breast Cancer Epidemiology (LACE) Study
Larger social networks have been associated with lower breast cancer mortality. The authors evaluated how levels of social support and burden influenced this association. We included 2,264 women from the Life After Cancer Epidemiology study who were diagnosed with early-stage, invasive breast cancer between 1997 and 2000, and provided data on social networks (spouse or intimate partner, religious/social ties, volunteering, time socializing with friends, and number of first-degree female relatives), social support, and caregiving. 401 died during a median follow-up of 10.8 years follow-up with 215 from breast cancer. We used delayed entry Cox proportional hazards regression to evaluate associations. In multivariate-adjusted analyses, social isolation was unrelated to recurrence or breast cancer-specific mortality. However, socially isolated women had higher all-cause mortality (HR = 1.34, 95 % CI: 1.03-1.73) and mortality from other causes (HR = 1.79, 95 % CI: 1.19-2.68). Levels of social support and burden modified associations. Among those with low, but not high, levels of social support from friends and family, lack of religious/social participation (HR = 1.58, 95 % CI: 1.07-2.36, p = 0.02, p interaction = 0.01) and lack of volunteering (HR = 1.78, 95 % CI: 1.15-2.77, p = 0.01, p interaction = 0.01) predicted higher all-cause mortality. In cross-classification analyses, only women with both small networks and low levels of support (HR = 1.61, 95 % CI: 1.10-2.38) had a significantly higher risk of mortality than women with large networks and high levels of support; women with small networks and high levels of support had no higher risk of mortality (HR = 1.13, 95 % CI: 0.74-1.72). Social networks were also more important for caregivers versus noncaregivers. Larger social networks predicted better prognosis after breast cancer, but associations depended on the quality and burden of family relationships.
Authors: Kroenke CH; Quesenberry C; Kwan ML; Sweeney C; Castillo A; Caan BJ
Breast Cancer Res Treat. 2013 Jan;137(1):261-71. Epub 2012 Nov 10.
Post-diagnosis Alcohol Consumption and Breast Cancer Prognosis in the After Breast Cancer Pooling Project
BACKGROUND: Alcohol consumption is an established risk factor for incident breast cancer. However, its role in breast cancer prognosis remains unclear. METHODS: We conducted an investigation of postdiagnosis alcohol consumption with recurrence and mortality among 9,329 breast cancer patients in the After Breast Cancer Pooling Project. Women were diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors from three prospective US cohorts. Alcohol intake was assessed at cohort entry (mean 2.1 years postdiagnosis) using a food frequency questionnaire. HR and 95% confidence intervals (CI) were estimated using delayed entry Cox proportional hazards models with adjustment for known prognostic factors. RESULTS: After a mean follow-up of 10.3 years, 1,646 recurrences and 1,543 deaths were ascertained. 5,422 women (58%) were considered drinkers (>/=0.36 g/day of alcohol, >/=0.25 drinks/week) with a median of 5.3 g/day. Overall, compared with nondrinking, regular alcohol intake (>/=6.0 g/day) was not associated with risk of recurrence (HR for 6 to less than 12 g/day, 1.03; 95% CI, 0.86-1.24; HR for 12 to less than 24 g/day, 1.12; 95% CI, 0.93-1.34; HR for >/=24 g/day, 1.04; 95% CI, 0.84-1.31). However, risk varied significantly by menopausal status (P for interaction < 0.05). Postmenopausal women who regularly consumed alcohol (>/=6.0 g/day) had increased risk of recurrence (HR, 1.19; 95% CI, 1.01-1.40). Alcohol intake was not associated with mortality. CONCLUSIONS: Regular alcohol consumption was not associated with breast cancer recurrence and total mortality overall, yet recurrence risk was only elevated in postmenopausal women. IMPACT: The association between alcohol intake and recurrence may depend on menopausal status at breast cancer diagnosis.
Authors: Kwan ML; Chen WY; Flatt SW; Weltzien EK; Nechuta SJ; Poole EM; Holmes MD; Patterson RE; Shu XO; Pierce JP; Caan BJ
Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):32-41. Epub 2012 Nov 13.
PTGS1, PTGS2, ALOX5, ALOX12, ALOX15, and FLAP SNPs: interaction with fatty acids in colon cancer and rectal cancer
Dietary polyunsaturated fatty acids (PUFAs) can be converted to prostaglandins and leukotrienes. Oxygenation of omega-6 PUFAs generally results in the production of pro-inflammatory mediators, whereas oxygenated products of omega-3 (n-3) PUFAs generally have lower inflammatory activity. We hypothesize that elevated n-3 PUFA intakes from fish are associated with lower risk of colorectal cancer among those with genetic variants that result in higher levels of pro-inflammatory mediators. In population-based case-control studies of colon (case n = 1,574) and rectal cancer (case n = 791) and disease-free controls (n = 2,969), we investigated interactions between dietary fatty acid intake and 107 candidate polymorphisms and tagSNPs in PTGS1, PTGS2, ALOX12, ALOX5, ALOX15, and FLAP. The two studies used an identical genotyping protocol. We observed interactions and statistically significant increases in colon cancer risk for low docosahexaenoic acid intake among those with the PTGS1 rs10306110 (-1,053 A > G) variant genotypes (OR = 1.6, 95 % confidence interval = 1.1-2.3, adj. p = 0.06) and rectal cancer risk for low total fat intake among those with the variant PTGS1 rs10306122 (7,135 A > G) (OR(vs.wt) = 1.80, 1.02-2.99; adj. p = 0.08). The ALOX15 rs11568131 (10,339 C > T) wild type in combination with a high inflammation score (low EPA intake, high AA intake, no regular NSAID use, high BMI, smoking) was associated with increased colon cancer risk (OR = 2.28, 1.7-3.07). Rectal cancer risk was inversely associated with a low inflammation score among PTGS2 rs4648276 (3,934 T > C) variant allele carriers (OR = 0.49, 0.25-0.75). Overall, these data provide some modest evidence for interactions between dietary fat intake and genetic variation in genes involved in eicosanoid metabolism and colorectal cancer risk.
Authors: Habermann N; Ulrich CM; Lundgreen A; Makar KW; Poole EM; Caan B; Kulmacz R; Whitton J; Galbraith R; Potter JD; Slattery ML
Genes Nutr. 2013 Jan;8(1):115-26. Epub 2012 Jun 8.
The Epidemiology of Herpes Zoster in Patients with Newly Diagnosed Cancer
BACKGROUND: Given the limited literature, we conducted a study to examine the epidemiology of herpes zoster (HZ) among newly diagnosed cancer patients. METHODS: We identified adult health plan members of Kaiser Permanente Northern California diagnosed with invasive cancer from 2001 to 2005. Electronic health records with inpatient and outpatient diagnoses, laboratory tests, and antiviral medications were used to identify HZ diagnoses from 2001 to 2006. HZ diagnoses and associated complications were confirmed by medical chart review. Treatment with chemotherapy and corticosteroids was used to classify patients by immunosuppression level. RESULTS: Among 14,670 cancer patients, 424 were diagnosed with HZ during follow-up (median 22 months). The incidence of HZ was 31/1,000 person-year (PY) in patients with hematologic malignancies and 12/1,000 PY in patients with solid tumors. The corresponding 2-year cumulative incidence of HZ was approximately 6% and 2%, respectively. Compared with incidence rates of HZ reported in a general US population, the age- and sex-standardized rates of HZ were 4.8 times higher [95% confidence interval (CI), 4.0-5.6] in patients with hematologic malignancies and 1.9 times higher (95% CI, 1.7-2.1) in those with solid tumors. HZ risk increased with increasing level of immunosuppression. Among HZ cases, 19% with hematologic malignancies and 14% with solid tumors had HZ-associated pain for at least 30 days. The corresponding numbers for nonpain-related complications were 30% and 18%, respectively. CONCLUSIONS: Cancer patients are at substantially increased risk of HZ and among those with HZ, complications are relatively common. IMPACT: Better HZ prevention and treatment options for cancer patients are needed.
Authors: Habel LA; Ray GT; Silverberg MJ; Horberg MA; Yawn BP; Castillo AL; Quesenberry CP Jr; Li Y; Sadier P; Tran TN
Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):82-90. Epub 2012 Nov 1.
Accelerated Cell Aging in Female APOE-epsilon4 Carriers: Implications for Hormone Therapy Use
Apolipoprotein-epsilon4 (APOE-epsilon4) is a major genetic risk factor for cognitive decline, Alzheimer’s disease (AD) and early mortality. An accelerated rate of biological aging could contribute to this increased risk. Here, we determined whether APOE-epsilon4 status impacts leukocyte telomere length (TL) and the rate of cellular senescence in healthy mid-life women and, further, whether hormone replacement therapy (HT) modifies this association. Post-menopausal women (N = 63, Mean age = 57.7), all HT users for at least one year, were enrolled in a randomized longitudinal study. Half of the participants (N = 32) remained on their HT regimen and half (N = 31) went off HT for approximately two years (Mean = 1.93 years). Participants included 24 APOE-epsilon4 carriers and 39 non-carrier controls. Leukocyte TL was measured at baseline and the end of year 2 using quantitative polymerase chain reaction. Logistic regression analysis indicated that the odds of an APOE-epsilon4 carrier exhibiting telomere shortening (versus maintenance/growth) over the 2-year study were more than 6 (OR = 6.26, 95% CI = 1.02, 38.49) times higher than a non-carrier, adjusting for established risk factors and potential confounds. Despite the high-functioning, healthy mid-life status of study participants, APOE-epsilon4 carriers had marked telomere attrition during the 2-year study window, the equivalent of approximately one decade of additional aging compared to non-carriers. Further analyses revealed a modulatory effect of hormone therapy on the association between APOE status and telomere attrition. APOE-epsilon4 carriers who went off their HT regimen exhibited TL shortening, as predicted for the at-risk population. APOE-epsilon4 carriers who remained on HT, however, did not exhibit comparable signs of cell aging. The opposite pattern was found in non-carriers. The results suggest that hormone use might buffer against accelerated cell aging in mid-life women at risk for dementia. Importantly, for non-carrier women there was no evidence that HT conferred protective effects on telomere dynamics.
Authors: Jacobs EG; Kroenke C; Lin J; Epel ES; Kenna HA; Blackburn EH; Rasgon NL
PLoS One. 2013;8(2):e54713. Epub 2013 Feb 13.
Validation of a large Basal cell carcinoma registry
The epidemiological study of basal cell carcinomas (BCCs) is difficult because BCCs lack distinct disease codes and are excluded from most cancer registries. To develop and validate a large BCC registry based on electronically assigned Systematized Nomenclature of Medicine (SNOMED) codes and text-string searches of electronic pathology reports from Kaiser Permanente Northern California. Potential BCCs were identified from electronic pathology reports (n=39,026) in 2005 and were reviewed by a dermatologist who assigned case/non-case status (gold-standard). A subset of the records (n=9,428) was independently reviewed by a second dermatologist to ascertain reliability of case assignment. In addition, a subset of excluded electronic pathology reports from 2005 (n=2,700) was reviewed to determine whether inclusion criteria had missed potential BCCs. We calculated the positive predictive value (PPV) of 3 different algorithms for identifying BCCs from electronic pathology data. BCC-specific SNOMED codes had the highest PPV for identifying BCCs, 0.992 (95 percent CI: 0.991-0.993). Inter-rater reliability for case assignment was high (kappa=0.92, 95 percent CI: 0.91-0.93). Standardized incidence rates were consistent with previously published rates in the United States. We created and validated a large BCC registry to serve as a unique resource for studying BCCs.
Authors: Asgari MM; Eide MJ; Warton EM; Fletcher SW
J Registry Manag. 2013 Summer;40(2):65-9.
An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population
We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. Our risk model included current smoking (multivariable adjusted odds ratio (OR) and 95% confidence interval: 2.20 [1.84-2.62]), heavy alcohol use (>3 drinks/day) (OR: 1.45 [1.19-1.76]), obesity (body mass index >30 kg/m(2)) (OR: 1.26 [1.09-1.45]), diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32]), family history of pancreatic cancer (OR: 1.60 [1.20-2.12]), non-O ABO genotype (AO vs. OO genotype) (OR: 1.23 [1.10-1.37]) to (BB vs. OO genotype) (OR 1.58 [0.97-2.59]), rs3790844(chr1q32.1) (OR: 1.29 [1.19-1.40]), rs401681(5p15.33) (OR: 1.18 [1.10-1.26]) and rs9543325(13q22.1) (OR: 1.27 [1.18-1.36]). The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.
Authors: Klein AP; Van Den Eeden SK; Kraft P; et al.
PLoS ONE. 2013;8(9):e72311. Epub 2013-09-13.
Patterns and predictors of breast cancer chemotherapy use in Kaiser Permanente Northern California, 2004-2007
Chemotherapy regimens for early stage breast cancer have been tested by randomized clinical trials, and specified by evidence-based practice guidelines. However, little is known about the translation of trial results and guidelines to clinical practice. We extracted individual-level data on chemotherapy administration from the electronic medical records of Kaiser Permanente Northern California (KPNC), a pre-paid integrated healthcare system serving 29 % of the local population. We linked data to the California Cancer Registry, incorporating socio-demographic and tumor factors, and performed multivariable logistic regression analyses on the receipt of specific chemotherapy regimens. We identified 6,004 women diagnosed with Stage I-III breast cancer at KPNC during 2004-2007; 2,669 (44.5 %) received at least one chemotherapy infusion at KPNC within 12 months of diagnosis. Factors associated with receiving chemotherapy included <50 years of age [odds ratio (OR) 2.27, 95 % confidence interval (CI) 1.81-2.86], tumor >2 cm (OR 2.14, 95 % CI 1.75-2.61), involved lymph nodes (OR 11.3, 95 % CI 9.29-13.6), hormone receptor-negative (OR 6.94, 95 % CI 4.89-9.86), Her2/neu-positive (OR 2.71, 95 % CI 2.10-3.51), or high grade (OR 3.53, 95 % CI 2.77-4.49) tumors; comorbidities associated inversely with chemotherapy use [heart disease for anthracyclines (OR 0.24, 95 % CI 0.14-0.41), neuropathy for taxanes (OR 0.45, 95 % CI 0.22-0.89)]. Relative to high-socioeconomic status (SES) non-Hispanic Whites, we observed less anthracycline and taxane use by SES non-Hispanic Whites (OR 0.63, 95 % CI 0.49-0.82) and American Indians (OR 0.23, 95 % CI 0.06-0.93), and more anthracycline use by high-SES Asians/Pacific Islanders (OR 1.72, 95 % CI 1.02-2.90). In this equal-access healthcare system, chemotherapy use followed practice guidelines, but varied by race and socio-demographic factors. These findings may inform efforts to optimize quality in breast cancer care.
Authors: Kurian AW; Lichtensztajn DY; Keegan TH; Leung RW; Shema SJ; Hershman DL; Kushi LH; Habel LA; Kolevska T; Caan BJ; Gomez SL
Breast Cancer Res Treat. 2013 Jan;137(1):247-60. Epub 2012 Nov 9.
Developing an Interactive Web-Based Learning Program on Skin Cancer: the Learning Experiences of Clinical Educators
Web-based learning in medical education is rapidly growing. However, there are few firsthand accounts on the rationale for and development of web-based learning programs. We present the experience of clinical educators who developed an interactive online skin cancer detection and management course in a time-efficient and cost-efficient manner without any prior skills in computer programming or technical construction of web-based learning programs. We review the current state of web-based learning including its general advantages and disadvantages as well as its specific utility in dermatology. We then detail our experience in developing an interactive online skin cancer curriculum for primary care clinicians. Finally, we describe the main challenges faced and lessons learned during the process. This report may serve medical educators who possess minimal computer programming and web design skills but want to employ the many strengths of web-based learning without the huge costs associated with hiring a professional development team.
Authors: Shaikh WR; Asgari MM; Weinstock MA; et al.
J Cancer Educ. 2012 Dec;27(4):709-16.
Body mass index in relation to oesophageal and oesophagogastric junction adenocarcinomas: a pooled analysis from the International BEACON Consortium
BACKGROUND: Previous studies suggest an association between obesity and oesophageal (OA) and oesophagogastric junction adenocarcinomas (OGJA). However, these studies have been limited in their ability to assess whether the effects of obesity vary by gender or by the presence of gastro-oesophageal reflux (GERD) symptoms. METHODS: Individual participant data from 12 epidemiological studies (8 North American, 3 European and 1 Australian) comprising 1997 OA cases, 1900 OGJA cases and 11 159 control subjects were pooled. Logistic regression was used to estimate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between body mass index (BMI, kg/m(2)) and the risk of OA and OGJA. Random-effects meta-analysis was used to combine these ORs. We also investigated effect modification and synergistic interaction of BMI with GERD symptoms and gender. RESULTS: The association of OA and OGJA increased directly with increasing BMI (P for trend <0.001). Compared with individuals with a BMI <25, BMI >/=40 was associated with both OA (OR 4.76, 95% CI 2.96-7.66) and OGJA (OR 3.07, 95% CI 1.89-4.99). These associations were similar when stratified by gender and GERD symptoms. There was evidence for synergistic interaction between BMI and GERD symptoms in relation to OA/OGJA risk. CONCLUSIONS: These data indicate that BMI is directly associated with OA and OGJA risk in both men and women and in those with and without GERD symptoms. Disentangling the relationship between BMI and GERD will be important for understanding preventive efforts for OA and OGJA.
Authors: Hoyo C; Corley DA; Gammon MD; et al.
Int J Epidemiol. 2012 Dec;41(6):1706-18. Epub 2012 Nov 12.
Patterns and predictors of first-line chemotherapy use among adults with advanced non-small cell lung cancer in the cancer research network
BACKGROUND: Relatively low rates of chemotherapy receipt have been observed in older patients diagnosed with advanced non-small cell lung cancer (NSCLC) in SEER-Medicare-based studies. However, little is known about variation in first-line NSCLC chemotherapy use in younger patients, health maintenance organization (HMO)-based settings, and for high-cost, novel agents, such as bevacizumab and erlotinib. METHODS: A cohort of 6614 stage IIIB/IV NSCLC patients aged >/= 21 years diagnosed between 2000 and 2007 was identified at four HMOs that participate in the Cancer Research Network (CRN). Demographic, comorbidity, tumor characteristics, and chemotherapy treatment data were included in logistic regression models to identify factors associated with chemotherapy receipt and tests of association examined secular and age-specific variation in first-line chemotherapy regimens. RESULTS: Within 120 days of diagnosis, 3612 (55%) patients received chemotherapy; increasing from 52% of patients diagnosed in 2000 to 59% in 2007 (p<0.001). Receipt was significantly higher for patients aged <65 years (64% versus 46% in >/= 65) and was inversely related to stage and comorbidites (all p<0.001). Carboplatin and paclitaxel were received most frequently. Erlotinib and bevacizumab use in the later years of the study was associated with a significant change in distributions of first-line chemotherapies (p<0.001). CONCLUSIONS: For patients alive 30 days post diagnosis, chemotherapy use was higher in the aged population (>65 years) than previously published estimates, and higher still among younger patients. Chemotherapy use increased over the observation period, and the mix of first-line therapies used changed substantially over time. Of note, novel, high cost treatments were used in first-line therapy prior to FDA approval, increasing significantly throughout the study period. These findings demonstrate the utility of HMO CRN data to augment SEER-Medicare to conduct comparative effectiveness research related to chemotherapy use and the use of specific agents, especially among younger patients.
Authors: Ritzwoller DP; Carroll NM; Delate T; Hornbrook MC; Kushi L; Aiello Bowles EJ; Freml JM; Huang K; Loggers ET
Lung Cancer. 2012 Dec;78(3):245-52. Epub 2012 Sep 27.
Utilization of HER2 genetic testing in a multi-institutional observational study
Human epidermal growth factor receptor 2 (HER2) expression is amplified in about 20% of breast cancer tumors, and evaluation of HER2 status should influence therapy selection. A critical gap in our knowledge is the real-world implementation of HER2 testing and its impact on treatment decisions for women diagnosed with breast cancer. To assess use of HER2 testing, to describe characteristics of patients who do or do not receive HER2 testing, to describe which HER2 tests were used (fluorescence in situ hybridization or immunohistochemistry), and to evaluate trastuzumab use as a function of HER2 results. The population included 6460 women diagnosed with invasive breast cancer between 1999 and 2007 at 8 geographically distributed Cancer Research Network healthcare delivery systems in the United States. Electronic records were used to identify patient and tumor characteristics and treatment with trastuzumab. Chart abstraction was performed for 400 women (50 per site) to identify receipt of HER2 testing and results. More than 90% of study participants received HER2 testing. Everyone who received trastuzumab had a HER2 test, and nearly all (>95%) who received trastuzumab had a positive HER2 test result recorded in their medical chart. Most (77%) eligible patients with a positive HER2 test result diagnosed after 2005 received trastuzumab. This study expands upon previous work in individual health plans. HER2 status has been successfully incorporated into medical practice to guide treatment decisions for breast cancer patients in diverse integrated healthcare delivery settings.
Authors: Goddard KA; Bowles EJ; Feigelson HS; Habel LA; Alford SH; McCarty CA; Nekhlyudov L; Onitilo AA; Rahm AK; Webster JA
Am J Manag Care. 2012 Nov;18(11):704-12.
A low-fat dietary pattern and risk of metabolic syndrome in postmenopausal women: The Women’s Health Initiative
OBJECTIVE: Nutrition plays an important role in metabolic syndrome etiology. We examined whether the Women’s Health Initiative (WHI) Dietary Modification Trial influenced metabolic syndrome risk. MATERIALS/METHODS: 48,835 postmenopausal women aged 50-79 years were randomized to a low-fat (20% energy from fat) diet (intervention) or usual diet (comparison) for a mean of 8.1 years. Blood pressure, waist circumference and fasting blood measures of glucose, HDL-cholesterol and triglycerides were measured on a subsample (n=2816) at baseline and years 1, 3 and 6 post-randomization. Logistic regression estimated associations of the intervention with metabolic syndrome risk and use of cholesterol-lowering and hypertension medications. Multivariate linear regression tested associations between the intervention and metabolic syndrome components. RESULTS: At year 3, but not years 1 or 6, women in the intervention group (vs. comparison) had a non-statistically significant lower risk of metabolic syndrome (OR=0.83, 95%CI 0.59-1.18). Linear regression models simultaneously modeling the five metabolic syndrome components revealed significant associations of the intervention with metabolic syndrome at year 1 (p<0.0001), but not years 3 (p=0.19) and 6 (p=0.17). Analyses restricted to intervention-adherent participants strengthened associations at years 3 (p=0.05) and 6 (p=0.06). Cholesterol-lowering and hypertension medication use was 19% lower at year 1 for intervention vs. comparison group women (OR=0.81, 95% CI 0.60-1.09).Over the entire trial, fewer intervention vs. comparison participants used these medications (26.0% vs. 29.9%), although results were not statistically significant (p=0.89). CONCLUSIONS: The WHI low-fat diet may influence metabolic syndrome risk and decrease use of hypertension and cholesterol-lowering medications. Findings have potential for meaningful clinical translation.
Authors: Neuhouser ML; Howard B; Lu J; Tinker LF; Van Horn L; Caan B; Rohan T; Stefanick ML; Thomson CA
Metabolism. 2012 Nov;61(11):1572-81. Epub 2012 May 26.
Noninitiation of Adjuvant Chemotherapy in Women With Localized Breast Cancer: The Breast Cancer Quality of Care Study
PURPOSE: For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. PATIENTS AND METHODS: We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years. RESULTS: Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor- and progesterone receptor-negative status) were associated with increased chemotherapy initiation. CONCLUSION: Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.
Authors: Neugut AI; Kushi LH; Hershman DL; et al.
J Clin Oncol. 2012 Nov 1;30(31):3800-9. Epub 2012 Sep 24.
A pooled analysis of smoking and colorectal cancer: timing of exposure and interactions with environmental factors
BACKGROUND: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association. METHODS: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors. RESULTS: Current smokers [OR, 1.26; 95% confidence interval (CI), 1.11-1.43] and former smokers (OR, 1.18; 95% CI, 1.09-1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, -0.01 to 0.31; P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16; 95% CI, 0.01-0.30; P = 0.04). CONCLUSION: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking. IMPACT: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology.
Authors: Gong J; Caan B; Peters U; et al.
Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):1974-85. Epub 2012 Sep 20.
Vitamin D in cutaneous carcinogenesis: Part II
The role of vitamin D in health maintenance and disease prevention in fields ranging from bone metabolism to cancer is currently under intensive investigation. A number of epidemiologic studies have suggested that vitamin D may have a protective effect on cancer risk and cancer-associated mortality. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar risk reducing effect. Potential mechanisms of action include inhibition of the hedgehog signaling pathway and upregulation of nucleotide excision repair enzymes. The key factor complicating the association between vitamin D and skin cancer is ultraviolet B radiation. The same spectrum of ultraviolet B radiation that catalyzes the production of vitamin D in the skin also causes DNA damage that can lead to epidermal malignancies. Part II of this continuing medical education article will summarize the literature on vitamin D and skin cancer to identify evidence-based optimal serum levels of vitamin D and to recommend ways of achieving those levels while minimizing the risk of skin cancer.
Authors: Tang JY; Fu T; Lau C; Oh DH; Bikle DD; Asgari MM
J Am Acad Dermatol. 2012 Nov;67(5):817.e1-11; quiz 827-8.
Vitamin D in cutaneous carcinogenesis: Part I
Skin cancer is the most common cancer in the United States. Exposure to ultraviolet radiation is a known risk factor for skin cancer but is also the principal means by which the body obtains vitamin D. Several studies have suggested that vitamin D plays a protective role in a variety of internal malignancies. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar protective effect. These noncalcemic actions of vitamin D have called into question whether the current recommended intake of vitamin D is too low for optimal health and cancer prevention. Part I will review the role of vitamin D in the epidermis; part II will review the role of vitamin D in keratinocyte-derived tumors to help frame the discussion on the possible role of vitamin D in the prevention of skin cancer.
Authors: Tang JY; Fu T; Lau C; Oh DH; Bikle DD; Asgari MM
J Am Acad Dermatol. 2012 Nov;67(5):803.e1-12, quiz 815-6.
Skin carotenoid levels may not reflect vitamin A (retinol) levels
Authors: Asgari MM
J Am Acad Dermatol. 2012 Nov;67(5):1073.
Smoking and survival after breast cancer diagnosis: a prospective observational study and systematic review
The association of smoking with outcomes following breast cancer prognosis is not well understood. In a cohort study called Life After Cancer Epidemiology (LACE), 2,265 women diagnosed with breast cancer were followed for a median of 12 years. We used multivariable proportional-hazards models to determine whether smoking, assessed approximately two years post-diagnosis, was associated with risk of death among these women. We also undertook a systematic review of all cohort studies to date that have examined the association between smoking and breast cancer mortality. Compared with never smokers, women who were current smokers had a twofold higher rate of dying from breast cancer [hazard ratio (HR) = 2.01, 95 % confidence interval (CI) 1.27-3.18] and an approximately fourfold higher rate of dying from competing (non-breast cancer) causes (HR = 3.84, 95 % CI 2.50-5.89). Among seven studies that met the inclusion criteria in the systematic review, three studies and our own reported significantly increased risk of breast cancer death with current smoking. We found little evidence of an association between former smoking and breast cancer mortality (HR = 1.24, 95 % CI 0.94-1.64). Consistent with findings from our prospective observational study, the systematic review of seven additional studies indicates positive association of current smoking with breast cancer mortality, but weak association with former smoking. Women who smoke following breast cancer diagnosis and treatment are at higher risk of death both from breast cancer and other causes.
Authors: Braithwaite D; Kwan ML; Kroenke CH; Habel L; Caan B; et al.
Breast Cancer Res Treat. 2012 Nov;136(2):521-33. Epub 2012 Sep 29.
A prognostic assay to identify patients at high risk of mortality despite small, node-negative lung tumors
Authors: Kratz JR; Van Den Eeden SK; He J; Jablons DM; Mann MJ
JAMA. 2012 Oct 24;308(16):1629-31.
Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett’s esophagus
Barrett’s esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett’s esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P(combined) = 4.09 x 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P(combined) = 2.74 x 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett’s esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett’s esophagus.
Authors: Su Z; Corley DA; Wellcome Trust Case Control Consortium 2; et al.
Nat Genet. 2012 Oct;44(10):1131-6. Epub 2012 Sep 9.
A Combination of Esomeprazole and Aspirin Reduce Tissue Concentrations of Prostaglandin E2 in Patients with Barrett’s Esophagus
BACKGROUND& AIMS: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett’s esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E(2) in patients with BE with no dysplasia or low-grade dysplasia. METHODS: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE(2) (the primary end point). RESULTS: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE(2) was reduced by 67.6 +/- 229.68 pg/mL in arm A, 123.9 +/- 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 +/- 263.62 pg/mL in arm C (P = .02 vs arm A). CONCLUSIONS: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE(2) in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903.
Authors: Falk GW; Corley DA; Della'Zanna G; et al.
Gastroenterology. 2012 Oct;143(4):917-26.e1. Epub 2012 Jul 11.
Antihypertensive Drugs and Lip Cancer in Non-Hispanic Whites
BACKGROUND: In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other commonly used antihypertensive drugs. METHODS: In a comprehensive medical care program, we evaluated prescriptions dispensed and cancer occurrence from August 1, 1994, to February 29, 2008. We identified 712 patients with lip cancer (cases) and 22,904 comparison individuals (controls) matched for age, sex, and cohort year of entry in the susceptible group, non-Hispanic whites. We determined use, at least 2 years before diagnosis or control index date, of the commonly prescribed diuretics hydrochlorothiazide and hydrochlorothiazide combined with triamterene, the angiotensin-converting enzyme inhibitor lisinopril, the calcium channel blocker nifedipine, and the beta-adrenergic blocker atenolol, the only nonphotosensitizer agent studied. We analyzed the use of each drug exclusively and regardless of use of the others, and focused on duration of use. Conditional logistic regression was used for analysis of matched case-control sets, with control for cigarette smoking. RESULTS: At least a 5-year supply of a drug yielded the following odds ratios (95% CIs), respectively, compared with no use: hydrochlorothiazide, 4.22 (2.82-6.31); hydrochlorothiazide-triamterene, 2.82 (1.74-4.55); lisinopril, 1.42 (0.95-2.13); nifedipine, 2.50 (1.29-4.84); and atenolol, 1.93 (1.29-2.91). When the other drugs were excluded, the odds ratio for atenolol was reduced to 0.54 (0.07-4.08). CONCLUSION: These data support an increased risk of lip cancer in non-Hispanic whites receiving treatment for hypertension with long-term use of photosensitizing drugs.
Authors: Friedman GD; Asgari MM; Warton EM; Chan J; Habel LA
Arch Intern Med. 2012 Sep 10;172(16):1246-51.
Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study
BACKGROUND: Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM. METHODS: We conducted a population-based, retrospective cohort study of 12,500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. RESULTS: Among 12 500 women (mean age = 60 years, range = 22-99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35). CONCLUSIONS: Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.
Authors: Bowles EJ; Habel LA; Pharmacovigilance Study Team; et al.
J Natl Cancer Inst. 2012 Sep 5;104(17):1293-305.
Patterns of Adjuvant Hormonal Therapy Use in the Northern California Breast Cancer Family Registry
BACKGROUND: In the United States, 5-year breast cancer survival is highest among Asian American women, followed by non-Hispanic white, Hispanic, and African American women. Breast cancer treatment disparities may play a role. We examined racial/ethnic differences in adjuvant hormonal therapy use among women aged 18-64 years, diagnosed with hormone receptor-positive breast cancer, using data collected by the Northern California Breast Cancer Family Registry (NC-BCFR), and explored changes in use over time. METHODS: Odds ratios (OR) comparing self-reported ever-use by race/ethnicity (African American, Hispanic, non-Hispanic white vs. Asian American) were estimated using multivariable adjusted logistic regression. Analyses were stratified by recruitment phase (phase I, diagnosed January 1995-September 1998, phase II, diagnosed October 1998-April 2003) and genetic susceptibility, as cases with increased genetic susceptibility were oversampled. RESULTS: Among 1385 women (731 phase I, 654 phase II), no significant racial/ethnic differences in use were observed among phase I or phase II cases. However, among phase I cases with no susceptibility indicators, African American and non-Hispanic white women were less likely than Asian American women to use hormonal therapy (OR 0.20, 95% confidence interval [CI]0.06-0.60; OR 0.40, CI 0.17-0.94, respectively). No racial/ethnic differences in use were observed among women with 1+ susceptibility indicators from either recruitment phase. CONCLUSIONS: Racial/ethnic differences in adjuvant hormonal therapy use were limited to earlier diagnosis years (phase I) and were attenuated over time. Findings should be confirmed in other populations but indicate that in this population, treatment disparities between African American and Asian American women narrowed over time as adjuvant hormonal treatments became more commonly prescribed.
Authors: Livaudais JC; Li C; John EM; Terry MB; Daly M; Buys SS; Habel L; Thompson B; Yanez ND; Coronado GD
J Womens Health (Larchmt). 2012 Sep;21(9):950-8. Epub 2012 Jun 25.
Barrett’s Esophagus: Who Should Receive Ablation and How Can We Get the Best Results?
Authors: Corley DA; Bergman JJ
Gastroenterology. 2012 Sep;143(3):524-6. Epub 2012 Jul 25.
The prevalence of obesity and obesity-related health conditions in a large, multiethnic cohort of young adults in California
PURPOSE: To identify population groups that are most susceptible to obesity-related health conditions at young age. METHODS: For this population-based cross-sectional study, measured weight and height, diagnosis, laboratory, and drug prescription information were extracted from electronic medical records of 1,819,205 patients aged 20 to 39 years enrolled in two integrated health plans in California in 2007 through 2009. RESULTS: Overall, 29.9% of young adults were obese. Extreme obesity (body mass index [BMI] >/= 40 kg/m(2)) was observed in 6.1% of women and 4.5% of men. The adjusted relative risk (RR) for diabetes, hypertension, dyslipidemia, and the metabolic syndrome increased sharply for those individuals with a BMI of 40 or greater, with the sharpest increase in the adjusted RR for hypertension and the metabolic syndrome. The association between weight class and dyslipidemia, hypertension, and the metabolic syndrome but not diabetes was stronger among 20.0- to 29.9-year-olds compared with 30.0- to 39.9-year-olds (P for interaction < .05). For example, compared with their normal weight counterparts of the same age group, young adults with a BMI of 40.0 to 49.9, 50.0 to 59.9, and 60 or greater kg/m(2) had a RR for hypertension of 11.73, 19.88, and 30.47 (95% confidence interval [CI], 26.39-35.17) at 20 to 29 years old, and 9.31, 12.41, and 15.43 (95% CI, 14.32-16.63) at 30 to 39 years old. CONCLUSIONS: Although older individuals were more likely to be extremely obese, the association between obesity-related health conditions was stronger in younger individuals. Hispanics and Blacks are also more likely to be obese, including extremely obese, putting them at an elevated risk for premature cardiovascular disease and some cancers relative to non-Hispanic Whites.
Authors: Koebnick C; Smith N; Huang K; Martinez MP; Clancy HA; Kushi LH
Ann Epidemiol. 2012 Jul 3.
Patient awareness and knowledge of breast cancer-related lymphedema in a large, integrated health care delivery system
Breast cancer patients have voiced dissatisfaction regarding their education on breast cancer-related lymphedema risk and risk reduction strategies from their clinicians. Informing patients about lymphedema can contribute to decrease their risk of developing the condition, or among those already affected, prevent it from progressing further. In this cross-sectional study, a lymphedema awareness score was calculated based on responses to a brief telephone interview conducted among 389 women diagnosed with invasive breast cancer at Kaiser Permanente Northern California from 2000 to 2008 and had a previous record of a lymphedema-related diagnosis or procedure in their electronic medical record. During the telephone interview, women self-reported a lymphedema clinical diagnosis, lymphedema symptoms but no lymphedema diagnosis, or neither a diagnosis nor symptoms, and responded to questions on lymphedema education and support services as well as health knowledge. Multivariable logistic regression [odds ratio (OR) and 95 % confidence interval (CI)] was used to determine the associations of selected sociodemographic and clinical factors with the odds of having lymphedema awareness (adequate vs. inadequate). The median (range) of the lymphedema awareness score was 4 (0-7). Compared with patients <50 years of age, patients 70+ years of age at breast cancer diagnosis had lower odds of adequate lymphedema awareness (OR 0.25; 95 % CI 0.07, 0.89), while patients 50-59 and 60-69 years had greater odds of adequate awareness although not statistically significant (OR 2.05; 95 % CI 0.88, 4.78 and OR 1.55; 95 % CI 0.60, 4.02, respectively; p for trend = 0.09). Higher educational level and greater health literacy were suggestive of adequate awareness yet were not significant. These results can help inform educational interventions to strengthen patient knowledge of lymphedema risk and risk reduction practices, particularly in an integrated health care delivery setting. With the growing population of breast cancer survivors, increasing patient awareness and education about lymphedema risk reduction and care after cancer diagnosis is warranted.
Authors: Kwan ML; Shen L; Munneke JR; Tam EK; Partee PN; Andre M; Kutner SE; Somkin CP; Ackerson LM; Thiadens SR
Breast Cancer Res Treat. 2012 Sep;135(2):591-602. Epub 2012 Aug 19.
Effects of a dietary intervention and weight change on vasomotor symptoms in the Women’s Health Initiative
OBJECTIVE: The aim of this study was to determine whether a dietary intervention designed to reduce fat intake and increase intake of fruit, vegetables, and whole grains, and weight loss, reduces vasomotor symptoms (VMS; ie, hot flashes or night sweats) in postmenopausal women. METHODS: We included 17,473 postmenopausal US women, ages 50 to 79 years, at baseline who participated in the Women’s Health Initiative Dietary Modification trial and were not taking menopausal hormone therapy. Logistic regression was used to evaluate associations. RESULTS: In multivariate-adjusted analyses, with simultaneous adjustment for the intervention and weight change, assignment to the dietary intervention versus the control arm was significantly (odds ratio [OR], 1.14; 95% CI, 1.01-1.28) related to a higher likelihood of symptom elimination among women with VMS at baseline. In addition, women with symptoms at baseline who lost 10 lb or more (OR, 1.23; 95% CI, 1.05-1.46) or lost 10% or more of their baseline body weight (OR, 1.56; 95% CI, 1.21-2.02) between baseline and year 1 were significantly more likely to eliminate VMS compared with those who maintained weight. Upon examining the joint effect of the dietary modification and weight loss, compared with women in the control arm who maintained weight, women who lost substantial weight (>/= 10%) as a part of the intervention (OR, 1.89; 95% CI, 1.39-2.57) but not as part of the control arm (OR, 1.40; 95% CI, 0.92-2.13) were significantly more likely to end VMS, although these two groups did not differ significantly from each other. Large weight loss (>22 lb), but not dietary changes, was related to the elimination of moderate/severe VMS. CONCLUSIONS: Weight loss as part of a healthy dietary modification may help eliminate VMS among postmenopausal women.
Authors: Kroenke CH; Caan BJ; LeBlanc E; et al.
Menopause. 2012 Sep;19(9):980-8.
Validation of AJCC TNM staging for breast tumors diagnosed before 2004 in cancer registries
PURPOSE: American Joint Committee on Cancer (AJCC) Tumor (T), Nodal (N), and Metastatic (M) staging is commonly used in clinical practice for treatment decisions, yet before 2004, Surveillance Epidemiology and End Results (SEER)-affiliated cancer registries did not routinely include TNM staging defined by AJCC criteria, reporting instead SEER Summary Staging. METHODS: We developed and validated an algorithm to determine AJCC TNM staging from Extent of Disease information for 17,133 female breast cancer cases diagnosed from 1988 to 2003 in the cancer registries of Kaiser Permanente Northern and Southern California. Test characteristics (percent agreement, Cohen’s kappa, sensitivity, specificity) were calculated to compare derived TNM with gold-standard TNM available in the registry. RESULTS: Agreement for TNM variables was excellent (range 0.91-1.00 for percent agreement and Cohen’s kappa). The sensitivity and specificity, respectively, of the algorithm for AJCC TNM Version 6 staging were as follows: Stage 0 (0.99, 1.00), Stage I (0.97, 0.98), Stage II (0.91, 0.96), Stage III (0.69, 0.99), and Stage IV (0.92, 1.00). Stage III had lower sensitivity due to reclassification of supraclavicular lymph node positivity from M1 (Stage IV) to N3 (Stage IIIC) in AJCC Version 6. CONCLUSIONS: Derived AJCC staging for breast tumors diagnosed before 2004 is feasible and accurate using cancer registry data.
Authors: Kwan ML; Haque R; Lee VS; Joanie Chung WL; Avila CC; Clancy HA; Quinn VP; Kushi LH
Cancer Causes Control. 2012 Sep;23(9):1587-91. Epub 2012 Jul 14.
Guidelines for Colonoscopy Surveillance After Screening and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer
Authors: Lieberman DA; Rex DK; Winawer SJ; Giardiello FM; Johnson DA; Levin TR
Gastroenterology. 2012 Sep;143(3):844-57. Epub 2012 Jul 3.
Clinical effectiveness of pneumococcal polysaccharide vaccine in men: California Men’s Health Study
OBJECTIVE: To examine the effectiveness of pneumococcal polysaccharide vaccine (PPV) among approximately 40,000 community-dwelling men aged 45 years and older in the California Men’s Health Study (CMHS) cohort. METHODS: All participants completed an extensive questionnaire at baseline (2002-2003) and were followed for the occurrence of invasive pneumococcal disease (IPD) or all-cause pneumonia hospitalization through the end of 2009. Immunization status and incident IPD and pneumonia cases were ascertained through electronic medical records. The associations between vaccination and IPD or pneumonia hospitalization were assessed using time-dependent Cox proportional models to account for sociodemographics, time-updated vaccination status, and comorbidities. RESULTS: The median follow-up period of the 39,222 participants was 7.3 years. Among them, 11,902 (30.3%) had received at least one PPV vaccine at baseline and 7653 (19.5%) received their first PPV vaccine during the follow-up. There were 17 pneumococcal bacteremia cases, 647 hospitalized pneumonia cases, and no pneumococcal meningitis cases. The results suggested a reduced risk of pneumococcal bacteremia among men vaccinated at age >/=65 (adjusted hazard ratio [HR]: 0.35; 95% confidence interval [CI]: 0.06-1.91; p=0.22). PPV vaccination did not show a protective effect against all-cause pneumonia hospitalization (adjusted HR: 1.18; 95% CI: 1.02-1.37, p=0.03) among men vaccinated before 65 years old, but a moderate protective effect was suggested among men without chronic obstructive pulmonary diseases who were vaccinated after 65 years old (adjusted HR: 0.84; 95% CI: 0.67-1.06, p=0.15). CONCLUSIONS: The findings in this large cohort of men in Southern California suggested a benefit of PPV for protection against pneumococcal bacteremia among men vaccinated at age 65 years and older. PPV might not provide adequate protection against all-cause pneumonia hospitalization among men.
Authors: Hechter RC; Chao C; Jacobsen SJ; Slezak JM; Quinn VP; Van Den Eeden SK; Tseng HF
Vaccine. 2012 Aug 17;30(38):5625-30. Epub 2012 Jul 10.
Diabetes, Hypertension and Hyperlipidemia: Prevalence Over Time and Impact on Long-Term Survival After Liver Transplantation
With increasing short-term survival, the transplant community has turned its focus to delineating the impact of medical comorbidities on long-term outcomes. Unfortunately, conditions such as diabetes, hypertension and hyperlipidemia are difficult to track and often managed outside of the transplant center by primary care providers. We collaborated with Kaiser Permanente Northern California to create a database of 598 liver transplant recipients, which incorporates diagnostic codes along with laboratory and pharmacy data. Specifically, we determined the prevalence of diabetes, hypertension and hyperlipidemia both before and after transplant and evaluated the influence of disease duration as a time-dependent covariate on posttransplant survival. The prevalence of these comorbidities increased steadily from the time of transplant to 7 years after transplant. The estimated risk for all-cause mortality (hazard ratio = 1.07 per year increment, 95% CI 1.01-1.13, p < 0.02) and mortality secondary to cardiovascular events, infection/multisystem organ failure and allograft failure (hazard ratio = 1.08 per year increment, 95% CI 1.00-1.16, p = 0.05) increased for each additional year of diabetes. No associations were found for duration of hypertension and hyperlipidemia. Greater attention to management of diabetes may mitigate its negative impact on long-term survival in liver transplant recipients.
Authors: Parekh J; Corley DA; Feng S
Am J Transplant. 2012 Aug;12(8):2181-7. Epub 2012 Apr 30.
What Epidemiological Studies are Telling Us About Lower Urinary Tract Symptoms that Should Change Practice
Authors: Van Den Eeden SK
J Urol. 2012 Aug;188(2):353-4. Epub 2012 Jun 14.
The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on imaging in Barrett’s Esophagus
Authors: Sharma P; Savides TJ; Canto MI; Corley DA; Falk GW; Goldblum JR; Wang KK; Wallace MB; Wolfsen HC
Gastrointest Endosc. 2012 Aug;76(2):252-4.
Consensus Statements for Management of Barrett’s Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process
BACKGROUND & AIMS: Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett’s esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS: We performed an international, multi-disciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS: Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: 1. specimens from endoscopic resection are better than biopsies for staging lesions, 2. it is important to carefully map the size of the dysplastic areas, 3. patients that receive ablative or surgical therapy require endoscopic follow-up, 4. high-resolution endoscopy is necessary for accurate diagnosis, 5. endoscopic therapy for HGD is preferred to surveillance, 6. endoscopic therapy for HGD is preferred to surgery, 7. the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and 8. following endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS: We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.
Authors: Bennett C; Corley DA; Jankowski JA; et al.
Gastroenterology. 2012 Aug;143(2):336-46. Epub 2012 Apr 24.
Incidence and Mortality of Colorectal Adenocarcinoma in Persons with Inflammatory Bowel Disease from 1998 to 2010
BACKGROUND & AIMS: The relationship between inflammatory bowel disease (IBD) and the incidence and mortality of colorectal adenocarcinoma (CRC) has not been evaluated recently. METHODS: We calculated the incidence and standardized incidence and mortality rate ratios of CRC among adult individuals with intact colons using Kaiser Permanente of Northern California’s database of members with IBD and general membership data for the period of 1998 to June 2010 (data through 2008 were used to calculate mortality). We also evaluated trends in medication use and rates of cancer detection over time. RESULTS: We identified 29 cancers among persons with Crohn’s disease (CD) and 53 among persons with ulcerative colitis (UC). Overall, the incidence rates of cancer among individuals with CD, UC, or in the general membership were 75.0, 76.0, and 47.1, respectively, per 100,000 person-years. In the general population, the incidence of CRC was 21% higher in 2007-2010 than in 1998-2001 (P for trend, <.0001), coincident with the growth of CRC screening programs. The incidence of CRC among individuals with CD or UC was 60% higher than in the general population (95% confidence interval [CI] for CD, 20%-200%; 95% CI for UC, 30%-200%) and was stable over time (P for trend was as follows: CD, .98; UC, .40). During 1998-2008, the standardized mortality ratio for CRC in individuals with CD was 2.3 (95% CI, 1.6-3.0) and 2.0 in those with UC (95% CI, 1.3-2.7). Over the study period, anti-tumor necrosis factor agents replaced other therapies for CD and UC; the rate of colonoscopy increased by 33% among patients with CD and decreased by 9% in those with UC. CONCLUSIONS: From 1998 to 2010, the incidence of CRC in patients with IBD was 60% higher than in the general population and essentially stable over time.
Authors: Herrinton LJ; Liu L; Levin TR; Allison JE; Lewis JD; Velayos F
Gastroenterology. 2012 Aug;143(2):382-9. Epub 2012 May 15.
Diabetes mellitus and sexual function in middle-aged and older women
Diabetes mellitus is an established risk factor for sexual dysfunction in men, but its effect on female sexual function is poorly understood. We examined the relationship of diabetes to sexual function in middle-aged and older women. Sexual function was examined in a cross-sectional cohort of ethnically diverse women aged 40-80 years using self-administered questionnaires. Multivariable regression models compared self-reported sexual desire, frequency of sexual activity, overall sexual satisfaction, and specific sexual problems (difficulty with lubrication, arousal, orgasm, or pain) among insulin-treated diabetic, non-insulin-treated diabetic, and nondiabetic women. Additional models assessed relationships between diabetic end-organ complications (heart disease, stroke, renal dysfunction, and peripheral neuropathy) and sexual function. Among the 2,270 participants, mean±standard deviation age was 55±9.2 years, 1,006 (44.4%) were non-Latina white, 486 (21.4%) had diabetes, and 139 (6.1%) were taking insulin. Compared with 19.3% of nondiabetic women, 34.9% of insulin-treated diabetic women (adjusted odds ratio [OR] 2.04, 95% confidence interval [CI] 1.32-3.15) and 26.0% of non-insulin-treated diabetic women (adjusted OR 1.42, 95% CI 1.03-1.94) reported low overall sexual satisfaction. Among sexually active women, insulin-treated diabetic women were more likely to report problems with lubrication (OR 2.37, 95% CI 1.35-4.16) and orgasm (OR 1.80, 95% CI 1.01-3.20) than nondiabetic women. Among all diabetic women, end-organ complications such as heart disease, stroke, renal dysfunction, and peripheral neuropathy were associated with decreased sexual function in at least one domain. Compared with nondiabetic women, diabetic women are more likely to report low overall sexual satisfaction. Insulin-treated diabetic women also appear at higher risk for problems such as difficulty with lubrication and orgasm. Prevention of end-organ complications may be important in preserving sexual activity and function in diabetic women. II.
Authors: Copeland KL; Brown JS; Creasman JM; Van Den Eeden SK; Subak LL; Thom DH; Ferrara A; Huang AJ
Obstet Gynecol. 2012 Aug;120(2 Pt 1):331-40.
Weight Change and Survival after Breast Cancer in the After Breast Cancer Pooling Project
BACKGROUND: Weight change after a breast cancer diagnosis has been linked to lower survival. To further understand effects of postdiagnostic weight variation on survival, we examined the relationship by comorbid status and initial body mass index (BMI). METHODS: The current analysis included 12,915 patients with breast cancer diagnosed between 1990 and 2006 with stage I-III tumors from four prospective cohorts in the United States and China. HRs and 95% confidence intervals (CI) representing the associations of five weight change categories [within <5% (reference); 5%-<10% and >/=10% loss and gain] with mortality were estimated using Cox proportional hazards models. RESULTS: Mean weight change was 1.6 kg. About 14.7% women lost and 34.7% gained weight. Weight stability in the early years postdiagnosis was associated with the lowest overall mortality risk. Weight loss >/=10% was related to a 40% increased risk of death (HR, 1.41; 95% CI, 1.14-1.75) in the United States and over three times the risk of death (HR, 3.25; 95% CI: 2.24, 4.73) in Shanghai. This association varied by prediagnosis BMI, and in the United States, lower survival was seen for women who lost weight and had comorbid conditions. Weight gain >/=10% was associated with a nonsignificant increased risk of death. CONCLUSIONS: Prevention of excessive weight gain is a valid public health goal for breast cancer survivors. Although intentionality of weight loss could not be determined, women with comorbid conditions may be particularly at risk of weight loss and mortality. IMPACT: Weight control strategies for breast cancer survivors should be personalized to the individual’s medical history.
Authors: Caan BJ; Kwan ML; Kroenke CH; Quesenberry CP Jr; Chen WY; et al.
Cancer Epidemiol Biomarkers Prev. 2012 Aug;21(8):1260-71. Epub 2012 Jun 13.
Estimating kinship in admixed populations
Genome-wide association studies (GWASs) are commonly used for the mapping of genetic loci that influence complex traits. A problem that is often encountered in both population-based and family-based GWASs is that of identifying cryptic relatedness and population stratification because it is well known that failure to appropriately account for both pedigree and population structure can lead to spurious association. A number of methods have been proposed for identifying relatives in samples from homogeneous populations. A strong assumption of population homogeneity, however, is often untenable, and many GWASs include samples from structured populations. Here, we consider the problem of estimating relatedness in structured populations with admixed ancestry. We propose a method, REAP (relatedness estimation in admixed populations), for robust estimation of identity by descent (IBD)-sharing probabilities and kinship coefficients in admixed populations. REAP appropriately accounts for population structure and ancestry-related assortative mating by using individual-specific allele frequencies at SNPs that are calculated on the basis of ancestry derived from whole-genome analysis. In simulation studies with related individuals and admixture from highly divergent populations, we demonstrate that REAP gives accurate IBD-sharing probabilities and kinship coefficients. We apply REAP to the Mexican Americans in Los Angeles, California (MXL) population sample of release 3 of phase III of the International Haplotype Map Project; in this sample, we identify third- and fourth-degree relatives who have not previously been reported. We also apply REAP to the African American and Hispanic samples from the Women’s Health Initiative SNP Health Association Resource (WHI-SHARe) study, in which hundreds of pairs of cryptically related individuals have been identified.
Authors: Thornton T; Tang H; Hoffmann TJ; Ochs-Balcom HM; Caan BJ; Risch N
Am J Hum Genet. 2012 Jul 13;91(1):122-38. Epub 2012 Jun 28.
Vitamin D Supplementation and Depression in the Women’s Health Initiative Calcium and Vitamin D Trial
While observational studies have suggested that vitamin D deficiency increases risk of depression, few clinical trials have tested whether vitamin D supplementation affects the occurrence of depression symptoms. The authors evaluated the impact of daily supplementation with 400 IU of vitamin D(3) combined with 1,000 mg of elemental calcium on measures of depression in a randomized, double-blinded US trial comprising 36,282 postmenopausal women. The Burnam scale and current use of antidepressant medication were used to assess depressive symptoms at randomization (1995-2000). Two years later, women again reported on their antidepressant use, and 2,263 completed a second Burnam scale. After 2 years, women randomized to receive vitamin D and calcium had an odds ratio for experiencing depressive symptoms (Burnam score >/=0.06) of 1.16 (95% confidence interval: 0.86, 1.56) compared with women in the placebo group. Supplementation was not associated with antidepressant use (odds ratio = 1.01, 95% confidence interval: 0.92, 1.12) or continuous depressive symptom score. Results stratified by baseline vitamin D and calcium intake, solar irradiance, and other factors were similar. The findings do not support a relation between supplementation with 400 IU/day of vitamin D(3) along with calcium and depression in older women. Additional trials testing higher doses of vitamin D are needed to determine whether this nutrient may help prevent or treat depression.
Authors: Bertone-Johnson ER; Larson J; Manson JE; et al.
Am J Epidemiol. 2012 Jul 1;176(1):1-13. Epub 2012 May 9.
Non-initiation of adjuvant hormonal therapy in women with hormone receptor-positive breast cancer: The Breast Cancer Quality of Care Study (BQUAL)
Adjuvant hormonal therapy for non-metastatic hormone receptor (HR)-positive breast cancer decreases risk of breast cancer recurrence and increases survival. However, some women do not initiate this life-saving treatment. We used a prospective cohort design to investigate factors related to non-initiation of hormonal therapy among women with newly diagnosed, non-metastatic HR-positive breast cancer recruited from three U.S. sites. Serial interviews were conducted at baseline and during treatment to examine sociodemographic factors, tumor characteristics, and treatment decision-making factors. Multivariate modeling assessed associations between variables of interest and hormonal therapy initiation. Of 1,050 breast cancer patients recruited, 725 (69 %) had HR-positive breast cancer, of whom 87 (12.0 %) based on self-report and 122 (16.8 %) based on medical record/pharmacy fill rates did not initiate hormonal therapy. In a multivariable analysis, non-initiation of hormonal therapy, defined by medical record/pharmacy, was associated with having greater negative beliefs about efficacy of treatment (OR 1.42, 95 % CI 1.18-1.70). Non-initiation was less likely in those who found the quality of patient/physician communication to be higher (OR 0.96, 95 % CI 0.93-0.99), the hormonal therapy treatment decision an easy one to make (OR 0.45, 95 % CI 0.23-0.90) or neither easy nor difficult (OR 0.34, 95 % CI 0.20-0.58); and had more positive beliefs about hormonal therapy efficacy (OR 0.40, 95 % CI 0.34-0.62). Factors influencing non-initiation of adjuvant hormonal therapy are complex and influenced by patient beliefs regarding treatment efficacy and side effects. Educational interventions to women about the benefits of hormonal therapy may decrease negative beliefs and increase hormone therapy initiation.
Authors: Neugut AI; Kushi LH; Hershman DL; et al.
Breast Cancer Res Treat. 2012 Jul;134(1):419-28. Epub 2012 Apr 22.
Population-based study of erectile dysfunction and polypharmacy
Study Type – Symptom prevalence (population cohort). Level of Evidence 1b. What’s known on the subject? and What does the study add? It is known that medical conditions such as diabetes, high blood pressure, high cholesterol, smoking and prescribed medications cause erectile dysfunction (ED). This has been studied at the molecular level and reported in population studies. The present study shows that, after accounting for known medical problems, there is a dose-response relationship, in which worsening degrees of ED are seen when a greater number of medications are taken, regardless if they are prescribed or over the counter. The study can help primary care doctors and urologists to make a differential diagnosis of ED and it can also help improve patient’s erectile function by tailoring and curtailing current medication use to maximize therapeutic benefit but minimize ED side effects in men, thus improving health-related quality of life. OBJECTIVE: * To study the association between erectile dysfunction (ED) and polypharmacy use in a large, ethnically and racially diverse cohort of men enrolled in the California Men’s Health Study (CMHS). PATIENTS AND METHODS: * Men from the Kaiser Permanente Southern California (KPSC) health plan, enrolled in the CMHS in 2002, had an age range of 45-69 years. ED and comorbidities of these subjects were identified by questionnaire responses. * The number of drugs taken was determined from the year before enrollment through electronic pharmacy records and questionnaire responses. RESULTS: * Among the 37 712 (KPSC) subjects, 10 717 (29%) reported moderate or severe ED. * Across all age groups, ED was more prevalent as the number of medications increased. * In men taking 0-2, 3-5,6-9 and >/= 10 medications, the percentage of men reporting moderate ED was 15.9, 19.7, 25.5 and 30.9%, respectively (P < 0.001). * With adjustment for age, race, smoking, diabetes, hypertension, hyperlipidaemia, peripheral vascular disease, coronary artery disease and body mass index, men taking >10 drugs were more likely to have ED (odds ratio = 2.32, 95% confidence interval 2.14-2.52) with evidence of a dose-response relationship. CONCLUSION: * These data suggest that the number of medications a man takes is associated with worse ED, even after comorbidities have been taken into account.
Authors: Londono DC; Slezak JM; Quinn VP; Loo RK; Jacobsen SJ; Van den Eeden SK
BJU Int. 2012 Jul;110(2):254-9. Epub 2011 Nov 15.
Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women
BACKGROUND: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. OBJECTIVE: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. DESIGN: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. RESULTS: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of >/=10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer-specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). CONCLUSION: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of >/=10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer-specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women’s Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.
Authors: Nechuta SJ; Caan BJ; Chen WY; Lu W; Chen Z; Kwan ML; Flatt SW; Zheng Y; Zheng W; Pierce JP; Shu XO
Am J Clin Nutr. 2012 Jul;96(1):123-32. Epub 2012 May 30.
Prognostic Impact of Comorbidity among Long-Term Breast Cancer Survivors: Results from the LACE Study
BACKGROUND: Little is known about the long-term impact of comorbidity among women with breast cancer. METHODS: We studied a prospective cohort of 2,272 women with breast cancer, who were recruited following initial breast cancer treatment. Associations of the Charlson comorbidity index (CCI) and hypertension with survival were evaluated in delayed entry Cox proportional hazards models. RESULTS: During a median follow-up of nine years, higher CCI scores were independently associated with an increased risk of death from all causes [HR, 1.32; 95% confidence interval (CI), 1.13-1.54] and from nonbreast cancer causes (HR, 1.55; 95% CI, 1.19-2.02), but not from breast cancer (HR, 1.14; 95% CI, 0.93-1.41). Hypertension was independently associated with an increased risk of death from all causes (HR, 1.55; 95% CI, 1.20-1.99), from nonbreast cancer causes (HR, 1.67; 95% CI, 1.10-2.54), and from breast cancer (HR, 1.47; 95% CI, 1.03-2.09), but these associations were no longer significant after adjustment for antihypertensive medication. The relationship between the CCI and overall survival was the strongest among women with stage I disease (stage I, HR, 1.65; 95% CI, 1.26-2.16 vs. stage III, HR, 0.53; 95% CI, 0.23-1.25). CONCLUSION: The CCI was independently associated with lower overall and nonbreast cancer survival, but not with breast cancer-specific survival. IMPACT: Comorbidity may play an important role in breast cancer outcomes.
Authors: Braithwaite D; Satariano WA; Kwan ML; Hiatt RA; Kroenke C; Caan BJ; Moore DH
Cancer Epidemiol Biomarkers Prev. 2012 Jul;21(7):1115-25. Epub 2012 May 9.
Automated phone and mail population outreach to promote colorectal cancer screening
OBJECTIVES: To evaluate a population outreach program to promote screening for colorectal cancer (CRC) among average-risk insured men and women. STUDY DESIGN: In 2008, 58,440 Kaiser Permanente Colorado members unscreened for CRC received an interactive voice response (IVR) call followed by mailed fecal immunochemical test (FIT), or colonoscopy if requested. We used a quasi-experimental design with staged implementation, in which a random subset of eligible members was selected each week to receive the intervention. This design allowed the entire group to ultimately receive the intervention. METHODS: Survival models summarized time-specific comparisons of screening behaviors for members who received immediate outreach compared with those who had not yet received it. RESULTS: A total of 26,003 (45%) of the unscreened population completed screening, predominately due to the mailed kits. The unadjusted hazard ratio (HR) for the outreach effect on screening completion was 4.08 (95% confidence interval: 3.93-4.25) and adjusted HR was 3.75 (3.60-3.91). Lower levels of screening were seen in African Americans (HR 0.83; 0.77-0.90) and Hispanics (HR 0.84; 0.80-0.88) compared with whites, and in smokers (HR 0.77; 0.74-0.80) compared with nonsmokers. The outreach had greater impact among those without a primary care (HR 4.5 vs 3.0, P <.0001) or specialty care (HR 5.2 vs 3.5, P <.0001) visit compared with those with 1 or more visits. CONCLUSIONS: The rate of colorectal cancer screening in members after mailed FIT with IVR was almost 4 times higher than usual care, particularly in those without an office visit. Targeted approaches are needed for groups at risk for not screening.
Authors: Kempe KL; Shetterly SM; France EK; Levin TR
Am J Manag Care. 2012 Jul;18(7):370-8.
Glutathione peroxidase tagSNPs: Associations with rectal cancer but not with colon cancer
Glutathione peroxidases (GPXs) are selenium-dependent enzymes that reduce and, thus, detoxify hydrogen peroxide and a wide variety of lipid hydroperoxides. We investigated tagSNPs in GPX1-4 in relation to colorectal neoplasia in three independent study populations capturing the range of colorectal carcinogenesis from adenoma to cancer. A linkage-disequilibrium (LD)-based tagSNP selection algorithm (r(2) >/= 0.90, MAF >/= 4%) identified 21 tagSNPs. We used an identical Illumina platform to genotype GPX SNPs in three population-based case-control studies of colon cancer (1,424 cases/1,780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). For gene-level associations, we conducted principal component analysis (PCA); multiple logistic regression was used for single SNPs. Analyses were adjusted for age, sex, and study center and restricted to non-Hispanic white participants. Analyses of cancer endpoints were stratified by molecular subtypes. Without correction for multiple testing, one polymorphism in GPX2 and three polymorphisms in GPX3 were associated with a significant risk reduction for rectal cancer at alpha = 0.05, specifically for rectal cancers with TP53 mutations. The associations regarding the three polymorphisms in GPX3 remained statistically significant after adjustment for multiple comparisons. The PCA confirmed an overall association of GPX3 with rectal cancer (P = 0.03). No other statistically significant associations were observed. Our data provide preliminary evidence that genetic variability in GPX3 contributes to risk of rectal cancer but not of colon cancer and thus provide additional support for differences in underlying pathogenetic mechanisms for colon and rectal cancer. (c) 2012 Wiley Periodicals, Inc.
Authors: Haug U; Caan BJ; Ulrich CM; et al.
Genes Chromosomes Cancer. 2012 Jun;51(6):598-605. Epub 2012 Feb 27.
Mood Patterns Based on Momentary Assessment of Positive and Negative Moods Over a Day and Coronary Artery Calcification in the CARDIA Study
OBJECTIVE: Retrospective assessments of negative mood have predicted coronary artery disease development and progression. Using momentary assessment, we evaluated associations between average positive and negative mood states and diurnal mood patterns, with prevalent and incident coronary artery calcification (CAC), a measure of calcified atherosclerosis. METHODS: In a prospective cohort study of 669 white and African American men and women, aged 33 to 45 years, from the Coronary Artery Risk Development in Young Adults Study, mood was assessed at Year 15 examination, six times over a weekday. Prevalent, progressive, and 5-year incident CAC (any detectable CAC [score >0]) and substantial CAC (CAC score >/= 20) were assessed at examinations at Years 15 and 20 by electron-beam tomographic scans. We employed a modified Poisson regression approach for binary data with robust error estimation to quantify relative risk. RESULTS: In multivariate-adjusted analyses, those with high-average positive mood that improved over a day had a lower risk of prevalent CAC higher than 0 (relative risk [RR] = 0.17 [95% confidence interval {CI} = 0.04-0.67]) and substantial CAC (RR = 0.25 [95% CI = 0.06-0.95]). In contrast, those with high-average, increasingly negative mood over a day had a higher risk of prevalent CAC (RR = 1.85 [95% CI = 0.86-3.99]) and substantial CAC (RR = 3.11 [95% CI = 1.29-7.49]). Findings were similar for progressive CAC at Year 20. This pattern of high/worsening negative mood (not positive mood) during the day was also predictive of 5-year incident CAC (RR = 2.99 [95% CI = 1.00-8.93]). CONCLUSIONS: Diurnal mood patterns were associated with the progression of calcified atherosclerosis, with negative mood predicting greater progression and positive mood predicting lower progression.
Authors: Kroenke CH; Seeman T; Matthews K; Adler N; Epel E
Psychosom Med. 2012 Jun;74(5):526-34.
The importance of exposure rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium
BACKGROUND: Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. METHODS: The authors pooled data from 12 case-control studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1242 (EAC), 1263 (EGJA) and 954 (ESCC) cases and 7053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. RESULTS: For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01). CONCLUSIONS: Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases.
Authors: Lubin JH; Corley DA; Whiteman DC; et al.
Cancer Epidemiol. 2012 Jun;36(3):306-16. Epub 2012 Apr 13.
The Breast Cancer Quality of Care Study (BQUAL): A Multi-Center Study to Determine Causes for Noncompliance with Breast Cancer Adjuvant Therapy
In oncology, quality of care is a major issue for patients and providers. Significant variations in care, including nonreceipt of adjuvant systemic therapy, nonadherence to therapy, and/or early discontinuation of therapy, occur frequently and may impact survival. Reasons for these variations are not well understood, but may play a role in the prominent disparity in breast cancer survival between blacks and whites. Since May 2006, the Breast Cancer Quality of Care Study (BQUAL) has recruited 1158 women with nonmetastatic breast cancer from several centers across the country, with completed data on 1057 participants to date. Detailed information on demographic, behavioral, biomedical, and emotional factors related to chemotherapy use was collected on each participant at baseline and at two follow-up interviews during the first 6 months. In addition, for women with ER+ tumors, further questionnaires were completed every 6 months regarding hormonal therapy use. Each participant was also asked to provide a DNA sample, and to allow medical record review. We surveyed physicians providing care to the study participants regarding attitudes toward adjuvant treatment. The mean age of participants was 58 years (SD 11.6), and 15% (n = 160) were black. The majority had an annual household income <$90,000 (n = 683), had college education or higher (n = 802), 55.9% were married, and 57.9% were not currently employed. Seventy-six percent had hormone-receptor-positive tumors, 49.9% initiated chemotherapy and 82.7% started hormonal therapy. Blacks were more likely to have lower annual household income (p < 0001), less education (p = 0.0005), ER negative tumor status (p = 0.02), and poorly differentiated cancer (p = 0.0002). The main endpoints of the study are noninitiation of chemotherapy or hormonal therapy, nonadherence to therapy and early discontinuation of therapy. Treatment and outcomes will be compared on the 15% of participants who are black versus other participants. The BQUAL Study will be a rich ongoing source of information regarding reasons for differences in receipt of both adjuvant chemotherapy and hormonal therapy. This information may be useful in planning interventions to improve quality of care.
Authors: Neugut AI; Kushi LH; Hershman DL; et al.
Breast J. 2012 May-Jun;18(3):203-13. Epub 2012 Apr 5.
The value of additional pathology comments indicating suspicion of adenocarcinoma among women diagnosed preoperatively with complex atypical endometrial hyperplasia
Over 40% of women with a preoperative diagnosis of complex atypical hyperplasia (CAH) will have endometrial cancer at hysterectomy. CAH diagnoses are often qualified by comments indicating suspicion of cancer. We examine whether these comments correlate with cancer found at hysterectomy. Pathology reports for 824 women with CAH diagnoses who underwent hysterectomy were reviewed to identify those qualified by comments indicating concern for cancer. The rate of cancer, severity of disease, and effects of endometrial sampling method and age were determined. Comments indicating suspicion of cancer qualified 219 of 824 (27%) CAH diagnoses and were associated with a significantly higher cancer rate at hysterectomy (69% versus 40%; P<0.0001), regardless of whether sampling consisted of curettage or biopsy. Cancer severity correlated independently with age. Comments indicating concern for underlying cancer frequently qualify CAH diagnoses and are associated with a high likelihood of cancer and with more extensive disease, especially for older women.
Authors: Suh-Burgmann E; Hung YY; Armstrong MA
Int J Gynecol Pathol. 2012 May;31(3):222-6.
Genetic Variation in the Transforming Growth Factor-beta-Signaling Pathway, Lifestyle Factors, and Risk of Colon or Rectal Cancer
BACKGROUND: The transforming growth factor-beta-signaling pathway has been identified as being involved in colorectal cancer. OBJECTIVE: The aim of this study was to determine how diet and lifestyle factors in combination with genetic variation in the transforming growth factor-beta-signaling pathway alters colorectal cancer risk. DESIGN: We used data from 2 population-based case-control studies. PATIENTS: Participants included patients with colon cancer (n = 1574) and controls (n = 1970) and patients with rectal cancer ( n = 791) and controls (n = 999). MAIN OUTCOME MEASURES: The primary outcomes measured were newly diagnosed cases of colon or rectal cancer. RESULTS: Colon and rectal cancer risk increased with the number of at-risk genotypes within the transforming growth factor-beta-signaling pathway (OR 3.68, 95% CI 2.74,4.94 for colon cancer; OR 3.89, 95% CI 2.66,5.69 for rectal cancer). A high at-risk lifestyle score also resulted in significant increased risk with number of at-risk lifestyle factors (OR 2.99, 95% CI 2.32,3.85 for colon cancer; OR 3.37, 95% CI 2.24,5.07 for rectal cancer). The combination of high-risk genotype and high-risk lifestyle results in the greatest increase in risk (OR 7.89, 95% CI 4.45,13.96 for colon cancer; OR 8.75, 95% CI 3.66,20.89 for rectal cancer). LIMITATIONS: The study results need validation in other large studies of colon and rectal cancer. CONCLUSIONS: In summary, our data suggest that there is increased colon and rectal cancer risk with increasing number of at-risk genotypes and at-risk lifestyle factors. Although the integrity of the pathway can be diminished by a number of high-risk genotypes, this risk can be offset, in part, by maintaining a healthy lifestyle.
Authors: Slattery ML; Lundgreen A; Wolff RK; Herrick JS; Caan BJ
Dis Colon Rectum. 2012 May;55(5):532-40.
Effect of Postdiagnosis Weight Change on Hot Flash Status Among Early-Stage Breast Cancer Survivors
PURPOSE: Hot flashes (HF) affect a large proportion of breast cancer (BC) survivors and can negatively affect their quality of life. Treatments other than estrogen replacement to alleviate HF are needed. Body weight is related to hot flashes, but little is known about the effect of weight change on HF. PATIENTS AND METHODS: We used data from 3,088 women previously treated for early-stage BC who were enrolled onto the Women’s Healthy Eating and Living study to examine the association between weight change after a breast cancer diagnosis and the odds of reporting HF. RESULTS: Overall, 36.1% of participants reported moderate to severe HF at study entry. At 2 years postdiagnosis, 69.2% of women remained within 10%, 4.8% lost at least 10%, and 26.0% gained at least 10% of their prediagnosis weight. Those who gained at least 10% of their prediagnosis weight had a greater risk of reporting HF than women who remained weight stable in that same period (odds ratio [OR], 1.33; 95% CI, 1.11 to 1.60; P = .003). Weight loss of at least 10% of prediagnosis weight was associated with a nonsignificant reduced risk (OR, 0.72; 95% CI, 0.47 to 1.08; P = .118) of reporting HF. However, the trend of weight change (weight loss and weight gain) on HF was significant both when examined categorically (P = .03) and continuously (P < .001). CONCLUSION: Prevention of weight gain after a BC diagnosis-a modifiable behavior-may offer a viable intervention for relief of HF. Effects of intentional weight loss in BC survivors requires further study.
Authors: Caan BJ; Emond JA; Su HI; Patterson RE; Flatt SW; Gold EB; Newman VA; Rock CL; Thomson CA; Pierce JP
J Clin Oncol. 2012 May 1;30(13):1492-7. Epub 2012 Mar 19.
Social networks, social support and burden in relationships, and mortality after breast cancer diagnosis
Though larger social networks are associated with reduced breast cancer mortality, there is a need to clarify how both social support and social burden influence this association. We included 4,530 women from the Women’s Health Initiative who were diagnosed with breast cancer between 1993 and 2009, and provided data on social networks (spouse or intimate partner, religious ties, club ties, and number of first-degree relatives) before diagnosis. Of those, 354 died during follow-up, with 190 from breast cancer. We used Cox proportional hazards regression to evaluate associations of social network members with risk of post-diagnosis mortality, further evaluating associations by social support and social burden (caregiving, social strain). In multivariate-adjusted analyses, among women with high but not low social support, being married was related to lower all-cause mortality. By contrast, among women with high but not low social burden, those with a higher number of first-degree relatives, including siblings, parents, and children, had higher all-cause and breast cancer mortality (among caregivers: 0-3 relatives (ref), 4-5 relatives, HR = 1.47 (95% CI: 0.62-3.52), 6-9 relatives, HR = 2.08 (95% CI: 0.89-4.86), 10+ relatives, HR = 3.55 (95% CI: 1.35-9.33), P-continuous = 0.02, P-interaction = 0.008). The association by social strain was similar though it was not modified by level of social support. Other social network members were unrelated to mortality. Social relationships may have both adverse and beneficial influences on breast cancer survival. Clarifying these depends on understanding the context of women’s relationships.
Authors: Kroenke CH; Michael Y; Tindle H; Gage E; Chlebowski R; Garcia L; Messina C; Manson JE; Caan BJ
Breast Cancer Res Treat. 2012 May;133(1):375-85. Epub 2012 Feb 14.
Complementary and Alternative Medicine Use, Patient-reported Outcomes, and Treatment Satisfaction Among Men With Localized Prostate Cancer
OBJECTIVE: To evaluate the association between complementary and alternative medicine (CAM) use, satisfaction with treatment, and patient-reported outcomes after treatment. METHODS: The Prostate CAncer Therapy Selection Study prospectively surveyed patients newly diagnosed with localized prostate cancer about their treatment decision-making process and outcomes. The Prostate CAncer Therapy Selection Study recruited patients from 3 geographic areas through hospital-based urology clinics and community urology practices. RESULTS: More than 700 patients completed the baseline and follow-up surveys. More than 50% of respondents reported using CAM; this decreased to 39% if prayer was excluded as a type of CAM. On multivariate analysis, factors related to communication with the treating physician, but not CAM use, were associated with treatment satisfaction. The likelihood of stability or improvement in urinary, bowel, and sexual function at 6 months was related to the choice of primary therapy but was unrelated to CAM use. CONCLUSION: In the present prospective observational study, CAM use was highly prevalent but unrelated to treatment satisfaction or changes in functional status. The effect of CAM on these endpoints remains to be established in comparative effectiveness studies.
Authors: Ramsey SD; Zeliadt SB; Blough DK; Fedorenko CR; Fairweather ME; McDermott CL; Penson DF; Van Den Eeden SK; Hamilton AS; Arora NK
Urology. 2012 May;79(5):1034-41.
Ten-Year Risk of Diagnostic Mammograms and Invasive Breast Procedures After Breast-Conserving Surgery for DCIS
BACKGROUND: Breast-conserving surgery (BCS) is the most common treatment for ductal carcinoma in situ (DCIS); however, how often women experience subsequent diagnostic evaluations over time is not known. METHODS: We identified 2948 women with DCIS who were treated with BCS from 1990 to 2001 and followed for up to 10 years at three integrated health-care delivery systems. We calculated the percentages of diagnostic mammograms and ipsilateral invasive procedures following the initial breast excision to treat DCIS, estimated the 10-year cumulative incidence of these procedures, and determined hazard ratios for both types of procedures with Cox regression modeling. All statistical tests were two-sided. RESULTS: Over 10 years, 907 women (30.8%) had 1422 diagnostic mammograms and 1813 (61.5%) had 2305 ipsilateral invasive procedures. Diagnostic mammograms occurred in 7.3% of women in the first 6 months and continued at a median annual rate of 4.3%. Ipsilateral invasive procedures occurred in 51.5% of women in the first 6 months and continued at a median annual rate of 3.1%. The estimated 10-year cumulative risk of having at least one diagnostic mammogram after initial DCIS excision was 41.0% (95% confidence interval [CI] = 38.5% to 43.5%); at least one invasive procedure, 65.7% (95% CI = 63.7% to 67.8%); and either event, 76.1% (95% CI = 74.1% to 78.1%). Excluding events in the first 6 months following initial DCIS excision, corresponding risks were 36.4% (95% CI = 33.8% to 39.0%) for diagnostic mammograms, 30.4% (95% CI = 26.9% to 33.8%) for invasive procedures, and 49.5% (95% CI = 45.6% to 53.5%) for either event. CONCLUSIONS: Women with DCIS treated with BCS continue to have diagnostic and invasive breast procedures in the conserved breast over an extended period. The frequency of ongoing diagnostic breast evaluations should be included in discussions about treatment.
Authors: Nekhlyudov L; Habel LA; Achacoso N; Jung I; Haque R; Collins LC; Schnitt SJ; Quesenberry CP Jr; Fletcher SW
J Natl Cancer Inst. 2012 Apr 18;104(8):614-21. Epub 2012 Apr 5.
Characterization of gene-environment interactions for colorectal cancer susceptibility loci
Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal P(interaction) = 1.3 x 10(-4); adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption.
Authors: Hutter CM; Caan BJ; Peters U; et al.
Cancer Res. 2012 Apr 15;72(8):2036-44. Epub 2012 Feb 24.
Antioxidant supplement use after breast cancer diagnosis and mortality in the Life After Cancer Epidemiology (LACE) cohort
BACKGROUND: There is concern that antioxidant supplement use during chemotherapy and radiation therapy may decrease treatment effects, yet the effects of such supplements on recurrence and survival are largely unknown. METHODS: The authors prospectively examined the associations between antioxidant use after breast cancer (BC) diagnosis and BC outcomes in 2264 women in the Life After Cancer Epidemiology (LACE) cohort. The cohort included women who were diagnosed with early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years postdiagnosis. Baseline data were collected on antioxidant supplement use since diagnosis and other factors. BC recurrence and mortality were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using delayed entry Cox proportional hazards models. All tests of statistical significance were 2-sided. RESULTS: Antioxidant supplement use after diagnosis was reported by 81% of women. Among antioxidant users, frequent use of vitamin C and vitamin E was associated with a decreased risk of BC recurrence (vitamin C: HR, 0.73; 95% CI, 0.55-0.97; vitamin E: HR, 0.71; 95% CI, 0.54-0.94); and vitamin E use was associated with a decreased risk of all-cause mortality (HR, 0.76; 95% CI, 0.58-1.00). Conversely, frequent use of combination carotenoids was associated with increased risk of death from BC (HR, 2.07; 95% CI, 1.21-3.56) and all-cause mortality (HR, 1.75; 95% CI, 1.13-2.71). CONCLUSIONS: Frequent use of vitamin C and vitamin E in the period after BC diagnosis was associated with a decreased likelihood of recurrence, whereas frequent use of combination carotenoids was associated with increased mortality. The effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant. Cancer 2011. (c) 2011 American Cancer Society.
Authors: Greenlee H; Kwan ML; Kushi LH; Song J; Castillo A; Weltzien E; Quesenberry CP Jr; Caan BJ
Cancer. 2012 Apr 15;118(8):2048-58. Epub 2011 Sep 27.
Association between serum interleukin-6 concentrations and mortality in older adults: the Rancho Bernardo study.
BACKGROUND: Interleukin-6 (IL-6) may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans.AIMS: To determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD), cancer, and liver-related mortality. METHODS: A prospective cohort study included 1843 participants who attended a research visit in 1984-87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed) variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality. RESULTS: The mean (± standard deviation) age and body-mass-index (BMI) of participants was 68 (± 10.6) years and 25 (± 3.7) Kg/m(2), respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978), 25.5%, 11.3%, and 1.3%, respectively. The median (± IQR) length of follow-up was 15.3 ± 10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33-1.64), 1.38 (95% CI, 1.16-1.65), 1.35 (95% CI, 1.02-1.79), and 1.88 (95% CI, 0.97-3.67), respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels. CONCLUSIONS: In community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality.
Authors: Lee, Jeffrey K JK; Bettencourt, Ricki R; Brenner, David D; Le, Thuy-Anh TA; Barrett-Connor, Elizabeth E; Loomba, Rohit R
PloS one. 2012 ;7(4):e34218. Epub 2012-04-13.
The importance of choosing colorectal cancer screening tests: comment on ‘adherence to colorectal cancer screening’
Authors: Levin TR
Arch Intern Med. 2012 Apr 9;172(7):582-3.
Does increased experience with laparoscopic cholecystectomy yield more complex bile duct injuries?
BACKGROUND: Two decades since the advent of laparoscopic cholecystectomy, the rate of bile duct injuries still remains higher than in the open cholecystectomy era. METHODS: The rate and complexity of bile duct injuries was evaluated in 83,449 patients who underwent laparoscopic cholecystectomy between 1995 and 2008 in the Kaiser Permanente Northern California system. Fifty-six surgeons who performed a laparoscopic cholecystectomy in the past were surveyed to determine factors that predispose to bile duct injuries. RESULTS: The overall incidence of bile duct injuries was .10%; 59.5% of the 84 injuries were cystic duct leaks. Incidence varied slightly from .10% (1995-1998) to .08% (1999-2003) and .12% (2004-2008). There was a trend toward more proximal injuries (injury <2 cm from the bifurcation: 14.3% to 44.4% to 50.0% of major injuries). The misinterpretation of anatomy was cited by 92.9% of surgeons as the primary cause of bile duct injuries; 70.9% cited a lack of experience as a contributing factor. CONCLUSIONS: Laparoscopic cholecystectomy has an overall low risk of bile duct injuries; the rate remains constant, but injury complexity may have increased over time.
Authors: Chuang KI; Corley D; Postlethwaite DA; Merchant M; Harris HW
Am J Surg. 2012 Apr;203(4):480-7. Epub 2012 Feb 9.
Cigarette Smoking Increases Risk of Barrett’s Esophagus: an Analysis of the Barrett’s and Esophageal Adenocarcinoma Consortium
BACKGROUND & AIMS: Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett’s esophagus (BE). We investigated whether tobacco smoking and other factors increase risk for BE. METHODS: We analyzed data from 5 case-control studies included in the international Barrett’s and Esophageal Adenocarcinoma Consortium. We compared data from subjects with BE (n=1059) with those from subjects with gastroesophageal reflux disease (GERD controls, n=1332) and population-based controls (n=1143), using multivariable logistic regression models to test associations with cigarette smoking. We also tested whether cigarette smoking has synergistic effects with other exposures, which might further increase risk for BE. RESULTS: Subjects with BE were significantly more likely to have ever-smoked cigarettes than the population-based controls (odds ratio [OR]=1.67; 95% confidence interval [CI], 1.04-2.67) or GERD controls (OR=1.61; 95% CI, 1.33-1.96). Increasing pack-years of smoking increased the risk for BE. There was evidence for a synergy between ever-smoking and heartburn or regurgitation; the attributable proportion of disease among individuals who ever smoked and had heartburn or regurgitation was estimated to be 0.39 (0.25-0.52). CONCLUSIONS: Cigarette smoking is a risk factor for BE. The association strengthened with increased exposure to smoking until ~ 20 pack-years, when it began to plateau. Smoking has synergistic effects with heartburn or regurgitation, indicating that there are various pathways by which tobacco smoking might contribute to the development of BE.
Authors: Cook MB; Shaheen NJ; Anderson LA; Giffen C; Chow WH; Vaughan TL; Whiteman DC; Corley DA
Gastroenterology. 2012 Apr;142(4):744-53. Epub 2012 Jan 11.
Genetic variability in IL23R and risk of colorectal adenoma and colorectal cancer
Inflammatory processes, including, specifically, the inflammatory conditions Crohn’s disease (CD) and ulcerative colitis (UC) predispose to colorectal cancer. Interleukin-23 is involved in pro-inflammatory signaling; genetic variation in the interleukin-23 receptor (IL23R) has been consistently associated with CD and UC risk. In three case-control studies of colorectal adenoma (n=485 cases/578 controls), colon cancer (n=1424 cases/1780 controls) and rectal cancer (n=583 cases/775 controls), we investigated associations with 18 candidate and tagSNPs in IL23R. The three studies used an identical Illumina GoldenGate assay, allowing thorough investigation across stages and locations of colorectal neoplasia. We further explored associations with molecular cancer subtypes (MSI+, CIMP+, KRAS2mut, TP53mut). In this comprehensive study of genetic variability in IL23R across the spectrum of colorectal carcinogenesis, as well as within colon and rectal tumor molecular subtypes, we observed associations between SNPs in IL23R and risk of rectal cancer: the 88413 C>A (rs10889675) and 69450 C>A (rs7542081) polymorphisms were associated with decreased rectal cancer risk overall (p-trend=0.04 and 0.05 respectively), and specifically with rectal tumors bearing a TP53 mutation (88413 CA/AA vs. CC OR: 0.66; 95% CI: 0.46-94; 69450 CA/AA vs. CC OR: 0.60; 95% CI: 0.37-0.98). However, none of associations remained statistically significant after correction for multiple testing. These data provide some evidence that genetic variability in IL23R may contribute to rectal cancer risk and should be evaluated in additional studies.
Authors: Poole EM; Curtin K; Hsu L; Duggan DJ; Makar KW; Xiao L; Carlson CS; Caan BJ; Potter JD; Slattery ML; Ulrich CM
Cancer Epidemiol. 2012 Apr;36(2):e104-10. Epub 2011 Dec 6.
Pre-diagnosis body mass index and survival after breast cancer in the After Breast Cancer Pooling Project
Obese and underweight women who develop breast cancer may have poorer survival compared with normal-weight women. However, the optimal weight for best prognosis is still under study. We conducted a prospective investigation of pre-diagnosis body mass index (BMI) and mortality among 14,948 breast cancer patients in the After Breast Cancer Pooling Project. Breast cancer patients diagnosed from 1990 to 2006 with AJCC Stage I-III breast tumors were drawn from four prospective cohorts. Hazard ratios (HR) and 95% confidence intervals (CI) representing the associations of BMI categories (World Health Organization international classifications) with recurrence and mortality were estimated using delayed entry Cox proportional hazards models. Obese (30 to <35 kg/m(2)), severely obese (35 to <40 kg/m(2)), and morbidly obese (>/=40 kg/m(2)) were examined. After a mean follow-up of 7.8 years, 2,140 deaths and 2,065 recurrences were documented. Both underweight (HR = 1.59; 95% CI: 1.18, 2.13) and morbidly obese women (HR = 1.81; 95% CI: 1.42, 2.32) had the greatest risk of overall mortality compared with normal weight (18.5-24.9 kg/m(2)) women. Severe obesity (HR = 1.09; 95% CI: 0.88, 1.36) and obesity (HR = 1.11; 95% CI: 0.97, 1.27) were related to small non-significant increased risks. Overweight (25.0-29.9 kg/m(2)) was not associated with any excess risk compared with normal weight. Similar associations were found for breast cancer death and non-breast cancer death but not recurrence. Women who were underweight and morbidly obese before breast cancer diagnosis were at the greatest risk of all-cause mortality. Morbidly obese women were also at increased risk of death from breast cancer. These results suggest that degree of obesity confers differential risk on survival.
Authors: Kwan ML; Kroenke CH; Quesenberry CP Jr; Caan BJ; et al.
Breast Cancer Res Treat. 2012 Apr;132(2):729-39. Epub 2011 Dec 21.
Validity of Eight Integrated Healthcare Delivery Organizations’ Administrative Clinical Data to Capture Breast Cancer Chemotherapy Exposure
BACKGROUND: Cancer Research Network (CRN) sites use administrative data to populate their Virtual Data Warehouse (VDW). However, information on VDW chemotherapy data validity is limited. The purpose of this study was to assess the validity of VRN chemotherapy data.METHODS: This was a retrospective, cohort study of women >/=18 years with incident, invasive breast cancer diagnosed between January 1999 and December 2007. Pharmacy and procedure chemotherapy data were extracted from each site’s VDW. Random samples of 50 patients stratified on trastuzumab, anthracyclines, and no chemotherapy exposure were selected from each site for detailed chart abstraction. Weighted sensitivities and specificities of VDW compared to abstracted data were calculated. Cumulative doses calculated from VDW data were compared to doses obtained from the medical chart review.RESULTS: The cohort included 13497 patients with 6456 (48%) chart-review eligible. Patients in the sample (N=400) had a mean age of 65 years. Trastuzumab, anthracycline, and other chemotherapy weighted sensitivities were 95%, 97%, and 100%, respectively; specificities were 99%, 99%, and 93%, respectively; positive predictive values were 96%, 99%, and 55%, respectively; and negative predictive values were 99%, 96%, and 100%. Trastuzumab and anthracyclines VDW mean doses were 873 mgs and 386 mgs, respectively, while abstracted mean doses were 1734 mgs and 369 mgs, respectively (R2=0.14, p<0.01 and R2=0.05, p=0.03, respectively).CONCLUSIONS: Sensitivities and specificities for CRN chemotherapy VDW data were high and dosages were correlated with chart information. Impact: The findings support the use of CRN data in evaluating chemotherapy exposures and related outcomes.
Authors: Delate T; Habel LA; Wagner E; et al.
Cancer Epidemiol Biomarkers Prev. 2012 Apr;21(4):673-80. Epub 2012 Feb 15.
A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies
BACKGROUND: The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. METHODS: A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I-III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). FINDINGS: Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71.4% (95% CI 60.5-80.0) in low-risk, 58.3% (48.9-66.6) in intermediate-risk, and 49.2% (42.2-55.8) in high-risk patients (p(trend)=0.0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74.1% (66.0-80.6) in low-risk, 57.4% (48.3-65.5) in intermediate-risk, and 44.6% (40.2-48.9) in high-risk patients (p(trend)<0.0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0.0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. INTERPRETATION: Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. FUNDING: UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
Authors: Kratz JR; Van Den Eeden SK; Quesenberry CP; Habel LA; Jablons DM; et al.
Lancet. 2012 Mar 3;379(9818):823-32. Epub 2012 Jan 27.
Non-Steroidal Anti-Inflammatory Drug Use Reduces Risk for Adenocarcinomas of the Esophagus and Esophagogastric Junction in a Pooled Analysis
BACKGROUND & AIMS: Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported to reduce risks of esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations. METHODS: We performed a pooled analysis of 6 population-based studies within the Barrett’s and Esophageal Adenocarcinoma Consortium to evaluate the association between NSAID use and the risk of EAC and EGJA, using uniform exposure definitions. We collected information from 6 studies (5 case-control and 1 cohort), with a total of 1226 EAC and 1140 EGJA cases, on aspirin and/or NSAID use. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate adjusted logistic regression models and then pooled using a random effects meta-analysis model. RESULTS: Compared with nonusers, individuals who have used NSAIDs had a statistically significant reduced risk of EAC (OR, 0.68; 95% CI, 0.56-0.83); they also appeared to have a reduced risk of EGJA (OR, 0.83; 95% CI, 0.66-1.03). Similar reductions in risk were observed among individuals who took aspirin or nonaspirin NSAIDs. The highest levels of frequency (daily or more frequently) and duration (>/=10 years) of NSAID use were associated with an approximately 40% reduction in risk of EAC, with ORs of 0.56 (95% CI, 0.43-0.73; P(trend) < .001) and 0.63 (95% CI, 0.45-0.90; P(trend) = .04), respectively. CONCLUSIONS: Although reverse causation could, in part, explain the inverse association observed between NSAID use and EAC risk, our pooled analysis suggests a possible role for NSAIDs in prevention of adenocarcinomas of the esophagus and esophagogastric junction.
Authors: Liao LM; Corley DA; Wu AH; et al.
Gastroenterology. 2012 Mar;142(3):442-452.e5; quiz e22-3. Epub 2011 Nov 19.
Valvular heart disease in patients exposed to pergolide: insights from the clinical presentation
PURPOSE: The aim of this study was to determine whether the presence of symptoms would aid in the detection of valvular heart disease (VHD) in those exposed to pergolide. METHODS: Utilizing a prospective, cross-sectional study design, patients with an exposure to pergolide were asked regarding the presence or absence of chest pain, shortness of breath or lower extremity edema through a questionnaire. Echocardiograms were obtained on the same day as the questionnaire and were blinded to all staff involved in the study. The sensitivity, specificity, positive and negative predictive value of the reported symptoms towards the outcome moderate or severe valvular regurgitation were obtained. Using the area under the receiver-operating characteristic curve, we also ascertained whether a relationship existed between symptoms, pergolide dose and presence of VHD. To understand the associations between symptoms and echocardiographic covariates, a logistic regression analysis was performed adjusted for age and gender. RESULTS: The sensitivity, specificity, positive and negative predictive value of symptom presentation and total dose was sufficiently low that it did not aid in the determination whether significant valvular regurgitation was present. Multivariable analysis noted a significant association with indexed left atrial volume (p = 0.011), estimated pulmonary artery pressure (p = 0.047) and shortness of breath. CONCLUSIONS: The presence or absence of symptoms does not help guide whether valvular regurgitation is present or absent in individuals exposed to pergolide. Therefore, echocardiography is needed to confirm or refute pergolide-associated VHD. Copyright (c) 2012 John Wiley & Sons, Ltd.
Authors: Krishnaswami A; Albers KB; Fross RD; Jang JJ; Berkheimer SB; Kwai Ben VC; Vandeneeden SK
Pharmacoepidemiol Drug Saf. 2012 Mar;21(3):276-80. Epub 2012 Jan 9.
Meta-analysis of new genome-wide association studies of colorectal cancer risk
Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 x 10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 x 10(-5)). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 x 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.
Authors: Peters U; Caan BJ; Casey G; et al.
Hum Genet. 2012 Feb;131(2):217-34. Epub 2011 Jul 15.
Risk of cancer in patients exposed to gabapentin in two electronic medical record systems
PURPOSE: High doses of gabapentin were associated with pancreatic acinar cell tumors in male Wistar rats, but there is little published epidemiological data regarding gabapentin and carcinogenicity. We explored the association between gabapentin and cancer in a US medical care program and followed up nominally significant associations in a UK primary care database. METHODS: In the US Kaiser Permanente Northern California (KPNC) health system, we performed nested case-control analyses of gabapentin and 55 cancer sites and all cancers combined using conditional logistic regression. Up to 10 controls were matched to each case on year of birth, sex, and year of cohort entry. No other covariates were included in models. Only dispensings for gabapentin 2 years or more before index date were considered. Nominally significant associations with an OR > 1.00 and p < 0.05 for three or more dispensings versus no dispensings were followed up by similar nested case-control analyses in the UK General Practice Research Database (GPRD), adjusting for potential indications for gabapentin and risk factors for the specific cancers. RESULTS: The following analyses had OR > 1.00 and p < 0.05 for three or more dispensings of gabapentin versus no dispensing (2-year lag) in KPNC and were also examined in the GPRD: all cancers, breast, lung and bronchus, urinary bladder, kidney/renal pelvis, stomach, anus/anal canal/anorectum, penis, and other nervous system. These cancers were not statistically significantly associated with gabapentin in the GPRD case-control studies (2-year lag). The GPRD and KPNC studies did not identify a statistically significant increased risk of pancreatic cancer with more than two prescriptions of gabapentin in the 2-year lagged analyses. CONCLUSIONS: The epidemiological data in a US cohort with up to 12 years of follow-up and a UK cohort with up to 15 years of follow-up do not support a carcinogenic effect of gabapentin use. However, the confidence intervals for some analyses were wide, and an important effect cannot be confidently excluded. Copyright (c) 2011 John Wiley & Sons, Ltd.
Authors: Irizarry MC; Webb DJ; Boudiaf N; Logie J; Habel LA; Udaltsova N; Friedman GD
Pharmacoepidemiol Drug Saf. 2012 Feb;21(2):214-25. Epub 2011 Dec 6.
Clinician awareness and knowledge of breast cancer-related lymphedema in a large, integrated health care delivery setting
Breast cancer survivors have reported dissatisfaction regarding their education on risk of breast cancer-related lymphedema (BCRL) from clinicians. We describe clinician knowledge and treatment referral of patients with BCRL among active oncologists, surgeons, and primary care physicians in the Kaiser Permanente Northern California Medical Care Program. A total of 887 oncologists, surgeons, and primary care clinicians completed a 10-minute web survey from May 2, 2010 to December 31, 2010 on BCRL knowledge, education, and referral patterns. A knowledge score of BCRL was calculated based on clinician responses. Multivariable regression models were used to determine the associations of selected covariates with BCRL knowledge score and clinician referral, respectively. Compared with primary care clinicians, oncologists had the highest mean score followed closely by surgeons (P < 0.0001). In multivariable analyses, being female, an oncologist or surgeon, and recently receiving BCRL materials were each significantly associated with higher BCRL knowledge scores. About 44% of clinicians (n = 381) indicated they had ever made a BCRL referral (100% oncologists, 79% surgeons, and 36% primary care clinicians). Clinicians with a higher knowledge score were more likely to make referrals. In stratified analyses by specialty, the significant associated factors remained for primary care but became non-significant for oncology and surgery. These results can inform educational interventions to strengthen clinician knowledge of the clinical management of BCRL, especially among primary care clinicians. With the growing number of breast cancer survivors, increasing clinician education about BCRL across all specialties is warranted.
Authors: Tam EK; Shen L; Munneke JR; Ackerson LM; Partee PN; Somkin CP; Andre M; Kutner SE; Thiadens SR; Kwan ML
Breast Cancer Res Treat. 2012 Feb;131(3):1029-38. Epub 2011 Oct 29.
Telomerase, telomere length, and coronary artery calcium in black and white men in the CARDIA study
OBJECTIVE: To evaluate whether telomerase activity, measured in circulating blood leukocytes, might be associated with prevalent atherosclerosis, or predict future coronary artery disease risk. METHODS AND RESULTS: We examined associations of telomerase activity levels measured at year 15 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study with prevalent coronary artery calcium (CAC), progressive CAC at year 20, and incident CAC between years 15 and 20, in 440 black and white men aged 33-45 years. Telomere length was also measured in a subset of participants (N=129). In age-adjusted analyses, higher telomerase activity levels were associated with black race/ethnicity, lower socioeconomic status, higher C-reactive protein levels, and smoking. In multivariate-adjusted analysis, higher quartiles of telomerase were cross-sectionally associated with greater odds of prevalent CAC at year 15 (quartile 2: OR=1.32, 95% CI: 0.54-3.23; quartile 3: OR=1.40, 95% CI: 0.60-3.30; quartile 4: OR=3.27, 95% CI: 1.39-7.71 compared with quartile 1, p-continuous=0.012) and progressive CAC at year 20, but telomerase was not significantly associated with incidence of newly detectable CAC. Higher telomerase activity levels predicted greater CAC progression at year 20 among persons with short telomere length; low telomerase and short TL predicted less CAC progression. CONCLUSION: Telomerase activity in leukocytes was associated with calcified atherosclerotic plaque, and was also a predictor of advancing plaque among persons with short telomeres.
Authors: Kroenke CH; Pletcher MJ; Lin J; Blackburn E; Adler N; Matthews K; Epel E
Atherosclerosis. 2012 Feb;220(2):506-12. Epub 2011 Nov 9.
Evaluating Racial/Ethnic Disparities in Lower Urinary Tract Symptoms in Men
PURPOSE: We examined whether there are racial/ethnic disparities in lower urinary tract symptoms in men. MATERIALS AND METHODS: Racial/ethnic disparities were examined using the American Urological Association symptom index in 2 large cohorts, including the California Men’s Health Study and the Research Program in Genes, Environment and Health. Prevalence and incidence were calculated in each age and race/ethnicity strata. Multivariate analysis was done to assess the association between race/ethnicity and lower urinary tract symptoms. RESULTS: The lower urinary tract symptom prevalence increased with age in each racial/ethnic category (p <0.05). The mean +/- SD age adjusted American Urological Association symptom index score for black, Hispanic, other/mixed, nonHispanic white and Asian men was 9.57 +/- 5.83, 9.35 +/- 6.30, 9.32 +/- 6.22, 8.99 +/- 5.89 and 8.41 +/- 5.59, respectively. In multivariate models Hispanic and black men were at increased risk for moderate lower urinary tract symptoms than white men while only Hispanic men were at higher risk for severe lower urinary tract symptoms. Asian men were at lower risk for moderate or severe lower urinary tract symptoms than white men. The incident rate of lower urinary tract symptoms increased with increasing baseline age for almost all racial/ethnic groups (range 32% to 56%). Asian and Hispanic men were at lower risk for incident lower urinary tract symptoms than white men even after adjusting for sociodemographic factors, health related behaviors and comorbidity. CONCLUSIONS: Racial/ethnic disparities in lower urinary tract symptoms persist after accounting for putative and established risk factors.
Authors: Van Den Eeden SK; Shan J; Jacobsen SJ; Aaronsen D; Haque R; Quinn VP; Quesenberry CP Jr; Urologic Diseases in America Project
J Urol. 2012 Jan;187(1):185-9. Epub 2011 Nov 17.
Change in physical activity during active treatment in a prospective study of breast cancer survivors
Physical activity offers many benefits to breast cancer survivors, yet research on physical activity during the immediate period following a breast cancer diagnosis is limited. In a prospective cohort study of 1,696 women diagnosed with invasive breast cancer in the Kaiser Permanente Northern California Medical Care Program from 2006-2009, we describe change in self-reported physical activity levels from around diagnosis to 6 months post-diagnosis and determine factors associated with change. Participants completed a comprehensive physical activity questionnaire at baseline (2 months post-diagnosis) and at follow-up (8 months post-diagnosis). Predictors of physical activity change were determined by multivariable linear regression. Reductions in all physical activity levels were observed (P < 0.0001); mean (SD) change (h/week) of moderate-vigorous physical activity (MVPA) was -1.28 (4.48) and sedentary behavior was -0.83 (6.95). In fully-adjusted models, overweight and obesity were associated with greater declines in MVPA of -1.58 h/week (SD = 0.92) and -1.29 h/week (SD = 0.93), respectively (P = 0.0079). Receipt of chemotherapy only was also associated with a greater decrease in MVPA (-2.12 h/week; SD = 0.92; P < 0.0001), specifically for recreational activities (-1.62 h/week; SD = 0.64; P = 0.0001). These data suggest challenges in maintaining physical activity levels during active treatment among women with breast cancer. Interventions to encourage physical activity in breast cancer survivors should be pursued.
Authors: Kwan ML; Sternfeld B; Ergas IJ; Timperi AW; Roh JM; Hong CC; Quesenberry CP; Kushi LH
Breast Cancer Res Treat. 2012 Jan;131(2):679-90. Epub 2011 Sep 28.
Preventive care and health behaviors among overweight/obese men in HMOs
OBJECTIVES: To examine potential weight-related disparities in receipt of preventive screening exams and to compare several quality indicators and health behaviors among overweight/obese men and healthy-weight men enrolled in 2 large managed care plans. STUDY DESIGN: Cross-sectional analysis nested within a diverse cohort of men participating in the California Men’s Health Study (CMHS) (N = 80,771). METHODS: We extracted utilization of serum cholesterol, triglycerides, glucose, glycosylated hemoglobin, sigmoidoscopy exams, and prostatespecific antigen tests from health plan electronic sources. CMHS survey data provided information about diet and physical activity. Adjusted odds ratios and 95% confidence intervals were estimated to assess the association of screening exams and behaviors with categories of body mass index (BMI). RESULTS: Tests for cholesterol, glucose, and diabetes control increased across categories of BMI, while overweight and obese men were less likely to undergo screening exams for colorectal and prostate cancer. Smoking and alcohol consumption were less frequent among overweight/obese men; however, they reported diets higher in fat and lower in fruits and vegetables, and were much less likely to report moderate/vigorous activity and much more likely to be sedentary. CONCLUSIONS: Managed care organizations might reduce weight-related health risks and disparities in care with targeted efforts to promote cancer screenings, healthy diets, and physical activity among overweight and obese patients.
Authors: Quinn VP; Jacobsen SJ; Slezak JM; Van Den Eeden SK; Caan B; Sternfeld B; Haque R
Am J Manag Care. 2012 Jan;18(1):25-32.
Effect of Sexually Transmitted Infections, Lifetime Sexual Partner Count, and Recreational Drug Use on Lower Urinary Tract Symptoms in Men Who Have Sex With Men
OBJECTIVE: To investigate the relationship of lower urinary tract symptoms (LUTS) to urinary tract infection, prostatitis, sexually transmitted infection, lifetime sexual partner count, and recreational drug use in a population of men who have sex with men. LUTS in men are a source of considerable morbidity, distress, and medical expense. METHODS: We conducted a cross-sectional, Internet-based survey of urinary quality-of-life outcomes in men who have sex with men. The main outcome was the International Prostate Symptom Score (IPSS), classified as none/mild (IPSS 0-7), moderate/severe (IPSS 8-35), or severe (IPSS 20-35). The participants were also asked whether they ever sought medical attention for urinary problems. RESULTS: The survey web site was accessed by 2783 men, of whom 2348 (84.3%) completed the questionnaire. The median age was 39 years (range 18-81). Age, depression, human immunodeficiency virus infection, gonorrhea, syphilis, prostatitis, and prescription drug abuse were all associated with LUTS. Men who sought medical attention for LUTS were more likely to report older age, diabetes, depression, gonorrhea, urinary tract infection history, and prostatitis. CONCLUSION: Specific infectious conditions of the urinary tract and depressive symptoms are independent predictors of LUTS in men who have sex with men. Although LUTS are often multifactorial, a common unifying explanation for our finding could be the effects of local and systemic inflammation on the lower urinary tract.
Authors: Breyer BN; Vittinghoff E; Van den Eeden SK; Erickson BA; Shindel AW
Urology. 2012 Jan;79(1):188-93. Epub 2011 Oct 2.
Diagnosis, Comorbidities, and Management of Irritable Bowel Syndrome in Patients in a Large Health Maintenance Organization
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) imposes significant clinical and economic burdens. We aimed to characterize practice patterns for patients with IBS in a large health maintenance organization, analyzing point of diagnosis, testing, comorbidities, and treatment. METHODS: Members of Kaiser Permanente Northern California who were diagnosed with IBS were matched to controls by age, sex, and period of enrollment. We compared rates of testing, comorbidities, and interventions. RESULTS: From 1995-2005, IBS was diagnosed in 141,295 patients (mean age, 46 years; standard deviation, 17 years; 74% female). Internists made 68% of diagnoses, gastroenterologists 13%, and others 19%. Lower endoscopy did not usually precede IBS diagnosis. Patients with IBS were more likely than controls to have blood, stool, endoscopic, and radiologic tests and to undergo abdominal or pelvic operations (odds ratios, 1.5-10.7; all P < .0001). Only 2.7% were tested for celiac disease, and only 1.8% were eventually diagnosed with inflammatory bowel disease. Chronic pain syndromes, anxiety, and depression were more common among IBS patients than among controls (odds ratios, 2.7-4.6; all P < .0001). Many patients with IBS were treated with anxiolytics (61%) and antidepressants (55%). Endoscopic and radiologic testing was most strongly associated with having IBS diagnosed by a gastroenterologist. Psychotropic medication use was most strongly associated with female sex. CONCLUSIONS: In a large, managed care cohort, most diagnoses of IBS were made by generalists, often without endoscopic evaluation. Patients with IBS had consistently higher rates of testing, chronic pain syndromes, psychiatric comorbidity, and operations than controls. Most patients with IBS were treated with psychiatric medications.
Authors: Ladabaum U; Boyd E; Zhao WK; Mannalithara A; Sharabidze A; Singh G; Chung E; Levin TR
Clin Gastroenterol Hepatol. 2012 Jan;10(1):37-45. Epub 2011 Aug 24.
American Cancer Society guidelines on nutrition and physical activity for cancer prevention: Reducing the risk of cancer with healthy food choices and physical activity
The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published approximately every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and they reflect the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines focus on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the 2010 Dietary Guidelines for Americans and the 2008 Physical Activity Guidelines for Americans. CA Cancer J Clin 2012. (c) 2012 American Cancer Society.
Authors: Kushi LH; Doyle C; McCullough M; Rock CL; Demark-Wahnefried W; Bandera EV; Gapstur S; Patel AV; Andrews K; Gansler T; The American Cancer Society 2010 Nutrition and Physical Activity Guidelines Advisory Committee
CA Cancer J Clin. 2012 Jan-Feb;62(1):30-67.
Editorial: Taking FIT to the People: Out of the Office and Into the Mail
Colorectal cancer (CRC) screening is most commonly performed in the United States using an opportunistic approach: patients coming to a physician’s office for other unrelated reasons are offered screening with either fecal occult blood tests or, more commonly, a referral for colonoscopy. This approach has been effective to a point. CRC screening rates are increasing, but are still suboptimal and vary across different regions of the United States. Mailed fecal immunochemical test (FIT) outreach has the potential to allow more consistent CRC screening, by moving beyond opportunistic, office visit-based screening, to an organized approach. The study by van Roon et al. in this issue of the American Journal of Gastroenterology demonstrates that mailing FIT collection devices will not result in decreased sensitivity for 10-14 days following the specimen collection.
Authors: Levin TR
Am J Gastroenterol. 2012 Jan;107(1):108-10.
OBAYA (obesity and adverse health outcomes in young adults): feasibility of a population-based multiethnic cohort study using electronic medical records
ABSTRACT: BACKGROUND: Although obesity is a risk factor for many chronic diseases, we have only limited knowledge of the magnitude of these associations in young adults. A multiethnic cohort of young adults was established to close current knowledge gaps; cohort demographics, cohort retention, and the potential influence of migration bias were investigated. METHODS: For this population-based cross-sectional study, demographics, and measured weight and height were extracted from electronic medical records of 1,929,470 patients aged 20 to 39 years enrolled in two integrated health plans in California from 2007 to 2009. RESULTS: The cohort included about 84.4% of Kaiser Permanente California members in this age group who had a medical encounter during the study period and represented about 18.2% of the underlying population in the same age group in California. The age distribution of the cohort was relatively comparable to the underlying population in California Census 2010 population, but the proportion of women and ethnic/racial minorities was slightly higher. The three-year retention rate was 68.4%. CONCLUSION: These data suggest the feasibility of our study for medium-term follow-up based on sufficient membership retention rates. While nationwide 6% of young adults are extremely obese, we know little to adequately quantify the health burden attributable to obesity, especially extreme obesity, in this age group. This cohort of young adults provides a unique opportunity to investigate associations of obesity-related factors and risk of cancer in a large multiethnic population.
Authors: Koebnick C; Smith N; Huang K; Martinez MP; Clancy HA; Williams AE; Kushi LH
Popul Health Metr. 2012 Aug 21;10(1):15.
Meeting the physical activity guidelines and survival after breast cancer: findings from the after breast cancer pooling project
The 2008 Physical Activity (PA) Guidelines recommend engaging in at least 2.5 h (10 MET-hours/week) of moderate intensity PA per week (defined as 4 METs) to reduce risk of morbidity and mortality. This analysis was conducted to investigate whether this recommendation can be extended to breast cancer survivors. Data from four studies of breast cancer survivors measuring recreational PA from semi-quantitative questionnaires a median of 23 months post-diagnosis (interquartile range 18-32 months) were pooled in the After Breast Cancer Pooling Project (n = 13,302). Delayed entry Cox proportional hazards models were applied in data analysis with adjustment for age, post-diagnosis body mass index, race/ethnicity, menopausal status, TNM stage, cancer treatment, and smoking history. Engaging in at least 10 MET-hours/week of PA was associated with a 27% reduction in all-cause mortality (n = 1,468 events, Hazard Ratio (HR) = 0.73, 95% CI, 0.66-0.82) and a 25% reduction in breast cancer mortality (n = 971 events, HR = 0.75, 95% CI 0.65-0.85) compared with women who did not meet the PA Guidelines (<10 MET-hours/week). Risk of breast cancer recurrence (n = 1,421 events) was not associated with meeting the PA Guidelines (HR = 0.96, 95% CI, 0.86-1.06). These data suggest that adhering to the PA guidelines may be an important intervention target for reducing mortality among breast cancer survivors.
Authors: Beasley JM; Kwan ML; Kroenke CH; Sternfeld B; Caan BJ; et al.
Breast Cancer Res Treat. 2012 Jan;131(2):637-43. Epub 2011 Sep 21.
A comparison of lifestyle and behavioral cardiovascular disease risk factors between Asian Indian and White non-Hispanic men
OBJECTIVE: We compared lifestyle CVD risk factors between Asian Indian and White non-Hispanic men within categories of BMI. DESIGN/SETTING/PARTICIPANTS: Participants included 51,901 White non-Hispanic men and 602 Asian Indian men enrolled in the California Men’s Health Study cohort. Men were aged 45-69 years and members of Kaiser Permanente Southern or Northern California at baseline (2001-2002). MAIN OUTCOME MEASURES: Lifestyle characteristics including diet, physical activity, alcohol intake and smoking were collected from a survey. Multivariable logistic regression, adjusting for demographics, was performed. RESULTS: Asian Indians more often reported a healthy BMI (18.5-24.9), and consumed < 30% calories from fat within each BMI category (healthy weight and overweight/obese). Among healthy weight men, Asian Indians were less likely to eat -5 fruit and vegetables a day. Overall, Asian Indians were more likely to have never smoked and to abstain from alcohol. Asian Indians were less likely to report moderate/vigorous physical activity > or = 3.5 hours/week. No differences were found in sedentary activity. CONCLUSIONS: We identified health behaviors that were protective (lower fat intake, lower levels of smoking and alcohol) and harmful (lower levels of physical activity and fruit and vegetable intake) for cardiovascular health among the Asian Indians in comparison to White non-Hispanics. Results stratified by BMI were similar to those overall. However, the likelihood of consuming a low fat diet was lower among healthy weight men, while fruit and vegetable consumption, physical activity and alcohol intake was greater. These results suggest risk factors other than lifestyle behaviors may be important contributors to CVD in the Asian Indian population.
Authors: Ghai NR; Jacobsen SJ; Ahmed AT; Haque R; Rhoads GG; Quinn VP; Van den Eeden SK
Ethn Dis. 2012 Spring;22(2):168-74.
Does neighborhood environment influence girls’ pubertal onset? Findings from a cohort study
BACKGROUND: Pubertal onset occurs earlier than in the past among U.S. girls. Early onset is associated with numerous deleterious outcomes across the life course, including overweight, breast cancer and cardiovascular health. Increases in childhood overweight have been implicated as a key reason for this secular trend. Scarce research, however, has examined how neighborhood environment may influence overweight and, in turn, pubertal timing. The current study prospectively examined associations between neighborhood environment and timing of pubertal onset in a multi-ethnic cohort of girls. Body mass index (BMI) was examined as a mediator of these associations. METHODS: Participants were 213 girls, 6-8 years old at baseline, in an on-going longitudinal study. The current report is based on 5 time points (baseline and 4 annual follow-up visits). Neighborhood environment, assessed at baseline, used direct observation. Tanner stage and anthropometry were assessed annually in clinic. Survival analysis was utilized to investigate the influence of neighborhood factors on breast and pubic hair onset, with BMI as a mediator. We also examined the modifying role of girls’ ethnicity. RESULTS: When adjusting for income, one neighborhood factor (Recreation) predicted delayed onset of breast and pubic hair development, but only for African American girls. BMI did not mediate the association between Recreation and pubertal onset; however, these associations persisted when BMI was included in the models. CONCLUSIONS: For African American girls, but not girls from other ethnic groups, neighborhood availability of recreational outlets was associated with onset of breast and pubic hair. Given the documented risk for early puberty among African American girls, these findings have important potential implications for public health interventions related to timing of puberty and related health outcomes in adolescence and adulthood.
Authors: Deardorff J; Fyfe M; Ekwaru JP; Kushi LH; Greenspan LC; Yen IH
BMC Pediatr. 2012 Mar 13;12:27.
A High-Density Genome-Wide Association Screen of Sporadic ALS in US Veterans
Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U.S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U.S. veterans. We tested approximately 1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4×10(-4)) and rs6985069 near ELP3 (p = 4.8×10(-4)). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder.
Authors: Kwee LC; Van Den Eeden SK; Hauser MA; et al.
PLoS One. 2012;7(3):e32768. Epub 2012 Mar 28.
Genome-wide search for gene-gene interactions in colorectal cancer
Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p<10(-4)). For the known locus rs10795668 (10p14), we found an interacting SNP rs367615 (5q21) with replication p = 0.01 and combined p = 4.19x10(-8). Among the top marginal SNPs after LD pruning (n = 163), we identified an interaction between rs1571218 (20p12.3) and rs10879357 (12q21.1) (nominal combined p = 2.51x10(-6); Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC.
Authors: Jiao S; Caan BJ; Peters U; et al.
PLoS One. 2012;7(12):e52535. Epub 2012 Dec 26.
Outpatient Use of Low Molecular Weight Heparin Monotherapy for First-Line Treatment of Venous Thromboembolism in Advanced Cancer
BACKGROUND: Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) monotherapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors. METHODS: Using administrative data from advanced lung, prostate, colon, or breast cancer patients diagnosed between January 2000 and December 2007 at four HMOs with integrated delivery systems, patients with an inpatient or outpatient VTE diagnosed within 2 years after cancer diagnosis and an outpatient purchase of warfarin, LMWH, and/or fondaparinux anticoagulant within 7 days of the VTE diagnosis were identified. First-line outpatient VTE pharmacological treatment and factors independently associated with receipt/non-receipt of LMWH monotherapy were assessed. RESULTS: Overall, 25% of the 1,089 eligible patients received LMWH monotherapy as primary VTE treatment. The percentage increased steadily over time from 18% among patients diagnosed in 2000 to 31% among those diagnosed in 2007. Factors associated with LMWH monotherapy included VTE diagnosis year, chemotherapy within 60 days prior to VTE diagnosis, history of VTE prior to cancer diagnosis, and invasive surgery in the 90 days following VTE diagnosis. Colorectal and prostate cancer patients versus lung cancer patients and stage III versus stage IV patients were less likely to be treated with LMWH monotherapy. CONCLUSIONS: Adoption of LMWH monotherapy as initial treatment for cancer-associated VTE was low but increased steadily over the study period. Future studies should explore reasons underlying the underutilization of this preferred evidence-based treatment as well as the comparative effectiveness of LMWH versus warfarin-based anticoagulation in real-world cancer patients with VTE.
Authors: Delate T; Witt DM; Ritzwoller D; Weeks JC; Kushi L; Hornbrook MC; Aiello Bowles EJ; Schrag D
Oncologist. 2012;17(3):419-27. Epub 2012 Feb 14.
Racial/ethnic differences in initiation of adjuvant hormonal therapy among women with hormone receptor-positive breast cancer
Mortality after breast cancer diagnosis is known to vary by race/ethnicity even after adjustment for differences in tumor characteristics. As adjuvant hormonal therapy decreases risk of recurrence and increases overall survival among women with hormone receptor-positive tumors, treatment disparities may play a role. We explored racial/ethnic differences in initiation of adjuvant hormonal therapy, defined as two or more prescriptions for tamoxifen or aromatase inhibitor filled within the first year after diagnosis of hormone receptor-positive localized or regional-stage breast cancer. The sample included women diagnosed with breast cancer enrolled in Kaiser Permanente Northern California (KPNC). Odds ratios [OR] and 95% confidence intervals [CI] compared initiation by race/ethnicity (Hispanic, African American, Chinese, Japanese, Filipino, and South Asian vs. non-Hispanic White [NHW]) using logistic regression. Covariates included age and year of diagnosis, area-level socioeconomic status, co-morbidities, tumor stage, histology, grade, breast cancer surgery, radiation and chemotherapy use. Our sample included 13,753 women aged 20-79 years, diagnosed between 1996 and 2007, and 70% initiated adjuvant hormonal therapy. In multivariable analysis, Hispanic and Chinese women were less likely than NHW women to initiate adjuvant hormonal therapy ([OR] = 0.82; [CI] 0.71-0.96 and [OR] = 0.78; [CI] 0.63-0.98, respectively). Within an equal access, insured population, lower levels of initiation of adjuvant hormonal therapy were found for Hispanic and Chinese women. Findings need to be confirmed in other insured populations and the reasons for under-initiation among these groups need to be explored.
Authors: Livaudais JC; Hershman DL; Habel L; Kushi L; Gomez SL; Li CI; Neugut AI; Fehrenbacher L; Thompson B; Coronado GD
Breast Cancer Res Treat. 2012 Jan;131(2):607-17. Epub 2011 Sep 16.
Genetic variability in EGFR, Src and HER2 and risk of colorectal adenoma and cancer
The EGFR signaling pathway is involved in carcinogenesis at multiple sites, particularly colorectal cancer, and is a target of colorectal cancer chemotherapy. EGFR signaling is linked to pro-carcinogenic mechanisms, including cell proliferation, survival, angiogenesis, and more recently prostaglandin synthesis. Genetic variability in this pathway has not yet been studied in relation to colorectal carcinogenesis. In three case-control studies of colorectal adenoma (n=485 cases/578 controls), colon cancer (n=1424 cases/1780 controls) and rectal cancer (n=583 cases/775 controls), we investigated associations between candidate SNPs, tagSNPs and haplotypes in EGFR signaling (EGFR, Src, and HER2) and risk. We also examined associations with tumor subtypes: TP53 and KRAS2 mutations, CpG island methylator phenotype, and microsatellite instability. All three studies were genotyped using an identical Illumina GoldenGate assay, allowing thorough investigation of genetic variability across stages and locations of colorectal neoplasia. The EGFR tagSNP 142572T>C (rs3752651) CC genotype was associated with a suggested increased risk for both colon (OR: 1.40; 95% CI: 1.00-1.96; p-trend=0.04) and rectal cancer (OR: 1.39; 95% CI: 0.81-2.41; p-trend=0.65). In tumor subtype analyses, the association was limited to TP53-mutated colon tumors. Using the Chatterjee 1 df Tukey test to assess gene-gene interactions, we observed a statistically significant (p<0.01) interaction between SNPs in EGFR and Src for colorectal adenoma risk. The association with EGFR 142572 should be investigated in additional studies and the significant gene-gene interaction between EGFR and Src in relation to adenoma risk suggests that these two genes are jointly affecting early stages in colorectal carcinogenesis and requires further follow-up.
Authors: Poole EM; Curtin K; Hsu L; Kulmacz RJ; Duggan DJ; Makar KW; Xiao L; Carlson CS; Slattery ML; Caan BJ; Potter JD; Ulrich CM
Int J Mol Epidemiol Genet. 2011;2(4):300-15. Epub 2011 Dec 3.
The Future of Colon Cancer Screening: What Do We Recommend and Will It Be Too Much, Too Little, or Just Right?
Authors: Corley DA
Gastroenterology. 2011 Dec;141(6):1956-8. Epub 2011 Oct 21.
Predictors of patient satisfaction with mohs surgery: analysis of preoperative, intraoperative, and postoperative factors in a prospective cohort
OBJECTIVE: To identify preoperative, intraoperative, and postoperative variables that predict higher short- and long-term patient satisfaction with Mohs surgery. DESIGN: Prospective cohort study. SETTING: A university-based dermatology practice and the affiliated Veterans Affairs medical center dermatology clinic. Patients A total of 339 consecutive patients treated with Mohs surgery in 1999 and 2000. MAIN OUTCOME MEASURES: Short-term satisfaction at 1 week and long-term satisfaction at 1 year. We used directed acyclic graphs to determine appropriate confounding adjustment for preoperative, intraoperative, and postoperative variables that influence satisfaction with Mohs surgery in logistic regression models. RESULTS: Better preoperative skin-related quality of life (measured using Skindex) and more intraoperative Mohs stages were the most salient predictors of higher short- and long-term satisfaction; these odds ratios (ORs) were 2.33 (95% CI, 1.01-5.35) and 5.19 (1.66-16.29), respectively, for preoperative skin-related quality of life and 7.06 (2.02-24.67) and 5.30 (1.24-22.64), respectively, for more intraoperative Mohs stages. Patients not bothered by postoperative bleeding were more likely to be satisfied short term (OR, 2.25; 95% CI, 1.25-4.05), as were those who considered themselves involved in decision making about their treatment (3.05; 1.52-6.10). Higher long-term satisfaction with Mohs surgery was observed among patients who were married (2.36; 1.10-5.09). CONCLUSIONS: Higher short- and long-term satisfaction with Mohs surgery is predicted by better preoperative skin-related quality of life and by more intraoperative Mohs stages. The effect of postoperative variables wanes over time, suggesting that factors influencing satisfaction can vary depending on the time frame when satisfaction is measured. Our results may help clinicians identify patients who are at higher risk of dissatisfaction following Mohs surgery.
Authors: Asgari MM; Warton EM; Neugebauer R; Chren MM
Arch Dermatol. 2011 Dec;147(12):1387-94.
Exercise in patients with lymphedema: a systematic review of the contemporary literature
BACKGROUND: Controversy exists regarding the role of exercise in cancer patients with or at risk for lymphedema, particularly breast. We conducted a systematic review of the contemporary literature to distill the weight of the evidence and provide recommendations for exercise and lymphedema care in breast cancer survivors. METHODS: Publications were retrieved from 11 major medical indices for articles published from 2004 to 2010 using search terms for exercise and lymphedema; 1,303 potential articles were selected, of which 659 articles were reviewed by clinical lymphedema experts for inclusion, yielding 35 articles. After applying exclusion criteria, 19 articles were selected for final review. Information on study design/objectives, participants, outcomes, intervention, results, and study strengths and weaknesses was extracted. Study evidence was also rated according to the Oncology Nursing Society Putting Evidence Into Practice(R) Weight-of-Evidence Classification. RESULTS: Seven studies were identified addressing resistance exercise, seven studies on aerobic and resistance exercise, and five studies on other exercise modalities. Studies concluded that slowly progressive exercise of varying modalities is not associated with the development or exacerbation of breast cancer-related lymphedema and can be safely pursued with proper supervision. Combined aerobic and resistance exercise appear safe, but confirmation requires larger and more rigorous studies. CONCLUSIONS: Strong evidence is now available on the safety of resistance exercise without an increase in risk of lymphedema for breast cancer patients. Comparable studies are needed for other cancer patients at risk for lymphedema. IMPLICATIONS FOR CANCER SURVIVORS: With reasonable precautions, it is safe for breast cancer survivors to exercise throughout the trajectory of their cancer experience, including during treatment.
Authors: Kwan ML; Cohn JC; Armer JM; Stewart BR; Cormier JN
J Cancer Surviv. 2011 Dec;5(4):320-36. Epub 2011 Oct 16.
Re: a case-control study of levothyroxine and the risk of colorectal cancer
Authors: Friedman GD; Schwalbe JS; Habel LA
J Natl Cancer Inst. 2011 Nov 2;103(21):1637-9. Epub 2011 Oct 18.
Is Diabetes Mellitus an Independent Risk Factor for Colon Cancer and Rectal Cancer?
OBJECTIVES: Diabetes mellitus (DM) has been associated with an increased risk of colorectal cancer (CRC). The American College of Gastroenterology Guidelines for Colorectal Cancer Screening 2008 recommend that clinicians be aware of an increased CRC risk in patients with smoking and obesity, but do not highlight the increase in CRC risk in patients with DM. To provide an updated quantitative assessment of the association of DM with colon cancer (CC) and rectal cancer (RC), we conducted a meta-analysis of case-control and cohort studies. We also evaluated whether the association varied by sex, and assessed potential confounders including obesity, smoking, and exercise. METHODS: We identified studies by searching the EMBASE and MEDLINE databases (from inception through 31 December 2009) and by searching bibliographies of relevant articles. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with fixed- and random-effects models. Several subgroup analyses were performed to explore potential study heterogeneity and bias. RESULTS: DM was associated with an increased risk of CC (summary RR 1.38, 95% CI 1.26-1.51; n=14 studies) and RC (summary RR 1.20, 95% CI 1.09-1.31; n=12 studies). The association remained when we limited the meta-analysis to studies that either controlled for smoking and obesity, or for smoking, obesity, and physical exercise. DM was associated with an increased risk of CC for both men (summary RR 1.43, 95% CI 1.30-1.57; n=11 studies) and women (summary RR 1.35, 95% CI 1.14-1.53; n=10 studies). For RC, there was a significant association between DM and cancer risk for men (summary RR 1.22, 95% CI 1.07-1.40; n=8 studies), but not for women (summary RR 1.09, 95% CI=0.99-1.19; n=8 studies). CONCLUSIONS: These data suggest that DM is an independent risk factor for colon and rectal cancer. Although these findings are based on observational epidemiological studies that have inherent limitations due to diagnostic bias and confounding, subgroup analyses confirmed the consistency of our findings across study type and population. This information can inform risk models and specialty society CRC screening guidelines.
Authors: Yuhara H; Steinmaus C; Cohen SE; Corley DA; Tei Y; Buffler PA
Am J Gastroenterol. 2011 Nov;106(11):1911-21; quiz 1922. Epub 2011 Sep 13.
Optimizing Colorectal Cancer Screening by Getting FIT Right
Authors: Levin TR
Gastroenterology. 2011 Nov;141(5):1551-5. Epub 2011 Sep 22.
Diet and Colorectal Cancer: Analysis of a Candidate Pathway Using SNPS, Haplotypes, and Multi-Gene Assessment
There is considerable biologic plausibility to the hypothesis that genetic variability in pathways involved in insulin signaling and energy homeostasis may modulate dietary risk associated with colorectal cancer. We utilized data from 2 population-based case-control studies of colon (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) cancer to evaluate genetic variation in candidate SNPs identified from 9 genes in a candidate pathway: PDK1, RP6KA1, RPS6KA2, RPS6KB1, RPS6KB2, PTEN, FRAP1 (mTOR), TSC1, TSC2, Akt1, PIK3CA, and PRKAG2 with dietary intake of total energy, carbohydrates, fat, and fiber. We employed SNP, haplotype, and multiple-gene analysis to evaluate associations. PDK1 interacted with dietary fat for both colon and rectal cancer and with dietary carbohydrates for colon cancer. Statistically significant interaction with dietary carbohydrates and rectal cancer was detected by haplotype analysis of PDK1. Evaluation of dietary interactions with multiple genes in this candidate pathway showed several interactions with pairs of genes: Akt1 and PDK1, PDK1 and PTEN, PDK1 and TSC1, and PRKAG2 and PTEN. Analyses show that genetic variation influences risk of colorectal cancer associated with diet and illustrate the importance of evaluating dietary interactions beyond the level of single SNPs or haplotypes when a biologically relevant candidate pathway is examined.
Authors: Slattery ML; Lundgreen A; Herrick JS; Caan BJ; Potter JD; Wolff RK
Nutr Cancer. 2011 Nov;63(8):1226-34. Epub 2011 Oct 14.
Multivitamin use and breast cancer outcomes in women with early-stage breast cancer: the Life After Cancer Epidemiology study
Little is known about the relation of multivitamin use to breast cancer outcomes. 2,236 women diagnosed from 1997 to 2000 with early-stage breast cancer (Stage I >/= 1 cm, II, or IIIA) were enrolled about 2 years post-diagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry (83%). Multivitamin use pre-diagnosis and post-diagnosis was assessed via mailed questionnaire. Outcomes were ascertained yearly by self-report and verified by medical record review. Delayed-entry Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sociodemographic, tumor, and lifestyle factors. Overall, 54 and 72% of the cohort reported using multivitamins pre- and post-diagnosis, respectively. A total of 380 recurrences, 212 breast cancer deaths, and 396 total deaths were confirmed. Compared to never use, multivitamin use after diagnosis was not associated with any outcome (recurrence HR = 0.92; 95% CI: 0.71, 1.20; total mortality HR = 0.92; 95% CI: 0.71, 1.19). Compared to never use, persistent use of multivitamins from pre- to post-diagnosis was associated with a non-significant decreased risk of recurrence (HR = 0.76; 95% CI: 0.54, 1.06) and total mortality (HR = 0.79; 95% CI: 0.56, 1.12). The protective associations were limited to women who had been treated by radiation only (P for trend = 0.048 and 0.083 for recurrence and total mortality, respectively) and both radiation and chemotherapy (P for trend = 0.015 and 0.095 for recurrence and total mortality, respectively). In stratified analyses, women who consistently used multivitamins before and after diagnosis and ate more fruits/vegetables (P for trend = 0.008) and were more physically active (P for trend = 0.034) had better overall survival. Multivitamin use along with practice of other health-promoting behaviors may be beneficial in improving breast cancer outcomes in select groups of survivors.
Authors: Kwan ML; Greenlee H; Lee VS; Castillo A; Gunderson EP; Habel LA; Kushi LH; Sweeney C; Tam EK; Caan BJ
Breast Cancer Res Treat. 2011 Nov;130(1):195-205. Epub 2011 May 11.
Contribution of Common Medications to Lower Urinary Tract Symptoms in Men
Authors: Wuerstle MC; Van den Eeden SK; Poon KT; Quinn VP; Hollingsworth JM; Loo RK; Jacobsen SJ; Urologic Diseases in America Project
Arch Intern Med. 2011 Oct 10;171(18):1680-2.
Reproductive and menstrual factors and risk of ductal carcinoma in situ of the breast in a cohort of postmenopausal women
PURPOSE: The contribution of menstrual and reproductive factors to risk of ductal carcinoma (DCIS) of the breast is poorly understood. METHODS: The association between menstrual and reproductive factors and subsequent DCIS risk was examined in Women’s Health Initiative (WHI) clinical trial participants, in which mammography was protocol mandated. The cohort consisted of 64,060 women, among whom 664 cases of DCIS were ascertained over a median follow-up of 12.0 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: After adjustment for covariates, only older age at menopause (HR >/= 55 vs. 45-54 : 1.39, 95% CI 1.08-1.79) was significantly associated with risk; however, greater parity (HR >/= 5 live births vs. 0: 0.70, 95% CI 0.47-1.03), among parous women, and age at first live birth (HR >/= 30 years relative to <20 years: 1.32, 95% CI 0.92-1.90) were of borderline significance. Age at menarche and months of breast-feeding were not associated with risk. Associations did not differ between high- and low-/moderate-grade DCIS, or by level of body mass index or family history of breast cancer; however, there was a suggestion that the associations of age at menopause, parity, and age at first live birth were limited to women who had ever used hormone therapy. CONCLUSIONS: Findings from this large cohort of postmenopausal women suggest that age at menopause, and possibly, age at first live birth, and parity are associated with risk of DCIS, whereas age at menarche and duration of breast-feeding are not.
Authors: Kabat GC; Kim MY; Woods NF; Habel LA; Messina CR; Wactawski-Wende J; Stefanick ML; Chlebowski RT; Wassertheil-Smoller S; Rohan TE
Cancer Causes Control. 2011 Oct;22(10):1415-24. Epub 2011 Jul 13.
Metabolic syndrome and mammographic density: The study of women’s health across the nation (SWAN)
The metabolic syndrome (MetS) is associated with an increase in breast cancer risk. In our study, we evaluated whether the MetS was associated with an increase in percent mammographic density (MD), a breast cancer risk factor. We used linear regression and mixed models to examine the cross-sectional and longitudinal associations of the MetS and components of the MetS to percent MD in 790 premenopausal and early perimenopausal women enrolled in the Study of Women’s Health Across the Nation (SWAN). In cross-sectional analyses adjusted for body mass index (BMI), modest inverse associations were observed between percent MD and the MetS [beta = -2.5, standard error (SE) = 1.9, p = 0.19], abdominal adiposity (beta = -4.8, SE = 1.9, p = 0.01) and raised glucose (beta = -3.7, SE = 2.4, p = 0.12). In longitudinal models adjusted for covariates including age and BMI, abdominal adiposity (beta = 0.34, SE = 0.17, p = 0.05) was significantly positively associated with slower annual decline in percent MD with time. In conclusion, our results do not support the hypothesis that the MetS increases breast cancer risk via a mechanism reflected by an increase in percent MD.
Authors: Conroy SM; Butler LM; Harvey D; Gold EB; Sternfeld B; Greendale GA; Habel LA
Int J Cancer. 2010 Nov 23.
Genetic variation in the transforming growth factor-beta signaling pathway and survival after diagnosis with colon and rectal cancer
BACKGROUND: The transforming growth factor-beta (TGF-beta) signaling pathway is involved in many aspects of tumorigenesis, including angiogenesis and metastasis. The authors evaluated this pathway in association with survival after a diagnosis of colon or rectal cancer. METHODS: The study included 1553 patients with colon cancer and 754 patients with rectal cancer who had incident first primary disease and were followed for a minimum of 7 years after diagnosis. Genetic variations were evaluated in the genes TGF-beta1 (2 single nucleotide polymorphisms [SNPs]), TGF-beta receptor 1 (TGF-betaR1) (3 SNPs), smooth muscle actin/mothers against decapentaplegic homolog 1 (Smad1) (5 SNPs), Smad2 (4 SNPs), Smad3 (37 SNPs), Smad4 (2 SNPs), Smad7 (11 SNPs), bone morphogenetic protein 1 (BMP1) (11 SNPs), BMP2 (5 SNPs), BMP4 (3 SNPs), bone morphogenetic protein receptor 1A (BMPR1A) (9 SNPs), BMPR1B (21 SNPs), BMPR2 (11 SNPs), growth differentiation factor 10 (GDF10) (7 SNPs), Runt-related transcription factor 1 (RUNX1) (40 SNPs), RUNX2 (19 SNPs), RUNX3 (9 SNPs), eukaryotic translation initiation factor 4E (eiF4E) (3 SNPs), eukaryotic translation initiation factor 4E-binding protein 3 (eiF4EBP2) (2 SNPs), eiF4EBP3 (2 SNPs), and mitogen-activated protein kinase 1 (MAPK1) (6 SNPs). RESULTS: After adjusting for American Joint Committee on Cancer stage and tumor molecular phenotype, 12 genes and 18 SNPs were associated with survival in patients with colon cancer, and 7 genes and 15 tagSNPs were associated with survival after a diagnosis of rectal cancer. A summary score based on ‘at-risk’ genotypes revealed a hazard rate ratio of 5.10 (95% confidence interval, 2.56-10.15) for the group with the greatest number of ‘at-risk’ genotypes; for rectal cancer, the hazard rate ratio was 6.03 (95% confidence interval, 2.83-12.75). CONCLUSIONS: The current findings suggest that the presence of several higher risk alleles in the TGF-beta signaling pathway increase the likelihood of dying after a diagnosis of colon or rectal cancer.
Authors: Slattery ML; Lundgreen A; Herrick JS; Wolff RK; Caan BJ
Cancer. 2011 Sep 15;117(18):4175-83. Epub 2011 Mar 1.
Associations of physical activity with quality of life and functional ability in breast cancer patients during active adjuvant treatment: the Pathways Study
Physical activity can improve quality of life (QOL) in breast cancer survivors but little is known about associations of physical activity and QOL during active cancer therapy. We examine associations between activity levels and QOL in a large cohort of breast cancer patients. Women with invasive, non-metastatic breast cancer (n=2,279) were enrolled between 2006 and 2009 from a managed care organization; assessment were done during active therapy. A physical activity frequency questionnaire was used to calculate the average weekly metabolic equivalent task (MET) hours spent in moderate and vigorous activity during active treatment. QOL was measured by the Functional Assessment of Cancer Therapy-Breast Cancer. Linear regression models tested cross-sectional associations of QOL and functional well-being with physical activity and covariates [socio-demographics, comorbidity, body mass index (BMI), clinical variables, social support, and assessment timing]. Physical activity had a significant positive unadjusted association with all QOL sub-scales (except emotional well-being) (all P values < 0.01). Overall QOL was 4.6 points higher for women in the highest quartile of moderate and vigorous activity versus women in the lowest quartile (P<0.001). In regression models, higher activity was associated with better overall QOL and functional well-being, controlling for covariates (P<0.05). Increasing BMI was also independently but inversely associated with overall QOL (P<0.001) but did not explain the relationship of activity and QOL. White women reported the higher levels of activity than minority women and activity was associated with QOL for Whites but not for minority women. Greater physical activity is associated with small but clinically meaningful increases in QOL during active breast cancer care therapy for Whites but this effect is not seen for minority women. If confirmed in longitudinal analyses, these differences may have implications for disparities research.
Authors: Mandelblatt JS; Luta G; Kwan ML; Makgoeng SB; Ergas IJ; Roh JM; Sternfeld B; Adams-Campbell LL; Kushi LH
Breast Cancer Res Treat. 2011 Sep;129(2):521-9. Epub 2011 Apr 8.
Colon Cancer Survival With Herbal Medicine and Vitamins Combined With Standard Therapy in a Whole-Systems Approach: Ten-Year Follow-up Data Analyzed With Marginal Structural Models and Propensity Score Methods
Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal evidence of survival efficacy. In a consecutive case series with 10-year follow-up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors compared survival in patients choosing short-term treatment lasting the duration of chemotherapy/radiotherapy with those continuing long-term. To put these data into the context of treatment responses seen in conventional medical practice, they also compared survival with Pan-Asian medicine + vitamins (PAM+V) with that of concurrent external controls from Kaiser Permanente Northern California and California Cancer Registries. Kaplan-Meier, traditional Cox regression, and more modern methods were used for causal inference-namely, propensity score and marginal structural models (MSMs), which have not been used before in studies of cancer survival and Chinese herbal medicine. PAM+V combined with conventional therapy, compared with conventional therapy alone, reduced the risk of death in stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%. There was no significant difference between short-term and long-term PAM+V. Combining PAM+V with conventional therapy improved survival, compared with conventional therapy alone, suggesting that prospective trials combining PAM+V with conventional therapy are justified.
Authors: McCulloch M; Broffman M; van der Laan M; Hubbard A; Kushi L; Gao J; Colford JM Jr; Abrams DI
Integr Cancer Ther. 2011 Sep;10(3):240-59. Epub 2011 Sep 30.
The After Breast Cancer Pooling Project: rationale, methodology, and breast cancer survivor characteristics
The After Breast Cancer Pooling Project was established to examine the role of physical activity, adiposity, dietary factors, supplement use, and quality of life (QOL) in breast cancer prognosis. This paper presents pooled and harmonized data on post-diagnosis lifestyle factors, clinical prognostic factors, and breast cancer outcomes from four prospective cohorts of breast cancer survivors (three US-based and one from Shanghai, China) for 18,314 invasive breast cancer cases diagnosed between 1976 and 2006. Most participants were diagnosed with stage I-II breast cancer (84.7%). About 60% of breast tumors were estrogen receptor (ER)+/progesterone receptor (PR)+; 21% were ER-/PR-. Among 8,118 participants with information on HER-2 tumor status, 74.8% were HER-2- and 18.5% were HER-2+. At 1-2 years post-diagnosis (on average), 17.9% of participants were obese (BMI >/= 30 kg/m2), 32.6% were overweight (BMI 25-29 kg/m2), and 59.9% met the 2008 Physical Activity Guidelines for Americans (>/= 2.5 h per week of moderate activity). During follow-up (mean = 8.4 years), 3,736 deaths (2,614 from breast cancer) and 3,564 recurrences have been documented. After accounting for differences in year of diagnosis and timing of post-diagnosis enrollment, five-year overall survival estimates were similar across cohorts. This pooling project of 18,000 breast cancer survivors enables the evaluation of associations of post-diagnosis lifestyle factors, QOL, and breast cancer outcomes with an adequate sample size for investigation of heterogeneity by hormone receptor status and other clinical predictors. The project sets the stage for international collaborations for the investigation of modifiable predictors for breast cancer outcomes.
Authors: Nechuta SJ; Caan BJ; Kwan ML; Shu XO; et al.
Cancer Causes Control. 2011 Sep;22(9):1319-31. Epub 2011 Jun 28.
Evaluation and comparison of food records, recalls, and frequencies for energy and protein assessment by using recovery biomarkers
The food frequency questionnaire approach to dietary assessment is ubiquitous in nutritional epidemiology research. Food records and recalls provide approaches that may also be adaptable for use in large epidemiologic cohorts, if warranted by better measurement properties. The authors collected (2007-2009) a 4-day food record, three 24-hour dietary recalls, and a food frequency questionnaire from 450 postmenopausal women in the Women’s Health Initiative prospective cohort study (enrollment, 1994-1998), along with biomarkers of energy and protein consumption. Through comparison with biomarkers, the food record is shown to provide a stronger estimate of energy and protein than does the food frequency questionnaire, with 24-hour recalls mostly intermediate. Differences were smaller and nonsignificant for protein density. Food frequencies, records, and recalls were, respectively, able to ‘explain’ 3.8%, 7.8%, and 2.8% of biomarker variation for energy; 8.4%, 22.6%, and 16.2% of biomarker variation for protein; and 6.5%, 11.0%, and 7.0% of biomarker variation for protein density. However, calibration equations that include body mass index, age, and ethnicity substantially improve these numbers to 41.7%, 44.7%, and 42.1% for energy; 20.3%, 32.7%, and 28.4% for protein; and 8.7%, 14.4%, and 10.4% for protein density. Calibration equations using any of the assessment procedures may yield suitable consumption estimates for epidemiologic study purposes.
Authors: Prentice RL; Caan B; Neuhouser ML; et al.
Am J Epidemiol. 2011 Sep 1;174(5):591-603. Epub 2011 Jul 15.
Examining the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence: results from the LACE cohort
There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer-related pharmaceutical exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort (women with early stage BC from the Kaiser Permanente Northern California Cancer Registry) to examine the association between beta blockers (BBs) and/or angiotensin-converting enzyme inhibitors (ACEi) and BC recurrence, BC-specific mortality, and overall mortality. Among 1,779 women, there were 292 BC recurrences, 174 BC deaths, and 323 total deaths. 23% were exposed to either a BB and/or an ACEi. These drugs were associated with older age, postmenopausal status, tamoxifen therapy, greater pre-diagnosis BMI, hypertension, and diabetes. In Cox proportional hazards models, ACEi exposure was associated with BC recurrence (HR 1.56, 95% CI 1.02, 2.39, P = 0.04), but not cause-specific or overall mortality. Combined ACEi and BB were associated with overall mortality (HR 1.94, 95% CI 1.22, 3.10, P = 0.01). BB exposure was associated with lower hazard of recurrence and cause-specific mortality. However, there was no evidence of a dose response with either medication. For recurrence and cause-specific mortality, BB combined with ACEi was associated with a lower HR for the outcome than when ACEi alone was used. These hypothesis generating findings suggest that BC recurrence and survival were associated with exposure to two commonly used classes of anti-hypertensive medications. These observations need to be confirmed and suggest that greater attention should focus on the potential role of these commonly used medications in BC outcomes.
Authors: Ganz PA; Habel LA; Weltzien EK; Caan BJ; Cole SW
Breast Cancer Res Treat. 2011 Sep;129(2):549-56. Epub 2011 Apr 11.
Can we improve adenoma detection rates? A systematic review of intervention studies
Authors: Corley DA; Jensen CD; Marks AR
Gastrointest Endosc. 2011 Sep;74(3):656-65. Epub 2011 Jul 13.
Autonomic and adrenocortical reactivity and buccal cell telomere length in kindergarten children
OBJECTIVE: To examine associations between autonomic nervous system and adrenocortical reactivity to laboratory stressors and buccal cell telomere length (BTL) in children. METHODS: The study sample comprised 78 children, aged 5 to 6 years, from a longitudinal cohort study of kindergarten social hierarchies, biologic responses to adversity, and child health. Buccal cell samples and reactivity measures were collected in the spring of the kindergarten year. BTL was measured by real-time polymerase chain reaction, as the telomere-to-single-copy gene ratio. Parents provided demographic information; parents and teachers reported children’s internalizing and externalizing behavior problems. Components of children’s autonomic (heart rate, respiratory sinus arrhythmia [RSA], and preejection period [PEP]) and adrenocortical (salivary cortisol) responses were monitored during standardized laboratory challenges. We examined relationships between reactivity, internalizing and externalizing behaviors, and BTL, adjusted for age, race, and sex. RESULTS: Heart rate and cortisol reactivity were inversely related to BTL, PEP was positively related to BTL, and RSA was unrelated to BTL. Internalizing behaviors were also inversely related to BTL (standardized beta = -0.33, p = .004). Split at the median of reactivity parameters, children with high sympathetic activation (decreasing PEP), and parasympathetic withdrawal (decreasing RSA) did not differ with regard to BTL. However, children with both this profile and high cortisol reactivity (n = 12) had significantly shorter BTL (0.80 versus 1.00; chi(2) = 7.6, p = .006), compared with other children. CONCLUSIONS: The combination of autonomic and adrenocortical reactivity was associated with shorter BTL in children. These data suggest that psychophysiological processes may influence, and that BTL may be a useful marker of, early biologic aging.
Authors: Kroenke CH; Epel E; Adler N; Bush NR; Obradovic J; Lin J; Blackburn E; Stamperdahl JL; Boyce WT
Psychosom Med. 2011 Sep;73(7):533-40. Epub 2011 Aug 26.
Lung Cancer Survival With Herbal Medicine and Vitamins in a Whole-Systems Approach: Ten-Year Follow-up Data Analyzed With Marginal Structural Models and Propensity Score Methods
Complementary and alternative medicines are used by up to 48% of lung cancer patients but have seen little formal assessment of survival efficacy. In this 10-year retrospective survival study, the authors investigated Pan-Asian medicine + vitamins (PAM+V) therapy in a consecutive case series of all non-small-cell lung cancer patients (n = 239) presenting at a San Francisco Bay Area Chinese medicine center (Pine Street Clinic). They compared short-term treatment lasting the duration of chemotherapy/radiotherapy with long-term therapy continuing beyond conventional therapy. They also compared PAM+V plus conventional therapy with conventional therapy alone, using concurrent controls from the Kaiser Permanente Northern California and California Cancer Registries. They adjusted for confounding with Kaplan-Meier, Cox regression, and newer methods – propensity score and marginal structural models (MSMs), which when analyzing data from observational studies or clinical practice records can provide results comparable with randomized trials. Long-term use of PAM+V beyond completion of chemotherapy reduced stage IIIB deaths by 83% and stage IV by 72% compared with short-term use only for the duration of chemotherapy. Long-term PAM+V combined with conventional therapy reduced stage IIIA deaths by 46%, stage IIIB by 62%, and stage IV by 69% compared with conventional therapy alone. Survival rates for stage IV patients treated with PAM+V were 82% at 1 year, 68% at 2 years, and 14% at 5 years. PAM+V combined with conventional therapy improved survival in stages IIIA, IIIB, and IV, compared with conventional therapy alone. Prospective trials using PAM+V with conventional therapy for lung cancer patients are justified.
Authors: McCulloch M; Broffman M; van der Laan M; Hubbard A; Kushi L; Kramer A; Gao J; Colford JM Jr
Integr Cancer Ther. 2011 Sep;10(3):260-79. Epub 2011 Aug 8.
Cost-effectiveness of a mailed educational reminder to increase colorectal cancer screening.
BACKGROUND: Colorectal cancer (CRC) screening rates are low in many areas and cost-effective interventions to promote CRC screening are needed. Recently in a randomized controlled trial, a mailed educational reminder increased CRC screening rates by 16.2% among U.S. Veterans. The aim of our study was to assess the costs and cost-effectiveness of a mailed educational reminder on fecal occult blood test (FOBT) adherence.METHODS: In a blinded, randomized, controlled trial, 769 patients were randomly assigned to the usual care group (FOBT alone, n = 382) or the intervention group (FOBT plus a mailed reminder, n = 387). Ten days after picking up the FOBT cards, a 1-page reminder with information related to CRC screening was mailed to the intervention group. Primary outcome was number of returned FOBT cards after 6 months. The costs and incremental cost-effectiveness ratio (ICER) of the intervention were assessed and calculated respectively. Sensitivity analyses were based on varying costs of labor and supplies. RESULTS: At 6 months after card distribution, 64.6% patients in the intervention group returned FOBT cards compared with 48.4% in the control group (P < 0.001). The total cost of the intervention was $962 or $2.49 per patient, and the ICER was $15 per additional person screened for CRC. Sensitivity analysis based on a 10% cost variation was $13.50 to $16.50 per additional patient screened for CRC. CONCLUSIONS: A simple mailed educational reminder increases FOBT card return rate at a cost many health care systems can afford. Compared to other patient-directed interventions (telephone, letters from physicians, mailed reminders) for CRC screening, our intervention was more effective and cost-effective.
Authors: Lee, Jeffrey K JK; Groessl, Erik J EJ; Ganiats, Theodore G TG; Ho, Samuel B SB
BMC gastroenterology. 2011 Aug 25;11():93. Epub 2011-08-25.
Alcohol intake and risk of oesophageal adenocarcinoma: a pooled analysis from the BEACON Consortium
BACKGROUND AND AIMS: Alcohol intake is a strong and well established risk factor for oesophageal squamous cell carcinoma (OSCC), but the association with oesophageal adenocarcinoma (OA) or adjacent tumours of the oesophagogastric junction (OGJA), remains unclear. Therefore, the association of alcohol intake with OSCC, OA, and OGJA was determined in nine case-control studies and two cohort studies of the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium (BEACON). MATERIALS AND METHODS: Information was collected on alcohol intake, age, sex, education, body mass index, gastro-oesophageal reflux, and tobacco smoking from each study. Along with 10,854 controls, 1821 OA, and 1837 OGJA, seven studies also collected OSCC cases (n=1016). Study specific ORs and 95% CIs were calculated from multivariate adjusted logistic regression models for alcohol intake in categories compared to non-drinkers. Summary risk estimates were obtained by random effects models. Results No increase was observed in the risk of OA or OGJA for increasing levels of any of the alcohol intake measures examined. ORs for the highest frequency category (>/= 7 drinks per day) were 0.97 (95% CI 0.68 to 1.36) for OA and 0.77 (95% CI = 0.54 to 1.10) for OGJA. Suggestive findings linked moderate intake (eg, 0.5 to <1 drink per day) to decreased risk of OA (OR 0.63, 95% CI 0.41 to 0.99) and OGJA (OR 0.78, 95% CI 0.62 to 0.99). In contrast, alcohol intake was strongly associated with increased risk of OSCC (OR for >/= 7 drinks per day 9.62, 95% CI 4.26 to 21.71). CONCLUSIONS: In contrast to OSCC, higher alcohol consumption was not associated with increased risk of either OA or OGJA. The apparent inverse association observed with moderate alcohol intake should be evaluated in future prospective studies.
Authors: Freedman ND; Corley DA; Whiteman DC; et al.
Gut. 2011 Aug;60(8):1029-37. Epub 2011 Mar 14.
The business of research: budgets, personnel, planning, and pitfalls–a report from the American Society of Preventive Oncology’s Junior Members Interest Group
Authors: Sprague BL; Thompson CL; Ganz PA; Kanetsky PA; Kushi LH; Nebeling L
Cancer Epidemiol Biomarkers Prev. 2011 Aug;20(8):1802-4. Epub 2011 Jul 22.
Understanding cancer incidence in Barrett’s esophagus: light at the end of the tunnel
Authors: Corley DA
J Natl Cancer Inst. 2011 Jul 6;103(13):994-5. Epub 2011 Jun 16.
Preservation of fertility after partial resection of bilateral ovarian cystadenofibromas: a case report
BACKGROUND: Benign cystadenofibromas and adenofibromas may represent precursors to malignant lesions. CASE: A 20-year-old woman undergoing infertility treatment was found to have cystadenofibromas involving both ovaries, with no separable normal ovarian tissue visible. Because complete resection of the tumors would have required bilateral oophorectomy, the tumors were only partially resected using a shave technique. This patient subsequently had 3 normal-term deliveries over 7 years and did not have any clinically significant regrowth of her tumors during this time. CONCLUSION: It may be reasonable to delay removing benign tumors in a young woman who has not completed her childbearing.
Authors: Ewing TL; Suh-Burgmann B
J Reprod Med. 2011 Jul-Aug;56(7-8):364-5.
The influence of neighborhood food stores on change in young girls’ body mass index
BACKGROUND: As the prevalence of childhood obesity has risen in past decades, more attention has been given to how the neighborhood food environment affects children’s health outcomes. PURPOSE: This exploratory study examined the relationship between the presence of neighborhood food stores within a girl’s neighborhood and 3-year risk of overweight/obesity and change in BMI, in girls aged 6 or 7 years at baseline. METHODS: A longitudinal analysis of participants in the Cohort Study of Young Girls’ Nutrition, Environment and Transitions (CYGNET) was conducted from 2005 to 2008. Neighborhood food stores were identified from a commercial database and classified according to industry codes in 2006. Generalized linear and logistic models were used to examine how availability of food stores within 0.25-mile and 1.0-mile network buffers of a girl’s residence were associated with BMI z-score change and risk of overweight or obesity, adjusting for baseline BMI/weight and family sociodemographic characteristics. Data were analyzed in 2010. RESULTS: Availability of convenience stores within a 0.25-mile network buffer of a girl’s residence was associated with greater risk of overweight/obesity (OR=3.38, 95% CI=1.07, 10.68) and an increase in BMI z-score (beta=0.13, 95% CI=0.00, 0.25). Availability of produce vendors/farmer’s markets within a 1.0-mile network buffer of a girl’s residence was inversely associated with overweight/obesity (OR=0.22, 95% CI=0.05, 1.06). A significant trend was observed between availability of produce vendors/farmer’s markets and lower risk of overweight/obesity after 3 years. CONCLUSIONS: Although food store inventories were not assessed and food store indices were not created, the availability of neighborhood food stores may affect a young girl’s weight trajectory over time.
Authors: Leung CW; Laraia BA; Kelly M; Nickleach D; Adler NE; Kushi LH; Yen IH
Am J Prev Med. 2011 Jul;41(1):43-51.
Variation in the CYP19A1 gene and risk of colon and rectal cancer
CYP19A1, or aromatase, influences estrogen-metabolizing enzymes and may influence cancer risk. We examine variation in the CYP19A1 gene and risk of colorectal cancer using data from population-based case-control studies (colon n = 1,574 cases, 1,970 controls; rectal n = 791 cases, 999 controls). Four SNPs were statistically significantly associated with colon cancer and four were associated with rectal cancer. After adjustment for multiple comparisons, the AA genotype of rs12591359 was associated with an increased risk of colon cancer (OR 1.44 95% CI 1.16-1.80) and the AA genotype of rs2470144 was associated with a reduced risk of rectal cancer (OR 0.65 95% CI 0.50-0.84). Variants of CYP19A1 were associated with CIMP+ and CIMP+/KRAS2-mutated tumors. CT/TT genotypes of rs1961177 were significantly associated with an increased likelihood of a MSI+ colon tumor (OR 1.77 95% CI 1.26-2.37). We observed statistically significant interactions between genetic variation in NFkappaB1 and CYP19A1 for both colon and rectal cancer. Our data suggest the importance of CYP19A1 in the development of colon and rectal cancer and that estrogen may influence risk through an inflammation-related mechanism.
Authors: Slattery ML; Lundgreen A; Herrick JS; Kadlubar S; Caan BJ; Potter JD; Wolff RK
Cancer Causes Control. 2011 Jul;22(7):955-63. Epub 2011 Apr 11.
Molecular Prognostic and Predictive Markers in Colorectal Cancer: Current Status.
In parallel with our growing understanding of the molecular pathways underlying colorectal neoplasia, significant advances have been made in the treatment of colorectal cancer (CRC). For the past few decades, 5-fluorouracil-based therapy has been the cornerstone of adjuvant therapy. More recently, additional cytotoxic drugs and molecular-targeted therapies have provided additional clinical benefit in certain patient populations. Unfortunately, overall survival remains about 45%. Notably, our understanding of why certain patients do or do not respond to treatment remains limited. Thus, as therapeutic options for CRC continue to expand, there is now an even greater imperative to identify reliable biomarkers that have the potential to predict prognosis as well as response to chemotherapy. In this review, we will summarize the current status of such molecular prognostic and predictive biomarkers in CRC and assess their usefulness in tailoring therapeutic options.
Authors: Lee, Jeffrey K JK; Chan, Andrew T AT
Current colorectal cancer reports. 2011 Jun 01;7(2):136-144. Epub --.
Genetic variation in C-reactive protein in relation to colon and rectal cancer risk and survival
C-reactive protein (CRP), a biomarker of inflammation, has been shown to be influenced by genetic variation in the CRP gene. In this study, we test the hypothesis that genetic variation in CRP influences both the risk of developing colon and rectal cancer and survival. Two population-based studies of colon cancer (n = 1,574 cases, 1,970 controls) and rectal (n = 791 cases, 999 controls) were conducted. We evaluated four CRP tagSNPs: rs1205 (G > A, 3′ UTR); rs1417938 (T > A, intron); rs1800947 (G > C, L184L); and rs3093075 (C > A, 3′ flanking). The CRP rs1205 AA genotype was associated with an increased risk of colon cancer (OR 1.3, 95%CI 1.1-1.7), whereas the rs3093075 A allele was associated with a reduced risk of rectal cancer (OR 0.7, 95%CI 0.5-0.9). The strongest association for the rs1205 polymorphism and colon cancer was observed among those with KRAS2 mutations (OR 1.5, 95%CI 1.1-2.0). The CRP rs1205 AA genotype also was associated with an increased risk of CIMP+ rectal tumors (OR 2.5, 95%CI 1.2-5.3); conversely, the rs1417938 A allele was associated with a reduced risk of CIMP+ rectal tumors (OR 0.5, 95%CI 0.3-0.9). We observed interactions between CRP rs1800947 and BMI and family history of CRC in modifying risk of both colon and rectal cancer. These data suggest that genetic variation in the CRP gene influences risk of both colon and rectal cancer development.
Authors: Slattery ML; Curtin K; Poole EM; Duggan DJ; Samowitz WS; Peters U; Caan BJ; Potter JD; Ulrich CM
Int J Cancer. 2011 Jun 1;128(11):2726-34. Epub 2010 Nov 28.
Following cancer prevention guidelines reduces risk of cancer, cardiovascular disease, and all-cause mortality
BACKGROUND: Few studies have evaluated the combined impact of following recommended lifestyle behaviors on cancer, cardiovascular disease (CVD) and all-cause mortality, and most included tobacco avoidance. Because 80% of Americans are never or former smokers, it is important to consider the impact of other recommended behaviors. METHODS: In 1992 and 1993, 111,966 nonsmoking men and women in the Cancer Prevention Study-II Nutrition Cohort completed diet and lifestyle questionnaires. A score ranging from 0 to 8 points was computed to reflect adherence to the American Cancer Society cancer prevention guidelines on body mass index, physical activity, diet, and alcohol consumption, with 8 points representing optimal adherence. Multivariable-adjusted relative risks (RR) of death and 95% CI were computed by Cox proportional hazard regression. RESULTS: During 14 years of follow-up, 10,369 men and 6,613 women died. The RR of all-cause mortality was lower for participants with high (7, 8) versus low (0-2) scores (men, RR = 0.58, 95% CI: 0.53-0.62; women, RR = 0.58, 95% CI: 0.52-0.64). Inverse associations were found with CVD mortality (men, RR = 0.52, 95% CI: 0.45-0.59; women, RR = 0.42, 95% CI: 0.35-0.51) and cancer mortality (men, RR = 0.70, 95% CI: 0.61-0.80; women, RR = 0.76, 95% CI: 0.65-0.89). Similar associations, albeit not all statistically significant, were observed for never and former smokers. CONCLUSION: Adherence to cancer prevention guidelines for obesity, diet, physical activity, and alcohol consumption is associated with lower risk of death from cancer, CVD, and all causes in nonsmokers. IMPACT: Beyond tobacco avoidance, following other cancer prevention guidelines may substantially lower risk of premature mortality in older adults.
Authors: McCullough ML; Patel AV; Kushi LH; Patel R; Willett WC; Doyle C; Thun MJ; Gapstur SM
Cancer Epidemiol Biomarkers Prev. 2011 Jun;20(6):1089-97. Epub 2011 Apr 5.
HIV status is an independent risk factor for reporting lower urinary tract symptoms
PURPOSE: HIV/AIDS is a worldwide epidemic. Limited evidence suggests that men infected with HIV/AIDS are at increased risk for lower urinary tract symptoms. We determined whether HIV/AIDS status is an independent risk factor for self-reported bothersome lower urinary tract symptoms in a large contemporary cohort. MATERIALS AND METHODS: We performed a cross-sectional, Internet based survey of urinary quality of life outcomes in adult HIV infected and HIV uninfected men who have sex with men. The main outcome measure was International Prostate Symptom Score. RESULTS: Of respondents with complete data 1,507 were HIV uninfected (median age 42 years, mean 43) and 323 HIV infected (median age 45 years, mean 45.1). Of the HIV infected respondents 148 were nonAIDS defining HIV infected and 175 were AIDS defining HIV infected. After adjusting for age and other comorbid conditions, nonAIDS defining HIV infected and AIDS defining HIV infected status increased the odds of severe lower urinary tract symptoms by 2.07 (95% CI 1.04-3.79) and 2.49 (95% CI 1.43-4.33), respectively. HIV infected men had a worse total International Prostate Symptom Score for all domains including quality of life compared to HIV uninfected men. Within the population of men with HIV, those with AIDS had worse mean total International Prostate Symptom Score and all individual International Prostate Symptom Score components relative to nonAIDS defining HIV infected men. CONCLUSIONS: HIV status is an independent risk factor for bothersome lower urinary tract symptoms. The odds of severe lower urinary tract symptoms are greater in HIV infected men with a history of AIDS.
Authors: Breyer BN; Van den Eeden SK; Horberg MA; Eisenberg ML; Deng DY; Smith JF; Shindel AW
J Urol. 2011 May;185(5):1710-5. Epub 2011 Mar 21.
Coffee; ADORA2A; and CYP1A2: the caffeine connection in Parkinson’s disease
BACKGROUND AND PURPOSE: In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson’s disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association. METHODS: Parkinson’s Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Two ADORA2A polymorphisms were inversely associated with PD risk – rs71651683, a 5′ variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04). CONCLUSION: In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms.
Authors: Popat RA; Van Den Eeden SK; Nelson LM; et al.
Eur J Neurol. 2011 May;18(5):756-65. Epub 2011 Jan 31.
Soy food consumption and breast cancer prognosis
BACKGROUND: Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women’s Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis. METHODS: Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model. RESULTS: As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (>16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death. CONCLUSION: Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis. IMPACT: These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer.
Authors: Caan BJ; Natarajan L; Parker B; Gold EB; Thomson C; Newman V; Rock CL; Pu M; Al-Delaimy W; Pierce JP
Cancer Epidemiol Biomarkers Prev. 2011 May;20(5):854-8. Epub 2011 Feb 25.
Father absence, body mass index, and pubertal timing in girls: differential effects by family income and ethnicity
PURPOSE: Numerous studies show associations between father absence and girls’ early puberty. However, most research has been retrospective, focused on menarche, and failed to consider body mass index (BMI), ethnicity, and income in the analyses. This study resolves these scientific gaps. METHODS: This was a prospective study of 444 girls aged 6-8 years and their caregivers (96% mothers). Data were collected annually in clinic, including weight, height, and Tanner stage for breast and pubic hair. Caregivers reported on father absence and demographics. This report focuses on the assessment of father absence at baseline and 2 years of follow-up for pubertal outcomes. Cox proportional hazards regression models were used to test whether father absence at baseline predicted pubertal onset by follow-up visit 2. BMI was assumed to be in the causal pathway. Differences by ethnicity and income were examined. RESULTS: Income and ethnicity moderated associations between father absence and pubertal onset when adjusting for BMI. Father absence predicted earlier onset of breast development only in higher-income families and onset of pubic hair development only in higher-income African Americans families. BMI was not related to father absence and therefore was not in the causal pathway. CONCLUSION: Among girls from higher-income families, father absence was linked to earlier puberty. This was particularly true for African Americans in terms of pubic hair development. These effects are not explained by body weight. Future research is needed to identify social and biophysiological mechanisms through which father absence, ethnicity, and income affect the pubertal onset.
Authors: Deardorff J; Ekwaru JP; Kushi LH; Ellis BJ; Greenspan LC; Mirabedi A; Landaverde EG; Hiatt RA
J Adolesc Health. 2011 May;48(5):441-7. Epub 2010 Sep 20.
Healthy lifestyles related to subsequent prevalence of age-related macular degeneration
OBJECTIVE: To investigate the relationships between lifestyle behaviors of diet, smoking, and physical activity and the subsequent prevalence of age-related macular degeneration (AMD). METHODS: The population included 1313 participants (aged 55-74 years) in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women’s Health Initiative Observational Study. Scores on a modified 2005 Healthy Eating Index were assigned using responses to a food frequency questionnaire administered at baseline of the Women’s Health Initiative Observational Study (1994-1998). Physical activity and lifetime smoking history were queried. An average of 6 years later, stereoscopic fundus photographs were taken to assess the presence and severity of AMD; it was present in 202 women, 94% of whom had early AMD, the primary outcome. RESULTS: In multivariate models, women whose diets scored in the highest quintile compared with the lowest quintile on the modified 2005 Healthy Eating Index had 46% lower odds for early AMD. Women in the highest quintile compared with those in the lowest quintile for physical activity (in metabolic energy task hours per week) had 54% lower odds for early AMD. Although smoking was not independently associated with AMD on its own, having a combination of 3 healthy behaviors (healthy diet, physical activity, and not smoking) was associated with 71% lower odds for AMD compared with having high-risk scores (P < .001). CONCLUSION: Modifying lifestyles might reduce risk for early AMD as much as 3-fold, lowering the risk for advanced AMD in a person's lifetime and the social and economic costs of AMD to society.
Authors: Mares JA; Chappell RJ; Wallace RB; et al.
Arch Ophthalmol. 2011 Apr;129(4):470-80. Epub 2010 Dec 13.
Regular nonsteroidal anti-inflammatory drug use and erectile dysfunction
PURPOSE: Previous data suggest a potential relationship between inflammation and erectile dysfunction. If it is causal, nonsteroidal anti-inflammatory drug use should be inversely associated with erectile dysfunction. To this end we examined the association between nonsteroidal anti-inflammatory drug use and erectile dysfunction in a large, ethnically diverse cohort of men enrolled in the California Men’s Health Study. MATERIALS AND METHODS: This prospective cohort study enrolled male members of the Kaiser Permanente managed care plans who were 45 to 69 years old beginning in 2002. Erectile dysfunction was assessed by questionnaire. Nonsteroidal anti-inflammatory drug exposure was determined by automated pharmacy data and self-reported use. RESULTS: Of the 80,966 men in this study 47.4% were considered nonsteroidal anti-inflammatory drug users based on the definitions used and 29.3% reported moderate or severe erectile dysfunction. Nonsteroidal anti-inflammatory drug use and erectile dysfunction strongly correlated with age with regular drug use increasing from 34.5% in men at ages 45 to 49 years to 54.7% in men 60 to 69 years old with erectile dysfunction increasing from 13% to 42%. The unadjusted OR for the association of nonsteroidal anti-inflammatory drugs and erectile dysfunction was 2.40 (95% CI 2.27, 2.53). With adjustment for age, race/ethnicity, smoking status, diabetes mellitus, hypertension, hyperlipidemia, peripheral vascular disease, coronary artery disease and body mass index, a positive association persisted (adjusted OR 1.38). The association persisted when using a stricter definition of nonsteroidal anti-inflammatory drug exposure. CONCLUSIONS: These data suggest that regular nonsteroidal anti-inflammatory drug use is associated with erectile dysfunction beyond what would be expected due to age and comorbidity.
Authors: Gleason JM; Slezak JM; Jung H; Reynolds K; Van den Eeden SK; Haque R; Quinn VP; Loo RK; Jacobsen SJ
J Urol. 2011 Apr;185(4):1388-93. Epub 2011 Feb 22.
A method to estimate off-schedule observations in a longitudinal study
PURPOSE: Data in epidemiological studies sometimes are collected off-schedule from planned study visits. In an ancillary study to the Study of Women’s Health Across the Nation (SWAN), longitudinal breast density data were collected retrospectively from mammograms that were not acquired at the study visits. We propose a method to estimate the off-schedule breast density measurements at the time of study visits. METHODS: This method uses local linear interpolation, with multiply imputed error terms drawn from assumed subject-specific normal distributions based on the within-subject standard deviations of mammographic density measurements. We evaluate the validity and implications of this approach. RESULTS: Coefficients of random intercept models used to assess the association between annual changes in body mass index and dense breast area estimated with this approach (beta = -0.17, p = .46) differed from those obtained when each mammogram was matched to the nearest study visit (beta = -0.30, p = .04). The proposed estimation approach had a small average prediction error (0.11 cm2). CONCLUSIONS: Because matching does not incorporate breast density changes over time, our local linear interpolation with multiple imputation approach may provide more accurate results. The proposed approach is applicable to other epidemiologic studies with off-schedule data in which the missing variable changes linearly over relatively short periods of time.
Authors: Reeves KW; Stone RA; Modugno F; Ness RB; Vogel VG; Weissfeld JL; Habel LA; Vuga M; Cauley JA
Ann Epidemiol. 2011 Apr;21(4):297-303.
Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study
OBJECTIVE: Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes. RESEARCH DESIGN AND METHODS: This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were >/=40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking. RESULTS: The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9-1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03-2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage. CONCLUSIONS: In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.
Authors: Lewis JD; Ferrara A; Peng T; Hedderson M; Bilker WB; Quesenberry CP Jr; Vaughn DJ; Nessel L; Selby J; Strom BL
Diabetes Care. 2011 Apr;34(4):916-22.
Cohort study of pioglitazone and cancer incidence in patients with diabetes
OBJECTIVE: To explore whether treatment with pioglitazone was associated with risk of incident cancer at the 10 most common sites (prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma [NHL], pancreas, kidney/renal pelvis, rectal, and melanoma). RESEARCH DESIGN AND METHODS: A cohort study of 252,467 patients aged >/=40 years from the Kaiser Permanente Northern California Diabetes Registry was conducted. All prescriptions for diabetes medications were identified by pharmacy records. Cox proportional hazards models were used to examine the association between risk of incident cancer and ever use, duration, dose, and time since initiation of pioglitazone (modeled as time-dependent variables). RESULTS: In models adjusted for age, sex, year of cohort entry, race/ethnicity, income, smoking, glycemic control, diabetes duration, creatinine levels, congestive heart failure, and use of other diabetes medications, the hazard ratio (HR) for each cancer associated with ever use of pioglitazone ranged from 0.7 to 1.3, with all 95% CIs including 1.0. There was a suggestion of an increased risk of melanoma (HR 1.3 [95% CI 0.9-2.0]) and NHL (1.3 [1.0-1.8]) and a decreased risk of kidney/renal pelvis cancers (0.7 [0.4-1.1]) associated with ever use of pioglitazone. These associations were unaltered with increasing dose, duration, or time since first use. CONCLUSIONS: We found no clear evidence of an association between use of pioglitazone and risk of the incident cancers examined. Because the maximum duration of follow-up was fewer than 6 years after the initiation of pioglitazone, longer-term studies are needed.
Authors: Ferrara A; Lewis JD; Quesenberry CP Jr; Peng T; Strom BL; Van den Eeden SK; Ehrlich SF; Habel LA
Diabetes Care. 2011 Apr;34(4):923-9.
IGF1 and risk of additional breast cancer in the WHEL study
IGF1, IGF-binding protein-3 (IGFBP-3), IGFBP-1, insulin, leptin, and adiponectin have been inconsistently associated with breast cancer incidence. We explore how these factors are related to breast cancer recurrence and how tamoxifen treatment is related to IGF1 levels among breast cancer survivors in the Women’s Healthy Eating and Living (WHEL) study. A nested case-control design was used to match breast cancer cases (who had an additional breast cancer event) to controls. Baseline blood samples from 510 matched cases and controls were analyzed for IGF1 levels; a subset of 188 pairs were analyzed for five other hormones and binding proteins. Median follow-up was 7.3 years. Matching was on recruitment site, cancer stage, age at cancer diagnosis, dates of cancer diagnosis, and randomization. Cox proportional hazards regression models, stratified on case-control pair, were used to assess the associations. Insulin, IGFBP-1, IGFBP-3, leptin, and adiponectin did not significantly predict recurrence of breast cancer. IGF1 was positively, but not significantly, associated with recurrence (hazard ratio (HR): 1.33 (95% confidence interval (CI) 0.98-1.81)) in the unadjusted analyses. Adjusting for menopausal status and tamoxifen use attenuated the HR to 1.07 (95% CI 0.76-1.40). Analyses of case-control pairs with discordant tamoxifen use show opposing HR: IGF1 predicts higher risk of recurrence if cases did not receive tamoxifen treatment. In conclusion, no significant association was found between IGF1 levels, or other related factors, and risk of additional breast cancer among breast cancer survivors. Tamoxifen can confound analysis of IGF1 and recurrence. This supports re-evaluating significance of IGF1 to breast cancer recurrence.
Authors: Al-Delaimy WK; Flatt SW; Natarajan L; Laughlin GA; Rock CL; Gold EB; Caan BJ; Parker BA; Pierce JP
Endocr Relat Cancer. 2011 Mar 3;18(2):235-44. Print 2011 Apr.
Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer
Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women with breast cancer (BC), many women are non-adherent with its use. We investigated the effects of early discontinuation and non-adherence to HT on mortality in women enrolled in Kaiser Permanente of Northern California (KPNC). We identified women diagnosed with hormone-sensitive stage I-III BC, 1996-2007, and used automated pharmacy records to identify prescriptions and dates of refill. We categorized patients as having discontinued HT early if 180 days elapsed from the prior prescription. For those who continued, we categorized patients as adherent if the medication possession ratio was >/=80%. We used Cox proportional hazards models to estimate the association between discontinuation and non-adherence with all-cause mortality. Among 8,769 women who filled at least one prescription for HT, 2,761 (31%) discontinued therapy. Of those who continued HT, 1,684 (28%) were non-adherent. During a median follow-up of 4.4 years, 813 women died. Estimated survival at 10 years was 80.7% for women who continued HT versus 73.6% for those who discontinued (P < 0.001). Of those who continued, survival at 10 years was 81.7 and 77.8% in women who adhered and non-adhered, respectively (P < 0.001). Adjusting for clinical and demographic variables, both early discontinuation (HR 1.26, 95% CI 1.09-1.46) and non-adherence (HR 1.49, 95% CI 1.23-1.81), among those who continued, were independent predictors of mortality. Both early discontinuation and non-adherence to HT were common and associated with increased mortality. Interventions to improve continuation of and adherence to HT may be critical to improve BC survival.
Authors: Hershman DL; Shao T; Kushi LH; Buono D; Tsai WY; Fehrenbacher L; Kwan M; Gomez SL; Neugut AI
Breast Cancer Res Treat. 2011 Apr;126(2):529-37. Epub 2010 Aug 28.
The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps
The PIVI (Preservation and Incorporation of Valuable endoscopic Innovations) initiative is an ASGE program whose objectives are to identify important clinical questions related to endoscopy and to establish a priori diagnostic and/or therapeutic thresholds for endoscopic technologies designed to resolve these clinical questions. Additionally; PIVIs may also outline the data and or the research study design required for proving an established threshold is met. Once endoscopic technologies meet an established PIVI threshold; those technologies are appropriate to incorporate into clinical practice presuming the appropriate training in that endoscopic technology has been achieved. The ASGE encourages and supports the appropriate use of technologies that meet its established PIVI thresholds. The PIVI initiative was developed primarily to direct endoscopic technology development toward resolving important clinical issues in endoscopy. The PIVI initiative is also designed to minimize the possibility that potentially valuable innovations are prematurely abandoned due to lack of utilization and to avoid widespread use of an endoscopic technology before clinical studies documenting their effectiveness have been performed. The following document; or PIVI; is one of a series of statements defining the diagnostic or therapeutic threshold that must be met for a technique or device to become considered appropriate for incorporation into clinical practice. It is also meant to serve as a guide for researchers or those seeking to develop technologies that are designed to improve digestive health outcomes. An ad hoc committee under the auspices of the existing ASGE Technology and Standards of Practice Committees Chairs develops PIVIs. An expert in the subject area chairs the PIVI; with additional committee members chosen for their individual expertise. In preparing this document; evidence-based methodology was employed; using a MEDLINE and PubMed literature search to identify pertinent clinical studies on the topic. PIVIs are ultimately submitted to the ASGE Governing Board for approval; as is done for all Technology and Standards of Practice documents. This document is provided solely for educational and informational purposes and to support incorporating these endoscopic technologies into clinical practice. It should not be construed as establishing a legal standard of care.
Authors: Rex DK; Kahi C; O'Brien M; Levin TR; Pohl H; Rastogi A; Burgart L; Imperiale T; Ladabaum U; Cohen J; Lieberman DA
Gastrointest Endosc. 2011 Mar;73(3):419-22.
Associations between genetic variation in RUNX1, RUNX2, RUNX3, MAPK1 and eIF4E and riskof colon and rectal cancer: additional support for a TGF-beta-signaling pathway
The Runt-related transcription factors (RUNX), mitogen-activated protein kinase (MAPK) 1 and eukaryotic translation initiation factor 4E (eIF4E) are potentially involved in tumorigenesis. We evaluated genetic variation in RUNX1 (40 tagSNPs), RUNX2 (19 tagSNPs), RUNX3 (9 tagSNPs), MAPK1 (6 tagSNPs), eIF4E (3 tagSNPs), eIF4EBP2 (2 tagSNP) and eIF4EBP3 (2 tagSNPs) to determine associations with colorectal cancer (CRC). We used data from population-based studies (colon cancer n = 1555 cases, 1956 controls; rectal cancer n = 754 cases, 959 controls with complete genotype data). Four statistically significant tagSNPs were identified with colon cancer and three tagSNPs were identified with rectal cancer. Whereas the independent risk estimates for each of the tagSNPs ranged from 1.21 to 1.52, the combined risk was greater than additive for any of the three combined high-risk genotypes {combined risk range 1.98 [95% confidence interval (CI) 1.45, 2.70] for eIF4E, RUNX1 and RUNX3 to 3.32 [95% CI 1.34, 8.23] for eIF43, RUNX2 and RUNX3}. For rectal cancer, the strongest association was detected for the combined genotype of RUNX1 and RUNX3 (odds ratio 1.87 95% CI 1.22, 2.87). Associations with specific molecular tumor phenotypes showed consistent and strong associations for CIMP+/MSI+ tumors where the risk estimates were consistently >10-fold and lower confidence bounds were over 3.00 for high-risk genotypes defined by RUNX1, RUNX2 and RUNX3. For CIMP+/KRAS2-mutated colon tumors, the combined risk for high-risk genotypes of RUNX2, eIF4E and RUNX1 was 7.47 (95% CI 1.58, 35.3). Although the associations need confirmation, the findings and their internal consistency underline the importance of genetic variation in these genes for the etiology of CRC.
Authors: Slattery ML; Lundgreen A; Herrick JS; Caan BJ; Potter JD; Wolff RK
Carcinogenesis. 2011 Mar;32(3):318-26. Epub 2010 Nov 18.
Genetic variation in bone morphogenetic protein and colon and rectal cancer
Bone morphogenetic proteins (BMP) are part of the TGF-beta-signaling pathway; genetic variation in these genes may be involved in colorectal cancer. In this study, we evaluated the association between genetic variation in BMP1 (11 tagSNPs), BMP2 (5 tagSNPs), BMP4 (3 tagSNPs), BMPR1A (9 tagSNPs), BMPR1B (21 tagSNPs), BMPR2 (11 tagSNPs) and GDF10 (7 tagSNPs) with risk of colon and rectal cancer and tumor molecular phenotype. We used data from population-based case-control studies (colon cancer n = 1,574 cases, 1,970 controls; rectal cancer n = 791 cases, 999 controls). We observed that genetic variation in BMPR1A, BMPR1B, BMPR2, BMP2 and BMP4 was associated with risk of developing colon cancer, with 20 to 30% increased risk for most high-risk genotypes. A summary of high-risk genotypes showed over a twofold increase in colon cancer risk at the upper risk category (OR = 2.49 95% CI = 1.95, 3.18). BMPR2, BMPR1B, BMP2 and GDF10 were associated with rectal cancer. BMPR2 rs2228545 was associated with an almost twofold increased risk of rectal cancer. The risk associated with the highest category of the summary score for rectal cancer was 2.97 (95% CI = 1.87, 4.72). Genes in the BMP-signaling pathway were consistently associated with CIMP+ status in combination with both KRAS-mutated and MSI tumors. BMP genes interacted statistically significantly with other genes in the TGF-beta-signaling pathway, including TGFbeta1, TGFbetaR1, Smad 3, Smad 4 and Smad 7. Our data support a role for genetic variation in BMP-related genes in the etiology of colon and rectal cancer. One possible mechanism is via the TGF-beta-signaling pathway.
Authors: Slattery ML; Lundgreen A; Herrick JS; Kadlubar S; Caan BJ; Potter JD; Wolff RK
Int J Cancer. 2012 Feb 1;130(3):653-64. Epub 2011 Apr 27.
Norepinephrine antagonists and cancer risk
Authors: Friedman GD; Udaltsova N; Habel LA
Int J Cancer. 2011 Feb 1;128(3):737-8; author reply 739.
Marine fatty acid intake is associated with breast cancer prognosis
EPA and DHA, long-chain (n-3) PUFA largely obtained from fish, inhibit the proliferation of breast cancer cells in vitro and reduce the initiation and progression of breast tumors in laboratory animals. Our purpose in this analysis was to examine whether intake of these marine fatty acids (EPA and DHA) were associated with prognosis in a cohort of women who had been diagnosed and treated for early stage breast cancer (n = 3,081). Median follow-up was 7.3 y. Dietary intake was assessed using 24-h recalls (~4 recalls per dietary assessment obtained at 7 time points over 6 y). Survival models with time-dependent covariates were used to examine the association of repeated measures of dietary intake of EPA and DHA from food (i.e., marine sources) and supplements with disease-free survival and overall survival. Women with higher intakes of EPA and DHA from food had an approximate 25% reduced risk of additional breast cancer events [tertile 2: HR = 0.74 (95% CI = 0.58-0.94); tertile 3: HR = 0.72 (95% CI = 0.57-0.90)] compared with the lowest tertile of intake. Women with higher intakes of EPA and DHA from food had a dose-dependent reduced risk of all-cause mortality [tertile 2: HR = 0.75 (95% CI = 0.55-1.04); tertile 3: HR = 0.59 (95% CI = 0.43-0.82)]. EPA and DHA intake from fish oil supplements was not associated with breast cancer outcomes. The investigation indicates that marine fatty acids from food are associated with reduced risk of additional breast cancer events and all-cause mortality.
Authors: Patterson RE; Flatt SW; Newman VA; Natarajan L; Rock CL; Thomson CA; Caan BJ; Parker BA; Pierce JP
J Nutr. 2011 Feb;141(2):201-6. Epub 2010 Dec 22.
The Effect of Calcium plus Vitamin D on Risk for Invasive Cancer: Results of the Women’s Health Initiative (WHI) Calcium Plus Vitamin D Randomized Clinical Trial
In the Women’s Health Initiative (WHI) trial of calcium plus vitamin D (CaD), we examined the treatment effect on incidence and mortality for all invasive cancers. Postmenopausal women (N = 36,282) were randomized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo. Cox models estimated risk of cancer incidence and mortality. After 7.0 yr, 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [hazard ratio (HR) = 0.98; CI = 0.90, 1.05, unweighted P = 0.54]. Mortality did not differ between supplement (315, annualized% = .26) and placebo [(347, 0.28%; P = 0.17; HR = 0.90 (0.77, 1.05)]. Significant treatment interactions on incident cancer were found for family history of cancer, personal total intake of vitamin D, smoking, and WHI dietary trial randomized group. Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality. Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer. The interactions are only suggestive given multiple testing considerations. The low vitamin D dose provided, limited adherence, and lack of serum 25(OH)D values should be considered when interpreting these findings.
Authors: Brunner RL; Caan BJ; Wallace RB; et al.
Nutr Cancer. 2011;63(6):827-41. Epub 2011 Jul 20.
Candidate pathway polymorphisms in one-carbon metabolism and risk of rectal tumor mutations
We examined candidate polymorphisms in genes involved in the folate-mediated, one-carbon metabolism pathway, DNMT1 1311V, MTHFD1 R134K and R653Q, MTHFR R594Q, MTR D919G, MTRR H595Y and I22M, SHMT1 L474F, SLC19A1 H27R, and TDG G199S, and associations with rectal tumor characteristics. We hypothesized that these candidate genes would influence CpG Island Methylator Phenotype and potentially KRAS2 or TP53 tumors. Data from a population-based study of 747 rectal cases (593 with tumor markers) and 956 controls were evaluated using generalized estimating equations. We observed an increased risk of TP53 tumor mutations in homozygous carriers of the MTHFD1 134K allele (0R=2.0, 95%CI 1.2-3.1, P- trend=0.02). In the presence of low folate intake, the R134K variant was associated with increased risk of CIMP+ tumors (OR=2.8, 95%CI 1.04-7.7). The MTRR I22M variant genotype was associated with a modest increased risk of TP53 mutations (OR=1.7, 95%CI 1.2-2.5, P-trend=0.001). Our findings offer limited support that polymorphisms in one-carbon metabolism genes influence rectal tumor phenotype, and that folate may interact with MTHFD1 to alter CIMP+ risk.
Authors: Curtin K; Ulrich CM; Samowitz WS; Wolff RK; Duggan DJ; Makar KW; Caan BJ; Slattery ML
Int J Mol Epidemiol Genet. 2011 Jan 1;2(1):1-8. Epub 2010 Nov 5.
Organized colorectal cancer screening in integrated health care systems
Colorectal cancer (CRC) is an ideal target for early detection and prevention through screening. Noninvasive screening options are the guaiac fecal occult blood test and the fecal immunochemical test. Organized screening offers the promise of uniformly delivering screening to all members of a population who are eligible and due. Organized screening is defined as an explicit policy with defined age categories, method, and interval for screening in a defined target population with a defined implementation and quality assurance structure, and tracking of cancer in the population. The UK National Health Service; the Ontario, Canada Ministry of Health and Long-Term Care; and the US Veteran’s Health Administration have used varied organized approaches to deliver guaiac fecal occult blood test screening to their populations. Kaiser Permanente Northern California began CRC screening in the 1960s, initially using flexible sigmoidoscopy. Implementation of organized fecal immunochemical test outreach was associated with improved Healthcare Effectiveness Data and Information Set CRC screening rates between 2005 and 2010 from 37% to 69% and from 41% to 78% in the commercial and Medicare populations, respectively. Organized fecal immunochemical test screening has been associated with an increase in annually detected CRCs, almost entirely because of increased detection of localized-stage cancers.
Authors: Levin TR; Jamieson L; Burley DA; Reyes J; Oehrli M; Caldwell C
Epidemiol Rev. 2011;33(1):101-10. Epub 2011 Jun 27.
Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women’s Healthy Eating and Living Study
The protective effect of vegetables on the risk of breast cancer recurrence is uncertain. We sought to evaluate the association between breast cancer recurrence and vegetable intake including analyses stratified on tamoxifen use. Experimental evidence of anti-carcinogenic activity of phytochemicals in cruciferous vegetables in combination with tamoxifen led to specific evaluation of this class of vegetables as well. To assess the association between vegetable intake and breast cancer recurrence, vegetable intake from repeat 24-h dietary recalls were examined as a secondary analysis of 3,080 breast cancer survivors enrolled in the Women’s Healthy Eating and Living (WHEL) Study. At the time of enrollment women were, on average, 23.5 months post-diagnosis. The hazard of recurrence, controlling for relevant and significant clinical and demographic variables, with vegetable intake was assessed overall and separately for women taking tamoxifen. WHEL participants reported mean baseline intakes (x, SE) of 3.1 +/- 0.05 and 0.5 +/- 0.02 servings/day of total and cruciferous vegetables, respectively. Baseline vegetable intake in the highest as compared to lowest tertiles was associated with an overall lower adjusted hazard ratios (HR) for recurrence of 0.69, 95% CI 0.55-0.87. Among women taking tamoxifen, the HRs were 0.56, 95% CI 0.41-0.77 for total vegetables and 0.65, 95% CI 0.47-0.89 for cruciferous vegetable intake. The hazard in women using tamoxifen who reported cruciferous vegetable intake above the median and who were within the highest tertile of total vegetable intake was HR 0.48; 95% CI 0.32-0.70. This secondary analysis in over 3,000 breast cancer survivors suggests that baseline vegetable intake may be associated with a reduction in the risk of breast cancer recurrent or new events particularly for those using tamoxifen. Such associations should be explored further as the possibility that vegetable intake is simply a surrogate for other health-promoting behaviors cannot be ruled out.
Authors: Thomson CA; Rock CL; Thompson PA; Caan BJ; Cussler E; Flatt SW; Pierce JP
Breast Cancer Res Treat. 2011 Jan;125(2):519-27. Epub 2010 Jul 6.
Lack of association between insulin sensitivity and colorectal adenoma risk
Insulin resistance is thought to mediate the association between obesity and colorectal neoplasia, but no prior studies have assessed stimulated insulin sensitivity as a risk factor for colorectal neoplasia. This prospective study examined the association between insulin sensitivity measured directly using the frequently sampled intravenous glucose tolerance test (FSIGT) and later risk of colorectal adenomas. Among participants with a range of glucose tolerance levels enrolled in the Insulin Resistance Atherosclerosis Study, colonoscopies were conducted on 600 participants ages >/=50 yr, regardless of symptoms, about 10 yr after the first FSIGT and 5 yr after the second. Multiple logistic regression analyses were used. Within this cohort, diabetes was not associated with colorectal adenoma risk [ approximately 10 yr prior to colonoscopy adjusted odds ratio (OR(adj)) 1.00; 95% confidence interval (CI), 0.62-1.62 or approximately 5 yr prior to colonoscopy OR(adj) 0.96; 95% CI, 0.62-1.50]. Among non-diabetic participants, insulin sensitivity was not associated with colorectal adenoma risk at either prior study visit [lowest vs. highest insulin sensitivity, approximately 10 yr prior to colonoscopy OR(adj) 0.93; 95% CI 0.50-1.71 and approximately 5 yr prior to colonscopy OR(adj) 0.74; 95% CI, 0.38-1.46]. These results suggest that factors other than insulin sensitivity mediate the relationship between obesity and colorectal neoplasia.
Authors: Sedjo RL; D'Agostino RB; Ahnen D; Levin TR; Haffner SM; Tooze JA; Byers T
Nutr Cancer. 2011 Jan;63(1):6-11.
Nutrients in folate-mediated, one-carbon metabolism and the risk of rectal tumors in men and women
In an investigation of rectal tumors characterized by CpG island methylator phenotype (CIMP), KRAS2 mutation, and TP53 mutation, we examined associations with dietary and supplemental folate, riboflavin, vitamins B(6) and B(12), and methionine, nutrients involved in folate-mediated 1-carbon metabolism. We also examined folate intake and common MTHFR polymorphisms in relation to CIMP. Data from a population-based study of 951 cases (750 with tumor markers) and 1,205 controls were evaluated using multiple logistic regression models and generalized estimating equations. Reduced risk of methylated tumors was suggested in women with the upper tertile of folate intake (>/=0.42 mg/day) vs. the lower tertile: OR = 0.6, 95%CI = 0.3-1.2. In men, a significant 3-fold increased risk of CIMP+ tumor was observed for the upper tertile of folate (>/=0.75 mg/day) vs. the lower tertile (<0.44 mg/day): OR = 3.2, 95%CI = 1.5-6.7. These men consumed a greater proportion of folic acid fortified foods relative to natural, primarily plant-based sources (52% vs. 48%) than women with CIMP+ tumors (22% vs. 78%). MTHFR 1298A>C influenced folate in male CIMP+ risk (P interaction < 0.01). Our findings suggest folate supplementation effects may differ between genders, perhaps due to variation in MTHFR and/or endogenous/exogenous hormones, and may be important in the initiation and progression of methylated rectal tumors in men.
Authors: Curtin K; Samowitz WS; Ulrich CM; Wolff RK; Herrick JS; Caan BJ; Slattery ML
Nutr Cancer. 2011;63(3):357-66.
Dietary factors and the risks of oesophageal adenocarcinoma and Barrett’s oesophagus
Incidence rates for oesophageal adenocarcinoma have increased by over 500% during the past few decades without clear reasons. Gastro-oesophageal reflux disease, obesity and smoking have been identified as risk factors, although the demographic distribution of these risk factors is not consistent with the demographic distribution of oesophageal adenocarcinoma, which is substantially more common among whites and males than any other demographic groups. Numerous epidemiological studies have suggested associations between dietary factors and the risks of oesophageal adenocarcinoma and its precursor, Barrett’s oesophagus, though a comprehensive review is lacking. The main aim of the present review is to consider the evidence linking dietary factors with the risks of oesophageal adenocarcinoma, Barrett’s oesophagus, and the progression from Barrett’s oesophagus to oesophageal adenocarcinoma. The existing epidemiological evidence is strongest for an inverse relationship between intake of vitamin C, beta-carotene, fruits and vegetables, particularly raw fruits and vegetables and dark green, leafy and cruciferous vegetables, carbohydrates, fibre and Fe and the risk of oesophageal adenocarcinoma and Barrett’s oesophagus. Patients at higher risk for Barrett’s oesophagus and oesophageal adenocarcinoma may benefit from increasing their consumption of fruits and vegetables and reducing their intake of red meat and other processed food items. Further research is needed to evaluate the relationship between diet and the progression of Barrett’s oesophagus to oesophageal adenocarcinoma. Evidence from cohort studies will help determine whether randomised chemoprevention trials are warranted for the primary prevention of Barrett’s oesophagus or its progression to cancer.
Authors: Kubo A; Corley DA; Jensen CD; Kaur R
Nutr Res Rev. 2010 Dec;23(2):230-46. Epub 2010 Jul 13.
Characterization of 9p24 risk locus and colorectal adenoma and cancer: gene-environment interaction and meta-analysis
BACKGROUND: A potential susceptibility locus for colorectal cancer on chromosome 9p24 (rs719725) was initially identified through a genome-wide association study, though replication attempts have been inconclusive. METHODS: We genotyped this locus and explored interactions with known risk factors as potential sources of heterogeneity, which may explain the previously inconsistent replication. We included Caucasians with colorectal adenoma or colorectal cancer and controls from 4 studies (total 3,891 cases, 4,490 controls): the Women’s Health Initiative (WHI); the Diet, Activity and Lifestyle Study (DALS); a Minnesota population-based case-control study (MinnCCS); and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). We used logistic regression to evaluate the association and test for gene-environment interactions. RESULTS: SNP rs719725 was statistically significantly associated with risk of colorectal cancer in WHI (OR per A allele 1.19; 95% CI, 1.01-1.40; P(trend) = 0.04), marginally associated with adenoma risk in PLCO (OR per A allele 1.11; 95% CI, 0.99-1.25; P(trend) = 0.07), and not associated in DALS and MinnCCS. Evaluating for gene-environment interactions yielded no consistent results across the studies. A meta-analysis of 17 studies (including these 4) gave an OR per A allele of 1.07 (95% CI, 1.03-1.12; P(trend) = 0.001). CONCLUSIONS: Our results suggest the Aallele for SNP rs719725 at locus 9p24 is positively associated with a small increase in risk for colorectal tumors. Environmental risk factors for colorectal cancer do not appear to explain heterogeneity across studies. IMPACT: If this finding is supported by further replication and functional studies, it may highlight new pathways underlying colorectal neoplasia.
Authors: Kocarnik JD; Caan BJ; Peters U; et al.
Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3131-9. Epub 2010 Oct 26.
A practical method for collecting food record data in a prospective cohort study of breast cancer survivors
Multiple-day diet records can be unsuitable for cohort studies because of high administrative and analytical costs. Costs could be reduced if a subsample of participants were analyzed in a nested case-control study. However, completed records are usually reviewed (‘documented’) with participants to correct errors and omissions before analysis. The authors evaluated the suitability of using undocumented 3-day food records in 2 samples of women in a Northern California cohort study of breast cancer survivorship (2006-2009). One group of participants (n = 130) received an introduction to the food record at enrollment, while another (n = 70) received more comprehensive instruction. Food records were mailed to participants 6 months later for follow-up and were analyzed as received and after phone documentation. Error rates for adequate completion were high in the first group but substantially lower among persons receiving instruction; prevalences of missing data on serving size and incomplete food descriptions changed from 30% to 4% and from 32% to 6%, respectively (P < 0.0001). Correlations between nutrient intakes calculated from undocumented and documented records were 0.72-0.93 in the first group and were significantly stronger (0.84-0.99) among persons receiving instruction. Documentation had little effect on intraclass correlation coefficients across days, but training increased the coefficients for many nutrients. When participants receive proper instruction, undocumented food records can be satisfactory for large epidemiologic studies.
Authors: Kwan ML; Kushi LH; Song J; Timperi AW; Boynton AM; Johnson KM; Standley J; Kristal AR
Am J Epidemiol. 2010 Dec 1;172(11):1315-23. Epub 2010 Oct 11.
Serial glycosylated hemoglobin levels and risk of colorectal neoplasia among patients with type 2 diabetes mellitus
BACKGROUND: Hyperglycemia may increase the risk of colorectal neoplasia by serving as an energy source for neoplastic growth. We sought to determine whether glycemic control measured by serial hemoglobin A1c (HbA1c) was associated with the risk of colorectal adenoma. METHODS: Among a cohort of patients with type 2 diabetes mellitus who received health care within the Kaiser Permanente Northern California from 1994 to 2005, we conducted 2 case-control analyses. Cases had at least 1 colorectal adenoma identified at either colonoscopy (analysis 1) or sigmoidoscopy (analysis 2). Controls had no colorectal neoplasia identified at the corresponding endoscopic examination. Serial HbA1c levels between the cases and the controls were compared using a longitudinal model. RESULTS: Case-control analysis 1 included 4,248 patients, of whom 1,296 (31%) had at least 1 adenoma. The adjusted mean HbA1c levels among those without any adenomas was 8.20% versus 8.26% among those with at least 1 adenoma, a difference of 0.06% (95% CI = -0.02 to 0.14, P = 0.16). Case-control analysis 2 included 9,813 patients, of whom 951 (10%) had at least 1 distal adenoma. The adjusted mean HbA1c levels among those without any distal adenomas was 8.32% versus 8.37% among those with at least 1 distal adenoma, a difference of 0.05% (95% CI = -00.04 to 0.14, P = 0.25). The results were similar for advanced adenomas. CONCLUSIONS: Glycemic control was not associated with the risk of colorectal adenoma among diabetic persons. IMPACT: These results would suggest that glycemic control is unlikely to confound the reported association between diabetes medications and the risk of colorectal cancer.
Authors: Yang YX; Habel LA; Capra AM; Achacoso NS; Ferrara A; Levin TR; Lewis JD; Quesenberry CP Jr
Cancer Epidemiol Biomarkers Prev. 2010 Dec;19(12):3027-36. Epub 2010 Oct 11.
Familial aggregation of Parkinson’s disease in a multiethnic community-based case-control study
To assess the familial aggregation of Parkinson’s disease (PD), we compared the cumulative incidence of PD among first-degree relatives of PD cases and controls. We identified newly diagnosed patients with PD (n = 573) during 1994 to 1995 within Kaiser Permanente Medical Care Program of Northern California and recruited 496 cases (87%) for the case-control study. Of 720 eligible controls matched by birth year and sex to cases, 541 (75%) agreed to participate. Information on family history of PD and other neurodegenerative diseases was obtained by in-person structured interview. We used the reconstructed cohort approach that provides a better estimate of the risk. The cumulative incidence of PD was significantly higher among relatives of PD patients compared with relatives of controls (2.0 vs. 0.7%; relative risk (RR) = 3.4, 95% confidence interval (CI) 1.9-5.9; P = 0.0001). The degree of familial aggregation was higher among first-degree relatives of Hispanic PD cases compared with Hispanic controls (3.7% vs. 0.4%; RR = 8.5, 95% CI 1.0-68.9) than it was among non-Hispanic Caucasian cases and controls (2.0% vs. 0.8%; RR = 2.7, 95% CI 1.5-5.1; P = 0.02). The familial aggregation of PD was stronger among the siblings of PD cases (RR = 5.4, 95% CI 1.8-16.0) than among parents (RR = 2.7, 95% CI 1.3-5.2). The incidence and familial aggregation of PD is highest among Hispanics, warranting further studies of genetic and environmental risk factors in the Hispanic population.
Authors: Shino MY; McGuire V; Van Den Eeden SK; Tanner CM; Popat R; Leimpeter A; Bernstein AL; Nelson LM
Mov Disord. 2010 Nov 15;25(15):2587-94.
Risk factors for lymphedema in a prospective breast cancer survivorship study: the Pathways Study
OBJECTIVE: To determine the incidence of breast cancer-related lymphedema (BCRL) during the early survivorship period as well as demographic, lifestyle, and clinical factors associated with BCRL development. DESIGN: The Pathways Study, a prospective cohort study of breast cancer survivors with a mean follow-up time of 20.9 months. SETTING: Kaiser Permanente Northern California medical care program. PARTICIPANTS: We studied 997 women diagnosed from January 9, 2006, through October 15, 2007, with primary invasive breast cancer and who were at least 21 years of age at diagnosis, had no history of any cancer, and spoke English, Spanish, Cantonese, or Mandarin. MAIN OUTCOME MEASURE: Clinical indication for BCRL as determined from outpatient or hospitalization diagnostic codes, outpatient procedural codes, and durable medical equipment orders. RESULTS: A clinical indication for BCRL was found in 133 women (13.3%), with a mean time to diagnosis of 8.3 months (range, 0.7-27.3 months). Being African American (hazard ratio, 1.93; 95% confidence interval, 1.00-3.72) or more educated (P for trend = .03) was associated with an increased risk of BCRL. Removal of at least 1 lymph node (hazard ratio, 1.04; 95% confidence interval, 1.02-1.07) was associated with an increased risk, yet no significant association was observed for type of lymph node surgery. Being obese at breast cancer diagnosis was suggestive of an elevated risk (hazard ratio, 1.43; 95% confidence interval, 0.88-2.31). CONCLUSIONS: In a large cohort study, BCRL occurs among a substantial proportion of early breast cancer survivors. Our findings agree with those of previous studies on the increased risk of BCRL with removal of lymph nodes and being obese, but they point to a differential risk according to race or ethnicity.
Authors: Kwan ML; Darbinian J; Schmitz KH; Citron R; Partee P; Kutner SE; Kushi LH
Arch Surg. 2010 Nov;145(11):1055-63.
Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women
CONTEXT: In the Women’s Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported. OBJECTIVE: To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009. DESIGN, SETTING, AND PARTICIPANTS: A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants. MAIN OUTCOME MEASURES: Invasive breast cancer incidence and breast cancer mortality. RESULTS: In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group. CONCLUSIONS: Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.
Authors: Chlebowski RT; Ockene J; WHI Investigators; et al.
JAMA. 2010 Oct 20;304(15):1684-92.
Alcohol consumption and breast cancer recurrence and survival among women with early-stage breast cancer: the life after cancer epidemiology study
PURPOSE: To examine the association of alcohol consumption after breast cancer diagnosis with recurrence and mortality among early-stage breast cancer survivors. PATIENTS AND METHODS: Patients included 1,897 LACE study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited on average 2 years postdiagnosis, primarily from the Kaiser Permanente Northern California Cancer Registry. Alcohol consumption (ie, wine, beer, and liquor) was assessed at cohort entry using a food frequency questionnaire. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% CI with adjustment for known prognostic factors. RESULTS: Two hundred ninety-three breast cancer recurrences and 273 overall deaths were ascertained after an average follow-up of 7.4 years. Nine hundred fifty-eight women (51%) were considered drinkers (> 0.5 g/d of alcohol), and the majority drank wine (89%). Drinking >/= 6 g/d of alcohol compared with no drinking was associated with an increased risk of breast cancer recurrence (HR, 1.35; 95% CI, 1.00 to 1.83) and death due to breast cancer (HR, 1.51; 95% CI, 1.00 to 2.29). The increased risk of recurrence appeared to be greater among postmenopausal (HR, 1.51; 95% CI, 1.05 to 2.19) and overweight and obese women (HR, 1.60; 95% CI, 1.08 to 2.38). Alcohol intake was not associated with all-cause death and possibly associated with decreased risk of non-breast cancer death. CONCLUSION: Consuming three to four alcoholic drinks or more per week after a breast cancer diagnosis may increase risk of breast cancer recurrence, particularly among postmenopausal and overweight/obese women, yet the cardioprotective effects of alcohol on non-breast cancer death were suggested.
Authors: Kwan ML; Kushi LH; Weltzien E; Tam EK; Castillo A; Sweeney C; Caan BJ
J Clin Oncol. 2010 Oct 10;28(29):4410-6. Epub 2010 Aug 30.
Long-term prognostic role of functional limitations among women with breast cancer
BACKGROUND: The long-term prognostic role of functional limitations among women with breast cancer is poorly understood. METHODS: We studied a cohort of 2202 women with breast cancer at two sites in the United States, who provided complete information on body functions involving endurance, strength, muscular range of motion, and small muscle dexterity following initial adjuvant treatment. Associations of baseline functional limitations with survival were evaluated in delayed entry Cox proportional hazards models, with adjustment for baseline sociodemographic factors, body mass index, smoking, physical activity, comorbidity, tumor characteristics, and treatment. Difference in covariates between women with and without limitations was assessed with Pearson chi(2) and Student t tests. All statistical tests were two-sided. RESULTS: During the median follow-up of 9 years, 112 deaths were attributable to competing causes (5% of the cohort) and 157 were attributable to breast cancer causes (7% of the cohort). At least one functional limitation was present in 39% of study participants. Proportionately, more breast cancer patients with functional limitations after initial adjuvant treatment were older, less educated, and obese (P < .001). In multivariable models, functional limitations were associated with a statistically significantly increased risk of death from all causes (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.03 to 1.92) and from competing causes (HR = 2.60, 95% CI = 1.69 to 3.98) but not from breast cancer (HR = 0.90, 95% CI = 0.64 to 1.26). The relationship between functional limitations and overall survival differed by tumor stage (among women with stage I and stage III breast cancer, HR = 2.02, 95% CI = 1.23 to 3.32 and HR = 0.74, 95% CI = 0.42 to 1.30, respectively). CONCLUSION: In this prospective cohort study, functional limitations following initial breast cancer treatment were associated with an important reduction in all-cause and competing-cause survival, irrespective of clinical, lifestyle, and sociodemographic factors.
Authors: Braithwaite D; Sternfeld B; Caan BJ; et al.
J Natl Cancer Inst. 2010 Oct 6;102(19):1468-77. Epub 2010 Sep 22.
Women with diabetes: understanding urinary incontinence and help seeking behavior
PURPOSE: We examined the association of urinary incontinence with diabetes status and race, and evaluated beliefs about help seeking for incontinence in a population based cohort of women with vs without diabetes. MATERIALS AND METHODS: We performed a cross-sectional analysis of 2,270 middle-aged and older racially/ethnically diverse women in the Diabetes Reproductive Risk factors for Incontinence Study at Kaiser. Incontinence, help seeking behavior and beliefs were assessed by self-report questionnaires and in-person interviews. We compared incontinence characteristics in women with and without diabetes using univariate analysis and multivariate models. RESULTS: Women with diabetes reported weekly incontinence significantly more than women without diabetes (weekly 35.4% vs 25.7%, p <0.001). Race prevalence patterns were similar in women with and without diabetes with the most vs the least prevalence of incontinence in white and Latina vs black and Asian women. Of women with diabetes 42.2% discussed incontinence with a physician vs 55.5% without diabetes (p <0.003). Women with diabetes were more likely than those without diabetes to report the belief that incontinence is rare (17% vs 6%, p <0.001). CONCLUSIONS: Incontinence is highly prevalent in women with diabetes. Race prevalence patterns are similar in those with and without diabetes. Understanding help seeking behavior is important to ensure appropriate patient care. Physicians should be alert for urinary incontinence since it is often unrecognized and, thus, under treated in women with diabetes.
Authors: Doshi AM; Van Den Eeden SK; Morrill MY; Schembri M; Thom DH; Brown JS; Reproductive Risks for Incontinence Study at Kaiser Research Group
J Urol. 2010 Oct;184(4):1402-7. Epub 2010 Aug 19.
Lipophilic statin use and risk of breast cancer subtypes
BACKGROUND/AIMS: Statins are widely used and of high interest as potential chemopreventive agents for cancer. Preclinical studies suggest that lipophilic statins have anticancer properties targeting hormone receptor (HR)-negative breast cancer. Few epidemiologic studies have investigated the relationship between lipophilic statin use and risk for breast cancer, stratified by HR status. We conducted a large case-control study within Kaiser Permanente of Northern California (KPNC) to determine whether chronic use of lipophilic statins is associated with decreased risk of HR-negative breast cancer or other breast cancer subtypes. METHODS: We identified 22,488 breast cancer cases diagnosed from 1997 to 2007, and 224,860 controls matched to cases based upon birth year and duration of KPNC pharmacy coverage. Use of lipophilic statins was ascertained using the comprehensive electronic pharmacy records of KPNC. RESULTS: We found no association between lipophilic statin use (>/=2 y versus never) and overall breast cancer risk (odds ratio(adj), 1.02; 95% CI, 0.97-1.08) in conditional logistic regression models adjusted for oral contraceptive and hormone therapy use. Women who used lipophilic statins did not have a decreased risk of HR-negative breast cancer (odds ratio(adj), 0.98; 95% CI, 0.84-1.14) nor altered risk of HR-positive disease (odds ratio(adj), 1.03; 95% CI, 0.97-1.10). Furthermore, lipophilic statin use was not associated with risk of any of the intrinsic subtypes, luminal A, luminal B, human epidermal growth factor receptor 2 positive/estrogen receptor negative, or triple negative. CONCLUSIONS: Our results do not support an association of lipophilic statin use with the risk for breast cancer in general or with risks of HR-negative or other breast cancer subtypes specifically. IMPACT: These findings do not confirm previous reports of a possible preventive association.
Authors: Woditschka S; Habel LA; Udaltsova N; Friedman GD; Sieh W
Cancer Epidemiol Biomarkers Prev. 2010 Oct;19(10):2479-87. Epub 2010 Aug 20.
Mammographic density and risk of second breast cancer after ductal carcinoma in situ
BACKGROUND: We examined whether mammographic density predicts risk of second breast cancers among patients with ductal carcinoma in situ (DCIS). METHODS: The study included DCIS patients diagnosed during 1990 to 1997 and treated with breast-conserving surgery at Kaiser Permanente Northern California. Medical records were reviewed for clinical factors and subsequent breast cancers (DCIS and invasive). Ipsilateral mammograms from the index DCIS were assessed for density without knowledge of subsequent cancer status. Cox regression modeling was used to examine the association between mammographic density and risk of breast cancer events. RESULTS: Of the 935 eligible DCIS patients, 164 (18%) had a subsequent ipsilateral breast cancer, and 59 (6%) had a new primary cancer in the contralateral breast during follow-up (median, 103 mo). Those with the greatest total area of density (upper 20% of values) were at increased risk for invasive disease in either breast [hazard ratio (HR), 2.1; 95% confidence interval (95% CI), 1.2-3.8] or any cancer (DCIS or invasive) in the ipsilateral (HR, 1.7; 95% CI, 1.0-2.9) or contralateral (HR, 3.0; 95% CI, 1.3-6.9) breast compared with those with the smallest area of density (bottom 20%). HRs for these same end points comparing those in the highest with those in the lowest American College of Radiology Breast Imaging Reporting and Data System category were 1.6 (95% CI, 0.7-3.6), 1.3 (95% CI, 0.7-2.6), and 5.0 (95% CI, 1.4-17.9), respectively. There was a suggestion of increasing risk of contralateral, but not ipsilateral, cancer with increasing percent density. CONCLUSIONS: Women with mammographically dense breasts may be at higher risk of subsequent breast cancer, especially in the contralateral breast. IMPACT: Information about mammographic density may help with DCIS treatment decisions.
Authors: Habel LA; Capra AM; Achacoso NS; Janga A; Acton L; Puligandla B; Quesenberry CP Jr
Cancer Epidemiol Biomarkers Prev. 2010 Oct;19(10):2488-95.
Human epidermal growth factor receptor 2 assessment in a case-control study: comparison of fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction performed by central laboratories
PURPOSE: The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate >/= 95% concordance to another approved laboratory or methodology. Here, we compare central laboratory HER2 assessed by fluorescence in situ hybridization (FISH) and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using Oncotype DX in lymph node-negative, chemotherapy-untreated patients from a large Kaiser Permanente case-control study. PATIENTS AND METHODS: Breast cancer specimens from the Kaiser-Genomic Health study were examined. Central FISH assessment of HER2 amplification and polysomy 17 was conducted by PhenoPath Laboratories (ratios > 2.2, 1.8 to 2.2, and < 1.8 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). HER2 expression by RT-PCR was conducted using Oncotype DX by Genomic Health (normalized expression units >/= 11.5, 10.7 to < 11.5, and < 10.7 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). Concordance analyses followed ASCO/CAP guidelines. RESULTS: HER2 concordance by central FISH and central RT-PCR was 97% (95% CI, 96% to 99%). Twelve percent (67 of 568 patients) and 11% (60 of 568 patients) of patients were HER2 positive by RT-PCR and FISH, respectively. HER2-positive patients had increased odds of dying from breast cancer compared with HER2-negative patients. Polysomy 17 was demonstrated in 12.5% of all patients and 33% of FISH-positive patients. Nineteen of 20 FISH-positive patients with polysomy 17 were also RT-PCR HER2 positive. Although not statistically significantly different, HER2-positive/polysomy 17 patients tended to have the worst prognosis, followed by HER2-positive/eusomic, HER2-negative/polysomy 17, and HER2-negative/eusomic patients. CONCLUSION: There is a high degree of concordance between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status, and the assay warrants additional study in a trastuzumab-treated population.
Authors: Baehner FL; Achacoso N; Maddala T; Shak S; Quesenberry CP Jr; Goldstein LC; Gown AM; Habel LA
J Clin Oncol. 2010 Oct 1;28(28):4300-6. Epub 2010 Aug 9.
Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients
PURPOSE: While studies have found that adjuvant hormonal therapy for hormone-sensitive breast cancer (BC) dramatically reduces recurrence and mortality, adherence to medications is suboptimal. We investigated the rates and predictors of early discontinuation and nonadherence to hormonal therapy in patients enrolled in Kaiser Permanente of Northern California health system. PATIENTS AND METHODS: We identified women diagnosed with hormone-sensitive stage I-III BC from 1996 to 2007 and used automated pharmacy records to identify hormonal therapy prescriptions and dates of refill. We used Cox proportional hazards regression models to analyze factors associated with early discontinuation and nonadherence (medication possession ratio < 80%) of hormonal therapy. RESULTS: We identified 8,769 patients with BC who met our eligibility criteria and who filled at least one prescription for tamoxifen (43%), aromatase inhibitors (26%), or both (30%) within 1 year of diagnosis. Younger or older age, lumpectomy (v mastectomy), and comorbidities were associated with earlier discontinuation, while Asian race, being married, earlier year at diagnosis, receipt of chemotherapy or radiotherapy, and longer prescription refill interval were associated with completion of 4.5 years of therapy. Of those who continued therapy, similar factors were associated with full adherence. Women age younger than 40 years had the highest risk of discontinuation (hazard ratio, 1.51; 95% CI, 1.23 to 1.85). By 4.5 years, 32% discontinued therapy, and of those who continued, 72% were fully adherent. CONCLUSION: Only 49% of patients with BC took adjuvant hormonal therapy for the full duration at the optimal schedule. Younger women are at high risk of nonadherence. Interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women.
Authors: Hershman DL; Kushi LH; Shao T; Buono D; Kershenbaum A; Tsai WY; Fehrenbacher L; Lin Gomez S; Miles S; Neugut AI
J Clin Oncol. 2010 Sep 20;28(27):4120-8. Epub 2010 Jun 28.
Evidence for an hMSH3 defect in familial hamartomatous polyps.
BACKGROUND: Patients with hamartomatous polyposis syndromes have increased risk for colorectal cancer (CRC). Although progression of polyps to carcinoma is observed, pathogenic mechanisms remain unknown. The authors examined whether familial hamartomatous polyps harbor defects in DNA mismatch repair (MMR), and assayed for somatic mutation of PTEN, a gene inactivated in the germline of some hamartomatous polyposis syndrome patients.METHODS: Ten hamartomatous polyposis syndrome patients were genotyped for germline mutations. Epithelial and nonepithelial polyp DNA were assayed for microsatellite instability (MSI) and PTEN frameshift mutation. DNA MMR and PTEN protein expression were assessed in all polyps by immunohistochemistry. In addition, 99 MSI-high sporadic CRCs and 50 each of hMLH1(-/-) and hMSH3(-/-) cell clones were examined for PTEN frameshifts.RESULTS: Twenty-five (58%) of 43 hamartomatous polyposis syndrome polyps demonstrated dinucleotide or greater MSI in polyp epithelium, consistent with hMSH3 deficiency. MSI domains lost hMSH3 expression, and PTEN expression was lost in polyps from germline PTEN patients; sporadic hamartomatous polyps did not show any of these findings. PTEN analysis revealed wild type exon 7 and 8 sequences suggestive of nonexistent or rare events for PTEN frameshifts; however, MSI-high sporadic CRC showed 11 (11%) of 99 frameshifts within PTEN, with 4 tumors having complete loss of PTEN expression. Subcloning hMLH1(-/-) and hMSH3(-/-) cells revealed somatic PTEN frameshifts in 4% and 12% of clones, respectively.CONCLUSIONS: Nondysplastic epithelium from hamartomatous polyposis syndrome polyps harbors hMSH3 defects, which may prime neoplastic transformation. Polyps from PTEN(+/-) patients lose PTEN expression, but loss is not a universal early feature of all hamartomatous polyposis syndrome. However, PTEN frameshifts can occur in hMSH3-deficient cells, suggesting that hMSH3 deficiency could drive hamartomatous polyposis syndrome tumorigenesis.
Authors: Huang, Sherry C SC; Lee, Jeffrey K JK; Smith, E Julieta EJ; Doctolero, Ryan T RT; Tajima, Akihiro A; Beck, Stayce E SE; Weidner, Noel N; Carethers, John M JM
Cancer. 2011 Feb 01;117(3):492-500. Epub 2010-09-15.
Comorbid cancer in Parkinson’s disease
The aim of this article was to evaluate cancer occurrence before and after diagnosis of Parkinson’s disease (PD). We investigated 692 patients newly diagnosed with PD and 761 age- and sex-matched control subjects identified during two periods (1994-1995 and 2000-2003) within Kaiser Permanente Medical Care Program of Northern California. Primary cancers were searched and dated, and all participants were followed up until the end of membership, death, or December 31, 2008. We used unconditional logistic regression to evaluate the PD-cancer association before the date of PD diagnosis or the index date and Cox proportional hazards regression to evaluate the PD-cancer association after the index date. Nearly 20% (140 of 692) of the PD patients and 25% (188 of 761) of the non-PD controls had ever had a cancer diagnosis. Before the index date, the prevalence of cancer was not significantly lower in patients with PD (8.1% PD vs. 9.2% controls; OR = 0.83; 95% CI 0.54-1.3). After the index date, the risk of developing a cancer did not differ between PD cases and controls (relative risk [RR] = 0.94; 95% CI 0.70-1.3). Among specific cancers, melanoma was more common among PD cases (before PD, OR = 1.5; 95% CI 0.40-5.2; after PD, RR = 1.6; 95% CI 0.71-3.6), but independent of dopaminergic therapy. Cancer occurrence is not significantly lower among patients with PD. The positive association between PD and subsequent melanoma merits further investigation, as it does not seem to be attributable to dopaminergic therapy, pigmentation, or confounding by smoking.
Authors: Lo RY; Tanner CM; Van Den Eeden SK; Albers KB; Leimpeter AD; Nelson LM
Mov Disord. 2010 Sep 15;25(12):1809-17.
Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the international BEACON consortium
BACKGROUND: Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose-response, and duration of cigarette smoking cessation. METHODS: We used primary data from 10 population-based case-control studies and two cohort studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided. RESULTS: The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose-response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (<10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and > or =10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar. CONCLUSIONS: Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.
Authors: Cook MB; Nyren O; Chow WH; et al.
J Natl Cancer Inst. 2010 Sep 8;102(17):1344-53. Epub 2010 Aug 17.
Quality of life among women recently diagnosed with invasive breast cancer: the Pathways Study
Few studies have assessed quality of life (QOL) of women diagnosed with breast cancer within the first few weeks of their initial diagnosis. We describe QOL among 950 women recently diagnosed with invasive breast cancer. Starting in January 2006, we invited women aged > or =21 years who were diagnosed with first primary invasive breast cancer within Kaiser Permanente Northern California (KPNC) to enroll in the Pathways Study, a prospective study of breast cancer survivorship. QOL was measured using the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), along with sociodemographic and social support information. Clinical characteristics were obtained from the KPNC cancer registry and electronic medical record. We used multivariable linear regression models to identify factors associated with QOL scores calculated from the FACT-B. The mean age +/- SD of the sample was 59.6 years (+/-11.9 years), and the mean time +/-SD from diagnosis until interview was 8.0 weeks (+/-3.2 weeks). Younger age at diagnosis was associated with lower scores in all QOL domains (P < 0.01), and later stage at diagnosis was associated with lower scores in all domains (P < 0.05) except for social well-being. Higher levels of social support were associated with higher QOL except for physical well-being (P < 0.05). These associations were stronger within 2 months of breast cancer diagnosis. Quality of life as influenced by a diagnosis of breast cancer is an important factor in cancer survivorship. Age, stage at diagnosis, and social support are key factors in this important variable.
Authors: Kwan ML; Ergas IJ; Somkin CP; Quesenberry CP Jr; Neugut AI; Hershman DL; Mandelblatt J; Pelayo MP; Timperi AW; Miles SQ; Kushi LH
Breast Cancer Res Treat. 2010 Sep;123(2):507-24. Epub 2010 Feb 6.
Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls
OBJECTIVES: The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years. METHODS: The method for pubertal maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The kappa statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity. RESULTS: The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage>or=2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage>or=2. The prime determinant of height velocity was pubertal status. CONCLUSIONS: In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.
Authors: Biro FM; Galvez MP; Greenspan LC; Succop PA; Vangeepuram N; Pinney SM; Teitelbaum S; Windham GC; Kushi LH; Wolff MS
Pediatrics. 2010 Sep;126(3):e583-90. Epub 2010 Aug 9.
Physicians’ approaches to recommending colorectal cancer screening: a qualitative study
Little is known about strategies that physicians use to encourage receipt of colorectal cancer screening (CRCS). This study conducted focus groups with physicians. Twenty-seven physicians participated in four focus groups. Physicians described four categories of approaches: (1) why screening is important, (2) providing test information, (3) motivational strategies, and (4) tailoring strategies. Participants reported tailoring based on their relationship with a patient, as well as to patient gender, education, and language. Tailoring to cultural background or ethnicity was not prominent. Most physicians reported a typical approach to CRCS and reported some tailoring based on gender, education, and language, but not on ethnicity.
Authors: Walsh JM; Karliner L; Burke N; Somkin CP; Pham LA; Pasick R
J Cancer Educ. 2010 Sep;25(3):385-90. Epub 2010 Mar 5.
Medical comorbidities predict mortality in women with a history of early stage breast cancer
This analysis was conducted to determine whether comorbid medical conditions predict additional breast cancer events and all-cause mortality in women with a history of early stage breast cancer. Women (n = 2,542) participating in a randomized diet trial completed a self-administered questionnaire regarding whether they were currently being treated for a wide variety of diseases (cardiovascular, diabetes, gallbladder, gastrointestinal, arthritis, and osteoporosis) and conditions (high blood pressure, elevated cholesterol level). Height and weight were measured at baseline. Participants were followed for a median of 7.3 years (range 0.8-15.0). Cox regression analysis was performed to assess whether comorbidities predicted disease-free and overall survival; hazard ratio (HR) was the measure of association. Overall, there were 406 additional breast cancer events and 242 deaths. Participants with diabetes had over twofold the risk of additional breast cancer events (HR 2.1, 95% CI: 1.3, 3.4) and mortality (HR 2.5, 95% CI: 1.4, 4.4). The presence of multiple comorbidities did not statistically significantly predict additional breast cancer events. However, compared to no comorbidities, participants with 3 or more comorbidities had a HR of 2.1, 95% CI: 1.3, 3.3 for mortality. In conclusion, type 2 diabetes is associated with poor breast cancer prognosis. Given that 85% of deaths were caused by breast cancer, these findings suggest that multiple comorbidities may reduce the likelihood of surviving additional breast cancer events.
Authors: Patterson RE; Flatt SW; Saquib N; Rock CL; Caan BJ; Parker BA; Laughlin GA; Erickson K; Thomson CA; Bardwell WA; Hajek RA; Pierce JP
Breast Cancer Res Treat. 2010 Aug;122(3):859-65. Epub 2010 Jan 14.
Diet, physical activity, and body size associations with rectal tumor mutations and epigenetic changes
Diet and lifestyle factors have been inconsistently associated with rectal tumors. It is possible that evaluation of specific tumor markers with these factors may help clarify these associations. In this study, we examine energy contributing nutrients, dietary fiber, BMI (kg/m2), and long-term physical activity with TP53 mutations, KRAS2 mutations, and CpG Island Methylator Phenotype (CIMP) in 750 population-based cases of rectal cancer compared to healthy controls. We observed that high levels of physical activity reduced the risk of having TP53 and KRAS2 rectal tumor mutations. Dairy products rich in fat were associated with an increased risk of CIMP+ tumors (OR 1.88 95% CI 0.92, 3.84), while low-fat dairy products reduced risk of CIMP+ tumors (OR 0.56 95% CI 0.29, 1.09). Omega-3 fatty acids were associated with a twofold increased risk of a CIMP+ tumor. High levels of vegetable intake reduced risk of both TP53 mutations (OR 0.73 95% CI 0.54, 1.00; p trend 0.02) and KRAS2 mutations (OR 0.60 95% CI 0.40, 0.89; p trend <0.01). High intake of whole grains reduced the likelihood of a TP53 mutation (OR 0.74 95% CI 0.56, 0.99), while high intake of refined grains increased the likelihood of a TP53 mutation (OR 1.41 95% CI 1.02, 1.96). Dietary fiber also was associated with reduced risk of TP53 and KRAS2 rectal tumor mutations. Overall, a prudent dietary pattern significantly reduced the likelihood of a KRAS2 tumor mutation (OR 0.68 95% CI 0.47, 0.98; p linear trend 0.03). These data suggest that diet and lifestyle factors are associated with specific types of rectal tumor mutations and epigenetic changes. Findings need confirmation in other studies.
Authors: Slattery ML; Curtin K; Wolff RK; Herrick JS; Caan BJ; Samowitz W
Cancer Causes Control. 2010 Aug;21(8):1237-45. Epub 2010 Apr 10.
Alcohol consumption and rectal tumor mutations and epigenetic changes
PURPOSE: An association between alcohol and rectal cancer has been reported in the epidemiological literature. In this study we further explore the association by examining specific tumor markers with alcohol consumption as well as types of alcoholic beverages consumed. METHODS: We assessed alcohol consumption with CpG Island Methylator Phenotype, TP53, and KRAS2 mutations in incident rectal cancer cases and compared them with population-based controls. We evaluated type, long-term, and recent alcohol consumption. RESULTS: We observed a trend toward increasing risk of CpG Island Methylator Phenotype positive tumors and long-term alcohol consumption. In contrast, after adjusting for total alcohol intake, recent high beer consumption significantly increased the odds of having a TP53 mutation compared with those who did not drink beer (odds ratio, 1.97; 95% CI 1.24, 3.12). We observed a nonstatistically significant reduced risk of a TP53 mutation among those who drank wine (in particular, red wine) vs nonconsumers of wine. The association between TP53 mutations and recent beer consumption was strongest for transversion mutations. CONCLUSIONS: These data suggest that both alcohol and specific constituents of alcoholic beverages contribute to rectal cancer risk among unique disease pathways.
Authors: Slattery ML; Wolff RK; Herrick JS; Curtin K; Caan BJ; Samowitz W
Dis Colon Rectum. 2010 Aug;53(8):1182-9.
Calcium/vitamin D supplementation and coronary artery calcification in the Women’s Health Initiative
OBJECTIVE: Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D (calcium/D) supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared CAC scores after trial completion between women randomized to calcium/vitamin D supplementation and women randomized to placebo. METHODS: In an ancillary substudy of women randomized to calcium carbonate (1,000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) or placebo, nested within the Women’s Health Initiative trial of estrogen among women who underwent hysterectomy, we measured CAC with cardiac CT in 754 women aged 50 to 59 years at randomization. Imaging for CAC was performed at 28 of 40 centers after a mean of 7 years of treatment, and scans were read centrally. CAC scores were measured by a central reading center with masking to randomization assignments. RESULTS: Posttrial CAC measurements were similar in women randomized to calcium/D supplementation and those receiving placebo. The mean CAC score was 91.6 for women receiving calcium/D and 100.5 for women receiving placebo (rank test P value = 0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, > or =10, and > or =100) for calcium/D versus placebo were 0.92 (95% CI, 0.64-1.34), 1.29 (0.88-1.87), and 0.90 (0.56-1.44), respectively. Corresponding odds ratios among women with a 50% or higher adherence to study pills and for higher levels of CAC (>300) were similar. CONCLUSIONS: Treatment with moderate doses of calcium plus vitamin D3 did not seem to alter coronary artery calcified plaque burden among postmenopausal women. Whether higher or lower doses would affect this outcome remains uncertain.
Authors: Manson JE; Carr JJ; Women's Health Initiative and Women's Health Initiative-Coronary Artery Calcium Study Investigators; et al.
Menopause. 2010 Jul;17(4):683-91.
Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls
BACKGROUND: Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins. OBJECTIVES: We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6-8 years of age at enrollment (2004-2007). METHODS: We measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age-specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones. RESULTS: Breast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with pubic hair development [adjusted PR, 0.94 (95% CI, 0.88-1.00), fifth vs. first quintile]. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed for low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23-1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone. CONCLUSIONS: Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.
Authors: Wolff MS; Erdmann C; Breast Cancer and Environment Research Centers; et al.
Environ Health Perspect. 2010 Jul;118(7):1039-46. Epub 2010 Mar 22.
Autoimmune diseases prior to the diagnosis of multiple sclerosis: a population-based case-control study
The objective of this study was to determine whether patients with multiple sclerosis (MS) are more likely to have other autoimmune disorders particularly prior to the diagnosis of MS. We conducted a population-based case-control study of patients enrolled in the Northern California Kaiser Permanente Medical Care Program. Electronic clinical records through 2005 were used to ascertain incident and prevalent MS cases and identify the presence and timing of 44 other diagnoses. Controls were matched 5:1 for gender, age, and Kaiser membership characteristics. We identified 5296 MS cases (including 924 diagnosed between 2001 and 2004) and 26,478 matched controls. Prior to MS diagnosis, cases were more likely than controls to have uveitis (OR = 3.2, 95%; CI 1.7-5.7), inflammatory bowel disease (IBD, OR = 1.7; 95%CI 1.2-2.5), and Bell’s palsy (OR = 3.2; 95%CI 1.2-8.3). Cases were also more likely to develop Guillain- Barre syndrome (GBS, OR = 5.0; 95%CI 1.6-15.4) and bullous pemphigoid (OR = 6.7; 95%CI 1.5-29.9). Cases were not more likely than controls to have or to develop rheumatoid arthritis, lupus or thyroiditis. MS may share environmental triggers, genetic susceptibilities and/or alterations in immune homeostasis with IBD and uveitis, but not with other autoimmune disorders.
Authors: Langer-Gould A; Albers KB; Van Den Eeden SK; Nelson LM
Mult Scler. 2010 Jul;16(7):855-61. Epub 2010 May 12.
Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake
Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics. Using primary breast tumors from 162 (AJCC stage I-IV) women from the Kaiser Division of Research Pathways Study and the Illumina GoldenGate methylation bead-array platform, we measured 1,413 autosomal CpG loci associated with 773 cancer-related genes and validated select CpG loci with Sequenom EpiTYPER. Tumor grade, size, estrogen and progesterone receptor status, and triple negative status were significantly (Q-values <0.05) associated with altered methylation of 209, 74, 183, 69, and 130 loci, respectively. Unsupervised clustering, using a recursively partitioned mixture model (RPMM), of all autosomal CpG loci revealed eight distinct methylation classes. Methylation class membership was significantly associated with patient race (P<0.02) and tumor size (P<0.001) in univariate tests. Using multinomial logistic regression to adjust for potential confounders, patient age and tumor size, as well as known disease risk factors of alcohol intake and total dietary folate, were all significantly (P<0.0001) associated with methylation class membership. Breast cancer prognostic characteristics and risk-related exposures appear to be associated with gene-specific tumor methylation, as well as overall methylation patterns.
Authors: Christensen BC; Kushi LH; Kwan ML; Wiencke JK; et al.
PLoS Genet. 2010 Jul 29;6(7):e1001043.
Reproductive and sex hormonal factors and oesophageal and gastric junction adenocarcinoma: a pooled analysis
BACKGROUND: The rapidly rising incidence and the striking male predominance are as yet unexplained features of oesophageal and gastric junction adenocarcinoma. Few and underpowered studies have examined the impact of female reproductive factors on risk of these adenocarcinomas in women. We therefore pooled data on women from four population-based case-control studies to examine the association of female reproductive and sex hormonal factors with oesophageal and gastric junction adenocarcinoma. METHODS: Data on women from case-control studies conducted in Ireland, the United Kingdom (UK), Australia and United States of America (USA) were pooled. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a range of reproductive factors, adjusted for age, study and major risk factors for oesophageal and gastric junction adenocarcinoma. RESULTS: We included 218 cases and 862 controls. Among parous women, a reduced risk of oesophageal and gastric junction adenocarcinoma was found after breastfeeding (OR=0.58, 95% CI=0.37-0.92) and the risk decreased with increased duration of breastfeeding (>12 months OR=0.42, 95% CI=0.23-0.77). The endogenous reproductive factors such as parity, menstruation, history of pregnancy and the exogenous factors such as use of oral contraceptives and of hormone replacement therapy were not statistically significantly associated with oesophageal and gastric junction adenocarcinoma. CONCLUSION: Our findings suggest that breastfeeding is associated with a decreased risk of oesophageal and gastric junction adenocarcinoma. The potential mechanism of this association warrants further investigation.
Authors: Cronin-Fenton DP; Murray LJ; Whiteman DC; Cardwell C; Webb PM; Jordan SJ; Corley DA; Sharp L; Lagergren J; Barrett's Esophagus ACBI
Eur J Cancer. 2010 Jul;46(11):2067-76. Epub 2010 Apr 22.
Unanticipated and underappreciated outcomes during management of local stage prostate cancer: a prospective survey
PURPOSE: Due to the complexity of factors that must be considered when choosing a therapy for prostate cancer, we hypothesized that many men will find that certain factors such as side effects gain or lose importance after therapy relative to their expectations before therapy. MATERIALS AND METHODS: We conducted a prospective survey of men deciding on a therapy for local stage prostate cancer in 3 geographic regions. Men were asked to rate the importance of 11 personal factors before starting therapy and again 6 months after therapy. RESULTS: Among 448 eligible men completing the most common treatment options, overall satisfaction with treatment choice was high across all therapies. While most men changed rankings of importance in at least 1 of the 11 factors, the majority of pre-post evaluations were highly consistent. In adjusted analyses the 2 factors that emerged as significantly underappreciated for all major prostate cancer treatments were 1) the impact of treatment on usual daily activities, and 2) the recommendations of friends and relatives who were affected with prostate cancer. CONCLUSIONS: Initial patient expectations of the importance of the majority of factors related to prostate cancer treatment are generally accurate. Better counseling may improve the accuracy of patient expectations of the personal burden of treatment, and their evaluation of the advice of affected friends and relatives.
Authors: Ramsey SD; Zeliadt SB; Arora NK; Blough DK; Penson DF; Oakley-Girvan I; Hamilton AS; Van Den Eeden SK; Fedorenko CR; Potosky AL
J Urol. 2010 Jul;184(1):120-5. Epub 2010 May 15.
Diabetes and cancer: a consensus report
Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis; 2) risk factors common to both diabetes and cancer; 3) possible biologic links between diabetes and cancer risk; and 4) whether diabetes treatments influence the risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.
Authors: Giovannucci E; Harlan DM; Archer MC; Bergenstal RM; Gapstur SM; Habel LA; Pollak M; Regensteiner JG; Yee D
CA Cancer J Clin. 2010 Jul-Aug;60(4):207-21. Epub 2010 Jun 16.
Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients
BACKGROUND & AIMS: Drugs that inhibit gastric acid might increase the risk of hip fracture. However, little long-term exposure data exist and no large studies have been conducted in the United States. METHODS: We conducted a case-control study using data from an integrated health services organization. We evaluated 33,752 patients with incident diagnoses of hip/femur fractures (cases), 130,471 matched members without fractures (controls), prescription data for use of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) (up to 10 years’ cumulative duration), and confounders. RESULTS: Patients with hip fractures were more likely than controls to have previously received a > or =2-year supply of PPIs (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.21-1.39) or H2RAs (OR, 1.18; 95% CI, 1.08-1.29). The risk was reduced after discontinuation of medication (OR of 1.30 [95% CI, 1.21-1.41] for current PPI users vs OR of 1.09 [95% CI, 0.64-1.85] for patients who received their last prescription 2-2.9 years ago). Higher dosages (but not increasing cumulative durations) were associated with increased risk (eg, > or =1.5 pills/day: OR, 1.41 [95% CI, 1.21-1.64]; <0.74 pills/day: OR, 1.12 [95% CI, 0.94-1.33]). Excess fracture risk for PPI use was only present among persons with at least one other fracture risk factor. CONCLUSIONS: Use of drugs that inhibit gastric acid is associated with an increased risk of hip fracture; however, this association was only found among persons with at least one other risk factor for hip fracture. Acid inhibition might therefore be associated with fracture risk in persons already at risk for osteoporosis, although other confounding cannot be excluded.
Authors: Corley DA; Kubo A; Zhao W; Quesenberry C
Gastroenterology. 2010 Jul;139(1):93-101. Epub 2010 Mar 27.
Achalasia, alcohol-stasis, and acute necrotizing esophagitis: connecting the dots.
Acute necrotizing esophagitis (ANE) or “black esophagus” is defined as a circumferential dark pigmentation of the esophagus on endoscopy and mucosal necrosis on histology. Due to its rarity, the etiopathogenesis of this alarming finding is poorly understood. We report a case of ANE in an alcoholic with achalasia and discuss the pathophysiologic insights gained from this unusual presentation.
Authors: Lee, Jeffrey K JK; Bhargava, Valmik V; Mittal, Ravinder K RK; Ghosh, Pradipta P
Digestive diseases and sciences. 2011 Feb ;56(2):612-4. Epub 2010-06-16.
Pneumococcal vaccination and risk of acute myocardial infarction and stroke in men
CONTEXT: Multiple studies have shown that preventing influenza by vaccination reduces the risk of vascular events. However, the effect of pneumococcal polysaccharide vaccine on vascular events remains controversial. OBJECTIVE: To examine the association between pneumococcal vaccination and risk of acute myocardial infarction (MI) and stroke among men. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of Kaiser Permanente Northern and Southern California health plans with 84 170 participants aged 45 to 69 years from the California Men’s Health Study who were recruited between January 2002 and December 2003, and followed up until December 31, 2007. The cohort was similar to the population of health plan members and men who responded to a general health survey in California on important demographic and clinical characteristics. Demographic and detailed lifestyle characteristics were collected from surveys. Vaccination records were obtained from the Kaiser Immunization Tracking System. MAIN OUTCOME MEASURE: Incidence of acute MI and stroke during the follow-up period in men who had no history of such conditions. RESULTS: During follow-up, there were 1211 first MIs in 112,837 vaccinated person-years (10.73 per 1000 person-years) compared with 1494 first MI events in 246,170 unvaccinated person-years (6.07 per 1000 person-years). For stroke, there were 651 events in 122,821 vaccinated person-years (5.30 per 1000 person-years) compared with 483 events in 254,541 unvaccinated person-years (1.90 per 1000 person-years). With propensity score adjustment, we found no evidence for an association between pneumococcal vaccination and reduced risk of acute MI (adjusted hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.98-1.21) or stroke (adjusted HR, 1.14; 95% CI, 1.00-1.31). An inverse association was also not found in men of different age and risk groups. The results appeared to be consistent, because using more specific International Classification of Diseases, Ninth Revision codes for the outcome definition did not change the estimations. CONCLUSION: Among a cohort of men aged 45 years or older, receipt of pneumococcal vaccine was not associated with subsequent reduced risk of acute MI and stroke.
Authors: Tseng HF; Slezak JM; Quinn VP; Sy LS; Van Den Eeden SK; Jacobsen SJ
JAMA. 2010 May 5;303(17):1699-706.
Treatment of ductal carcinoma in situ among patients cared for in large integrated health plans
OBJECTIVE: To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts. STUDY DESIGN: Cross-sectional study nested within a cohort of women diagnosed as having DCIS between 1990 and 2001. METHODS: We reviewed medical records of 3000 non-Hispanic white (69%), black (10%), Hispanic (9%), and Asian or Pacific Islander (12%) women diagnosed as having DCIS between 1990 and 2001 and treated with breast-conserving therapy. chi(2) Test and multinomial logistic regression analysis were used to examine the association between race/ethnicity and use of adjuvant treatments after controlling for patient and clinical variables, including certain pathologic factors. RESULTS: We found no significant differences in DCIS adjuvant treatment among racial/ethnic groups in bivariate or multinomial analyses after adjusting for demographic characteristics, comorbidity, and clinical factors. Minority women were as likely to undergo adjuvant radiation therapy as non-Hispanic white women. However, women 70 years or older (odds ratio, 0.40; 95% confidence interval, 0.31-0.51) and women who lived in areas with low geocoded median family income (odds ratio, 0.65; 95% confidence interval, 0.48-0.89) were less likely to receive adjuvant radiation therapy. Tumor size and comedo histologic growth pattern were associated with increased likelihood of receiving radiation therapy. CONCLUSION: Use of adjuvant therapy by minority women in these managed care plans is similar to that by non-Hispanic white women, although use was less among older women and among women who lived in poorer neighborhoods.
Authors: Haque R; Achacoso NS; Fletcher SW; Nekhlyudov L; Collins LC; Schnitt SJ; Quesenberry CP Jr; Habel LA
Am J Manag Care. 2010 May;16(5):351-60.
Increased risk of high-grade prostate cancer among infertile men
BACKGROUND: It has been reported that fatherhood status may be a risk factor for prostate cancer. In the current study, the authors examined the subsequent occurrence of prostate cancer in a cohort of men evaluated for infertility to determine whether male infertility is a risk factor for prostate cancer. METHODS: A total of 22,562 men who were evaluated for infertility from 1967 to 1998 were identified from 15 California infertility centers and linked to the California Cancer Registry. The incidence of prostate cancer was compared with the incidence in an age-matched and geography-matched sample of men from the general population. The risk of prostate cancer in men with and those without male factor infertility was modeled using a Cox proportional hazards regression model. RESULTS: A total of 168 cases of prostate cancer that developed after infertility were identified. Men evaluated for infertility but not necessarily with male factors were not found to have an increased risk of cancer compared with the general population (standardized incidence ratio [SIR], 0.9; 95% confidence interval [95% CI], 0.8-1.1). This risk was found to be highest for men with male factor infertility who developed high-grade prostate cancer (SIR, 2.0; 95% CI, 1.2-3.0). On multivariate analyses, men with male factor infertility were found to be 2.6 times more likely to be diagnosed with high-grade prostate cancer (hazard ratio, 2.6; 95% CI, 1.4-4.8). CONCLUSIONS: Men with male factor infertility were found to have an increased risk of subsequently developing high-grade prostate cancer. Male infertility may be an early and identifiable risk factor for the development of clinically significant prostate cancer.
Authors: Walsh TJ; Schembri M; Turek PJ; Chan JM; Carroll PR; Smith JF; Eisenberg ML; Van Den Eeden SK; Croughan MS
Cancer. 2010 May 1;116(9):2140-7.
Physical activity and change in mammographic density: the Study of Women’s Health Across the Nation
One potential mechanism by which physical activity may protect against breast cancer is by decreasing mammographic density. Percent mammographic density, the proportion of dense breast tissue area to total breast area, declines with age and is a strong risk factor for breast cancer. The authors hypothesized that women who were more physically active would have a greater decline in percent mammographic density with age, compared with less physically active women. The authors tested this hypothesis using longitudinal data (1996-2004) from 722 participants in the Study of Women’s Health Across the Nation (SWAN), a multiethnic cohort of women who were pre- and early perimenopausal at baseline, with multivariable, repeated-measures linear regression analyses. During an average of 5.6 years, the mean annual decline in percent mammographic density was 1.1% (standard deviation = 0.1). A 1-unit increase in total physical activity score was associated with a weaker annual decline in percent mammographic density by 0.09% (standard error = 0.03; P = 0.01). Physical activity was inversely associated with the change in nondense breast area (P < 0.01) and not associated with the change in dense breast area (P = 0.17). Study results do not support the hypothesis that physical activity reduces breast cancer through a mechanism that includes reduced mammographic density.
Authors: Conroy SM; Butler LM; Harvey D; Gold EB; Sternfeld B; Oestreicher N; Greendale GA; Habel LA
Am J Epidemiol. 2010 May 1;171(9):960-8. Epub 2010 Mar 30.
Body burdens of brominated flame retardants and other persistent organo-halogenated compounds and their descriptors in US girls
BACKGROUND: Levels of brominated flame retardants are increasing in US populations, yet little data are available on body burdens of these and other persistent hormonally active agents (HAAs) in school-aged children. Exposures to such chemicals may affect a number of health outcomes related to development and reproductive function. OBJECTIVE: Determine the distribution of biomarkers of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organo-chlorinated pesticides (OCPs), such as DDT/DDE, in children, and their variation by key descriptor variables. METHODS: Ethnically diverse cohorts of girls 6-8 y old at baseline are being followed for growth and pubertal development in a multi-site, longitudinal study. Nearly 600 serum samples from the California and Ohio sites were analyzed for lipids, 35 PCB congeners, 11 PBDE congeners, and 9 OCPs. The biomarker distributions were examined and geometric means compared for selected analytes across categories of age, race, site, body mass index (BMI), parental education, maternal age at delivery, and breast feeding in adjusted models. RESULTS: Six PBDE congeners were detected among greater than 70% of samples, with BDE-47 having the highest concentration (median 42.2, range 4.9-855 ng/g lipid). Girls in California had adjusted geometric mean (GM) PBDE levels significantly higher than girls in Ohio. Furthermore, Blacks had significantly higher adjusted GMs of all six PBDE congeners than Whites, and Hispanics had intermediate values. GMs tended to be lower among more obese girls, while other variables were not strongly associated. In contrast, GMs of the six PCB congeners most frequently detected were significantly lower among Blacks and Hispanics than Whites. PCBs and the three pesticides most frequently detected were also consistently lower among girls with high BMI, who were not breast-fed, whose mothers were younger, or whose care-givers (usually parents) were less educated. Girls in California had higher GMs than in Ohio for the pesticides and most PCB congeners, but the opposite for CB-99 and -118. CONCLUSIONS: Several of these potential HAAs were detected in nearly all of these young girls, some at relatively high levels, with variation by geographic location and other demographic factors that may reflect exposure pathways. The higher PBDE levels in California likely reflect differences in fire regulation and safety codes, with potential policy implications.
Authors: Windham GC; Pinney SM; Sjodin A; Lum R; Jones RS; Needham LL; Biro FM; Hiatt RA; Kushi LH
Environ Res. 2010 Apr;110(3):251-7. Epub 2010 Feb 2.
Association between nonsteroidal anti-inflammatory drug use and cutaneous squamous cell carcinoma
OBJECTIVE: To examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and cutaneous squamous cell carcinoma (SCC). DESIGN: Retrospective case-control study. SETTING: Kaiser Permanente Northern California (KPNC), a large population based-health maintenance organization. PATIENTS: Random sample of 415 KPNC members diagnosed as having a pathologically verified SCC in 2004 and 415 age-, sex-, and race-matched controls with no history of skin cancer. MAIN EXPOSURE MEASURE: Self-reported NSAID use in the 10 years prior to baseline. Use of NSAIDs was categorized based on type (any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression to estimate the association of SCC with regular use, dose, and duration of exposure to the different NSAID types. Information on pharmacy-dispensed NSAIDs was also examined to assess its association with SCC risk. Models were adjusted for all ascertained SCC risk factors (fully adjusted model) and only those variables associated with both SCC risk and NSAID use (parsimonious model). RESULTS: Fully adjusted analyses showed no statistically significant reduction in SCC risk with self-reported regular use of any NSAID (OR, 1.32; 95% CI, 0.92-1.89), aspirin (OR, 1.38; 95% CI, 0.96-1.97), ibuprofen (OR, 0.74; 95% CI, 0.46-1.19), or nonaspirin NSAIDs (OR, 0.84; 95% CI, 0.56-1.26). Analyses examining duration, dose, and variables combining duration and dose of NSAID exposure did not appreciably change results. An analysis using the parsimonious model showed similar results. The data on pharmacy-dispensed NSAIDs also showed no association with SCC risk. CONCLUSION: Neither self-reported nor pharmacy-dispensed NSAID exposure was associated with cutaneous SCC risk.
Authors: Asgari MM; Chren MM; Warton EM; Friedman GD; White E
Arch Dermatol. 2010 Apr;146(4):388-95. Epub 2010 Feb 15.
A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33
We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.
Authors: Petersen GM; Van Den Eeden SK; Chanock SJ; et al.
Nat Genet. 2010 Mar;42(3):224-8. Epub 2010 Jan 24.
Low to moderate alcohol intake is not associated with increased mortality after breast cancer
BACKGROUND: Both alcohol consumption and obesity have been linked with breast cancer morbidity and mortality. An inverse association between alcohol intake and obesity suggests possible confounding between these variables (and perhaps other factors) with breast cancer outcomes. METHODS: Alcohol intake (beer, wine, spirits, and total) was examined in 3,088 women previously diagnosed and treated for breast cancer within an intervention trial that targeted vegetables, fiber, and fat but not alcohol or weight loss. Factors associated with baseline alcohol intake were included in Cox proportional hazards models for recurrence and mortality. RESULTS: Alcohol intake was significantly associated with higher education and physical activity levels. Neither light alcohol intake nor obesity was significantly associated with breast cancer recurrence, but moderate alcohol intake >300 g/mo was protective against all-cause mortality (hazard ratio, 0.69; 95% confidence intervals, 0.49-0.97) in a proportional hazards model adjusted for obesity. Obese women were 61% more likely to be nondrinkers than drinkers, and 76% more likely to be light drinkers than moderate/heavy drinkers. In nonobese women, alcohol intake >10 g/mo was associated with lower risk of all-cause mortality (hazard ratio, 0.68; 95% confidence intervals, 0.51-0.91). CONCLUSION: Light alcohol intake, regardless of body weight, did not increase the risk of breast cancer recurrence or all-cause mortality in this cohort of middle-aged women previously diagnosed with breast cancer. Alcohol intake was associated with other favorable prognostic indicators, which may explain its apparent protective effect in nonobese women.
Authors: Flatt SW; Thomson CA; Gold EB; Natarajan L; Rock CL; Al-Delaimy WK; Patterson RE; Saquib N; Caan BJ; Pierce JP
Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):681-8. Epub 2010 Feb 16.
Migraine history and breast cancer risk among postmenopausal women
PURPOSE Both migraine and breast cancer are hormonally mediated. Two recent reports indicate that women with a migraine history may have a lower risk of postmenopausal breast cancer than those who never suffered migraines. This finding requires confirmation; in particular, an assessment of the influence of use of nonsteroidal anti-inflammatory drugs (NSAID) is needed, because many studies indicate that NSAID use also may confer a reduction in breast cancer risk. METHODS We assessed the relationship between self-reported history of migraine and incidence of postmenopausal breast cancer in 91,116 women enrolled on the Women’s Health Initiative Observational Study prospective cohort from 1993 to 1998 at ages 50 to 79 years. Through September 15, 2005, there were 4,006 eligible patients with breast cancer diagnosed. Results Women with a history of migraine had a lower risk of breast cancer (hazard ratio [HR], 0.89; 95% CI, 0.80 to 98) than women without a migraine history. This risk did not vary by recent NSAID use. The lower risk was somewhat more pronounced for invasive estrogen-receptor-positive and progesterone-receptor-positive tumors (HR, 0.83; 95% CI, 0.71 to 0.97), as no reduction in risk was observed for invasive ER-negative/PR-negative tumors (HR, 1.16; 95% CI, 0.86 to 1.57), and this difference in risk estimates was borderline statistically significant (P = .06). CONCLUSION This study supports the hypothesis that a history of migraine is associated with a lower risk of breast cancer and that this relationship is independent of recent NSAID use.
Authors: Li CI; Mathes RW; Bluhm EC; Caan B; Cavanagh MF; Chlebowski RT; Michael Y; O'Sullivan MJ; Stefanick ML; Prentice R
J Clin Oncol. 2010 Feb 20;28(6):1005-10. Epub 2010 Jan 25.
Increased risk of colon cancer associated with a genetic polymorphism of SMAD7
Genome-wide association studies (GWAS) have identified SMAD7 on 8q21 as being associated with colorectal cancer. We evaluated single nucleotide polymorphisms (SNP) in the SMAD7 gene, including rs4939827, rs12953717, and rs4464148, previously identified from GWAS in a large population-based case-control study of colon cancer. We observed that rs12953717 was associated with a statistically significant increased risk of colon cancer [odds ratio, 1.38; 95% confidence intervals (CI), 1.13-1.68; P linear trend < 0.01] for the TT genotype compared with the CC genotype, whereas the CC genotype of the rs4939827 SNP was inversely associated with colon cancer (0.77; 95% CI, 0.64-0.93) relative to the TT genotype. There were no significant differences in association for either of these polymorphisms when stratified by age, tumor site, sex, or family history. The odds ratios between SMAD7 and colon cancer among individuals reporting recent aspirin/nonsteroidal anti-inflammatory drug use was 0.60 (95% CI, 0.43-0.85) for the CC genotype of the rs4939827 polymorphism and 1.69 (95% CI, 1.20-2.38) for the TT genotype of the rs1295371 polymorphism. This result compares to odds ratios of 0.86 (95% CI, 0.68-1.09) for rs4939827 and 1.22 (95% CI, 0.96-1.56) among individuals who did not use aspirin/nonsteroidal anti-inflammatory drugs. An assessment of SMAD7 genotypes with tumor markers did not reveal any significant differences by KRAS2, TP53, CpG island methylator phenotype, or microsatellite instability status. No significant associations were observed for the rs4464148 SNP or other SNPs evaluated in the SMAD7. These results corroborate the findings of GWAS in colon cancer pointing to SMAD7 and reinforce interest in SNPs in this gene.
Authors: Slattery ML; Herrick J; Curtin K; Samowitz W; Wolff RK; Caan BJ; Duggan D; Potter JD; Peters U
Cancer Res. 2010 Feb 15;70(4):1479-85. Epub 2010 Feb 2.
Active, but not passive cigarette smoking was inversely associated with mammographic density
PURPOSE: The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism. METHODS: We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women’s Health Across the Nation (SWAN). RESULTS: We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked > or =20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked > or =20 cigarettes/day was associated with 23.8% lower density, compared to having smoked < or = 9 cigarettes/day (p<0.001). CONCLUSIONS: Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density.
Authors: Butler LM; Gold EB; Conroy SM; Crandall CJ; Greendale GA; Oestreicher N; Quesenberry CP Jr; Habel LA
Cancer Causes Control. 2010 Feb;21(2):301-11.
Reliability and validity of two self-administered questionnaires for screening restless legs syndrome in population-based studies
BACKGROUND: A reliable and valid questionnaire for screening restless legs syndrome (RLS) is essential for determining accurate estimates of disease frequency. In a 2002 NIH-sponsored workshop, experts suggested three mandatory questions for identifying RLS in epidemiologic studies. We evaluated the reliability and validity of this RLS-NIH questionnaire in a community-based sample and concurrently developed and evaluated the utility of an expanded screening questionnaire, the RLS-EXP. METHODS: The study was conducted at Kaiser Permanente of Northern California and the Stanford University Sleep Clinic. We evaluated test-retest reliability in a random sample of subjects with prior physician-assigned RLS (n=87), subjects with conditions frequently misclassified as RLS (n=31), and healthy subjects (n=9). Validity of both instruments was evaluated in a random sample of 32 subjects, and in-person examination by two RLS specialists was used as the gold standard. RESULTS: For the first three RLS-NIH questions, the kappa statistic for test-retest reliability ranged from 0.5 to 1.0, and sensitivity and specificity was 86% and 45%, respectively. For the subset of five questions on RLS-EXP that encompassed cardinal features for diagnosing RLS, kappas were 0.4-0.8, and sensitivity and specificity were 81% and 73%, respectively. CONCLUSIONS: Sensitivity of RLS-NIH is good; however, the specificity of the instrument is poor when examined in a sample that over-represents subjects with conditions that are commonly misclassified as RLS. Specificity can be improved by including separate questions on cardinal features, as used in the RLS-EXP, and by including a few questions that identify RLS mimics, thereby reducing false positives.
Authors: Popat RA; Van Den Eeden SK; Nelson LM; et al.
Sleep Med. 2010 Feb;11(2):154-60. Epub 2010 Jan 20.
Intentional weight loss and risk of lymphohematopoietic cancers
OBJECTIVES: We hypothesized that intentional weight loss may be associated with development of lymphohematopoietic cancers, based on observations of immune suppression following weight loss in short-term studies. METHODS: At the baseline of the Women’s Health Initiative Observational Study (1994-1998), participants reported information about intentional weight loss episodes in the past 20 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) among 81,219 women for associations between past intentional weight loss and risk of developing non-Hodgkin lymphoma (NHL), leukemia, and multiple myeloma during an average 9.9 years of follow-up. RESULTS: The risk of NHL was associated with having lost a large maximum amount of weight (> or =50 pounds, HR = 1.68, 95% CI 1.13-2.50). NHL risk also varied by the frequency of intentional weight loss; women had increased risk if they lost 50 pounds or more > or =3 times (HR = 1.97, 95% CI 0.93-4.16; p trend by frequency = 0.09) or 20-49 pounds > or =3 times (HR = 1.55, 95% CI 1.00-2.40; p trend = 0.05), but there was no risk associated with smaller amounts of weight loss (10-19 pounds > or =3 times, HR = 0.78, 95% CI 0.46-1.33). These associations persisted with adjustment for body mass index at different ages. We observed non-significant associations of similar magnitude for multiple myeloma, but past intentional weight loss episodes were not associated with leukemia. CONCLUSION: Further assessment of intentional weight loss as a possible risk factor for lymphomas may provide insight into the etiology of these cancers.
Authors: De Roos AJ; Ulrich CM; Ray RM; Mossavar-Rahmani Y; Rosenberg CA; Caan BJ; Thomson CA; McTiernan A; LaCroix AZ
Cancer Causes Control. 2010 Feb;21(2):223-36. Epub 2009 Oct 23.
Prostatitis, sexually transmitted diseases, and prostate cancer: the California Men’s Health Study
BACKGROUND: Prostatitis and sexually transmitted diseases (STDs) have been positively associated with prostate cancer in previous case-control studies. However, results from recent prospective studies have been inconclusive. METHODOGY/PRINCIPAL FINDINGS: We investigated the association between prostatitis, STDs, and prostate cancer among African American, Asian American, Latino, and White participants of the California Men’s Health Study. Our analysis included 68,675 men, who completed a detailed baseline questionnaire in 2002-2003. We identified 1,658 incident prostate cancer cases during the follow-up period to June 30, 2006. Cox proportional hazards models were used to estimate relative risks and 95% confidence intervals. Overall, men having a history of prostatitis had an increased risk of prostate cancer than men with no history (RR = 1.30; 95% CI: 1.10-1.54). Longer duration of prostatitis symptoms was also associated with an increased risk of prostate cancer (P trend = 0.003). In addition, among men screened for prostate cancer (1 or 2 PSA tests), a non-significant positive association was observed between prostatitis and prostate cancer (RR = 1.10; 95% CI: 0.75-1.63). STDs were not associated with overall prostate cancer risk. In racial/ethnic stratified analysis, Latinos reporting any STDs had an increased risk of disease than those with no STDs (RR = 1.43; 95% CI: 1.07-1.91). Interestingly, foreign-born Latinos displayed a larger risk associated with STDs (RR = 1.87; 95% CI: 1.16-3.02) than U.S. born Latinos (RR = 1.15; 95% CI: 0.76-3.02). CONCLUSION: In summary, results from this prospective study suggest that prostatitis and STDs may be involved in prostate cancer susceptibility. While we cannot rule out the possible influence of incidental detection, future studies are warranted to further investigate the role of infectious agents related to prostatitis and STDs in prostate cancer development.
Authors: Cheng I; Witte JS; Jacobsen SJ; Haque R; Quinn VP; Caan BJ; Van Den Eeden SK; Quesenberry CP Jr
PLoS One. 2010 Jan 15;5(1):e8736.
Red wine consumption not associated with reduced risk of colorectal cancer
Red wine contains polyphenol antioxidants that inhibit colorectal cancer (CRC) development in animal studies. We investigated the effect of red wine intake on risk of CRC in the California Men’s Health Study (CMHS). CMHS is a prospective, multiethnic cohort of middle-aged men who were members of the Kaiser Permanente (KP) California Health Plans and completed study questionnaires between 2002-2003. Incident CRC were identified from the health plan cancer registries through the end of 2007 (n = 287). To properly account for potential confounding by previous endoscopy screening, we restricted the primary analyses to CMHS men continuously enrolled in KP between 1998-2002 (n = 43,483 and CRC = 176). We used multivariable Cox regression to adjust for important confounders. We did not find an inverse association between moderate red wine intake and risk of CRC. The hazard ratio for consuming >/=1 drink/day (average = 2 drinks/day) was 1.16, 95% confidence intervals 0.56-2.40. There was no linear dose-response. The lack of clear association for red wine intake was consistently observed when we stratified the analyses by CRC stage at diagnosis and cancer site (colon or rectum). Moderate red wine consumption was not associated with reduced risk of colorectal cancer in this population of middle-aged men.
Authors: Chao C; Haque R; Caan BJ; Poon KY; Tseng HF; Quinn VP
Nutr Cancer. 2010;62(6):849-55.
Medical history, body size, and cigarette smoking in relation to fatal prostate cancer
OBJECTIVES: Prostate cancer has few known risk factors. As part of a population-based case-control study conducted in four health maintenance organizations, the authors examined the associations between fatal prostate cancer and several medical and behavioral characteristics. METHODS: Cases were 768 health plan members who died of prostate adenocarcinoma during the period 1997-2001. We randomly selected controls (929) from the health plan membership and matched them to cases on health plan, age, race, and pattern of health plan membership. We examined medical records to obtain information on potential risk factors during the 10 years before the date on which prostate cancer was first suspected; the same reference date was used for the matched controls. RESULTS: Anthropometric characteristics, as well as personal histories of benign prostatic hypertrophy, transurethral prostatectomy, cancer, diabetes, prostatitis, hypertension, and vasectomy were largely similar for cases and controls. Men who died from prostate cancer were more likely than controls to have been cigarette smokers according to the most recent smoking notation before the reference date (odds ratio 1.5, 95% confidence interval 1.1-2.0). CONCLUSIONS: The observed increase in risk associated with recent cigarette smoking is consistent with the findings of several other studies. However, in contrast with some reports, we observed no connection between fatal prostate cancer and some prior health conditions or measures of body size.
Authors: Weinmann S; Shapiro JA; Rybicki BA; Enger SM; Van Den Eeden SK; Richert-Boe KE; Weiss NS
Cancer Causes Control. 2010 Jan;21(1):117-25. Epub 2009 Oct 9.
Measuring the neighborhood environment: associations with young girls’ energy intake and expenditure in a cross-sectional study
ABSTRACT: BACKGROUND: Neighborhood environments affect children’s health outcomes. Observational methods used to assess neighborhoods can be categorized as indirect, intermediate, or direct. Direct methods, involving in-person audits of the neighborhoods conducted by trained observers, are recognized as an accurate representation of current neighborhood conditions. The authors investigated the associations of various neighborhood characteristics with young girls’ diet and physical activity. METHODS: This study is based on a subset of participants in the Cohort Study of Young Girls’ Nutrition, Environment and Transitions (CYGNET). In-person street audits were conducted within 215 girls’ residential neighborhoods using a modified St. Louis Audit Tool. From the street audit data, exploratory factor analysis revealed five neighborhood scales: ‘mixed residential and commercial,’ ‘food and retail,’ ‘recreation,’ ‘walkability,’ and ‘physical disorder.’ A Neighborhood Deprivation Index was also derived from census data. The authors investigated if the five neighborhood scales and the Neighborhood Deprivation Index were associated with quartiles of total energy intake and expenditure (metabolic equivalent (MET) hours/week) at baseline, and whether any of these associations were modified by race/ethnicity. RESULTS: After adjustment for demographic characteristics, there was an inverse association between prevalence of ‘food and retail’ destinations and total energy intake (for a one quartile increase, OR = 0.84, 95% CI 0.74, 0.96). Positive associations were also observed between the ‘recreation’ and ‘walkability’ scales with physical activity among Hispanic/Latina girls (for a one quartile increase in MET, OR = 1.94, 95% CI 1.31, 2.88 for recreation; OR = 1.71, 95% CI 1.11, 2.63 for walkability). Among African-American girls, there was an inverse association between ‘physical disorder’ and physical activity (OR = 0.31, 95% CI 0.12, 0.80). CONCLUSIONS: These results suggest that neighborhood food and retail availability may be inversely associated with young girls’ energy intakes in contrast to other studies’ findings that focused on adults. There is considerable variation in neighborhoods’ influences on young girls’ physical activity behaviors, particularly for young girls of different racial/ethnic backgrounds.
Authors: Leung CW; Gregorich SE; Laraia BA; Kushi LH; Yen IH
Int J Behav Nutr Phys Act. 2010 Jun 1;7:52.
Characterization of the association between 8q24 and colon cancer: gene-environment exploration and meta-analysis
BACKGROUND: Genome-wide association studies and subsequent replication studies have shown that single nucleotide polymorphisms (SNPs) in the chromosomal region 8q24 are associated with colorectal cancer susceptibility. METHODS: We examined 11 SNP markers in the 8q24 region between 128.47 and 128.54 Mb, using a total of 1,987 colon cases and 2,339 controls who self-reported as white from two independent, well-characterized study populations. Analysis was performed separately within each study, and combined using random effects meta-analysis. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) and to test for effect modification by known colon cancer risk factors. We also performed a meta-analysis combining our results with previous studies. RESULTS: We observed evidence of association for four SNPs in low to high linkage disequilibrium (r2 ranging from 0.18 to 0.93) localized in a 16.2 kb region defined by rs10505477 and rs1056368. The combined results for our two studies of colon cancer showed an OR of 1.10 (95% CI: 1.01-1.20, Ptrend = 0.023), and a meta-analysis of our results with previously reported studies of colon and colorectal cancer strongly support the association for this SNP (combined OR for rs6983267 = 1.21, 95% CI: 1.18-1.24, p = 5.5 x 10-44). We did not observe any notable evidence of effect modification by known colon cancer risk factors, and risk did not differ significantly by tumor site or stage. CONCLUSIONS: Our study confirms the association between polymorphisms on chromosome 8q24 and colon cancer risk and suggests that the susceptibility locus in region 8q24 is not strongly modified by various lifestyle, environmental, and demographic risk factors for colon cancer.
Authors: Hutter CM; Caan BJ; Peters U; et al.
BMC Cancer. 2010 Dec 4;10:670.
Calcium, vitamin D, VDR genotypes, and epigenetic and genetic changes in rectal tumors
Calcium, vitamin D, exposure to sunshine, and vitamin D receptor (VDR) genotypes have been associated rectal cancer. We used data from 750 rectal tumors and 1,205 population-based controls examine associations with TP53, KRAS2, and CpG Island methylator phenotype (CIMP) markers. Rectal tumors were associated with high levels of calcium overall and with TP53 tumor mutations specifically (OR = 0.6, 95% CI = 0.42-0.84). High levels of sunshine exposure had a borderline protective effect for TP53 tumor mutations (OR = 0.78, 95% CI = 0.59-1.03). A mutation at codon 248 was significantly associated with dietary calcium intake (OR = 0.26, 95% CI = 0.09-0.77); having the Ff/ff genotypes of the FOK1 VDR polymorphism significantly increased the odds of a mutation at codon 245 (OR = 4.74, 95% CI = 1.05-21.39); high levels of dietary vitamin D (OR = 3.42, 95% CI = 1.15-10.17) and the Ff/ff genotypes of FOK1 (OR = 3.34, 95% CI = 1.11-10.02) and the GA/AA genotypes of the CDX2 VDR polymorphism (OR = 2.85, 95% CI = 1.23-6.58) increased the odds of a TP53 mutation at codon 273. These data support an association between calcium and rectal tumors overall as well as specifically with TP53 mutations. However, given the number of comparisons, findings need to be confirmed in other studies.
Authors: Slattery ML; Wolff RK; Herrick JS; Caan BJ; Samowitz W
Nutr Cancer. 2010;62(4):436-42.
Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma
BACKGROUND: Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis. METHODS: Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV) and conducted for all (including proxy) subjects and for a subset of self-reported subjects. RESULTS: Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n=748) to self-reported cases only (n=450). For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg) intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg), for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases; high intake of vitamin C and genistein and the highest level of the antioxidant index were associated with poorer survival for all cases. CONCLUSIONS: The associations observed in our study suggest that the influence of some antioxidants on survival following a diagnosis of malignant glioma are inconsistent and vary by histology group. Further research in a large sample of glioma patients is needed to confirm/refute our results.
Authors: DeLorenze GN; McCoy L; Tsai AL; Quesenberry CP Jr; Rice T; Il'yasova D; Wrensch M
BMC Cancer. 2010 May 19;10:215.
Identification of patients with nonmelanoma skin cancer using health maintenance organization claims data
Cancer registries usually exclude nonmelanoma skin cancers (NMSC), despite the large population affected. Health maintenance organization (HMO) and health system administrative databases could be used as sampling frames for ascertaining NMSC. NMSC patients diagnosed between January 1, 1988, and December 31, 2007, from such defined US populations were identified by using 3 algorithms: NMSC International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, NMSC treatment Current Procedural Terminology (CPT) codes, or both codes. A subset of charts was reviewed to verify NMSC diagnosis, including all records from HMO-enrollee members in 2007. Positive predictive values for NMSC ascertainment were calculated. Analyses of data from 1988-2007 ascertained 11,742 NMSC patients. A random sample of 965 cases was selected for chart review, and NMSCs were validated in 47.0% of ICD-9-CM-identified patients, 73.4% of CPT-identified patients, and 94.9% identified with both codes. All charts from HMO-health plan enrollees in 2007 were reviewed (n = 1,116). Cases of NMSC were confirmed in 96.5% of ICD-9-CM-identified patients, 98.3% of CPT-identified patients, and 98.7% identified with both codes. HMO administrative data can be used to ascertain NMSC with high positive predictive values with either ICD-9-CM or CPT code, but both codes may be necessary among non-HMO patient populations.
Authors: Eide MJ; Krajenta R; Johnson D; Long JJ; Jacobsen G; Asgari MM; Lim HW; Johnson CC
Am J Epidemiol. 2010 Jan 1;171(1):123-8. Epub 2009 Dec 6.
Red wine consumption and risk of prostate cancer: the California men’s health study
Red wine contains polyphenol antioxidants that inhibit prostate cancer development in animal studies. We investigated the effect of red wine intake on the risk of prostate cancer using data prospectively collected in the California Men’s Health Study (CMHS). CMHS is a multiethnic cohort of 84,170 men aged 45-69 years who were members of the Kaiser Permanente Southern and Northern California Health Plans. Information on demographic and lifestyle factors was collected using mailed questionnaires between 2002 and 2003. We used Cox models to estimate the effect of red wine on prostate cancer risk, adjusting for potential confounders. A total of 1,340 incident prostate cancer cases identified from Surveillance, Epidemiology and End Result-affiliated cancer registries were included in the analyses. We did not find a clear association between red wine intake and risk of prostate cancer. Hazard ratio (HR) estimates for consuming <1 drink/week, > or =1 drink/week but <1 drink/day and > or =1 drink/day were 0.89, 95% confidence interval (0.74-1.07), 0.99 (0.83-1.17) and 0.88 (0.70-1.12), respectively. Further, we observed no linear dose response. The lack of association for red wine intake was consistently observed when we restricted the analyses to those with and without a history of PSA screening. In addition, we also did not observe any association with prostate cancer for beer, white wine, liquor or combined alcoholic beverage intake (HR for combined alcoholic beverage intake of > or =5 drinks/day = 1.16 (0.83-1.63). Neither red wine nor total alcohol consumption were associated with prostate cancer risk in this population of moderate drinkers.
Authors: Chao C; Haque R; Van Den Eeden SK; Caan BJ; Poon KY; Quinn VP
Int J Cancer. 2010 Jan 1;126(1):171-9.
Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer
BACKGROUND: The Women’s Health Initiative dietary modification (DM) trial provided suggestive evidence of a benefit of a low-fat dietary pattern on breast cancer risk, with stronger evidence among women whose baseline diet was high in fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to breast cancer risk and could influence intervention effects. METHODS: All 48,835 trial participants were postmenopausal and ages 50 to 79 years at enrollment (1993-1998). We interrogated eight SNPs in intron 2 of the FGFR2 gene for 1,676 women who developed breast cancer during trial follow-up (1993-2005). Case-only analyses were used to estimate odds ratios for the DM intervention in relation to SNP genotype. RESULTS: Odds ratios for the DM intervention did not vary significantly with the genotype for any of the eight FGFR2 SNPs (P > or = 0.18). However, odds ratios varied (P < 0.05) with the genotype of six of these SNPs, among women having baseline percent of energy from fat in the upper quartile (> or =36.8%). This variation is most evident for SNP rs3750817, with odds ratios for the DM intervention at 0, 1, and 2 minor SNP alleles of 1.06 [95% confidence intervals (95% CI), 0.80-1.41], 0.53 (95% CI, 0.38-0.74), and 0.62 (95% CI, 0.33-1.15). The nominal significance level for this interaction is P = 0.005, and P = 0.03 following multiple testing adjustment, with most evidence deriving from hormone receptor-positive tumors. CONCLUSION: Invasive breast cancer odds ratios for a low-fat dietary pattern, among women whose usual diets are high in fat, seem to vary with SNP rs3750817 in the FGFR2 gene.
Authors: Prentice RL; Huang Y; Hinds DA; Peters U; Cox DR; Beilharz E; Chlebowski RT; Rossouw JE; Caan B; Ballinger DG
Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):74-9.
Citalopram provides little or no benefit in nondepressed patients with irritable bowel syndrome
BACKGROUND & AIMS: Data on the benefit of selective serotonin reuptake inhibitors (SSRIs) in irritable bowel syndrome (IBS) are conflicting. The longitudinal relationship between clinical symptoms and sensitivity to barostat-mediated rectal distension in IBS remains unclear. We assessed the benefit of citalopram and explored the relationships between symptoms, quality of life (QOL), and rectal sensitivity to barostat distension in non-depressed IBS patients. METHODS: Patients from primary, secondary, and tertiary care settings were randomly assigned to receive citalopram (20 mg/day for 4 weeks, then 40 mg/day for 4 weeks) or placebo in a study with double-masking and concealed allocation. Symptoms were assessed weekly, and IBS-QOL and rectal sensation by barostat were assessed at the beginning and end of the study. RESULTS: Patients receiving citalopram did not achieve a higher rate of adequate relief of IBS symptoms than patients receiving placebo (12/27 [44%] vs 15/27 [56%]; P = .59), regardless of IBS subtype. The odds ratio for weekly response with citalopram vs placebo was 0.80 (95% confidence interval, 0.61-1.04). Improvements in specific symptom and IBS-QOL scores were not superior for citalopram. Changes in IBS-QOL score and pressure eliciting pain showed a modest correlation (r = 0.33; 95% confidence interval, 0.03-0.57), but changes in symptoms and IBS-QOL scores or rectal sensitivity were not correlated substantially. CONCLUSIONS: Citalopram was not superior to placebo in treating non-depressed IBS patients. Changes in symptoms were not substantially correlated with changes in rectal sensation assessed by barostat. Any benefit of citalopram in non-depressed IBS patients is likely to be modest at best.
Authors: Ladabaum U; Sharabidze A; Levin TR; Zhao WK; Chung E; Bacchetti P; Jin C; Grimes B; Pepin CJ
Clin Gastroenterol Hepatol. 2010 Jan;8(1):42-48.e1. Epub 2009 Sep 16.
Activin signaling in microsatellite stable colon cancers is disrupted by a combination of genetic and epigenetic mechanisms.
BACKGROUND: Activin receptor 2 (ACVR2) is commonly mutated in microsatellite unstable (MSI) colon cancers, leading to protein loss, signaling disruption, and larger tumors. Here, we examined activin signaling disruption in microsatellite stable (MSS) colon cancers.METHODS: Fifty-one population-based MSS colon cancers were assessed for ACVR1, ACVR2 and pSMAD2 protein. Consensus mutation-prone portions of ACVR2 were sequenced in primary cancers and all exons in colon cancer cell lines. Loss of heterozygosity (LOH) was evaluated for ACVR2 and ACVR1, and ACVR2 promoter methylation by methylation-specific PCR and bisulfite sequencing and chromosomal instability (CIN) phenotype via fluorescent LOH analysis of 3 duplicate markers. ACVR2 promoter methylation and ACVR2 expression were assessed in colon cancer cell lines via qPCR and IP-Western blots. Re-expression of ACVR2 after demethylation with 5-aza-2′-deoxycytidine (5-Aza) was determined. An additional 26 MSS colon cancers were assessed for ACVR2 loss and its mechanism, and ACVR2 loss in all tested cancers correlated with clinicopathological criteria.RESULTS: Of 51 MSS colon tumors, 7 (14%) lost ACVR2, 2 (4%) ACVR1, and 5 (10%) pSMAD2 expression. No somatic ACVR2 mutations were detected. Loss of ACVR2 expression was associated with LOH at ACVR2 (pCONCLUSIONS: Only a small percentage of MSS colon cancers lose expression of activin signaling members. ACVR2 loss occurs through LOH and ACVR2 promoter hypermethylation, revealing distinct mechanisms for ACVR2 inactivation in both MSI and MSS subtypes of colon cancer.
Authors: Jung, Barbara B; Gomez, Jessica J; Chau, Eddy E; Cabral, Jennifer J; Lee, Jeffrey K JK; Anselm, Aimee A; Slowik, Przemyslaw P; Ream-Robinson, Deena D; Messer, Karen K; Sporn, Judith J; Shin, Sung K SK; Boland, C Richard CR; Goel, Ajay A; Carethers, John M JM
PloS one. 2009 Dec 14;4(12):e8308. Epub 2009-12-14.
Relationship between clinical and pathologic features of ductal carcinoma in situ and patient age: an analysis of 657 patients
Prior studies have shown that young patient age at diagnosis is associated with an increased risk of local recurrence among women with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy. Whether this can be explained by differences in clinical or pathologic features of DCIS according to age is an unresolved issue. We compared clinical and pathologic features of DCIS among 657 women in 4 age groups: <45 years (n=111), 45 to 54 years (n=191), 55 to 64 years (n=160), and 65+ years (n=195). DCIS presented as a mammographic abnormality less often in younger than in older women (68%, 82%, 81%, and 86% for women <45, 45 to 54, 55 to 64, and 65+ y, respectively; P=0.003). Among the pathologic features analyzed, DCIS extent as determined by the number of low power fields was greater in younger than in older women (mean number of low power fields were 18.6, 14.2, 10.8, and 11.3 in women <45, 45 to 54, 55 to 64 and 65+ y; P<0.001). In addition, cancerization of lobules was present more often in younger than in older women (77%, 73%, 66%, and 50% for women <45, 45 to 54, 55 to 64 and 65+ y, respectively; P<0.0001). Of note, we found no statistically significant relationship between age and DCIS architectural pattern, nuclear grade, comedo necrosis or expression of estrogen receptor, progesterone receptor or human epidermal growth factor receptor 2. We conclude that DCIS in younger women is more often symptomatic, is more extensive, and more often shows cancerization of lobules than DCIS in older women. Whether these features contribute to the higher local recurrence risk in young women with DCIS treated with the breast-conserving therapy requires further study.
Authors: Collins LC; Quesenberry CP Jr; Habel LA; et al.
Am J Surg Pathol. 2009 Dec;33(12):1802-8.
Assessing tumor mutations to gain insight into base excision repair sequence polymorphisms and smoking in colon cancer
DNA repair enzymes function in major pathways to reverse DNA damage, including base excision repair (BER). Missense polymorphisms in BER repair genes may contribute to differences in DNA repair capacity, specific mutations, and susceptibility to cancer in the presence of exposure to carcinogens such as cigarette smoking. In a study of 1,604 incident colon cancer cases and 1,969 matched population-based controls genotyped for BER variants OGG1 (S326C) and XRCC1 (R194W, R280H, and R399Q), we found no associations with colon cancer overall. However, a 2-fold increased risk of BRAF V600E tumor mutation was observed in current and former cigarette smokers homozygous for the OGG1 polymorphism (odds ratio, 2.2; 95% confidence interval, 1.02-4.9, recessive model); similar associations were not observed for microsatellite instability, CpG island methylator phenotype, KRAS2 mutations, or TP53 mutations. The XRCC1 R194W polymorphism was associated with a modest increased risk of TP53 tumor mutations in those who regularly smoked cigarettes (odds ratio, 1.4; 95% confidence interval, 1.02-1.9). These findings point to the importance of studying tumor mutations when examining DNA repair polymorphisms and cigarette smoke exposure to identify potentially relevant associations with colorectal cancer.
Authors: Curtin K; Samowitz WS; Wolff RK; Ulrich CM; Caan BJ; Potter JD; Slattery ML
Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12):3384-8.
Chemoprevention in Barrett’s esophagus: are we there yet, are we there yet…?
Authors: Corley DA
Clin Gastroenterol Hepatol. 2009 Dec;7(12):1266-8. Epub 2009 Sep 16.
Repeated measures of serum glucose and insulin in relation to postmenopausal breast cancer
Experimental and epidemiological evidence suggests that circulating glucose and insulin may play a role in breast carcinogenesis. However, few cohort studies have examined breast cancer risk in association with glucose and insulin levels, and studies to date have had only baseline measurements of exposure. We conducted a longitudinal study of postmenopausal breast cancer risk using the 6% random sample of women in the Women’s Health Initiative clinical trials whose fasting blood samples, provided at baseline and at years 1, 3 and 6, were analyzed for glucose and insulin. In addition, a 1% sample of women in the observational study, who had glucose and insulin measured in fasting blood samples drawn at baseline and in year 3, were included in the analysis. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for the association of baseline and follow-up measurements of serum glucose and insulin with breast cancer risk. All statistical tests were 2-sided. Among 5,450 women with baseline serum glucose and insulin values, 190 incident cases of breast cancer were ascertained over a median of 8.0 years of follow-up. The highest tertile of baseline insulin, relative to the lowest, was associated with a 2-fold increase in risk in the total population (multivariable hazard ratio 2.22, 95% confidence interval 1.39-3.53) and with a 3-fold increase in risk in women who were not enrolled in the intervention arm of any clinical trial (multivariable hazard ratio 3.15, 95% confidence interval 1.61-6.17). Glucose levels showed no association with risk. Analysis of the repeated measurements supported the results of the baseline analysis. These data suggest that elevated serum insulin levels may be a risk factor for postmenopausal breast cancer.
Authors: Kabat GC; Kim M; Caan BJ; Chlebowski RT; Gunter MJ; Ho GY; Rodriguez BL; Shikany JM; Strickler HD; Vitolins MZ; Rohan TE
Int J Cancer. 2009 Dec 1;125(11):2704-10.
Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened
OBJECTIVE: To screen commonly used prescription drugs for possible carcinogenic effects. METHODS: In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12(1/2) years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least 2 years between drug dispensing and cancer. Positive associations entailed a relative risk of 1.50, with p
Authors: Friedman GD; Udaltsova N; Chan J; Quesenberry CP Jr; Habel LA
Cancer Causes Control. 2009 Dec;20(10):1821-35.
Correlates of prostate-specific antigen testing in a large multiethnic cohort
OBJECTIVE: To examine factors associated with prostate-specific antigen (PSA) testing in the multiethnic California Men’s Health Study. STUDY DESIGN: Cross-Sectional analysis nested within a cohort of male health plan members (n = 55,278). METHODS: We extracted laboratory serum PSA values during the study period from 1998 to 2002. Using selected demographic and healthcare factors, we estimated the proportion of men who underwent PSA testing at least once during the 5-year period. Odds ratios and corresponding 95% confidence intervals were estimated to assess the association between these factors and PSA screening use. RESULTS: African American men had substantially higher PSA screening prevalence than white men (82.6% vs 73.7%). Low PSA screening use was associated with Latino race/ethnicity, lower level of education, residency in the United States for 25 years or less, current smoking, and lack of PSA test discussion with healthcare providers. The strongest positive predictors of PSA testing were African American race/ethnicity (odds ratio, 1.66; 95% confidence interval, 1.50-1.83) and high concern about prostate cancer (odds ratio, 1.53; 95% confidence interval, 1.38-1.69). In contrast, when men did not discuss PSA testing with their physicians, they were 80% less likely to undergo screening. CONCLUSIONS: In this insured population for whom financial barriers are minimized, PSA screening varied by race/ethnicity and by other patient and clinical factors, possibly reflecting inconsistencies in prostate cancer screening guidelines. Despite these differences, healthcare providers have a key role in patients’ likelihood of undergoing PSA screening.
Authors: Haque R; Van Den Eeden SK; Jacobsen SJ; Caan B; Avila CC; Slezak J; Sternfeld B; Loo RK; Quinn VP
Am J Manag Care. 2009 Nov;15(11):793-9.
Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study
Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally mediated and non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. A cohort of 1,954 female breast cancer survivors, diagnosed during 1997-2000, was prospectively followed for 6.31 years and 282 breast cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed entry Cox proportional hazards models. Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women (P for trend: P = 0.08 for daidzein, P = 0.06 for glycetin) and among tamoxifen users (P = 0.10 for daidzein, P = 0.05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1,453 vs. <7.7 microg/day; HR, 0.48; 95% CI, 0.21-0.79, P = 0.008). Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer survivors.
Authors: Guha N; Kwan ML; Quesenberry CP Jr; Weltzien EK; Castillo AL; Caan BJ
Breast Cancer Res Treat. 2009 Nov;118(2):395-405. Epub 2009 Feb 17.
MSH6 G39E polymorphism and CpG island methylator phenotype in colon cancer
The MSH6 G39E germline polymorphism is not associated with an increased risk of either microsatellite stable or unstable sporadic colorectal cancer. Other than microsatellite instability, however, most genetic and epigenetic changes of tumors associated with this common variant have not been studied. The objective of our investigation was to evaluate associations between the MSH6 G39E (116G>A) polymorphism and CpG island methylator phenotype (CIMP) and BRAF V600E mutations in tumors from a sample of 1048 individuals with colon cancer and 1964 controls from Utah, Northern California, and Minnesota. The G39E polymorphism (rs1042821) was determined by the five prime nuclease assay. CIMP was determined by methylation-specific polymerase chain reaction (PCR) of CpG islands in MLH1, methylated in tumors (MINT)1, MINT2, MINT31, and CDKN2A. The BRAF V600E mutation was determined by sequencing exon 15. In microsatellite stable tumors, homozygous carriers of the G39E polymorphism had an increased risk of CIMP+ colon cancer (odds ratio (OR) 2.2, 95% confidence interval (CI) 1.1, 4.2) and BRAF V600E mutation (OR 3.1, 95% CI 1.01, 9.7) in a case-control comparison. This finding was not observed in unstable tumors; however, power may have been low to detect an association. Age at diagnosis, family history, and alcohol use did not interact with MSH6 G39E and CIMP. The MSH6 G39E germline polymorphism may be associated with CIMP+ colon cancer.
Authors: Curtin K; Samowitz WS; Wolff RK; Caan BJ; Ulrich CM; Potter JD; Slattery ML
Mol Carcinog. 2009 Nov;48(11):989-94.
Variation in the FGFR2 gene and the effects of postmenopausal hormone therapy on invasive breast cancer
BACKGROUND: Breast cancer concern is a major reason for the recent marked reduction in use of postmenopausal hormone therapy, although equally effective means of controlling menopausal symptoms are lacking. Single nucleotide polymorphisms (SNP) in the fibroblast growth factor receptor 2 (FGFR2) gene are substantially associated with postmenopausal breast cancer risk and could influence hormone therapy effects. PARTICIPANTS AND METHODS: We interrogated eight SNPs in intron 2 of the FGFR2 gene for 2,166 invasive breast cancer cases from the Women’s Health Initiative clinical trial and one-to-one matched controls to confirm an association with breast cancer risk. We used case-only analyses to examine the dependence of estrogen plus progestin and estrogen-alone odds ratios on SNP genotype. RESULTS: Seven FGFR2 SNPs, including six in a single linkage disequilibrium region, were found to associate strongly (P < 10(-7)) with breast cancer risk. SNP rs3750817 (minor allele T with frequency 0.39) had an estimated per-minor-allele odds ratio of 0.78, and was not in such strong linkage disequilibrium with the other SNPs. The genotype of this SNP related significantly (P < 0.05) to hormone therapy odds ratios. For estrogen plus progestin, the odds ratios (95% confidence intervals) at 0, 1, and 2 minor SNP alleles were 1.52 (1.14-2.02), 1.33 (1.01-1.75), and 0.69 (0.41-1.17), whereas the corresponding values for estrogen alone were 0.74 (0.51-1.09), 0.99 (0.68-1.44), and 0.34 (0.15-0.76). CONCLUSIONS: Postmenopausal women having TT genotype for SNP rs3750817 have a reduced breast cancer risk and seem to experience comparatively favorable effects of postmenopausal hormone therapy.
Authors: Prentice RL; Huang Y; Hinds DA; Peters U; Pettinger M; Cox DR; Beilharz E; Chlebowski RT; Rossouw JE; Caan B; Ballinger DG
Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):3079-85. Epub 2009 Oct 27.
Epidemiologic evaluation of pharmaceuticals with limited evidence of carcinogenicity
Thorough review by the International Agency for Research on Cancer (IARC) has resulted in classifying many substances, including pharmaceuticals, as probably or possibly carcinogenic to humans, based on experiments on animals or limited data on humans. We evaluated 9 such pharmaceuticals for evidence of carcinogenicity in patients receiving them in a large medical care program with automated pharmacy records and a cancer registry. Nested case-control analyses were performed in a cohort of 6.5 million subscribers with up to 12 years of follow-up, focusing on cancer sites suggested by previous evidence and other sites with odds ratio of at least 1.50, p < 0.01 and some evidence of dose-response. Unmeasured confounding was estimated in sensitivity analyses. We found some supportive evidence for carcinogenicity of griseofulvin, metronidazole and phenytoin and for the known carcinogen, cyclophosphamide, which was added for validation of our data and analyses. Findings for chloramphenicol, iron-dextran complex, phenoxybenzamine and phenobarbital were essentially non-contributory. Confounding by cigarette smoking and prior thyroid disease could account, respectively, for associations of oxazepam with lung cancer and propylthiouracil with thyroid cancer. Although not definitive, these findings should be considered in the evaluations of these pharmaceuticals.
Authors: Friedman GD; Jiang SF; Udaltsova N; Quesenberry CP Jr; Chan J; Habel LA
Int J Cancer. 2009 Nov 1;125(9):2173-8.
Clinical features in early Parkinson disease and survival
OBJECTIVE: To examine the association between demographic and clinical features in early Parkinson disease (PD) and length of survival in a multiethnic population. DESIGN: Clinical features within 2 years of diagnosis were determined for an inception cohort established during 1994-1995. Vital status was determined through December 31, 2005. Predictor variables included age at diagnosis, sex, race/ethnicity, as well as clinical subtype (modified tremor dominant, postural instability gait difficulty), symmetry, cognitive impairment, depression, dysphagia, and hallucinations. Cox proportional hazards regression analysis was used to identify factors associated with shorter survival. SETTING: Kaiser Permanente Medical Care Program, northern California. PATIENTS: Five hundred seventy-three men and women with newly diagnosed PD. RESULTS: Three hundred fifty-two participants in the PD cohort (61.4%) had died in the follow-up period. Older age at diagnosis (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.09-1.12), modified postural instability gait difficulty subtype (HR, 1.8; 95% CI, 1.3-2.7), symmetry of motor signs (HR, 2.0; 95% CI, 1.1-3.7), mild (HR, 1.7; 95% CI, 1.3-2.2) and severe (HR, 2.7; 95% CI, 1.9-3.9) cognitive impairment, dysphagia (HR, 1.4; 95% CI, 1.1-1.9), and hallucinations (HR, 2.1; 95% CI, 1.3-3.2) were associated with increased all-cause mortality, after adjusting for age, sex, and race/ethnicity. None of the other factors altered mortality risk. In an empirical predictive analysis, most previous significant predictors remained associated with shorter survival. CONCLUSIONS: Both motor and nonmotor features in early PD predict increased mortality risk, particularly postural instability gait difficulty, cognitive impairment, and hallucinations. These predictors may be useful in clinical practice and when designing clinical trials.
Authors: Lo RY; Tanner CM; Albers KB; Leimpeter AD; Fross RD; Bernstein AL; McGuire V; Quesenberry CP; Nelson LM; Van Den Eeden SK
Arch Neurol. 2009 Nov;66(11):1353-8.
Microsatellite instability and survival in rectal cancer
OBJECTIVE: High levels of microsatellite instability (MSI-H) have been associated in many studies with improved prognosis in colon cancer. Very few studies have evaluated the effect of MSI-H on rectal cancer survival. We assessed MSI-H and other genetic and epigenetic changes on survival of 990 individuals diagnosed with first primary rectal cancer. METHODS: MSI was assessed primarily by instability in the mononucleotide repeat BAT-26. The BRAF V600E mutation was assessed by TaqMan assay. The CpG island methylator phenotype (CIMP) was determined by methylation-specific PCR of CpG islands in MLH1, methylated in tumors (MINT)1, (MINT)2, (MINT)31 and CDKN2A. KRAS2 codons 12 and 13 mutations, and TP53 mutations in exons 5-8 were determined by sequencing. RESULTS: Multivariate analysis revealed that MSI-H (HRR 2.47, 95% CI 1.13-5.40) and KRAS2 mutations (HRR 1.37, 95% CI 1.04-1.81) were associated with a significantly higher risk of dying of rectal cancer. Only one of 22 MSI-H tumors showed a BRAF V600E mutation. Of 15 MSI-H rectal cancers evaluated for methylation, two exhibited MLH1 methylation and four exhibited CIMP. CONCLUSION: The genetic and epigenetic characteristics of MSI-H rectal cancers suggest that they are enriched for Lynch-associated tumors; adverse prognosis associated with MSI-H in these tumors may reflect the relatively high frequency of Lynch-associated cancers and/or the effect of radiation or chemotherapy on Lynch-associated rectal cancers or MSI tumors in general.
Authors: Samowitz WS; Curtin K; Wolff RK; Tripp SR; Caan BJ; Slattery ML
Cancer Causes Control. 2009 Nov;20(9):1763-8. Epub 2009 Aug 11.
Complementary and alternative therapy use before and after breast cancer diagnosis: the Pathways Study
Many women use complementary and alternative medicine (CAM) to maintain or improve their health. We describe CAM use among the first 1,000 participants enrolled in the Pathways Study, an ongoing prospective cohort study of women diagnosed with breast cancer (BC). Participants, identified by rapid case ascertainment in Kaiser Permanente Northern California, are women > or = 21 years diagnosed with first invasive BC. Comprehensive baseline data are collected on CAM use through in-person interviews. Study participants include 70.9% non-Hispanic whites, 10.2% Hispanics, 9.0% Asians, 6.5% African-Americans, and 3.4% others. Most women (82.2%) were diagnosed with AJCC stage I/II BC at average (+/-SD) age 59.5 (+/-12.0) years and reported prior use of at least one form of CAM (96.5% of participants). In the 5 years before diagnosis, CAM therapies used at least weekly by >20% of women included green tea, glucosamine, omega-3 fatty acids, prayer and religion. CAM use was high (86.1% of participants) in the period immediately following diagnosis; 47.5% used botanical supplements, 47.2% used other natural products, 28.8% used special diets, 64.2% used mind-body healing, and 26.5% used body/energy/other treatments. In multivariable analyses, frequent use of each CAM modality before and after diagnosis was associated with use of other CAM modalities and other health behaviors (i.e., high fruit/vegetable intake, lower BMI). CAM use before and after BC diagnosis is common in this diverse group of women. Our results emphasize the need for clinicians to discuss CAM use with all BC patients.
Authors: Greenlee H; Kwan ML; Ergas IJ; Sherman KJ; Krathwohl SE; Bonnell C; Lee MM; Kushi LH
Breast Cancer Res Treat. 2009 Oct;117(3):653-65. Epub 2009 Jan 31.
Tumor markers and rectal cancer: support for an inflammation-related pathway
Inflammation may be a key element in the etiology of colorectal cancer. In our study, we examine associations between factors related to inflammation and specific rectal cancer mutations. A population-based study of 750 rectal cancer cases with interview and tumor DNA were compared to 1,205 population-based controls. Study participants were from Utah and the Northern California Kaiser Permanente Medical Care Program. Tumor DNA was analyzed for TP53 and KRAS2 mutations and CpG Island methylator phenotype. We assessed how these tumor markers were associated with use of anti-inflammatory drugs, polymorphisms in the IL6 genes (rs1800795 and rs1800796) and dietary antioxidants. Ibuprofen-type drugs, IL6 polymorphisms (rs1800796) and dietary alpha-tocopherol and lycopene significantly altered likelihood of having a TP53 mutation. This was especially true for TP53 transversion mutations and dietary antioxidants (OR for beta-carotene 0.51 95% CI 0.27, 0.97, p trend 0.03; alpha-tocopherol 0.41 95% CI 0.20, 0.84, p trend 0.02) Beta-carotene and ibuprofen significantly altered risk of KRAS2 tumors. The associations between lutein and tocopherol and TP53 and KRAS2 mutations were modified by IL6 genotype. These results suggest that inflammation-related factors may have unique associations with various rectal tumor markers. Many factors involved in an inflammation-related pathway were associated with TP53 mutations and some dietary factors appeared to be modified by IL6 genotype.
Authors: Slattery ML; Wolff RK; Herrick J; Caan BJ; Samowitz W
Int J Cancer. 2009 Oct 1;125(7):1698-704.
Improving fecal occult blood testing compliance using a mailed educational reminder.
BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths in the United States. Randomized controlled trials have shown that annual screening fecal occult blood testing (FOBT) reduces CRC mortality and incidence. However, patient compliance with FOBT is low.OBJECTIVE: To determine whether a mailed educational reminder increases FOBT card return rates and to examine predictors of FOBT compliance. DESIGN: Blinded, randomized, controlled trial at the Veteran Affairs Medical Center, San Diego, California. PATIENTS: Seven hundred and seventy-five consecutive patients > or =50 years of age referred by their primary care physicians for FOBT. INTERVENTION: Patients were randomly assigned to the usual care group or the intervention group. Ten days after picking up the FOBT cards, a 1-page reminder with information related to CRC screening was mailed to the intervention group only. MEASUREMENTS: The primary outcome was proportion of returned FOBT cards after 6 months. Patient demographic, clinical characteristics and prior FOBT completed were collected for multivariate regression analysis. RESULTS: At 6 months after card distribution, 64.6% of patients in the intervention group returned cards compared with 48.4% in the control group (P < 0.001). Patients who received a mailed reminder (OR 2.02; 95% CI: 1.48-2.74) or have a prior history of returning the FOBT cards (OR 1.87; 95% CI: 1.29-2.70) were more likely to return the FOBT cards. Patients with current or recent illicit drug use were less likely to return the FOBT cards (OR 0.26; 95% CI: 0.13-0.50). CONCLUSION: A simple mailed educational reminder significantly increases compliance with FOBT for CRC screening.
Authors: Lee, Jeffrey K JK; Reis, Veronica V; Liu, Shanglei S; Conn, Lorraine L; Groessl, Erik J EJ; Ganiats, Theodore G TG; Ho, Samuel B SB
Journal of general internal medicine. 2009 Nov ;24(11):1192-7. Epub 2009-09-23.
Vasomotor symptoms, adoption of a low-fat dietary pattern, and risk of invasive breast cancer: a secondary analysis of the Women’s Health Initiative randomized controlled dietary modification trial
PURPOSE: To assess whether the effect of a low-fat dietary pattern on breast cancer incidence varied by report of baseline vasomotor symptoms. METHODS: Postmenopausal women age 50 to 79 years enrolled onto the Women’s Health Initiative (WHI) Dietary Modification trial from 1993 to 1998 were randomly assigned to a low-fat dietary intervention (n = 19,541) or comparison (n = 29,294). Presence of vasomotor symptoms at baseline was ascertained from a 34-item self-report symptom inventory. Women were queried semi-annually for a new diagnosis of breast cancer. Each case report was verified by medical record and pathology report review by centrally trained WHI physician adjudicators. RESULTS: Among participants who reported hot flashes (HFs) at baseline (n = 3,375), those assigned to the low-fat diet had a breast cancer rate of 0.27 compared with their counterparts in the control group who had a rate of 0.41 (hazard ratio [HR] = 0.65; 95% CI, 0.42 to 1.01). Among women reporting no HFs (n = 45,160), the breast cancer rate was 0.42 in those assigned to the low-fat diet compared with 0.46 in the control group (HR = 0.93; 95% CI, 0.84 to 1.03; P for interaction = .12 by HF status). Furthermore, the dietary benefits observed seemed to be specific to estrogen receptor (ER) -positive/progesterone receptor (PR) -positive tumors (ER positive/PR positive v other, P for risk = .03). Although women with and without HFs differed with regard to breast cancer risk factors, the effect of the diet intervention on breast cancer incidence by HF status was consistent across risk factor strata. CONCLUSION: The results of this trial, which are hypothesis generating, suggest that HFs may identify a subgroup of postmenopausal women whose risk of invasive breast cancer might be reduced with the adoption of a low-fat eating pattern.
Authors: Caan BJ; Aragaki A; Thomson CA; Stefanick ML; Chlebowski R; Hubbell FA; Tinker L; Vitolins M; Rajkovic A; Bueche M; Ockene J
J Clin Oncol. 2009 Sep 20;27(27):4500-7. Epub 2009 Aug 17.
ArterioVenous Malformation within Jejunal Diverticulum: an unusual cause of massive gastrointestinal bleeding.
Massive gastrointestinal (GI) bleeding can occur with multiple jejunal diverticulosis. However, significant bleeding in the setting of few diverticulae is very unusual and rare. We report a case of massive gastrointestinal bleeding from an arteriovenous malformation (AVM) within a jejunal diverticulum to underscore the significance of such coexisting pathologies. Mesenteric angiogram was chosen to help identify the source of bleeding and to offer an intervention. Despite endovascular coiling, emergent intestinal resection of the bleeding jejunal segment was warranted to ensure definitive treatment. However several reports have shown jejunal diverticulosis as a rare cause of massive GI bleeding. The coexistence of jejunal diverticulum and AVM is rare and massive bleeding from an acquired Dieulafoy-like AVM within a diverticulum has never previously been described. Awareness of Dieulafoy-like AVM within jejunoileal diverticulosis is useful in preventing delay in treatment.
Authors: Lee, Jeffrey K JK; Carethers, John M JM; Ghosh, Pradipta P
Gastroenterology research and practice. 2009 ;2009():384506. Epub 2009-09-10.
Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer
We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
Authors: Amundadottir L; Van Den Eeden SK; Hoover RN; et al.
Nat Genet. 2009 Sep;41(9):986-90. Epub 2009 Aug 2.
Access to information sources and treatment considerations among men with local stage prostate cancer
OBJECTIVES: To determine the role of information sources in the treatment decision-making process of men diagnosed with local stage prostate cancer. Diagnosed men have access to a large number of information sources about therapy, including print and broadcast media, the Internet, books, and friends with the disease. METHODS: Prospective survey of men with local stage prostate cancer in 3 geographically separate regions was carried out. Most men were surveyed after diagnosis but before starting therapy. RESULTS: On average, men with local prostate cancer consulted nearly 5 separate sources of information before treatment. The most common source of information was the patient’s physician (97%), followed by lay-literature (pamphlets, videos) (76%), other health professionals (71%), friends with prostate cancer (67%), and the Internet (58%). Most men rated the sources they consulted as helpful. Consulting the Internet was associated with considering more treatment options. Several information sources were significantly associated with considering particular treatments, but the magnitude of association was small in relation to patient age, comorbidity, and Gleason score. More than 70% of men stated that they were considering or planning only one type of therapy. CONCLUSIONS: Men with local stage prostate cancer consult a wide range of information sources. Nonphysician information sources appear to influence their treatment considerations, but to a smaller degree than clinical factors.
Authors: Ramsey SD; Zeliadt SB; Arora NK; Potosky AL; Blough DK; Hamilton AS; Van Den Eeden SK; Oakley-Girvan I; Penson DF
Urology. 2009 Sep;74(3):509-15. Epub 2009 Jul 9.
Survival differences by race/ethnicity and treatment for localized hepatocellular carcinoma within the United States
Racial differences among hepatocellular carcinoma survival have been reported, but the etiology behind these disparities remains unclear. Using multi-variable logistic regression analysis, our restrospective cohort study investigated the demographic disparities in survival among localized hepatocellular carcinoma in the United States. From 1998 to 2001, 2,776 cases of localized hepatocellular carcinoma were identified. Significant racial/ethnic disparities in overall survival and utilization of therapies were identified. Compared with non-Hispanic white males, black females were 56% less likely to survive 3 years (OR 0.44; 95% CI 0.21-0.93). Treatment-specific models also demonstrated disparities, e.g., compared with non-Hispanic whites, Asians receiving transplantation were 77% more likely to survive 3 years (OR, 1.77; 95% CI 1.28-2.44). There are significant racial/ethnic disparities in 3-year survival among patients with localized hepatocellular carcinoma. These differences are partially explained by demographic differences in utilization of therapy and in stage-specific survival for each therapy.
Authors: Wong RJ; Corley DA
Dig Dis Sci. 2009 Sep;54(9):2031-9. Epub 2009 Jan 1.
Vitamin D related genes, CYP24A1 and CYP27B1, and colon cancer risk
Genetic association studies investigating the role of vitamin D in colon cancer have primarily focused on the vitamin D receptor (VDR), with limited data available for other genes in the vitamin D pathway, including vitamin D activating enzyme 1-alpha hydroxylase (CYP27B1) and vitamin D deactivating enzyme 24-alpha hydroxylase (CYP24A1). We evaluated whether 12 tagging single nucleotide polymorphisms (SNP) in CYP24A1, identified by resequencing the gene in 32 Caucasian samples, and 1 SNP in CYP27B1 were associated with colon cancer risk. In addition, we evaluated whether these two genes modify associations between colon cancer on the one hand and total vitamin D intake and UV-weighted sun exposure on the other, as well as other variants in VDR. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between polymorphisms and haplotypes in CYP27B1 and CYP24A1 in a multicenter population-based case-control study of 1,600 cases and 1,949 controls. The CYP24A1 polymorphism IVS4-66T > G showed a statistically significant association with risk of colon cancer overall, particularly for proximal colon cancer. When stratified by anatomic site, we also found statistically significant associations for three CYP24A1 polymorphisms with risk of distal colon cancer (IVS4 + 1653C > T: OR for CT/TT versus CC, 0.81; 95% CI, 0.68-0.96; IVS9 + 198T > C: OR for CC versus TT, 1.33; 95% CI, 1.03-1.73; and within whites only: +4125bp 3′ of STPC > G: OR for GG versus CC, 1.44; 95% CI, 1-2.05). In addition, a possible interaction between CYP27B1 and UV-weighted sun exposure with proximal colon cancer was observed. As this is the first study to evaluate these genes in relation to colon cancer, additional studies are needed to confirm these results.
Authors: Dong LM; Caan BJ; Peters U; et al.
Cancer Epidemiol Biomarkers Prev. 2009 Sep;18(9):2540-8. Epub 2009 Aug 25.
Complex atypical endometrial hyperplasia: the risk of unrecognized adenocarcinoma and value of preoperative dilation and curettage
OBJECTIVE: To evaluate whether preoperative dilation and curettage (D&C) lowers the risk of unexpected cancer at hysterectomy. METHODS: Women with complex atypical endometrial hyperplasia on sampling from January 2000 to May 2008 who underwent hysterectomy within 6 months were identified using a pathology database. Patient age, sampling procedures, and hysterectomy pathology were recorded. Women were categorized as having either an office biopsy-based evaluation or a curettage-based evaluation. The proportion of women with cancer at surgery was estimated and compared for the two groups. RESULTS: Of 824 women with complex atypical endometrial hyperplasia on initial sampling, 48% were found to have cancer. For 100 women, cancer was diagnosed preoperatively by additional sampling before hysterectomy. For the remaining 724, 298 (41%) had unexpected cancer at hysterectomy. The diagnosis of complex atypical endometrial hyperplasia was biopsy-based for 531 (73%) and curettage-based for 193 (27%). The risk of cancer for women who had a D&C was significantly lower than for those who had biopsy, but still of concern (30% compared with 45%, P<.001), as was the risk of myometrial invasion (18% compared with 25%, P=.05). Age was strongly correlated to risk of cancer, invasive cancer, and deeply invasive or grade 3 disease. CONCLUSION: Dilation and curettage lowered the risk of unexpected cancer compared with biopsy, but 18% of women still had invasive cancer found at hysterectomy. The risk of unexpected cancer is strongly related to age. Dilation and curettage can help detect cancer preoperatively but is not reliable for excluding cancer. LEVEL OF EVIDENCE: II.
Authors: Suh-Burgmann E; Hung YY; Armstrong MA
Obstet Gynecol. 2009 Sep;114(3):523-9.
The inflammatory response in transgastric surgery: gastric content leak leads to localized inflammatory response and higher adhesive disease.
BACKGROUND: Risk of gastric spillage during transgastric surgery is a potential complication of NOTES procedures. The aim of this study was to determine risk outcomes from gastric spillage in a rat survival model by measuring local and systemic inflammatory markers, adhesive disease, and morbidity.METHODS: We performed a minilaparotomy with needle aspiration of 2 ml of gastric contents mixed with 2 ml of sterile saline (study group, SG) or 4 ml of sterile saline (control group, CG) injected into the peritoneal cavity of 60 male rats. Inflammatory markers (TNFalpha, IL-6, and IL-10) were analyzed at 1, 3, 6, and 24 h postoperatively by obtaining plasma levels and peritoneal washings. At necropsy, the peritoneal cavity was examined grossly for adhesions. RESULTS: Adhesions were seen more frequently in the SG versus the CG (100% vs. 33.3%, p < 0.014). There was a significant difference in the peritoneal TNFalpha levels in the SG compared with the CG, which peaked 1 h after surgery (p < 0.02). Both peritoneal IL-6 and IL-10 levels were higher in the SG versus the CG, which peaked 3 h after surgery (p < 0.005 and p < 0.001, respectively). All peritoneal inflammatory markers returned to undetectable levels at 24 h for both groups. Plasma cytokines were undetectable at all time intervals. CONCLUSION: The inflammatory response was found to be a localized and not systemic event, with plasma cytokine levels remaining normal while peritoneal washings revealed a brisk, short-lived localized inflammatory response. There was a significantly higher rate of adhesive disease in the SG compared with the CG; this, however did not translate into a difference in apparent clinical outcome. We conclude that gastric leakage in this NOTES rodent model induces a localized inflammatory response, followed by mild to moderate adhesive disease. This may be important in human NOTES.
Authors: Ramamoorthy, Sonia L SL; Lee, Jeffrey K JK; Luo, Linda L; Mintz, Yoav Y; Cullen, John J; Easter, David W DW; Savu, Michelle K MK; Chock, Alana A; Carethers, John J; Horgan, Santiago S; Talamini, Mark A MA
Surgical endoscopy. 2010 Mar ;24(3):531-5. Epub 2009-08-18.
Antioxidant supplementation and risk of incident melanomas: results of a large prospective cohort study
OBJECTIVE: To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study, which reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants. DESIGN: Population-based prospective study (Vitamins and Lifestyle [VITAL] cohort). SETTING: Western Washington State. PARTICIPANTS: A total of 69 671 men and women who self-reported (1) intake of multivitamins and supplemental antioxidants, including selenium and beta carotene, during the past 10 years and (2) melanoma risk factors on a baseline questionnaire. Main Outcome Measure Incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. RESULTS: Cox proportional hazards regression models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs) for multivitamin, supplemental selenium, and supplemental beta carotene use. After adjusting for melanoma risk factors, we did not detect a significant association between multivitamin use and melanoma risk in women (RR, 1.14; 95% CI, 0.78-1.66) or in men (RR, 1.09; 95% CI, 0.83-1.43). Moreover, we did not observe increased melanoma risk with the use of supplemental beta carotene (RR, 0.87; 95% CI, 0.48-1.56) or selenium (RR, 0.98; 95% CI, 0.69-1.41) at doses comparable with those of the SUVIMAX study. Conclusion Antioxidants taken in nutritional doses do not seem to increase melanoma risk.
Authors: Asgari MM; Maruti SS; Kushi LH; White E
Arch Dermatol. 2009 Aug;145(8):879-82.
Statin use and risk of colorectal cancer in a cohort of middle-aged men in the US: a prospective cohort study
BACKGROUND: Numerous modifiable factors have been associated with a reduced risk of colorectal cancer, including the chronic use of NSAIDs. Thus, it is biologically plausible that HMG-CoA reductase inhibitors (statins), therapeutic agents that also possess anti-inflammatory effects, are also associated with a lowered risk of colorectal cancer. OBJECTIVE: To examine the association between statin use and the risk of colorectal cancer in a large cohort of middle-aged men enrolled in a prepaid, integrated health maintenance organization. METHODS: We conducted a prospective cohort study of 69 115 Northern and Southern California Kaiser Permanente (KP) members aged 45-69 years who enrolled in the California Men’s Health Study in 2002-3. Colorectal cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and 1994 in Northern California), was treated as time-varying. Cox proportional hazards regression analyses were used to estimate hazard ratios and 95% confidence intervals (CIs), while controlling for potential confounders. RESULTS: During a maximum of 3.5 years of follow-up, 171 colorectal cancer cases were identified. Compared with nonuse, the adjusted hazard ratio for ever use of statins was 0.89 (95% CI 0.61, 1.30). The hazard ratio for statin use of >or=5 years was 0.83 (95% CI 0.43, 1.63). The results did not differ markedly by type or severity of disease. There was also no evidence of effect modification by regular NSAID use. However, the stratified analyses were limited by small numbers. CONCLUSION: These findings provide little support for an association between the use of statins and the risk of colorectal cancer in men. There was some suggestion of a modest inverse association between statin use for >or=5 years and risk of colorectal cancer; however, the possibility that this observation may be related to regular NSAID use cannot be ruled out.
Authors: Flick ED; Habel LA; Chan KA; Haque R; Quinn VP; Van Den Eeden SK; Sternfeld B; Orav EJ; Seeger JD; Quesenberry CP Jr; Caan BJ
Drugs. 2009 Jul 30;69(11):1445-57.
Generalized megaviscera of lupus: refractory intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus.
Dilated dysfunction involving multiple visceral organs has been reported in patients with systemic lupus erythematosus (SLE). Chronic intestinal pseudo-obstruction (CIPO) resulting from intestinal smooth muscle damage has presented in conjunction with ureterohydronephrosis and, more rarely, biliary dilatation (megacholedochus). While the molecular pathogenesis is largely unknown, observed histopathologic features include widespread myositis, myocyte necrosis in the intestinal muscularis propria with subsequent atrophy and fibrosis, preserved myenteric innervations and little vasculitis. High dose immunosuppression usually results in resolution of symptoms with recovery of smooth muscle function, indicative of an autoimmune etiology. We report a patient with SLE who presented with intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus, and present images that illustrate megaviscera simultaneously involving all 3 visceral organs. Since the co-manifestation of all 3 is unusual and has been reported only once previously, we have termed this rare clinical syndrome generalized megaviscera of lupus (GML). Although the SLE disease-activity parameters responded to aggressive immunomodulative therapy in our patient, clinical evidence of peristaltic dysfunction persisted in all involved viscera. This is a variation from the favorable outcomes reported previously in SLE patients with GML and we attribute this poor clinical outcome to disease severity and, most importantly, delayed clinical presentation. Since inflammation followed by atrophy and fibrosis are key aspects in the pathogenesis and natural history of GML, the poor response in our patient who presented late in the clinical course may be the result of ‘burnt out’ inflammation with irreversible end-stage fibrosis. Thus, early recognition and timely initiation of treatment may be the key to recover visceral peristaltic function in patients with GML.
Authors: Park, Frederick-D FD; Lee, Jeffrey-K JK; Madduri, Ganga-D GD; Ghosh, Pradipta P
World journal of gastroenterology. 2009 Jul 28;15(28):3555-9. Epub --.
Longitudinal study of serum carotenoid, retinol, and tocopherol concentrations in relation to breast cancer risk among postmenopausal women
BACKGROUND: Prospective studies have examined the association of serum and plasma carotenoids and micronutrients and breast cancer; however, to date, studies have only assessed exposure at one point in time. OBJECTIVE: This study analyzed baseline and repeated serum measurements of carotenoids, retinol, and tocopherols to assess their associations with postmenopausal breast cancer risk. DESIGN: Serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol were measured in a 6% sample of women in the Women’s Health Initiative clinical trials at baseline and at years 1, 3, and 6 and in a 1% sample of women in the observational study at baseline and at year 3. The association of baseline compounds and breast cancer risk was estimated by Cox proportional hazards models. In addition, repeated measurements were analyzed as time-dependent covariates. Of 5450 women with baseline measurements, 190 incident cases of breast cancer were ascertained over a median of 8.0 y of follow-up. RESULTS: After multivariable adjustment, risk of invasive breast cancer was inversely associated with baseline serum alpha-carotene concentrations (hazard ratio for highest compared with the lowest tertile: 0.55; 95% CI: 0.34, 0.90; P = 0.02) and positively associated with baseline lycopene (hazard ratio: 1.47; 95% CI: 0.98, 2.22; P = 0.06). Analysis of repeated measurements indicated that alpha-carotene and beta-carotene were inversely associated with breast cancer and that gamma-tocopherol was associated with increased risk. CONCLUSIONS: The present study, which was the first to assess repeated measurements of serum carotenoids and micronutrients in relation to breast cancer, adds to the evidence of an inverse association of specific carotenoids with breast cancer. The positive associations observed for lycopene and gamma-tocopherol require confirmation. This trial was registered at ClinicalTrials.gov as NCT00000611.
Authors: Kabat GC; Kim M; Adams-Campbell LL; Caan BJ; Chlebowski RT; Neuhouser ML; Shikany JM; Rohan TE; WHI Investigators
Am J Clin Nutr. 2009 Jul;90(1):162-9. Epub 2009 May 27.
Adherence to long-term surveillance mammography among women with ductal carcinoma in situ treated with breast-conserving surgery
PURPOSE Breast-conserving surgery (BCS) is an effective treatment for ductal carcinoma in situ (DCIS) but women who undergo BCS remain at risk for recurrences. Whether mammographic surveillance after BCS occurs and by whom is not known. METHODS We reviewed medical records of women diagnosed with DCIS between 1990 and 2001 and treated with BCS. Using descriptive statistics, generalized estimating, and logistic regression modeling, we examined the rates and predictors of surveillance mammography over a 10-year period after BCS. Results The cohort included 3,037 women observed for a median of 4.8 years (range, 0.5 to 15.7). Of the 2,676 women observed for at least 1 year after BCS, most (79%) had at least one surveillance mammogram during the first year of follow-up; 69% in year 5 and 61% in year 10. Among those observed for 5 years, surveillance mammograms were more likely among women age 60 to 69 years (odds ratio [OR], 1.72; 95% CI, 1.26 to 2.34), users of menopausal hormone therapy at diagnosis (OR, 1.26; 95% CI, 1.01 to 1.57) as well as those treated with adjuvant radiation (OR, 1.28; 95% CI, 1.08 to 1.53) and adjuvant radiation with tamoxifen (OR, 1.61; 95% CI, 1.13 to 2.30). Surveillance mammograms were less likely among obese women (OR, 0.70; 95% CI, 0.56 to 0.86). The findings were similar among women observed for 10 years. Only 34% and 15% of women observed for 5 and 10 years, respectively, had a surveillance mammogram during each year of follow-up. CONCLUSION Surveillance mammography after BCS among insured women with DCIS often did not occur yearly and declined over time after treatment. Patients and providers must remain vigilant about surveillance after BCS.
Authors: Nekhlyudov L; Habel LA; Achacoso NS; Jung I; Haque R; Collins LC; Schnitt SJ; Quesenberry CP Jr; Fletcher SW
J Clin Oncol. 2009 Jul 1;27(19):3211-6. Epub 2009 May 11.
Statin use and risk of basal cell carcinoma
OBJECTIVE: We examined the association between statin use and basal cell carcinoma (BCC) risk. METHODS: We identified all members of a large integrated health care delivery system with a diagnosis of a histologically proven BCC in 1997. Subsequent BCCs were identified through 2006 from health plan electronic pathology records. Longitudinal exposure to statins and other lipid-lowering agents was determined from automated pharmacy records. We used extended Cox regression to examine the independent association between receipt of statin therapy (ever vs never, cumulative duration) and risk of subsequent BCC. To minimize confounding by indication, we conducted sensitivity analyses in the subset of individuals considered eligible for lipid-lowering therapy based on national guidelines. RESULTS: Among 12,123 members given a diagnosis of BCC who had no prior statin exposure, 6381 developed a subsequent BCC during follow-up. Neither ‘ever use of statins’ (adjusted hazard ratio 1.02, 95% confidence interval: 0.92-1.12) or cumulative duration of statin (adjusted hazard ratio 1.02/year, 95% confidence interval: 0.99-1.11) was associated with subsequent BCC after adjustment for age, sex, and health care use. Risk estimates did not change appreciably when the analysis was limited to the subset of individuals who met eligibility criteria for initiating statin therapy. There was also no significant association between use of non-statin antilipemics and subsequent BCC (adjusted hazard ratio 1.10, 95% confidence interval: 0.76-1.58). LIMITATIONS: No information was available for BCC risk factors, such as sun sensitivity and sun exposure. CONCLUSIONS: Among a large cohort of individuals with BCC, statin therapy was not significantly associated with risk of subsequent BCC.
Authors: Asgari MM; Tang J; Epstein EH Jr; Chren MM; Warton EM; Quesenberry CP Jr; Go AS; Friedman GD
J Am Acad Dermatol. 2009 Jul;61(1):66-72. Epub 2009 May 21.
Pharmaceuticals that cause mammary gland tumors in animals: findings in women
Risk of breast cancer in women was assessed for eight pharmaceuticals that produce mammary tumors in experimental animals, using nested case-control analyses in two cohorts with prescription records in a comprehensive medical care program. The two cohorts were: (1) earlier cohort: 78,118 female members who received prescriptions in 1969-1973, of whom 2,467 developed breast cancer, and (2) later cohort: 3,289,408 female members who received prescriptions in 1994-2006 of whom 24,528 developed breast cancer. Longest follow-up was until June 30, 2006. Ten randomly selected concurrent control women were age-matched to almost every case. Relative risks were estimated by conditional logistic regression. Case ascertainment was lagged by 2 years, or unlagged and subdivided by number of prescriptions received. Some analyses were controlled for hormone use and sensitivity analyses were conducted to estimate the effects of uncontrolled confounding. In the later cohort furosemide, and metronidazole showed statistically significant but very small increases in relative risk (ranging from 1.07 to 1.13). Of these, only furosemide showed increased risk in the earlier cohort: 2-year lag relative risk 1.66 (95% confidence interval 1.23-2.24) or as low as 0.97, assuming uncontrolled positive confounding. Griseofulvin showed significant increases in the later cohort: relative risk for three or more prescriptions 1.48 (1.08-2.03) or as low as 1.23 assuming uncontrolled positive confounding and non-significant increases were noted in the earlier cohort. Our findings are limited by their inconsistency across the two cohorts and our inability to directly control for most established breast cancer risk factors. Although inconclusive, our findings suggest a need for more research on furosemide and griseofulvin.
Authors: Friedman GD; Jiang SF; Udaltsova N; Chan J; Quesenberry CP Jr; Habel LA
Breast Cancer Res Treat. 2009 Jul;116(1):187-94. Epub 2008 Jul 16.
Maternal diet and risk of childhood acute lymphoblastic leukemia
OBJECTIVE: Intrauterine environmental factors, including maternal diet, may play an etiologic role in acute lymphoblastic leukemia (ALL), a common childhood cancer. Expanding on previous findings from phase 1 of the Northern California Childhood Leukemia Study (NCCLS), a population-based case-control study, we sought to further elucidate and replicate the relationships between maternal diet and ALL risk. METHODS: We matched 282 case-control sets of children (205 pairs and 77 triplets) from phases 1 and 2 of the NCCLS on sex, date of birth, mother’s race, Hispanic racial/ethnic status, and county of residence at birth. We used an interviewer-administered food frequency questionnaire to obtain information on maternal dietary intake in the 12 months prior to pregnancy. RESULTS: Risk of ALL was inversely associated with maternal consumption of vegetable (adjusted odds ratio [AOR] = 0.65, 95% confidence interval [CI] 0.50, 0.84); protein sources (AOR = 0.55, 95% CI 0.32, 0.96); fruit (AOR = 0.81, 95% CI 0.65, 1.00); and legume food groups (AOR = 0.75, 95% CI 0.59, 0.95). The risk reduction was strongest for consumption of the protein sources and vegetable food groups, independent of the child’s diet up to age 2 years, and consistent across phases 1 and 2 of data collection for vegetable consumption. CONCLUSIONS: These data suggest that it may be prudent for women to consume a diet rich in vegetables and adequate in protein prior to and during pregnancy as a possible means of reducing childhood ALL risk in their offspring.
Authors: Kwan ML; Jensen CD; Block G; Hudes ML; Chu LW; Buffler PA
Public Health Rep. 2009 Jul-Aug;124(4):503-14.
Somatic alterations, metabolizing genes and smoking in rectal cancer
Cigarette smoking has been identified as a risk factor for rectal cancer. Our investigation evaluates associations between active and passive smoking and TP53, KRAS2, and BRAF V600E mutations, microsatellite instability (MSI), and CpG Island Methylator Phenotype (CIMP) in rectal tumors. We examine how genetic variants of GSTM1 and NAT2 alter these associations in a population-based, case-control study of 750 incident rectal cancer cases and 1,201 controls. Detailed tobacco exposure data were collected in an extensive questionnaire. DNA from blood was examined for GSTM1 and NAT2 variants. Tumor DNA was assessed to determine TP53 (exons 5-8), KRAS2 (codons 12-13) and BRAF mutations, MSI (BAT26 and TGFbetaRII analysis), and CIMP (methylation of CpG islands in CDKN2A, MLH1, MINT1, MINT2 and MINT31). Cigarette smoking (>20 pack-years, relative to nonsmokers) was associated with increased risk of TP53 mutations (OR = 1.4, 95% CI 1.02-2.0), BRAF mutations (OR = 4.2, 95% CI 1.3-14.2) and MSI (OR = 5.7, 95% CI 1.1-29.8) in rectal tumors. Long-term environmental tobacco smoke (ETS) exposure of >10 hr/wk was associated with increased risk of KRAS2 mutation (OR = 1.5, 95% CI 1.04-2.2). All smoking indicators were suggestive of increased risk in CIMP+ rectal cancer. GSTM1 and NAT2 were generally not associated with rectal tumor alterations; however, we observed an interaction of ETS and NAT2 in TP53-mutated tumors (p < 0.01). Our investigation shows active smoking is associated with increased risk of TP53, BRAF and MSI+ in rectal tumors and is suggestive of increased risk of CIMP+ tumors. ETS may increase risk of KRAS2 mutations; association with TP53 mutations and ETS may be influenced by NAT2.
Authors: Curtin K; Samowitz WS; Wolff RK; Herrick J; Caan BJ; Slattery ML
Int J Cancer. 2009 Jul 1;125(1):158-64.
A cohort study of vitamin D intake and melanoma risk
Data suggest that vitamin D intake may have chemopreventive efficacy against melanoma, but there have been no published epidemiologic studies examining the association between vitamin D intake and melanoma risk in a large prospective cohort. We examined whether dietary and supplemental vitamin D intake was associated with melanoma risk among 68,611 men and women who were participants of the Vitamins and Lifestyle cohort study. Participants reported dietary vitamin D intake over the past year and 10-year use of multivitamin and individual vitamin D supplements on a baseline questionnaire. After follow-up through 2006, 455 incident melanomas were identified through linkage to the Surveillance, Epidemiology, and End Results cancer registry. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for vitamin D intake after adjustment for melanoma risk factors. Compared with the lowest quartile, we did not detect a risk reduction of melanoma in the highest quartiles of dietary vitamin D intake (RR=1.31, CI=0.94-1.82), 10-year average supplemental vitamin D intake (RR=1.13, CI=0.89-1.43), or combined dietary and supplemental intake (1.05, CI=0.79-1.40). In this large prospective cohort, we did not find an association between vitamin D intake and melanoma risk.
Authors: Asgari MM; Maruti SS; Kushi LH; White E
J Invest Dermatol. 2009 Jul;129(7):1675-80. Epub 2009 Feb 5.
The impact of proton-pump inhibitors on intraperitoneal sepsis: a word of caution for transgastric NOTES procedures.
BACKGROUND: During transgastric natural orifice transluminal endoscopic surgery (NOTES), there is an iatrogenic perforation of the gastric wall with leakage of gastric contents into the peritoneal cavity. The aim of this study is to determine the effect of proton-pump inhibitors (PPI) and alterations of gastric pH on infection during transgastric surgery.METHODS: Thirty 250-g male Sprague-Dawley rats were divided into a study group (SG, n = 15) and a control group (CG, n =15). SG were given 5 mg/kg pantoprazole for 3 days before procedure and another dose 1 h before. CG received saline at similar time points. A mini-laparotomy with gastrotomy was performed. Aspiration of 2.0 cc gastric contents was removed from the stomach and injected into the peritoneal cavity of both groups. Gastric pH and peritoneal pH levels were obtained. Gastric aspirate was sent for culture. White blood cell counts (WBC) were obtained on postoperative days 1, 7, and 14, and C-reactive protein (CRP) levels were obtained on postoperative day 1. At day 14, a necropsy was performed and aerobic and anaerobic cultures of the peritoneal cavity were obtained.RESULTS: There were no deaths in either group. The average gastric pH in the SG was 5.13 versus 3.26 (p = 0.03) in the CG. The average peritoneal pH was similar in both groups. The WBC in the SG was 4.5 vs. 3.5 (1,000 cells/mm) in the CG. There was no elevation in CRP levels in either group. Bacterial cultures were positive in 3/15 (20%) rats in the CG and in 9/15 (60%) in the SG (p = 0.008). Intra-abdominal abscesses were found in 2/15 (13%) rats in the CG and in 5/15 (33%) in the SG (p = 0.08).CONCLUSIONS: Pretreatment with a PPI resulted in a higher rate of peritoneal bacterial contamination and abscess formation. The acidic environment of the stomach appears to be protective against infection when intraperitoneal contamination occurs as a result of gastrotomy.
Authors: Ramamoorthy, Sonia L SL; Lee, Jeffrey K JK; Mintz, Yoav Y; Cullen, John J; Savu, Michelle K MK; Easter, David W DW; Chock, Alana A; Mittal, Ravi R; Horgan, Santiago S; Talamini, Mark A MA
Surgical endoscopy. 2010 Jan ;24(1):16-20. Epub 2009-06-24.
Time-varying effects of prognostic factors associated with disease-free survival in breast cancer
Early detection and effective treatments have dramatically improved breast cancer survivorship, yet the risk of relapse persists even 15 years after the initial diagnosis. It is important to identify prognostic factors for late breast cancer events. The authors investigated time-varying effects of tumor characteristics on breast-cancer-free survival using data on 3,088 breast cancer survivors from 4 US states who participated in a randomized dietary intervention trial in 1995-2006, with maximum follow-up through 15 years (median, 9 years). A piecewise constant penalized spline approach incorporating time-varying coefficients was adopted, allowing for deviations from the proportional hazards assumption. This method is more flexible than standard approaches, provides direct estimates of hazard ratios across time intervals, and is computationally tractable. Having a stage II or III tumor was associated with a 3-fold higher hazard of breast cancer than having a stage I tumor during the first 2.5 years after diagnosis; this hazard ratio decreased to 2.1 after 7.7 years, but higher tumor stage remained a significant risk factor. Similar diminishing effects were found for poorly differentiated tumors. Interestingly, having a positive estrogen receptor status was protective up to 4 years after diagnosis but detrimental after 7.7 years (hazard ratio = 1.5). These results emphasize the importance of careful statistical modeling allowing for possibly time-dependent effects in long-term survivorship studies.
Authors: Natarajan L; Flatt SW; Pierce JP; et al.
Am J Epidemiol. 2009 Jun 15;169(12):1463-70. Epub 2009 Apr 29.
Dietary change and reduced breast cancer events among women without hot flashes after treatment of early-stage breast cancer: subgroup analysis of the Women’s Healthy Eating and Living Study
BACKGROUND: A diet high in vegetables, fruit, and fiber and low in fat decreased additional risk of secondary breast cancer events in women without hot flashes (HF-) compared with that in women with hot flashes (HF+), possibly through lowered concentrations of circulating estrogens. OBJECTIVE: The objective was to investigate the intervention effect by baseline quartiles of dietary pattern among breast cancer survivors in the HF- subgroup of the Women’s Healthy Eating and Living Study. Design: A randomized controlled trial compared a putative cancer prevention diet with a diet of 5 servings of vegetables and fruit daily in early-stage breast cancer survivors. Participants did not experience hot flashes at baseline (n = 896). We confirmed cancer status for 96% of participants approximately 7.3 y after enrollment. RESULTS: The study intervention achieved a large between-group difference in dietary pattern that, at 4 y, was not significantly different across baseline quartiles of dietary pattern. The intervention group experienced fewer breast cancer events than did the comparison group for all of the baseline quartiles. This difference was significant only in upper baseline quartiles of intake of vegetables, fruit, and fiber and in the lowest quartile of fat. A significant trend for fewer breast cancer events was observed across quartiles of vegetable-fruit and fiber consumption. CONCLUSIONS: The secondary analysis showing the decreased risk in the HF- subgroup was not explained by amount of change in dietary pattern achieved. The difference was strongest in the quartile with the most putatively cancer-preventive dietary pattern at baseline.
Authors: Pierce JP; Caan BJ; Parker B; et al.
Am J Clin Nutr. 2009 May;89(5):1565S-1571S. Epub 2009 Apr 1.
Diagnosing Barrett’s esophagus: reliability of clinical and pathologic diagnoses
BACKGROUND: The accuracy of a Barrett’s esophagus diagnosis is not well studied. OBJECTIVE: Our purpose was to evaluate the accuracy of a clinical Barrett’s esophagus diagnosis and the reproducibility of an esophageal intestinal metaplasia diagnosis. METHODS: All patients with a Barrett’s esophagus diagnosis between 1994 and 2005 were identified by use of International Classification of Disease (ICD) and Systematized Nomenclature of Medicine (SNOMED) coding. Subsets received manual record review (endoscopy/pathology reports), slide review by a referral pathologist (interrater reliability), and 2 blinded reviews by the same pathologist (intrarater reliability). SETTING: An integrated health services delivery system. MAIN OUTCOME MEASUREMENTS: Accuracy of electronic clinical diagnosis and reproducibility of esophageal intestinal metaplasia diagnosis. RESULTS: A total of 2470 patients coded with Barrett’s esophagus underwent record review; a subgroup (616) received manual pathology slide review. Review confirmed a Barrett’s esophagus diagnosis for 1533 (61.9%) patients: 437 of 798 subjects (54.8%) with a SNOMED diagnosis alone, 153 of 671 subjects (26.8%) with an ICD diagnosis alone, and 940 of 1101 subjects (85%) who had both a SNOMED and an ICD diagnosis. The same metaplasia diagnosis occurred with 88.3% of subjects (original vs referral pathologist, interrater reliability; kappa = .42, 95% CI, 0.34-0.48). The referral pathologist made the same metaplasia diagnosis twice for a given patient for 88.6% of subjects (intrarater reliability, 2 reviews by same pathologist; kappa = 0.65, 95% CI, 0.35-0.93). LIMITATIONS: The accuracy of a Barrett’s esophagus diagnosis likely represents the minimum number, given the strict criteria. CONCLUSIONS: A community pathologist’s diagnosis of esophageal intestinal metaplasia is likely to be confirmed by a referral pathologist. Electronic diagnoses of Barrett’s esophagus overestimate the prevalence, although they are usually confirmed in patients with both a SNOMED and ICD diagnosis of Barrett’s esophagus.
Authors: Corley DA; Kubo A; DeBoer J; Rumore GJ
Gastrointest Endosc. 2009 May;69(6):1004-10. Epub 2009 Jan 18.
Biomarker-calibrated energy and protein consumption and increased cancer risk among postmenopausal women
The authors previously reported equations, derived from the Nutrient Biomarker Study within the Women’s Health Initiative, that produce calibrated estimates of energy, protein, and percentage of energy from protein consumption from corresponding food frequency questionnaire estimates and data on other factors, such as body mass index, age, and ethnicity. Here, these equations were applied to yield calibrated consumption estimates for 21,711 women enrolled in the Women’s Health Initiative dietary modification trial comparison group and 59,105 women enrolled in the observational study. These estimates were related prospectively to total and site-specific invasive cancer incidence (1993-2005). In combined cohort analyses that do not control for body mass, uncalibrated energy was not associated with total cancer incidence or site-specific cancer incidence for most sites, whereas biomarker-calibrated energy was positively associated with total cancer (hazard ratio = 1.18, 95% confidence interval: 1.10, 1.27, for 20% consumption increase), as well as with breast, colon, endometrial, and kidney cancer (respective hazard ratios of 1.24, 1.35, 1.83, and 1.47). Calibrated protein was weakly associated, and calibrated percentage of energy from protein was inversely associated, with total cancer. Calibrated energy and body mass index associations were highly interdependent. Implications for the interpretation of nutritional epidemiology studies are described.
Authors: Prentice RL; Caan B; Tinker LF; et al.
Am J Epidemiol. 2009 Apr 15;169(8):977-89. Epub 2009 Mar 3.
Effect of intensive glycemic control and diabetes complications on lower urinary tract symptoms in men with type 1 diabetes: Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study
OBJECTIVE: Although diabetes is known to result in lower urinary tract symptoms (LUTS) in men, it remains unclear if glycemic control can mitigate urinary symptoms. We studied how diabetic characteristics are related to LUTS in the men who completed the urological assessment component (UroEDIC) of the Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study of the Diabetes Control and Complications Trial (DCCT) participants. RESEARCH DESIGN AND METHODS: Study participants were men who completed the UroEDIC questionnaire at the year 10 DCCT/EDIC follow-up examination, which included data on genitourinary tract function and the American Urological Association Symptom Index (AUASI). Analyses were conducted to assess how treatment arm and diabetes characteristics were associated with LUTS using logistic regression. RESULTS: Of the 591 men who completed the AUASI questions, nearly 20% (n = 115) had AUASI scores in the moderate to severe category for LUTS (AUASI score >or=8). No associations were observed between LUTS and treatment arm, or A1C levels at the DCCT baseline or end-of-study or at the year 10 EDIC (UroEDIC) examination. Of the diabetes complications studied, only erectile dysfunction at the UroEDIC examination was associated with LUTS. CONCLUSIONS: These data from the UroEDIC cohort do not support the assumption that intensive glycemic control results in decreased lower urinary tract symptom severity in men with type 1 diabetes. This result may be due to a true lack of effect, or it may be due to other factors, for example, the relatively young age of the cohort.
Authors: Van Den Eeden SK; Sarma AV; Rutledge BN; Cleary PA; Kusek JW; Nyberg LM; McVary KT; Wessells H; Diabetes Control and Complications Trial/Epidemiology of Diabetes Research Group
Diabetes Care. 2009 Apr;32(4):664-70. Epub 2009 Jan 26.
Editorial: It’s time to make organized colorectal cancer screening convenient and easy for patients
Colorectal cancer (CRC) screening is widely recommended, but underused. To increase screening rates, we need to implement organized and population-based systems to promote CRC screening among people in a single region, health plan, or health system. This is ideally accomplished using fecal immunochemical tests (FITs), which can be sent through a mass mailing. The study by Levi and colleagues shows that patients using aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), anti-platelet agents, or anti-coagulants do not need to stop these medications while doing the fecal collection. This makes the testing more convenient for patients, and avoids the risk of adverse cardiovascular events caused by stopping these medications.
Authors: Levin TR
Am J Gastroenterol. 2009 Apr;104(4):939-41. Epub 2009 Mar 17.
Cigarette smoking and the risk of Barrett’s esophagus
INTRODUCTION: We examined the association between smoking and the risk of Barrett’s esophagus (BE), a metaplastic precursor to esophageal adenocarcinoma. METHODS: We conducted a case-control study within the Kaiser Permanente Northern California population. Patients with a new diagnosis of BE (n = 320) were matched to persons with gastroesophageal reflux disease (GERD) (n = 316) and to population controls (n = 317). Information was collected using validated questionnaires from direct in-person interviews and electronic databases. Analyses used multivariate unconditional logistic regression that controlled for age, gender, race, and education. RESULTS: Ever smoking status, smoking intensity (pack-years), and smoking cessation were not associated with the risk of BE. Stratified analyses suggested that ever smoking may be associated with an increased risk of BE among some groups (compared to population controls): persons with long-segment Barrett’s esophagus (odds ratio [OR] = 1.72, 95% confidence interval [CI] 1.12-2.63); subjects without GERD symptoms (OR = 3.98, 95% CI 1.58-10.0); obese subjects (OR = 3.38, 95% CI 1.46-7.82); and persons with a large abdominal circumference (OR = 3.02, 95% CI (1.18-2.75)). CONCLUSION: Smoking was not a strong or consistent risk factor for BE in a large community-based study, although associations may be present in some population subgroups.
Authors: Kubo A; Levin TR; Block G; Rumore G; Quesenberry CP Jr; Buffler P; Corley DA
Cancer Causes Control. 2009 Apr;20(3):303-11. Epub 2008 Oct 14.
Longitudinal association of anthropometry with mammographic breast density in the Study of Women’s Health Across the Nation
High percent mammographic breast density is strongly associated with increased breast cancer risk. Though body mass index (BMI) is positively associated with risk of postmenopausal breast cancer, BMI is negatively associated with percent breast density in cross-sectional studies. Few longitudinal studies have evaluated associations between BMI and weight and mammographic breast density. We studied the longitudinal relationships between anthropometry and breast density in a prospective cohort of 834 pre- and perimenopausal women enrolled in an ancillary study to the Study of Women’s Health Across the Nation (SWAN). Routine screening mammograms were collected and read for breast density. Random intercept regression models were used to evaluate whether annual BMI change was associated with changes over time in dense breast area and percent density. The study population was 7.4% African-American, 48.8% Caucasian, 21.8% Chinese, and 21.9% Japanese. Mean follow-up was 4.8 years. Mean annual weight change was +0.32 kg/year, mean change in dense area was -0.77 cm(2)/year, and mean change in percent density was -1.14%/year. In fully adjusted models, annual change in BMI was not significantly associated with changes in dense breast area (-0.17 cm(2), 95% CI -0.64, 0.29). Borderline significant negative associations were observed between annual BMI change and annual percent density change, with percent density decreasing 0.36% (95% CI -0.74, 0.02) for a one unit increase in BMI over a year. This longitudinal study provides modest evidence that changes in BMI are not associated with changes in dense area, yet may be negatively associated with percent density.
Authors: Reeves KW; Stone RA; Modugno F; Ness RB; Vogel VG; Weissfeld JL; Habel LA; Sternfeld B; Cauley JA
Int J Cancer. 2009 Mar 1;124(5):1169-77.
Alcohol types and sociodemographic characteristics as risk factors for Barrett’s esophagus
BACKGROUND & AIMS: Little is known about the effects of alcohol use and sociodemographics on the risk of Barrett’s esophagus, a precursor to esophageal adenocarcinoma. We evaluated the association between alcohol use, alcohol type, sociodemographic profiles, other lifestyle factors, and the risk of Barrett’s esophagus. METHODS: With the use of a case-control study within the Kaiser Permanente Northern California membership, patients with a new diagnosis of Barrett’s esophagus (n = 320) diagnosed between 2002 and 2005 were matched to persons with gastroesophageal reflux disease (GERD; n = 316) and to population controls (n = 317). We collected information using validated questionnaires during direct in-person interviews. Analyses used multivariate unconditional logistic regression. RESULTS: Total alcohol use was not significantly associated with the risk of Barrett’s esophagus, although stratification by beverage type showed an inverse association for wine drinkers compared with nondrinkers (>/=7 drinks of wine per week vs none: odds ratio, 0.44; 95% confidence interval, 0.20-0.99; multivariate analysis). Among population controls, those who preferred wine were more likely to have college degrees and regularly take vitamin supplements than those who preferred beer or liquor, although adjustment for these factors or GERD symptoms did not eliminate the inverse association between wine consumption and Barrett’s esophagus. Education status was significantly inversely associated with the risk of Barrett’s esophagus. CONCLUSIONS: There are associations between alcohol types, socioeconomic status, and the risk of Barrett’s esophagus. Although choice of alcoholic beverages was associated with several factors, multiple adjustments (including for GERD) did not eliminate the association between alcohol and Barrett’s esophagus. Further research to evaluate the associations among socioeconomic status, GERD, and Barrett’s esophagus is warranted.
Authors: Kubo A; Levin TR; Block G; Rumore GJ; Quesenberry CP Jr; Buffler P; Corley DA
Gastroenterology. 2009 Mar;136(3):806-15. Epub 2008 Nov 27.
Dietary patterns and breast cancer recurrence and survival among women with early-stage breast cancer
PURPOSE: To determine the association of dietary patterns with cancer recurrence and mortality of early-stage breast cancer survivors. PATIENTS AND METHODS: Patients included 1,901 Life After Cancer Epidemiology Study participants diagnosed with early-stage breast cancer between 1997 and 2000 and recruited primarily from the Kaiser Permanente Northern California Cancer Registry. Diet was assessed at cohort entry using a food frequency questionnaire. Two dietary patterns were identified: prudent (high intakes of fruits, vegetables, whole grains, and poultry) and Western (high intakes of red and processed meats and refined grains). Two hundred sixty-eight breast cancer recurrences and 226 all-cause deaths (128 attributable to breast cancer) were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: Increasing adherence to a prudent dietary pattern was associated with a statistically significant decreasing risk of overall death (P trend = .02; HR for highest quartile = 0.57; 95% CI, 0.36 to 0.90) and death from non-breast cancer causes (P trend = .003; HR for highest quartile = 0.35; 95% CI, 0.17 to 0.73). In contrast, increasing consumption of a Western dietary pattern was related to an increasing risk of overall death (P trend = .05) and death from non-breast cancer causes (P = .02). Neither dietary pattern was associated with risk of breast cancer recurrence or death from breast cancer. These observations were generally not modified by physical activity, being overweight, or smoking. CONCLUSION: Women diagnosed with early-stage breast cancer might improve overall prognosis and survival by adopting more healthful dietary patterns.
Authors: Kwan ML; Weltzien E; Kushi LH; Castillo A; Slattery ML; Caan BJ
J Clin Oncol. 2009 Feb 20;27(6):919-26. Epub 2008 Dec 29.
Endoscopy is accurate, safe, and effective in the assessment and management of complications following gastric bypass surgery.
OBJECTIVES: Roux-en-Y gastric bypass (RYGB) is a common intervention for morbid obesity. Upper gastrointestinal (UGI) symptoms are frequent and difficult to interpret following RYGB. The aim of our study was to examine the role of endoscopy in evaluating UGI symptoms after RYGB and to assess the safety and efficacy of endoscopic therapy.METHODS: Between 1998 and 2005, a total of 1,079 patients underwent RYGB for clinically severe obesity and were followed prospectively. Patients with UGI symptoms after RYGB who were referred for endoscopy were studied. RESULTS: Of 1,079 patients, 76 (7%) who underwent RYGB were referred for endoscopy to evaluate UGI symptoms. Endoscopic findings included normal surgical anatomy (n=24, 31.6%), anastomotic stricture (n=40, 52.6%), marginal ulcer (n=12, 15.8%), unraveled nonabsorbable sutures causing functional obstruction (n=3, 4%) and gastrogastric fistula (n=2, 2.6%). Patients with abnormal findings on endoscopy presented with UGI symptoms at a mean of 110.7 days from their RYGB, which was significantly shorter than the time of 347.5 days for patients with normal endoscopy (PCONCLUSIONS: Patients presenting with UGI symptoms less than 3 months after surgery are more likely to have an abnormal finding on endoscopy. Endoscopic balloon dilation is safe and effective in managing anastomotic strictures. Endoscopic scissors are safe and effective in removing unraveled, nonabsorbable sutures contributing to obstruction.
Authors: Lee, Jeffrey K JK; Van Dam, Jacques J; Morton, John M JM; Curet, Myriam M; Banerjee, Subhas S
The American journal of gastroenterology. 2009 Mar ;104(3):575-82; quiz 583. Epub 2009-02-03.
Longitudinal biological exposure to carotenoids is associated with breast cancer-free survival in the Women’s Healthy Eating and Living Study
In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4, and 6 years and breast cancer-free survival in the Women’s Healthy Eating and Living Study participants (N = 3,043), who had been diagnosed with early-stage breast cancer. The primary end point was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared with the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83) after adjustment. The interaction between the study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.
Authors: Rock CL; Caan BJ; Women's Healthy Eating and Living Study Group; et al.
Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):486-94. Epub 2009 Feb 3.
Race, ethnicity, sex and temporal differences in Barrett’s oesophagus diagnosis: a large community-based study, 1994-2006
OBJECTIVE: To evaluate the demographics and incidence of Barrett’s oesophagus diagnosis using community-based data. DESIGN: Observational study. SETTING: Kaiser Permanente, Northern California healthcare membership, 1994-2006. PATIENTS: Members with an electronic diagnosis of Barrett’s oesophagus. MAIN OUTCOME MEASURES: Incidence and prevalence of a new Barrett’s oesophagus diagnosis by race, sex, age and calendar year. RESULTS: 4205 persons met the study definition for a diagnosis of Barrett’s oesophagus. The annual incidence in 2006 was highest among non-Hispanic whites (39/100,000 race-specific member-years, 95% confidence interval (95% CI) 35 to 43), with lower rates among Hispanics (22/100,000, 95% CI 16 to 29), Asians (16/100,000, 95% CI 11 to 22), and blacks (6/100,000, 95% CI 2 to 12). The annual incidence was higher among men than women (31 vs 17/100,000, respectively, year 2006; p<0.01). The incidence increased with age from 2 per 100,000 for persons aged 21-30 years, to a peak of 31 per 100,000 member-years for persons aged 61-70 years (year 2006). There was no increase in the incidence of new diagnoses until the last two observation years, which coincided with changes in data collection methods and may be due to bias. The overall prevalence among active members increased almost linearly to 131/100,000 member-years by 2006. CONCLUSIONS: The demographic distributions of Barrett's oesophagus differ markedly by race, age and sex and were comparable to those for oesophageal adenocarcinoma. Thus, demographic disparities in oesophageal adenocarcinoma risk may arise partly from the risk of having Barrett's oesophagus, rather than from differing risks of progression from Barrett's oesophagus to cancer. There has been an almost linear increase in the prevalence of diagnosed disease.
Authors: Corley DA; Kubo A; Levin TR; Block G; Habel L; Rumore G; Quesenberry C; Buffler P
Gut. 2009 Feb;58(2):182-8. Epub 2008 Oct 31.
Pure and predominantly pure intralymphatic breast carcinoma after neoadjuvant chemotherapy: an unusual and adverse pattern of residual disease
Neoadjuvant chemotherapy is standard of care for patients with locally advanced breast cancer. Patients who achieve a pathologic complete response have a more favorable outcome than those who do not; however, a standard system for classifying residual disease has not been adopted. Various definitions of complete response exist, some of which allow for minimal residual invasive or in situ carcinoma. The pattern of residual carcinoma restricted to lymphatic spaces without stromal invasion, herein called pure intralymphatic carcinoma, has not been well addressed. Neither has the pattern of minimal residual stromal invasive cancer accompanied by an extensive intralymphatic component, herein called predominantly pure intralymphatic carcinoma. We report the incidence, clinicopathologic features, and clinical significance of pure and predominantly pure intralymphatic carcinoma in a cohort of 146 neoadjuvant-treated breast cancer patients. We also evaluate the use of the immunohistochemical lymphatic marker D2-40 in these tissues exposed to neoadjuvant chemotherapy. Six patients (4%) had residual pure intralymphatic carcinoma. No gross abnormalities were present in the mastectomy specimens except for 1 case that had a discrete mass, corresponding to residual in situ carcinoma. Residual intralymphatic tumor size ranged from 0.2 to 6 cm. All but one had residual positive lymph nodes. Residual predominantly pure intralymphatic carcinoma was found in 5/146 (4%) patients. A discrete gross mass was observed in 3/5 specimens. Whereas residual stromal invasive carcinoma ranged in size from 0.1 to 1.8 cm, the intralymphatic component ranged from 6 to 9.3 cm. All had residual positive lymph nodes. D2-40 adequately marked lymphatic endothelium in all cases tested. Death occurred in 6/11 (55%) versus 17/135 (13%) patients with or without pure/predominantly pure intralymphatic carcinoma, respectively. After controlling for tumor stage, the presence of either of these residual intralymphatic patterns was associated with a 3-fold increase in death (Cox proportional hazards ratio=3.59, 95% confidence interval, 1.29, 9.99, P=0.014). Elevated risk for disease progression was also observed but this was not statistically significant. We conclude that pure/predominantly pure intralymphatic carcinoma is a clinically significant pattern of residual disease. This may be an underrecognized pattern because of the discordance between gross and microscopic findings and because of challenges in diagnosing intralymphatic carcinoma. D2-40 immunostaining is useful in this setting. Current staging criteria should be clarified to define whether extensive intralymphatic tumor should be incorporated in tumor stage assignment.
Authors: Rabban JT; Glidden D; Kwan ML; Chen YY
Am J Surg Pathol. 2009 Feb;33(2):256-63.
Dietary pattern influences breast cancer prognosis in women without hot flashes: the women’s healthy eating and living trial
PURPOSE: To determine whether a low-fat diet high in vegetables, fruit, and fiber differentially affects prognosis in breast cancer survivors with hot flashes (HF) or without HF after treatment. PATIENTS AND METHODS: A secondary analysis was conducted on 2,967 breast cancer survivors, age 18 to 70 years, who were randomly assigned between 1995 and 2000 in a multicenter, controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1, 2006. We compared the dietary intervention group with a group who received five-a-day dietary guidelines. RESULTS: Independent of HF status, a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day (54% higher; 10 v 6.5 servings/d, respectively), fiber (31% higher; 25.5 v 19.4 g/d, respectively), and percent energy from fat (14% lower; 26.9% v 31.3%, respectively). Adjusting for tumor characteristics and antiestrogen treatment, HF-negative women assigned to the intervention had 31% fewer events than HF-negative women assigned to the comparison group (hazard ratio [HR] = 0.69; 95% CI, 0.51 to 0.93; P = .02). The intervention did not affect prognosis in the women with baseline HFs. Furthermore, compared with HF-negative women assigned to the comparison group, HF-positive women had significantly fewer events in both the intervention (HR = 0.77; 95% CI, 0.59 to 1.00; P = .05) and comparison groups (HR = 0.65; 95% CI, 0.49 to 0.85; P = .002). CONCLUSION: A diet with higher vegetable, fruit, and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors. This suggestive finding needs confirmation in a trial in which it is the primary hypothesis.
Authors: Gold EB; Caan BJ; Mortimer JE; et al.
J Clin Oncol. 2009 Jan 20;27(3):352-9. Epub 2008 Dec 15.
Colon tumor mutations and epigenetic changes associated with genetic polymorphism: insight into disease pathways
Variation in genes associated with serum levels of proteins may be useful for examining specific disease pathways. Using data from a large study of colon cancer, we examine genetic variants in insulin, inflammation, estrogen, metabolizing enzymes, and energy homeostasis genes to explore associations with microsatellite instability (MSI), CpG Island methylator phenotype (CIMP), mutations of p53 in exons 5 through 8, and mutations in codons 12 and 13 of Ki-ras. Insulin-related genes were associated with CIMP-positive and MSI tumors, with the strongest associations among aspirin users. The Fok1 vitamin D receptor (VDR) polymorphism was associated with CIMP-positive/Ki-ras-mutated tumors; the Poly A and CDX2 VDR polymorphisms were associated only with Ki-ras-mutated tumors. NAT2 was associated with CIMP-positive/Ki-ras-mutated tumors but not with MSI tumors. The TCF7L2 rs7903146 polymorphism was associated with p53 mutated tumors. Most associations varied by recent aspirin/NSAID use: IL6 rs1800796 and rs1800795 polymorphisms were associated inversely with tumor mutations in the presence of aspirin/NSAIDs; POMC significantly reduced risk of Ki-ras-mutated tumors when aspirin/NSAIDs were not used; the TCF7L2 rs7903146 was associated with reduced risk of Ki-ras-mutated tumors in the presence of aspirin and increased risk in the absence of aspirin. These data, although exploratory, identify specific tumor subsets that may be associated with specific exposures/polymorphism combinations. The important modifying effects of aspirin/NSAIDs on associations with genetic polymorphisms reinforce the underlying role of inflammation in the etiology of colon cancer.
Authors: Slattery ML; Wolff RK; Curtin K; Fitzpatrick F; Herrick J; Potter JD; Caan BJ; Samowitz WS
Mutat Res. 2009 Jan 15;660(1-2):12-21. Epub 2008 Oct 15.
Epidemiology of breast cancer subtypes in two prospective cohort studies of breast cancer survivors
INTRODUCTION: The aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization. METHODS: Tumor data on 2544 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) status were obtained (1868 luminal A tumors, 294 luminal B tumors, 288 triple-negative tumors and 94 Her2-overexpressing tumors). Demographic, reproductive and lifestyle information was collected either in person or by mailed questionnaires. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis, race/ethnicity, and study origin. RESULTS: Compared with luminal A cases, luminal B cases were more likely to be younger at diagnosis (P = 0.0001) and were less likely to consume alcohol (OR = 0.74, 95% CI = 0.56 to 0.98), use hormone replacement therapy (HRT) (OR = 0.66, 95% CI = 0.46 to 0.94), and oral contraceptives (OR = 0.73, 95% CI = 0.55 to 0.96). Compared with luminal A cases, triple-negative cases tended to be younger at diagnosis (P < or = 0.0001) and African American (OR = 3.14, 95% CI = 2.12 to 4.16), were more likely to have not breastfed if they had parity greater than or equal to three (OR = 1.68, 95% CI = 1.00 to 2.81), and were more likely to be overweight (OR = 1.82, 95% CI = 1.03 to 3.24) or obese (OR = 1.97, 95% CI = 1.03 to 3.77) if premenopausal. Her2-overexpressing cases were more likely to be younger at diagnosis (P = 0.03) and Hispanic (OR = 2.19, 95% CI = 1.16 to 4.13) or Asian (OR = 2.02, 95% CI = 1.05 to 3.88), and less likely to use HRT (OR = 0.45, 95% CI = 0.26 to 0.79). CONCLUSIONS: These observations suggest that investigators should consider tumor heterogeneity in associations with traditional breast cancer risk factors. Important modifiable lifestyle factors that may be related to the development of a specific tumor subtype, but not all subtypes, include obesity, breastfeeding, and alcohol consumption. Future work that will further categorize triple-negative cases into basal and non-basal tumors may help to elucidate these associations further.
Authors: Kwan ML; Kushi LH; Weltzien E; Maring B; Kutner SE; Fulton RS; Lee MM; Ambrosone CB; Caan BJ
Breast Cancer Res. 2009;11(3):R31. Epub 2009 May 22.
Physical activity and risk of recurrence and mortality in breast cancer survivors: findings from the LACE study
INTRODUCTION: Identifying modifiable factors that reduce the risk of recurrence and improve survival in breast cancer survivors is a pressing concern. The purpose of this study was to examine the association of physical activity following diagnosis and treatment with the risk of breast cancer recurrence and mortality and all-cause mortality in women with early-stage breast cancer. MATERIALS AND METHODS: The sample consisted of 1,970 women from the Life After Cancer Epidemiology study, a prospective investigation of behavioral risk factors and health outcomes. Self-reported frequency and duration of work-related, household and caregiving, recreational, and transportation-related activities during the six months prior to enrollment were assessed. Outcomes were ascertained from electronic or paper medical charts. Hazard ratios and 95% confidence intervals were estimated from delayed entry Cox proportional hazards models. RESULTS: Although age-adjusted results suggested that higher levels of physical activity were associated with reduced risk of recurrence and breast cancer mortality (P for trend = 0.05 and 0.07, respectively for highest versus lowest level of hours per week of moderate physical activity), these associations were attenuated after adjustment for prognostic factors and other confounding variables (P for trend = 0.36 and 0.26). In contrast, a statistically significant protective association between physical activity and all-cause mortality remained in multivariable analyses (hazard ratio, 0.66; 95% confidence interval, 0.42-1.03; P for trend = 0.04). CONCLUSIONS: These findings do not support a protective effect of physical activity on breast cancer recurrence or mortality but do suggest that regular physical activity is beneficial for breast cancer survivors in terms of total mortality.
Authors: Sternfeld B; Weltzien E; Quesenberry CP Jr; Castillo AL; Kwan M; Slattery ML; Caan BJ
Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):87-95.
Declining recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting
INTRODUCTION: Randomized trials indicate that adjuvant radiotherapy plus tamoxifen decrease the five-year risk of recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery from about 20% to 8%. The aims of this study were to examine the use and impact of these therapies on risk of recurrence among ductal carcinoma in situ patients diagnosed and treated in the community setting. METHODS: We identified 2,995 patients diagnosed with ductal carcinoma in situ between 1990 and 2001 and treated with breast-conserving surgery at three large health plans. Medical charts were reviewed to confirm diagnosis and treatment and to obtain information on subsequent breast cancers. On a subset of patients, slides from the index ductal carcinoma in situ were reviewed for histopathologic features. Cumulative incidence curves were generated and Cox regression was used to examine changes in five-year risk of recurrence across diagnosis years, with and without adjusting for trends in use of adjuvant therapies. RESULTS: Use of radiotherapy increased from 25.8% in 1990-1991 to 61.3% in 2000-2001; tamoxifen increased from 2.3% to 34.4%. A total of 245 patients had a local recurrence within five years of their index ductal carcinoma in situ. The five-year risk of any local recurrence decreased from 14.3% (95% confidence interval 9.8 to 18.7) for patients diagnosed in 1990-1991 to 7.7% (95% confidence interval 5.5 to 9.9) for patients diagnosed in 1998-1999; invasive recurrence decreased from 7.0% (95% confidence interval 3.8 to 10.3) to 3.1% (95% confidence interval 1.7 to 4.6). In Cox models, the association between diagnosis year and risk of recurrence was modestly attenuated after accounting for use of adjuvant therapy. Between 1990-1991 and 2000-2001, the proportion of patients with tumors with high nuclear grade decreased from 46% to 32% (P = 0.03) and those with involved surgical margins dropped from 15% to 0% (P = 0.03). CONCLUSIONS: The marked increase in the 1990s in the use of adjuvant therapy for ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting only partially explains the 50% decline in risk of recurrence. Changes in pathology factors have likely also contributed to this decline.
Authors: Habel LA; Achacoso NS; Haque R; Nekhlyudov L; Fletcher SW; Schnitt SJ; Collins LC; Geiger AM; Puligandla B; Acton L; Quesenberry CP Jr
Breast Cancer Res. 2009;11(6):R85. Epub 2009 Nov 18.
Meeting report: consensus statement-Parkinson’s disease and the environment: collaborative on health and the environment and Parkinson’s Action Network (CHE PAN) conference 26-28 June 2007
BACKGROUND: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. METHODS: In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. RESULTS: We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. CONCLUSIONS: PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.
Authors: Bronstein J; Van Den Eeden S; Weisskopf M; et al.
Environ Health Perspect. 2009 Jan;117(1):117-21. Epub 2008 Aug 26.
Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors
Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and TP16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population-based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and TP16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis.
Authors: Sweeney C; Boucher KM; Samowitz WS; Wolff RK; Albertsen H; Curtin K; Caan BJ; Slattery ML
Genes Chromosomes Cancer. 2009 Jan;48(1):1-9.
Nutritional factors in ovarian cancer survival
Ovarian cancer is the leading cause of death from gynecologic malignancies in the United States. Because symptoms tend be nonspecific, early detection is difficult, and most ovarian cancers are diagnosed at an advanced stage when the prognosis is poor. Nonetheless, there is clinical evidence that even given the same tumor characteristics (histologic type, stage, and grade), some cases experience much better survival than others. This has led to extensive research on molecular prognostic factors to enable more efficient and targeted therapeutic regimens. However, little is known about the impact that lifestyle factors, such as diet or physical activity, may have in the prognosis of ovarian cancer, whether on disease-free survival or on the response to and complications from treatment. The role of obesity on ovarian cancer survival is unclear. Obesity may delay diagnosis, hinder optimal surgical and cytotoxic treatment, and cause postoperative complications. As overweight and obesity rates reach epidemic proportions, the impact of body mass index in the clinical management of ovarian cancer is increasingly significant, whereas current evidence of its impact is limited and inconclusive.
Authors: Bandera EV; Kushi LH; Rodriguez-Rodriguez L
Nutr Cancer. 2009;61(5):580-6.
Effects of dietary fiber, fats, and meat intakes on the risk of Barrett’s esophagus
Animal and human models suggest associations between fat intake, fiber intake, and the risk of esophageal adenocarcinoma. We evaluated whether these factors may act early in the carcinogenic pathway as a risk factor for Barrett’s esophagus, a potentially premalignant precursor to esophageal adenocarcinoma using a case-control design within the Kaiser Permanente, Northern California population. Incident Barrett’s esophagus cases (n = 296) were matched to persons with gastroesophageal reflux disease (GERD) (n = 308) and to population controls (n = 309). Higher intakes of omega-3-fatty-acids [cases vs. population controls; OR = 0.46, 95% CI = 0.22-0.97, 4th vs. 1st quartiles of intake], polyunsaturated fat, total fiber (OR = 0.34, 95% CI = 0.15-0.76), and fiber from fruits and vegetables (OR = 0.47 95% CI = 0.25-0.88) were associated with a lower risk of Barrett’s esophagus. Higher meat intakes were associated with a lower risk of long-segment Barrett’s esophagus (OR = 0.25, 95% CI = 0.09-0.72). In contrast, higher trans-fat intakes were associated with increased risk (OR = 1.11; 95% CI = 1.03-1.21 per g/day). Total fat intake, barbecued foods, and fiber intake from sources other than fruits and vegetables were not associated with Barrett’s esophagus. Future studies to evaluate whether dietary interventions might influence the risk of Barrett’s esophagus or esophageal adenocarcinoma in high risk persons are needed.
Authors: Kubo A; Block G; Quesenberry CP Jr; Buffler P; Corley DA
Nutr Cancer. 2009;61(5):607-16.
Mothers of children diagnosed with attention-deficit/hyperactivity disorder: health conditions and medical care utilization in periods before and after birth of the child
BACKGROUND: Analyzing health conditions and medical utilization of mothers of children with attention-deficit/hyperactivity disorder (ADHD) can shed light on biologic, environmental, and psychosocial factors relating to ADHD. OBJECTIVE: To examine health conditions, health care utilization, and costs of mothers of children with ADHD in periods before the child was diagnosed. METHODS: Using automated data from Northern California Kaiser Permanente we identified mothers of children with ADHD, mothers of children without ADHD, and mothers of children with asthma. Mothers’ diagnostic clusters, health care utilization, and costs were compared. Mothers of children with ADHD were compared with mothers of children without ADHD and, separately, to mothers of children with asthma. RESULTS: Compared with mothers of children without ADHD, mothers of children with ADHD were more likely to be diagnosed with numerous medical and mental health problems in the 2 years after birth of their child, including depression [odds ratio (OR): 1.88], anxiety neuroses (OR: 1.64), obesity (OR: 1.70), and musculoskeletal symptoms (OR: 1.51). Results were similar for the year before delivery. Mothers of children with ADHD also had higher total health care costs per person in the year before ($1,003) and the 2 years after ($953) the birth of their child. Mothers of children with ADHD also were diagnosed with more health conditions and had higher health care costs than mothers of children with asthma. CONCLUSIONS: Our findings suggest that the likelihood of being diagnosed with ADHD is related to maternal conditions and use of health services that precede the child’s diagnosis. Future studies are needed to clarify whether this is due to biologic, psychosocial, or environmental factors, or a combination.
Authors: Ray GT; Croen LA; Habel LA
Med Care. 2009 Jan;47(1):105-14.
Generational status and duration of residence predict diabetes prevalence among Latinos: the California Men’s Health Study
BACKGROUND: Diabetes disproportionately affects Latinos. However, examining Latinos as one group obscures important intra-group differences. This study examined how generational status, duration of US residence, and language preference are associated with diabetes prevalence and to what extent these explain the higher prevalence among Latinos. METHODS: We determined nativity, duration of US residence, language preference, and diabetes prevalence among 11 817 Latino, 6109 black, and 52 184 white participants in the California Men’s Health Study. We combined generational status and residence duration into a single migration status variable with levels: > or = third generation; second generation; and immigrant living in the US for > 25, 16-25, 11-15, or < or = 10 years. Language preference was defined as language in which the participant took the survey. Logistic regression models were specified to assess the associations of dependent variables with prevalent diabetes. RESULTS: Diabetes prevalence was 22%, 23%, and 11% among Latinos, blacks, and whites, respectively. In age-adjusted models, we observed a gradient of risk of diabetes by migration status among Latinos. Further adjustment for socioeconomic status, obesity and health behaviors only partially attenuated this gradient. Language preference was a weak predictor of prevalent diabetes in some models and not significant in others. In multivariate models, we found that odds of diabetes were higher among US-born Latinos than US-born blacks. CONCLUSION: Generational status and residence duration were associated with diabetes prevalence among middle-aged Latino men in California. As the Latino population grows, the burden of diabetes-associated disease is likely to increase and demands public health attention.
Authors: Ahmed AT; Quinn VP; Caan B; Sternfeld B; Haque R; Van den Eeden SK
BMC Public Health. 2009 Oct 19;9:392.
The Pathways Study: a prospective study of breast cancer survivorship within Kaiser Permanente Northern California
OBJECTIVE: With 2.3 million breast cancer survivors in the US today, identification of modifiable factors associated with breast cancer recurrence and survival is increasingly important. Only recently new studies have been designed to examine the impact of lifestyle factors on prognosis, including Pathways, a prospective study of women with breast cancer in Kaiser Permanente Northern California (KPNC). METHODS: Pathways aims to examine the effect on recurrence and survival of (1) lifestyle factors such as diet, physical activity, quality of life, and use of alternative therapies and (2) molecular factors such as genetic polymorphisms involved in metabolism of chemotherapeutic agents. Eligibility includes any woman diagnosed with invasive breast cancer within KPNC, no previous diagnosis of other invasive cancer, age 21 years or older, and ability to speak English, Spanish, Cantonese, or Mandarin. Newly diagnosed patients are identified daily from electronic pathology records and are enrolled within two months of diagnosis. An extensive baseline interview is conducted, blood and saliva samples are collected, and body measurements are taken. Women are followed for lifestyle updates, treatment, and outcomes by self-report and query of KPNC databases. RESULTS: Recruitment began in 9 January, 2006, and as of 16 January, 2008, 1,539 women have been enrolled along with collection of 1,323 blood samples (86%) and 1,398 saliva samples (91%). CONCLUSIONS: The Pathways Study will become a rich resource to examine behavioral and molecular factors and breast cancer prognosis.
Authors: Kwan ML; Ergas IJ; Caan BJ; Quesenberry CP; Kushi LH; et al.
Cancer Causes Control. 2008 Dec;19(10):1065-76. Epub 2008 May 14.
Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis among women with early stage breast cancer
OBJECTIVE: We examined the association between body mass index (BMI) around the time of diagnosis, weight change post-diagnosis, and breast cancer prognosis in a prospective cohort study of 1,692 breast cancer survivors. METHODS: Pre-diagnosis weight, weight at study entry, and height was obtained from mailed questionnaires and then weight change and BMI were calculated. After approximately seven years of follow-up, 207 recurrences, 99 deaths due to breast cancer, and 162 deaths due to any cause were reported. Delayed entry Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI), controlling for treatment and known prognostic factors. RESULTS: Being obese one year before diagnosis was associated with an increased risk of death from any cause (HR = 1.6; 95% CI: 1.1-2.3) and a suggestion of increased risk of death from breast cancer (HR = 1.6; 95% CI: 0.9-2.7). However, weight gain up to four years after a breast cancer diagnosis was not associated with an increased risk of recurrence or death from any cause nor did moderate weight loss (5-10%) decrease risk of these outcomes. There was some evidence that women who had larger weight losses (>or=10%) between pre-diagnosis and study entry had an increased risk of recurrence (HR = 1.7; 95% CI 1.0-2.6) and death due to any cause (HR = 2.1; 95% CI 1.3-3.4) compared to being weight stable. This elevated risk was more pronounced among women who were obese before diagnosis (BMI >or= 30 kg/m(2)) or who had ER- or PR- tumors. CONCLUSION: We found that being obese before breast cancer diagnosis was associated with increased risk of recurrence and poorer survival, corroborating results from previous studies. However, weight gain after diagnosis did not confer additional risk. Body weight pre-diagnosis appears to be the strongest predictor of an adverse breast cancer prognosis.
Authors: Caan BJ; Kwan ML; Hartzell G; Castillo A; Slattery ML; Sternfeld B; Weltzien E
Cancer Causes Control. 2008 Dec;19(10):1319-28. Epub 2008 Aug 28.
Hemochromatosis gene status as a risk factor for Barrett’s esophagus
Conditions causing high iron levels, such as hemochromatosis, are proposed risk factors for esophageal adenocarcinoma. Although this hypothesis is supported by animal models, no human data currently exist. We conducted a case-control study of persons with a new Barrett’s esophagus diagnosis (cases), persons with gastroesophageal reflux disease (GERD) (without Barrett’s esophagus), and population controls. Subjects completed detailed examinations and assays for hemochromatosis mutations and serum iron stores. We evaluated 317 cases, 306 GERD patients, and 308 population controls. There was no significant association between Barrett’s esophagus and any hemochromatosis gene defect (odds ratio [OR] = 1.32, 95% confidence interval [CI]: 0.95-1.84), a moderate or severe mutation (OR = 1.54, 95% CI: 0.94-2.52), or a severe mutation (C282Y homozygote or C282Y/H63D heterozygote; OR = 0.77, 95% CI: 0.24-2.48) compared with the population controls. As expected, gene defects were associated with increased iron stores. We can conclude from our findings that Barrett’s esophagus was not associated with hemochromatosis gene defects, although we cannot exclude small effects.
Authors: Corley DA; Kubo A; Levin TR; Block G; Habel L; Rumore GJ; Quesenberry C; Buffler P
Dig Dis Sci. 2008 Dec;53(12):3095-102. Epub 2008 May 10.
Iron intake and body iron stores as risk factors for Barrett’s esophagus: a community-based study
OBJECTIVE: High iron stores are a proposed modifiable risk factor for esophageal adenocarcinoma, but minimal human data exist. We evaluated whether iron intake and iron stores were associated with Barrett’s esophagus, a metaplastic change that is a strong risk factor for esophageal adenocarcinoma. METHODS: We conducted a case-control study within the Kaiser Permanente Northern California population. We identified all persons with a new diagnosis of Barrett’s esophagus (cases); they were matched to persons with GERD (without Barrett’s esophagus) and to population controls. Subjects completed examinations, dietary questionnaires, and testing for serum iron stores (ferritin and transferrin saturation). Analyses used unconditional logistic regression. RESULTS: We evaluated 319 cases, 312 GERD patients, and 313 population controls. Compared with population controls, Barrett’s esophagus patients had lower dietary iron intakes (4th vs 1st quartiles, odds ratio [OR]= 0.37, 95% confidence interval [CI] 0.17-0.80), similar total iron intakes (including supplement use), and lower iron stores (4th vs 1st quartiles, ferritin OR = 0.24, 95% CI 0.14-0.40;% transferrin saturation OR = 0.66, 95% CI 0.41-1.04; P value trend <0.01 and 0.03, respectively). Similar associations were observed in comparisons with GERD controls and among subjects without clear sources of blood loss on endoscopy. CONCLUSIONS: Patients with Barrett's esophagus had lower dietary iron intakes and lower serum iron stores than controls in our population. These findings do not provide support for the current hypothesis that high iron stores or a high iron intake are risk factors for Barrett's esophagus, a potential early event in the carcinogenic sequence for esophageal adenocarcinoma.
Authors: Corley DA; Kubo A; Levin TR; Habel L; Zhao W; Leighton P; Rumore G; Quesenberry C; Buffler P; Block G
Am J Gastroenterol. 2008 Dec;103(12):2997-3004. Epub 2008 Oct 1.
Thiazolidinedione therapy is not associated with increased colonic neoplasia risk in patients with diabetes mellitus
BACKGROUND & AIMS: Thiazolidinedione ligands for peroxisome proliferator-activated receptor gamma (PPARgamma), are used to treat diabetes. PPARgamma is highly expressed in the colon, and exposure to thiazolidinediones has been proposed to affect the risk for colorectal neoplasia. In vitro models suggest that thiazolidinediones have antineoplastic effects, whereas in vivo studies have produced mixed results: Some indicate an increased risk for intestinal tumors. This study examined the association between PPARgamma-targeted therapies and the risk of colonic neoplasia in patients with diabetes. METHODS: We conducted 3 retrospective case-control studies nested within the cohort of diabetic patients who were cared for within the Kaiser Permanente of Northern California system from 1994 to 2005. Case subjects were those with colonic neoplasia identified at the time of colonoscopy (study 1), sigmoidoscopy (study 2), or at follow-up lower endoscopy (study 3). Controls had no neoplasia identified at the endoscopic examination. A minimum of 1 year of therapy was used to define medication exposure. RESULTS: Fourteen thousand eighty-six patients were included. Among patients undergoing colonoscopy, there was an inverse association between thiazolidinedione exposure and prevalence of neoplasia (adjusted odd ratio [OR], 0.73; 95% confidence interval [CI], 0.57-0.92); however, this was not evident among patients without anemia (adjusted OR, 0.97; 95% CI, 0.64-1.49). Significant associations between any or long-term thiazolidinedione use and colonic neoplasia were not observed among patients undergoing sigmoidoscopy or serial lower endoscopies. CONCLUSIONS: These results indicate that thiazolidinedione therapy is not associated with an increased risk for colonic neoplasia.
Authors: Lewis JD; Capra AM; Achacoso NS; Ferrara A; Levin TR; Quesenberry CP Jr; Habel LA
Gastroenterology. 2008 Dec;135(6):1914-23, 1923.e1. Epub 2008 Sep 13.
Calcium plus vitamin D supplementation and the risk of breast cancer
BACKGROUND: Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships. METHODS: Postmenopausal women (N = 36 282) who were enrolled in a Women’s Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided. RESULTS: Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (P(trend) = .20). CONCLUSIONS: Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.
Authors: Chlebowski RT; Khandekar J; Women's Health Initiative Investigators; et al.
J Natl Cancer Inst. 2008 Nov 19;100(22):1581-91. Epub 2008 Nov 11.
Refinement and psychometric evaluation of the impact of cancer scale
BACKGROUND: Instruments are needed to measure the influence of cancer on quality of life in the expanding population of long-term cancer survivors. We conducted refinement and psychometric evaluation of the Impact of Cancer (IOC) scale by use of data from a large sample of long-term breast cancer survivors and developed an instrument, the Impact of Cancer version 2 (IOCv2), to measure quality of life outcomes. METHODS: Questionnaires including 81 potential IOC scale items, the Center for Epidemiologic Studies-Depression (CES-D) scale, and the Breast Cancer Prevention Trial (BCPT) symptom scales, as well as demographic, treatment, and medical information, were completed by 1188 disease-free breast cancer survivors 5-10 years after diagnosis. We used exploratory factor analysis to identify scales and assessed reproducibility by split-sample cross-validation. Higher-order scales were extracted and all scales were evaluated for internal consistency and construct and concurrent validity. RESULTS: The analysis yielded a factor structure relating IOC items to psychosocial impact domains that exhibited high factor loadings (factor-item correlations of 0.59-0.94), high internal consistency (Cronbach’s alpha statistics of 0.76-0.89), and a total congruence of 0.98 across the split samples. The Impact of Cancer version 2 (IOCv2) scales consist of a Positive Impact Summary scale with four subscales (Altruism and Empathy, Health Awareness, Meaning of Cancer, and Positive Self-Evaluation), a Negative Impact Summary scale with four subscales (Appearance Concerns, Body Change Concerns, Life Interferences, and Worry), and subscales for Employment and Relationship Concerns. Patterns of association between IOCv2 scale scores and CES-D and BCPT scores indicated good concurrent validity. Patterns of associations between IOCv2 scale scores and demographic, medical, and treatment characteristics indicated good construct validity. CONCLUSION: The IOCv2 scales provide a validated tool for measuring the impact of cancer on quality of life in long-term cancer survivors.
Authors: Crespi CM; Ganz PA; Petersen L; Castillo A; Caan B
J Natl Cancer Inst. 2008 Nov 5;100(21):1530-41. Epub 2008 Oct 28.
Menstrual and reproductive factors in relation to mammographic density: the Study of Women’s Health Across the Nation (SWAN)
Menstrual and reproductive factors may increase breast cancer risk through a pathway that includes increased mammographic density. We assessed whether known or suspected menstrual and reproductive breast cancer risk factors were cross-sectionally associated with mammographic density, by measuring area of radiographic density and total breast area on mammograms from 801 participants in the Study of Women’s Health Across the Nation (SWAN), a multi-ethnic cohort of pre- and early perimenopausal women. From multivariable linear regression, the following menstrual or reproductive factors were independently associated with percent mammographic density (area of dense breast/breast area): older age at menarche (beta=10.3, P<0.01, for >13 vs. <12 years), premenstrual cravings and bloating (beta=-3.36, P=0.02), younger age at first full-term birth (beta=-8.12, P<0.01 for
Authors: Butler LM; Gold EB; Greendale GA; Crandall CJ; Modugno F; Oestreicher N; Quesenberry CP Jr; Habel LA
Breast Cancer Res Treat. 2008 Nov;112(1):165-74. Epub 2007 Dec 9.
Mutation rates of TGFBR2 and ACVR2 coding microsatellites in human cells with defective DNA mismatch repair.
Microsatellite instability promotes colonic tumorigenesis through generating frameshift mutations at coding microsatellites of tumor suppressor genes, such as TGFBR2 and ACVR2. As a consequence, signaling through these TGFbeta family receptors is abrogated in DNA Mismatch repair (MMR)-deficient tumors. How these mutations occur in real time and mutational rates of these human coding sequences have not previously been studied. We utilized cell lines with different MMR deficiencies (hMLH1-/-, hMSH6-/-, hMSH3-/-, and MMR-proficient) to determine mutation rates. Plasmids were constructed in which exon 3 of TGFBR2 and exon 10 of ACVR2 were cloned +1 bp out of frame, immediately after the translation initiation codon of an enhanced GFP (EGFP) gene, allowing a -1 bp frameshift mutation to drive EGFP expression. Mutation-resistant plasmids were constructed by interrupting the coding microsatellite sequences, preventing frameshift mutation. Stable cell lines were established containing portions of TGFBR2 and ACVR2, and nonfluorescent cells were sorted, cultured for 7-35 days, and harvested for flow cytometric mutation detection and DNA sequencing at specific time points. DNA sequencing revealed a -1 bp frameshift mutation (A9 in TGFBR2 and A7 in ACVR2) in the fluorescent cells. Two distinct fluorescent populations, M1 (dim, representing heteroduplexes) and M2 (bright, representing full mutants) were identified, with the M2 fraction accumulating over time. hMLH1 deficiency revealed 11 (5.91 x 10(-4)) and 15 (2.18 x 10(-4)) times higher mutation rates for the TGFBR2 and ACVR2 microsatellites compared to hMSH6 deficiency, respectively. The mutation rate of the TGFBR2 microsatellite was approximately 3 times higher in both hMLH1 and hMSH6 deficiencies than the ACVR2 microsatellite. The -1 bp frameshift mutation rates of TGFBR2 and ACVR2 microsatellite sequences are dependent upon the human MMR background.
Authors: Chung, Heekyung H; Young, Dennis J DJ; Lopez, Claudia G CG; Le, Thuy-Anh T TA; Lee, Jeffrey K JK; Ream-Robinson, Deena D; Huang, Sherry C SC; Carethers, John M JM
PloS one. 2008 ;3(10):e3463. Epub 2008-10-21.
Stool DNA and occult blood testing for screen detection of colorectal neoplasia
BACKGROUND: Stool DNA testing is a new approach to colorectal cancer detection. Few data are available from the screening setting. OBJECTIVE: To compare stool DNA and fecal blood testing for detection of screen-relevant neoplasia (curable-stage cancer, high-grade dysplasia, or adenomas >1 cm). DESIGN: Blinded, multicenter, cross-sectional study. SETTING: Communities surrounding 22 participating academic and regional health care systems in the United States. PARTICIPANTS: 4482 average-risk adults. MEASUREMENTS: Fecal blood and DNA markers. Participants collected 3 stools, smeared fecal blood test cards and used same-day shipment to a central facility. Fecal blood cards (Hemoccult and HemoccultSensa, Beckman Coulter, Fullerton, California) were tested on 3 stools and DNA assays on 1 stool per patient. Stool DNA test 1 (SDT-1) was a precommercial 23-marker assay, and a novel test (SDT-2) targeted 3 broadly informative markers. The criterion standard was colonoscopy. RESULTS: Sensitivity for screen-relevant neoplasms was 20% by SDT-1, 11% by Hemoccult (P = 0.020), 21% by HemoccultSensa (P = 0.80); sensitivity for cancer plus high-grade dysplasia did not differ among tests. Specificity was 96% by SDT-1, compared with 98% by Hemoccult (P < 0.001) and 97% by HemoccultSensa (P = 0.20). Stool DNA test 2 detected 46% of screen-relevant neoplasms, compared with 16% by Hemoccult (P < 0.001) and 24% by HemoccultSensa (P < 0.001). Stool DNA test 2 detected 46% of adenomas 1 cm or larger, compared with 10% by Hemoccult (P < 0.001) and 17% by HemoccultSensa (P < 0.001). Among colonoscopically normal patients, the positivity rate was 16% with SDT-2, compared with 4% with Hemoccult (P = 0.010) and 5% with HemoccultSensa (P = 0.030). LIMITATIONS: Stool DNA test 2 was not performed on all subsets of patients without screen-relevant neoplasms. Stools were collected without preservative, which reduced detection of some DNA markers. CONCLUSION: Stool DNA test 1 provides no improvement over HemoccultSensa for detection of screen-relevant neoplasms. Stool DNA test 2 detects significantly more neoplasms than does Hemoccult or HemoccultSensa, but with more positive results in colonoscopically normal patients. Higher sensitivity of SDT-2 was particularly apparent for adenomas.
Authors: Ahlquist DA; Levin TR; Allison JE; Hillman SL; et al.
Ann Intern Med. 2008 Oct 7;149(7):441-50, W81.
Alcoholic beverage intake and risk of lung cancer: the California Men’s Health Study
We investigated the effect of alcoholic beverage consumption on the risk of lung cancer using the California Men’s Health Study. METHODS: The California Men’s Health Study is a multiethnic cohort of 84,170 men ages 45 to 69 years who are members of the Kaiser Permanente California health plans. Demographics and detailed lifestyle characteristics were collected from surveys mailed between 2000 and 2003. Incident lung cancer cases were identified by health plan cancer registries through December 2006 (n=210). Multivariable Cox’s regression was used to examine the effects of beer, red wine, white wine (including rose), and liquor consumption on risk of lung cancer adjusting for age, race/ethnicity, education, income, body mass index, history of chronic obstructive pulmonary disease/emphysema, and smoking history. RESULTS: There was a significant linear decrease in risk of lung cancer associated with consumption of red wine among ever-smokers: hazard ratio (HR), 0.98; 95% confidence interval (95% CI), 0.96-1.00 for increase of 1 drink per month. This relationship was slightly stronger among heavy smokers (>or=20 pack-years): HR, 0.96; 95% CI, 0.93-1.00. When alcoholic beverage consumption was examined by frequency of intake, consumption of >or=1 drink of red wine per day was associated with an approximately 60% reduced lung cancer risk in ever-smokers: HR, 0.39; 95% CI, 0.14-1.08. No clear associations with lung cancer were seen for intake of white wine, beer, or liquor. CONCLUSION: Moderate red wine consumption was inversely associated with lung cancer risk after adjusting for confounders. Our results should not be extrapolated to heavy alcohol consumption.
Authors: Chao C; Slezak JM; Caan BJ; Quinn VP
Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2692-9.
Genetic variation in calcium-sensing receptor and risk for colon cancer
BACKGROUND: Experimental and epidemiologic studies have suggested that high calcium intake is associated with decreased colon cancer risk, yet very limited data are available for candidate genes in the calcium-vitamin D pathway and colon cancer risk. To address this, we evaluated whether calcium-sensing receptor (CASR) single-nucleotide polymorphisms are associated with colon cancer risk. We also examined interactions among CASR, calcium, and vitamin D intake and previously genotyped vitamin D-related genes. METHODS: We conducted a large multicenter population-based case-control study of 1,600 cases and 1,949 controls. Seventeen tagging single-nucleotide polymorphisms for CASR were selected from common single-nucleotide polymorphisms (minor allele frequency, >or=5%) based on resequencing data. Haplotypes were estimated and evaluated using HaploStats. RESULTS: We did not observe an association between any CASR genotypes or haplotypes and colon cancer risk overall. However, when stratified by anatomic site, statistically significant associations were seen with risk for proximal colon cancer [rs10934578 TT: odds ratio, 1.35; 95% confidence interval (95% CI), 1.01-1.81; rs12485716 AG/AA: odds ratio, 0.84; 95% CI, 0.71-1.00; rs4678174 CT/CC: odds ratio, 0.83; 95% CI, 0.70-0.98; rs2270916 CC: odds ratio, 0.43; 95% CI, 0.19-0.97]. Concordantly, we observed a suggested association for a CASR haplotype (rs4678174, rs2270916) with risk for proximal colon cancer (global P=0.08). We did not observe any meaningful gene-environment (calcium and vitamin D) or gene-gene (CYP24A1, CYP27B1, and VDR) interactions with CASR genotypes and colon cancer risk. CONCLUSION: Our study does not provide evidence for an overall association between CASR single-nucleotide polymorphisms and colon cancer; however, results suggest a possible role of CASR on proximal colon cancer, and subsite differences are consistent with known calcium biology. Nonetheless, these findings require confirmation.
Authors: Dong LM; Ulrich CM; Hsu L; Duggan DJ; Benitez DS; White E; Slattery ML; Caan BJ; Potter JD; Peters U
Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2755-65.
The MLH1 -93 G>A promoter polymorphism and genetic and epigenetic alterations in colon cancer
The MLH1 -93 G>A promoter polymorphism has been reported to be associated with an increased risk of microsatellite unstable colorectal cancer. Other than microsatellite instability, however, the genetic and most epigenetic changes of tumors associated with this polymorphism have not been studied. We evaluated associations between the -93 G>A polymorphism and CpG island methylator phenotype (CIMP), BRAF V600E mutations, and MLH1 methylation in tumors from a sample of 1,211 individuals with colon cancer and 1,968 controls from Utah, Northern California, and Minnesota. The -93 G>A polymorphism was determined by the five prime nuclease assay. CIMP was determined previously by methylation-specific PCR of CpG islands in MLH1, methylated in tumors (MINT)1, MINT2, MINT31, and CDKN2A (p16). The BRAF V600E mutation was determined by sequencing exon 15. The MLH1 -93 G>A promoter polymorphism was associated with CIMP (odds ratio (OR) 3.44, 95% confidence interval (CI) 1.85, 6.42), MLH1 methylation (OR 4.16, 95%CI 2.20, 7.86), BRAF mutations (OR 4.26, 95%CI 1.83, 9.91), and older age at diagnosis (OR 3.65, 95%CI 2.08, 6.39) in microsatellite unstable tumors. These associations were not observed in stable tumors. Increased age at diagnosis and tumor characteristics of microsatellite unstable tumors associated with MLH1 -93 G>A suggests the polymorphism is acting at a relatively late stage of colorectal carcinogenesis to drive CIMP+ tumors down the microsatellite instability pathway.
Authors: Samowitz WS; Curtin K; Wolff RK; Albertsen H; Sweeney C; Caan BJ; Ulrich CM; Potter JD; Slattery ML
Genes Chromosomes Cancer. 2008 Oct;47(10):835-44.
Helicobacter pylori and gastroesophageal reflux disease: a case-control study
BACKGROUND: Gastric colonization with Helicobacter pylori is a proposed protective factor against gastroesophageal reflux disease (GERD), but little population-based data exist and other data conflict. METHODS: We conducted a case-control study within the membership of a large integrated health-care system that compared GERD-free subjects with two groups: subjects with a physician-assigned GERD diagnosis and randomly selected members with self-described weekly GERD symptoms. Subjects completed interviews, GERD questionnaires, and antibody testing for H. pylori and its cagA protein. RESULTS: Serologic data were available for 301 physician-assigned GERD patients, 81 general membership subjects with GERD symptoms, and 175 general membership subjects without GERD symptoms. Physician-assigned GERD patients were less likely to have H. pylori antibodies than GERD-free member controls (odds ratio (OR) = 0.27, 95% confidence interval (CI) 0.15-0.47); there was also an inverse association between H. pylori and GERD symptom severity (OR = 0.18, 95% CI 0.08-0.41; severe or very severe symptoms) and GERD frequency (OR = 0.18, 95% CI 0.09-0.38; for symptoms at least weekly). The association was stronger among persons with erosive GERD and was similar between H. pylori-positive subjects with and without cagA. There was no association among persons who were cagA positive, but H. pylori negative. Similar findings were found in analyses of the general membership with self-described GERD symptoms. CONCLUSIONS: H. pylori antibody status was inversely associated with a GERD diagnosis and GERD symptoms compared with a general membership population.
Authors: Corley DA; Kubo A; Levin TR; Block G; Habel L; Rumore G; Quesenberry C; Buffler P; Parsonnet J
Helicobacter. 2008 Oct;13(5):352-60.
Comparison of baseline dietary intake of Hispanic and matched non-Hispanic white breast cancer survivors enrolled in the Women’s Healthy Eating and Living study
OBJECTIVE: To assess the reported baseline dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women’s Healthy Eating and Living study, a randomized plant-based dietary intervention clinical trial. DESIGN: Dietary data from 4 days repeated 24-hour recalls within 3 weeks included daily total intake of energy, protein, carbohydrates, cholesterol, total fat, monounsaturated fat, saturated fat, polyunsaturated fat, fruit/vegetable servings, carotenoids, alcohol, caffeine, and percentage of energy from protein, carbohydrates, alcohol, and fats. SUBJECTS: One hundred sixty-five Hispanic breast cancer survivors age-matched to 165 non-Hispanic white breast cancer survivors diagnosed with Stage I, II, or IIIA primary operable breast cancer. STATISTICAL ANALYSES: Two-sample t tests and Wilcoxon rank sum tests to compare dietary intake, and logistic and ordinal logistic regression analyses to examine the association between ethnicity, alcohol, and lycopene consumption, while controlling for place of birth, education, body mass index, and time since diagnosis. RESULTS: Hispanics were more likely to be foreign-born (P<0.001), less educated (P<0.0001) and to consume higher amounts of lycopene (P=0.029), while non-Hispanic whites were more likely to consume alcohol (P=0.001). However, no differences were observed in the average amounts of alcohol consumed or total percents of energy from alcohol. Both groups consumed more than five servings of fruits and vegetables daily. Being Hispanic remained a significant predictor of lower alcohol use (P=0.004) and higher lycopene consumption (P=0.005) after controlling for place of birth, education, body mass index, and time since diagnosis. CONCLUSIONS: There are more similarities than differences in the dietary intake of Hispanic and non-Hispanic white breast cancer survivors in the Women's Healthy Eating and Living study. Further analysis is needed to determine if higher lycopene consumption shown among the Hispanic participants will translate to greater protection against breast cancer recurrence or increased survival.
Authors: Hernandez-Valero MA; Thomson CA; Hernandez M; Tran T; Detry MA; Theriault RL; Hajek RA; Pierce JP; Flatt SW; Caan BJ; Jones LA
J Am Diet Assoc. 2008 Aug;108(8):1323-9.
Low-fat dietary pattern and risk of treated diabetes mellitus in postmenopausal women: the Women’s Health Initiative randomized controlled dietary modification trial
BACKGROUND: Decreased fat intake with weight loss and increased exercise may reduce the risk of diabetes mellitus in persons with impaired glucose tolerance. This study was undertaken to assess the effects of a low-fat dietary pattern on incidence of treated diabetes among generally healthy postmenopausal women. METHODS: A randomized controlled trial was conducted at 40 US clinical centers from 1993 to 2005, including 48,835 postmenopausal women aged 50 to 79 years. Women were randomly assigned to a usual-diet comparison group (n = 29,294 [60.0%]) or an intervention group with a 20% low-fat dietary pattern with increased vegetables, fruits, and grains (n = 19,541 [40.0%]). Self-reported incident diabetes treated with oral agents or insulin was assessed. RESULTS: Incident treated diabetes was reported by 1303 intervention participants (7.1%) and 2039 comparison participants (7.4%) (hazard ratio, 0.96; 95% confidence interval, 0.90-1.03; P = .25). Weight loss occurred in the intervention group, with a difference between intervention and comparison groups of 1.9 kg after 7.5 years (P < .001). Subgroup analysis suggested that greater decreases in percentage of energy from total fat reduced diabetes risk (P for trend = .04), which was not statistically significant after adjusting for weight loss. CONCLUSIONS: A low-fat dietary pattern among generally healthy postmenopausal women showed no evidence of reducing diabetes risk after 8.1 years. Trends toward reduced incidence were greater with greater decreases in total fat intake and weight loss. Weight loss, rather than macronutrient composition, may be the dominant predictor of reduced risk of diabetes.
Authors: Tinker LF; Larson J; Women's Health Initiative; et al.
Arch Intern Med. 2008 Jul 28;168(14):1500-11.
Evidence for colorectal sarcomatoid carcinoma arising from tubulovillous adenoma.
Sarcomatoid carcinomas of the colorectum are rare tumors that display both malignant epithelial and stromal components. Clinically, they are aggressive tumors with early metastasis. Due to their infrequent occurrence, the pathogenesis is poorly understood. We report a case of a 52-year-old woman who presented with a rectal mass and intermittent hematochezia. Superficial biopsies during colonoscopy revealed a tubulovillous adenoma with high-grade dysplasia. Endoscopic ultrasonography confirmed an invasive nature of the mass, and deeper biopsies revealed the presence of neoplasm with mixed histological components. The surgically-excised specimen demonstrated the presence of poorly differentiated spindle cells underneath the tubulovillous adenoma and an intermediate stage of invasive adenocarcinoma. Based on the histological appearance and immunohistochemical studies, a diagnosis of sarcomatoid carcinoma was made. Only nine cases of sarcomatoid carcinomas of the colorectum have been reported to date. As a result, the terminology and pathogenesis of sarcomatoid carcinoma remain speculative. To the best of our knowledge, this is the first report of co-existence of sarcomatoid carcinoma and invasive adenocarcinoma with tubulovillous adenoma; all stages represented within the same tumor. This observation supports the "monoclonal theory" of pathogenesis with an adenoma-sarcoma progression with or without an intermediate stage of carcinoma.
Authors: Lee, Jeffrey-K JK; Ghosh, Pradipta P; McWhorter, Valerie V; Payne, Misty M; Olson, Ryan R; Krinsky, Mary-L ML; Ramamoorthy, Sonia S; Carethers, John-M JM
World journal of gastroenterology. 2008 Jul 21;14(27):4389-94. Epub --.
Association of Preexisting Symptoms with Treatment Decisions among Newly Diagnosed Prostate Cancer Patients
BACKGROUND: The choice between surgical versus non-surgical treatment options is a fundamental decision for men with local stage prostate cancer because of differences in risks of genitourinary side effects among available treatments. OBJECTIVES: We assessed whether preexisting genitourinary symptoms at the time of diagnosis influenced men’s preferences for surgery versus other management options. METHODS: We recruited 593 patients with newly diagnosed local stage prostate cancer prior to initiating treatment from an integrated health care system, an academic urology center, and community urology clinics. Using logistic regression we compared whether men had a preference for non-surgical options or only preferred surgery. RESULTS: Nearly 60% indicated they were considering non-surgical options. Age and clinical characteristics but not preexisting genitourinary symptoms influenced the decision between preferences for surgical or non-surgical options. A total of 62% of men reported side effects as a main factor in their treatment decision. Men with more aggressive tumor types were less likely to consider side effects, however, men who reported poor ability to have an erection were more likely to consider side effects (p<0.001). CONCLUSION: Sexual dysfunction at time of diagnosis, but not other genitourinary symptoms, is associated with men considering treatment-related side effects when considering surgery versus other options. Men who are not experiencing sexual dysfunction at diagnosis may discount the risks of side effects in the decision making process.
Authors: Zeliadt SB; Ramsey SD; Potosky AL; Arora NK; Blough DK; Oakley-Girvan I; Hamilton AS; Van Den Eeden SK; Penson DF
Patient. 2008 Jul 01;1(3):189.
Dietary antioxidants, fruits, and vegetables and the risk of Barrett’s esophagus
OBJECTIVE: The present study evaluated the associations among antioxidants, fruit and vegetable intake, and the risk of Barrett’s esophagus (BE), a potential precursor to esophageal adenocarcinoma. METHODS: We conducted a case-control study within the Kaiser Permanente Northern California population. Incident BE cases (N = 296) were matched to persons with gastroesophageal reflux disease (GERD) (GERD controls N = 308) and to population controls (N = 309). Nutrient intake was measured using a validated 110-item food frequency questionnaire. The antioxidant results were stratified by dietary versus total intake of antioxidants. RESULTS: Comparing cases to population controls, dietary intake of vitamin C and beta-carotene were inversely associated with the risk of BE (4th vs 1st quartile, adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.26-0.90; OR 0.56, 95% CI 0.32-0.99, respectively), and the inverse association was strongest for vitamin E (OR 0.25, 95% CI 0.11-0.59). The inverse trends for antioxidant index (total and dietary) and fruit and vegetable intake were statistically significant, while most total intakes were not associated with reduced risk. The use of antioxidant supplements did not influence the risk of BE, and antioxidants and fruits and vegetables were inversely associated with a GERD diagnosis. CONCLUSION: Dietary antioxidants, fruits, and vegetables are inversely associated with the risk of BE, while no association was observed for supplement intake. Our results suggest that fruits and vegetables themselves or associated undetected confounders may influence early events in the carcinogenesis of esophageal adenocarcinoma.
Authors: Kubo A; Levin TR; Block G; Rumore GJ; Quesenberry CP Jr; Buffler P; Corley DA
Am J Gastroenterol. 2008 Jul;103(7):1614-23; quiz 1624.
Racial differences in treatment of early-stage prostate cancer
OBJECTIVES: To determine whether differences existed in prostate cancer treatment received by white and African American men at a health maintenance organization where access to medical care is theoretically equal for all members and, if so, to determine the reasons for these differences. METHODS: We used information from the Kaiser Permanente Northwest Tumor Registry to identify all men diagnosed with local- or regional-stage prostate cancer between 1980 and 2000. We compared the likelihood of treatment with curative intent (TCI) between the two races, adjusting for age, tumor grade, stage, and the presence of comorbid conditions. We reviewed medical records of all 79 African American men and a sample of 158 white men (matched for age, stage, grade, and year of diagnosis) to determine the reasons that men did or did not receive TCI. RESULTS: Seventy-one percent of African American men and 82% of white men were treated with curative intent (P = 0.01). African American men were not more likely than white men to refuse TCI when it was offered (10.6% versus 8.1%, respectively; P = 0.6). However, urologists offered TCI less often to African American men than to white men (85% versus 91%, respectively; P = 0.02), and this difference could not be explained by differences in age, tumor grade, stage, or presence of comorbid conditions. CONCLUSIONS: African American men were less likely to receive TCI than white men. Because all of the men were insured, economic factors did not cause this difference. Furthermore, the cause did not seem to be differences in age, tumor grade, stage, or comorbid conditions.
Authors: Richert-Boe KE; Weinmann S; Shapiro JA; Rybicki BA; Enger SM; Van Den Eeden SK; Weiss NS
Urology. 2008 Jun;71(6):1172-6. Epub 2008 Feb 15.
Post-diagnosis statin use and breast cancer recurrence in a prospective cohort study of early stage breast cancer survivors
PURPOSE: We examined the association between post-diagnosis statin use (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] inhibitors) and risk of breast cancer recurrence. MATERIALS AND METHODS: The study included 1945 early stage breast cancer survivors participating in the Life After Cancer Epidemiology (LACE) Study. Women who were diagnosed from 1997 to 2000 and identified from the Kaiser Permanente Northern California (KPNC) Cancer Registry entered the cohort on average 2 years post-diagnosis. Information on statin use was obtained from the KPNC pharmacy database. A total of 210 breast cancer recurrences were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). RESULTS: The mean duration of statin use in the cohort among those who initiated use post-diagnosis was 1.96 years, and lipophilic statins were mainly used (97.8%). Starting statins after diagnosis was suggestive of a decreased risk of breast cancer recurrence (RR = 0.67; 95% CI: 0.39-1.13). Risk of recurrence decreased with increasing duration of statin use after diagnosis (p linear trend = 0.02). CONCLUSION: Our findings provide initial support for an inverse association between post-diagnosis, lipophilic statin use and risk of breast cancer recurrence.
Authors: Kwan ML; Habel LA; Flick ED; Quesenberry CP; Caan B
Breast Cancer Res Treat. 2008 Jun;109(3):573-9. Epub 2007 Aug 3.
Racial and ethnic variations in hepatocellular carcinoma incidence within the United States
BACKGROUND: The increasing incidence of hepatocellular carcinoma coupled with this cancer’s high mortality is a public health problem. Delineating high-risk populations and cancer patterns can provide valuable information. This is necessary to broaden screening and surveillance guidelines related to early detection and prevention. METHODS: By using data collected by the Surveillance, Epidemiology, and End Results program, a population-based cancer registry in the United States, our retrospective cohort study evaluated sex-specific, race/ethnicity-specific, and age-specific variations in hepatocellular carcinoma incidence from 1992 to 2004. RESULTS: With men and women combined, the incidence of hepatocellular carcinoma among Asians was the highest, nearly double that of white Hispanics (11.0 vs 6.8 per 100,000/y), and more than 4 times higher than that of Caucasians (11.0 vs 2.6 per 100,000/y). Although male subjects demonstrated a doubling of cancer rates every 10 years from 30 to 50 years of age, female subjects reached male-comparable rates of cancer 10 to 15 years later and peaked at significantly lower values for all race and ethnic groups. CONCLUSION: Marked differences in the incidence rates of hepatocellular carcinoma by sex, ethnicity, and age of diagnosis likely represent variations in risk factor distributions (eg, viral hepatitis) and possibly in host genetics or other environmental factors. An individualized approach tailored to specific risk profiles may more effectively identify treatable tumors than more general guidelines.
Authors: Wong R; Corley DA
Am J Med. 2008 Jun;121(6):525-31.
Detection of human papillomavirus DNA in cutaneous squamous cell carcinoma among immunocompetent individuals
The presence of certain types of human papillomavirus (HPV) is a known risk factor for the development of anogenital squamous cell carcinomas (SCCs). A similar association has been hypothesized for cutaneous SCCs, although, to our knowledge, no studies to date have combined sensitive HPV DNA detection techniques with epidemiologic data controlling for known risk factors to explore the association. We designed a case-control study examining HPV prevalence using highly sensitive PCR-detection assays in tissue samples from 85 immunocompetent patients with histologically confirmed SCCs and 95 age-matched individuals without a prior history of skin cancer. A standardized interview was administered to all study subjects to collect information pertaining to potential confounding variables. The overall detection rate of HPV DNA was high in case lesions (54%) and perilesions (50%) and in both sun-exposed normal tissue (59%) and non-sun-exposed normal tissue (49%) from controls. In comparing case tissue to control tissue, there was no differential detection of HPV DNA across various HPV species. However, HPV DNA from beta-papillomavirus species 2 was more likely to be identified in tumors than in adjacent healthy tissue among cases (paired analysis, odds ratio=4.0, confidence interval=1.3-12.0). The high prevalence of HPV DNA detected among controls suggests that HPV DNA is widely distributed among the general population. However, the differential detection of HPV beta-papillomavirus species in tumors among cases suggests that certain HPV types may be involved in the progression of cutaneous SCCs.
Authors: Asgari MM; Kiviat NB; Critchlow CW; Stern JE; Argenyi ZB; Raugi GJ; Berg D; Odland PB; Hawes SE; de Villiers EM
J Invest Dermatol. 2008 Jun;128(6):1409-17. Epub 2008 Jan 10.
Helicobacter pylori infection and the risk of Barrett’s oesophagus: a community-based study
OBJECTIVE: Gastric colonisation with the Helicobacter pylori bacterium is a proposed protective factor against oesophageal adenocarcinoma, but its point of action is unknown. Its associations with Barrett’s oesophagus, a metaplastic change that is a probable early event in the carcinogenesis of oesophageal adenocarcinoma, were evaluated METHODS: A case-control study was carried out in the Kaiser Permanente Northern California population, a large health services delivery organisation. Persons with a new Barrett’s oesophagus diagnosis (cases) were matched to subjects with gastro-oesophageal reflux disease (GORD) without Barrett’s oesophagus and to population controls. Subjects completed direct in-person interviews and antibody testing for H pylori and its CagA (cytotoxin-associated gene product A) protein. RESULTS: Serological data were available on 318 Barrett’s oesophagus cases, 312 GORD patients and 299 population controls. Patients with Barrett’s oesophagus were substantially less likely to have antibodies for H pylori (OR = 0.42, 95% CI 0.26 to 0.70) than population controls; this inverse association was stronger among those with lower body mass indexes (BMIs < 25, OR = 0.03, 95% CI 0.00 to 0.20) and those with CagA+ strains (OR = 0.08, 95% CI 0.02 to 0.35). The associations were diminished after adjustment for GORD symptoms. The H pylori status was not an independent risk factor for Barrett's oesophagus compared with the GORD controls. CONCLUSIONS: Helicobacter pylori infection and CagA+ status were inversely associated with a new diagnosis of Barrett's oesophagus. The findings are consistent with the hypothesis that H pylori colonisation protects against Barrett's oesophagus and that the association may be at least partially mediated through GORD.
Authors: Corley DA; Kubo A; Levin TR; Block G; Habel L; Zhao W; Leighton P; Rumore G; Quesenberry C; Buffler P; Parsonnet J
Gut. 2008 Jun;57(6):727-33. Epub 2007 Sep 25.
Dietary flavonoids and colorectal adenoma recurrence in the Polyp Prevention Trial
Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non-steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; P(trend) = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence.
Authors: Bobe G; Caan B; Lanza E; et al.
Cancer Epidemiol Biomarkers Prev. 2008 Jun;17(6):1344-53.
Re: Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population
Authors: Caan B; Habel L; Quesenberry C; Kushi L; Herrinton L
J Natl Cancer Inst. 2008 Apr 16;100(8):597-8; author reply 599. Epub 2008 Apr 8.
Tamoxifen, hot flashes and recurrence in breast cancer
We utilized data from the comparison group of the Women’s Healthy Eating and Living randomized trial to investigate an ‘a priori’ hypothesis suggested by CYP2D6 studies that hot flashes may be an independent predictor of tamoxifen efficacy. A total of 1551 women with early stage breast cancer were enrolled and randomized to the comparison group of the WHEL multi-institutional trial between 1995 and 2000. Their primary breast cancer diagnoses were between 1991 and 2000. At study entry, 864 (56%) of these women were taking tamoxifen, and hot flashes were reported by 674 (78%). After 7.3 years of follow-up, 127 of those who took tamoxifen at baseline had a confirmed breast cancer recurrence. Women who reported hot flashes at baseline were less likely to develop recurrent breast cancer than those who did not report hot flashes (12.9% vs 21%, P = 0.01). Hot flashes were a stronger predictor of breast cancer specific outcome than age, hormone receptor status, or even the difference in the stage of the cancer at diagnosis (Stage I versus Stage II). These findings suggest an association between side effects, efficacy, and tamoxifen metabolism. The strength of this finding suggests that further study of the relationship between hot flashes and breast cancer progression is warranted. Additional work is warranted to clarify the mechanism of hot flashes in this setting.
Authors: Mortimer JE; Flatt SW; Parker BA; Gold EB; Wasserman L; Natarajan L; Pierce JP; WHEL Study Group
Breast Cancer Res Treat. 2008 Apr;108(3):421-6. Epub 2007 May 31.
Dietary patterns and the risk of Barrett’s esophagus
The objective of this study was to examine the associations between dietary patterns and the risk of Barrett’s esophagus, a precursor to esophageal adenocarcinoma. The authors conducted a case-control study within the Kaiser Permanente Northern California population between 2002 and 2005. Patients with a new diagnosis of Barrett’s esophagus (n = 296 cases) were matched to persons with gastroesophageal reflux disease (n = 308) without Barrett’s esophagus and to population controls (n = 309). Dietary information was obtained from a validated, 110-item food frequency questionnaire. A principal component analysis was used to identify major dietary patterns. Two major dietary patterns were ‘Western’ (high in fast food and meat) and ‘health-conscious’ (high in fruits, vegetables, and nonfried fish). When cases and population controls were compared, strong adherence to the health-conscious dietary pattern was inversely associated with Barrett’s esophagus (odds ratio = 0.35, 95% confidence interval: 0.20, 0.64; fourth vs. first quartile comparison). In contrast, data suggested an adverse effect of the Western dietary pattern on the risk of Barrett’s esophagus, although no dose-effect relation was found. Results suggest strong associations between a diet rich in fruits and vegetables and the risk of Barrett’s esophagus.
Authors: Kubo A; Levin TR; Block G; Rumore GJ; Quesenberry CP Jr; Buffler P; Corley DA
Am J Epidemiol. 2008 Apr 1;167(7):839-46. Epub 2008 Jan 23.
Transcription factor 7-like 2 polymorphism and colon cancer
Polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been associated with insulin sensitivity and diabetes, and the TCF7L2 gene is involved in the Wnt/beta-catenin signaling pathway, all factors thought to be important in the etiology of colon cancer. In this confirmatory study, we evaluated the rs7903146 TCF7L2 polymorphism with colon cancer using previously collected data on 1,578 cases and 1,966 controls. We did not observe a statistically significant association between the rs7903146 polymorphisms and risk of colon cancer [odds ratio (OR), 1.12; 95% confidence interval (95% CI), 0.98-1.28] when evaluating the total population. We did, however, observe a statistically significant interaction between the rs7903146 TCF7L2 polymorphism and recent use of aspirin/nonsteroidal anti-inflammatory drugs (NSAID; P = 0.001). Increased colon cancer risk associated with the T allele was restricted to those without recent use of aspirin/NSAIDs (OR, 1.65; 95% CI, 1.35-2.02, relative to recent aspirin users, i.e., use of aspirin/NSAIDS within the 2 years before diagnosis, with the CC genotype). Among individuals who reported recent use of aspirin/NSAIDs, the T allele reduced risk of colon cancer (OR, 0.78; 95% CI, 0.62-0.98) in a dose-response fashion (P for linear trend across genotypes = 0.03). These data suggest that colon cancer risk associated with the rs7903146 TCF7L2 polymorphism is modified by use of aspirin/NSAIDs.
Authors: Slattery ML; Folsom AR; Wolff R; Herrick J; Caan BJ; Potter JD
Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):978-82.
Postpolypectomy colonoscopy surveillance guidelines: predictive accuracy for advanced adenoma at 4 years
BACKGROUND: Lack of confidence in postpolypectomy surveillance guidelines may be a factor in the observed low adherence rates among providers. OBJECTIVE: To assess the 2006 postpolypectomy colonoscopy surveillance guidelines, which recommend 3-year follow-up colonoscopy for individuals with high-risk adenomas (defined as > or =3 adenomas or any advanced adenomas) and 5- to 10-year follow-up for patients with 2 or fewer nonadvanced adenomas, who are considered to be at low risk. DESIGN: Analysis of prospective data from the Polyp Prevention Trial. SETTING: United States. PARTICIPANTS: 1905 patients who had colorectal adenomas removed at baseline screening or diagnostic colonoscopy and completed the trial. MEASUREMENTS: Baseline adenoma characteristics, risk-stratified according to definitions used in the guidelines, were examined as predictors for advanced adenoma recurrence. RESULTS: 125 patients (6.6%) had advanced and 629 (33.0%) had nonadvanced adenoma recurrence; 1151 (60.4%) had no recurrence within 4 years of follow-up. The probability of advanced adenoma recurrence was 0.09 (95% CI, 0.07 to 0.11) among patients with high-risk adenomas at baseline and 0.05 (CI, 0.04 to 0.06) among those with low-risk adenomas at baseline. The relative risk for advanced adenoma recurrence for patients with high-risk adenomas versus those with low-risk adenomas at baseline was 1.68 (CI, 1.19 to 2.38) when advanced adenoma recurrence was compared with no advanced adenoma recurrence and 1.76 (CI, 1.26 to 2.46) when advanced adenoma recurrence was compared with no adenoma recurrence. The c-statistics for these 2 comparisons were 0.68 and 0.72, respectively. Limitation: Participants were self-selected and had restrictions on the degree of obesity. CONCLUSION: Although the risk for recurrence of advanced adenoma within 4 years is greater for patients with high-risk adenomas at baseline than for those with low-risk adenomas, the discrimination of this risk stratification scheme is relatively low.
Authors: Laiyemo AO; Caan B; Schatzkin A; et al.
Ann Intern Med. 2008 Mar 18;148(6):419-26.
Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin
CONTEXT: The Women’s Health Initiative (WHI) trial of estrogen plus progestin vs placebo was stopped early, after a mean 5.6 years of follow-up, because the overall health risks of hormone therapy exceeded its benefits. OBJECTIVE: To report health outcomes at 3 years (mean 2.4 years of follow-up) after the intervention was stopped. DESIGN, SETTING, AND PARTICIPANTS: The intervention phase was a double-blind, placebo-controlled, randomized trial of conjugated equine estrogens (CEE) 0.625 mg daily plus medroxyprogesterone acetate (MPA) 2.5 mg daily, in 16,608 women aged 50 through 79 years, recruited by 40 centers from 1993 to 1998. The postintervention phase commenced July 8, 2002, and included 15 730 women. MAIN OUTCOME MEASURES: Semi-annual monitoring and outcomes ascertainment continued per trial protocol. The primary end points were coronary heart disease and invasive breast cancer. A global index summarizing the balance of risks and benefits included the 2 primary end points plus stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: The risk of cardiovascular events after the intervention was comparable by initial randomized assignments, 1.97% (annualized rate) in the CEE plus MPA (343 events) and 1.91% in the placebo group (323 events). A greater risk of malignancies occurred in the CEE plus MPA than in the placebo group (1.56% [n = 281] vs 1.26% [n = 218]; hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.04-1.48). More breast cancers were diagnosed in women who had been randomly assigned to receive CEE plus MPA vs placebo (0.42% [n = 79] vs 0.33% [n = 60]; HR, 1.27; 95% CI, 0.91-1.78) with a modest trend toward a lower HR during the follow-up after the intervention. All-cause mortality was somewhat higher in the CEE plus MPA than in the placebo group (1.20% [n = 233] vs 1.06% [n = 196]; HR, 1.15; 95% CI, 0.95-1.39). The global index of risks and benefits was unchanged from randomization through March 31, 2005 (HR, 1.12; 95% CI, 1.03-1.21), indicating that the risks of CEE plus MPA exceed the benefits for chronic disease prevention. CONCLUSIONS: The increased cardiovascular risks in the women assigned to CEE plus MPA during the intervention period were not observed after the intervention. A greater risk of fatal and nonfatal malignancies occurred after the intervention in the CEE plus MPA group and the global risk index was 12% higher in women randomly assigned to receive CEE plus MPA compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.
Authors: Heiss G; Rossouw J; WHI Investigators; et al.
JAMA. 2008 Mar 5;299(9):1036-45.
Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women’s Health Initiative
OBJECTIVE: To evaluate associations between nuclear cataract (determined from slitlamp photographs between May 2001 and January 2004) and lutein and zeaxanthin in the diet and serum in patients between 1994 and 1998 and macula between 2001 and 2004. DESIGN: A total of 1802 women aged 50 to 79 years in Iowa, Wisconsin, and Oregon with intakes of lutein and zeaxanthin above the 78th (high) and below the 28th (low) percentiles in the Women’s Health Initiative Observational Study (1994-1998) were recruited 4 to 7 years later (2001-2004) into the Carotenoids in Age-Related Eye Disease Study. RESULTS: Women in the group with high dietary levels of lutein and zeaxanthin had a 23% lower prevalence of nuclear cataract (age-adjusted odds ratio, 0.77; 95% confidence interval, 0.62-0.96) compared with those with low levels. Multivariable adjustment slightly attenuated the association (odds ratio, 0.81; 95% confidence interval, 0.65-1.01). Women in the highest quintile category of diet or serum levels of lutein and zeaxanthin as compared with those in the lowest quintile category were 32% less likely to have nuclear cataract (multivariable-adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.97; P for trend = .04; and multivariable-adjusted odds ratio, 0.68; 95% confidence interval, 0.47-0.98; P for trend = .01, respectively). Cross-sectional associations with macular pigment density were inverse but not statistically significant. CONCLUSIONS: Diets rich in lutein and zeaxanthin are moderately associated with decreased prevalence of nuclear cataract in older women. However, other protective aspects of such diets may in part explain these relationships.
Authors: Moeller SM; Chappell RJ; Women's Helath Initiative; et al.
Arch Ophthalmol. 2008 Mar;126(3):354-64.
Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer
Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women’s Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer.
Authors: Rock CL; Caan BJ; Women's Healthy Eating and Living Study Group; et al.
Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):614-20. Epub 2008 Mar 6.
Nonmetastatic cancer of the colon associated with pyogenic liver abscess.
Authors: Lee, Jeffrey K JK; Kum, Jennifer J; Ghosh, Pradipta P
The American journal of gastroenterology. 2008 Mar ;103(3):798-9. Epub --.
Current surveillance and therapeutic options for barrett esophagus
Authors: Douglas C
Gastroenterol Hepatol (N Y). 2008 Mar;4(3):183-6.
Cancer incidence in Barrett’s esophagus: does it really matter, and who’s counting anyway?
Authors: Corley DA
Gastrointest Endosc. 2008 Mar;67(3):399-401.
Physical activity and mammographic density in a cohort of midlife women
PURPOSE: Physical activity (PA) is one of few modifiable breast cancer risk factors. There have been few studies of the relation between PA and mammographic density, especially in multiethnic populations. METHODS: In a cohort of pre- and early perimenopausal women of non-Hispanic white (N = 373), African American (N = 55), Chinese (N = 178), and Japanese (N = 166) ethnicity, we used multivariable linear regression to examine the association between two measures of mammographic density (percent density and area of density) and mutually exclusive components of recent physical activity (sports, household/caregiving and work activity, active living). RESULTS: After adjusting for race/ethnicity, menopausal status, parity, past use of hormones, body mass index, waist circumference and education, we observed nonsignificant inverse associations for percent mammographic density and the highest versus the lowest category of each of our PA domains. For example, the adjusted beta for active living = -2.62, 95% confidence interval (CI) (-5.84, 0.60). Nonsignificant inverse associations also were observed for area of density and each PA domain except work activity. However, most associations were nonlinear. CONCLUSION: Our results are consistent with a modest inverse association between multiple domains of PA and mammographic density, although findings may have been attributable to chance alone.
Authors: Oestreicher N; Capra A; Bromberger J; Butler LM; Crandall CJ; Gold EB; Greendale GA; Modugno F; Sternfeld B; Habel LA
Med Sci Sports Exerc. 2008 Mar;40(3):451-6.
Reliability of plasma carotenoid biomarkers and its relation to study power
BACKGROUND: The reliability of biomarkers profoundly impacts validity of their use in epidemiology and can have serious implications for study power and the ability to find true associations. We assessed reliability of plasma carotenoid levels over time and how it could influence study power through sample size and effect-size. METHODS: Plasma carotenoid levels were measured in a cohort study of 1323 women participating in the control arm of the Women’s Healthy Eating and Living Study. We compared mean plasma levels at baseline, year 1, and year 4 of the study for alpha-carotene, beta-carotene, lycopene, lutein, and beta-cryptoxanthin. Reliability of these levels over time was assessed by Spearman correlations and intraclass correlation. RESULTS: We found limited variation in mean levels between any 2 time points. Variation did not exceed 8% for lycopene, lutein, and beta-cryptoxanthin, 15% for alpha-carotene, and 18% for beta-carotene. Spearman correlations for individual carotenoids over time varied between 0.50 and 0.80, with lycopene having the lowest correlation. Intraclass correlations ranged from 0.47 to 0.66 for carotenoids. CONCLUSION: Intraclass correlations for plasma carotenoids over a period of several years are acceptable for epidemiologic studies. However, such variation is enough to decrease statistical power and increase the sample size needed to detect a given effect.
Authors: Al-Delaimy WK; Natarajan L; Sun X; Rock CL; Pierce JP; Women's Healthy Eating and Living (WHEL) Study Group
Epidemiology. 2008 Mar;19(2):338-44.
Glycemic status and risk of prostate cancer
BACKGROUND: To examine the risk of prostate cancer and glucose tolerance in a large, racially diverse cohort. METHODS: We conducted a cohort study of 47,209 male members of Kaiser Permanente Northern California who had completed at least one Multiphasic Health Checkup (MHC) between 1964 and 1973. The MHC provided information on diabetes, serum glucose 1 h after a 75-g oral glucose challenge test, demographics, and other health conditions. Cox proportional hazards were used to estimate relative risks (RR) while adjusting for confounders. RESULTS: During a median follow-up of 18.4 years, a total of 2,833 men developed prostate cancer. At baseline, 4.6% (n = 2,159) of the cohort had diabetes and 33% had serum glucose of >or=200 mg/dL. After adjusting for age, race, birth year, and body mass index, RR (95% confidence interval) of prostate cancer associated with 1-h serum glucose >or=200 mg/dL and diabetes were 0.90 (0.81-1.01) and 0.71 (0.62-0.79), respectively, when compared with those with serum glucose <140 mg/dL. During the first 10 years of follow-up, risk was increased among those with serum glucose >or=200 mg/dL or diabetes [RR (95% confidence interval), 1.42 (0.95-2.13) and 1.56 (0.91-2.67), respectively]. In contrast, inverse associations between serum glucose >or=200 mg/dL and diabetes and prostate cancer risk were observed [0.87 (0.77-0.97) and 0.68 (0.52-0.88), respectively] when follow-up began 10 years after MHC. CONCLUSION: Our findings are consistent with the hypothesis that prostate cancer risk differs by time since diabetes diagnosis or occurrence of metabolic aberrations associated with impaired glucose tolerance.
Authors: Darbinian JA; Ferrara AM; Van Den Eeden SK; Quesenberry CP Jr; Fireman B; Habel LA
Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):628-35.
Abdominal obesity and the risk of esophageal and gastric cardia carcinomas
BACKGROUND: Esophageal adenocarcinoma is rapidly increasing in incidence. Body mass index (BMI) is a risk factor, but its distribution does not reflect the demographic distribution of the cancer (which is highest among White men). Abdominal obesity patterns may explain this discordance, but no studies exist to date. METHODS: Nested case-control study within 206,974 members of the Kaiser Permanente multiphasic health checkup cohort; subjects received detailed questionnaires, a standardized examination including BMI and anthropometric measurements, and follow-up of esophageal and cardia cancers using registry data. RESULTS: 101 incident esophageal adenocarcinomas, 105 cardia adenocarcinomas, and 144 esophageal squamous cell carcinomas were detected (BMI data available for all cases; abdominal measurements for a subset). Increasing abdominal diameter was strongly associated with an increased risk of esophageal adenocarcinoma [odds ratio (OR), 3.47; 95% confidence interval (95% CI), 1.29-9.33; abdominal diameter, > or =25 versus <20 cm]. Adjustment for BMI did not diminish this association (BMI-adjusted OR, 4.78; 95% CI, 1.14-20.11). The association was also not diminished by adjustment for gastroesophageal reflux-type symptoms, although reflux-type symptoms were separately associated with both abdominal diameter and cancer risk. Abdominal diameter was not associated with the risk of cardia adenocarcinomas (OR, 1.28; 95% CI, 0.38-4.25; diameter, > or =25 versus <20 cm) or esophageal squamous cell carcinomas (OR, 0.78; 95% CI, 0.32-1.92). CONCLUSIONS: Increasing abdominal diameter was associated with an increased risk of esophageal adenocarcinoma, independent of BMI. Cancer risk was not substantially mediated through gastroesophageal reflux-type symptoms, although symptoms may imperfectly measure reflux severity. Given abdominal obesity is more common among males, these findings suggest that increases in obesity may disproportionately increase the risk of esophageal adenocarcinoma in males.
Authors: Corley DA; Kubo A; Zhao W
Cancer Epidemiol Biomarkers Prev. 2008 Feb;17(2):352-8.
Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361,859 recipients
PURPOSE: Determine the risk of cancer in statin users. METHODS: Risk of cancer in up to 9.4 years after first recorded receipt of statins was evaluated in subscribers of an integrated health care program in northern California. Statin use and cancer development were ascertained from the program’s pharmacy records and cancer registry from August 1994 to December 2003. RESULTS: Most of the 361,859 statin users received lovastatin, simvastatin or both. Results are presented from analyses with 2-year lag and use for over 5 years. Most of the observed associations were likely due to chance or confounding. The few associations that seemed less readily explainable were increased risk of cancers of the thyroid, esophagus and urinary tract and decreased risk of colon cancer in men. Increased risk of lung cancer was the only nominally statistically significant positive association in women and could be partially attributable to their smoking habits. CONCLUSIONS: Overall this study provided no strong evidence of either causation or prevention of cancer by statins.
Authors: Friedman GD; Flick ED; Udaltsova N; Chan J; Quesenberry CP Jr; Habel LA
Pharmacoepidemiol Drug Saf. 2008 Jan;17(1):27-36.
Methylphenidate use in children and risk of cancer at 18 sites: results of surveillance analyses
PURPOSE: A recent report linked methylphenidate (MPH) use in children to cytologic abnormalities in plasma lymphocytes, a possible cancer biomarker. The purpose of this study was to investigate the association of MPH use and childhood cancer risk. METHODS: Using automated pharmacy databases and the SEER-affiliated cancer registry of the Kaiser Permanente Medical Care Program (KPMCP), we compared cancer rates at 18 sites among 35,400 MPH users who received it before age 20 to rates among KPMCP membership (age, sex, and calendar year standardized). Medical records of MPH exposed cancer cases were reviewed to identify the presence of established risk factors. RESULTS: There were 23 cancers among MPH users, versus 20.4 expected (standardized morbidity ratio, SMR = 1.13, 95% confidence interval (0.72, 1.70)). Given the small number of cancers, site-specific SMR estimates were imprecise. Only one SMR was statistically significant at the p < 0.05 level, which given the number of comparisons is consistent with the absence of a true association at any site. MPH use was associated with increased risk of lymphocytic leukemia (SMR = 2.64 (1.14, 5.20)), based on eight observed cases). The medical records of these exposed cases did not reveal any lymphocytic leukemia risk factors (prior cancer, radiotherapy or chemotherapy, or Down syndrome). CONCLUSIONS: Our results are consistent with no moderate or strong association between MPH use and cancer risk in children, although our ability to examine dose and duration of use or risk at specific sites was limited by small numbers. Further study of MPH use and lymphocytic leukemia risk is needed to determine whether our results are due to chance alone.
Authors: Oestreicher N; Friedman GD; Jiang SF; Chan J; Quesenberry C Jr; Habel LA
Pharmacoepidemiol Drug Saf. 2007 Dec;16(12):1268-72.
Clinical and pathologic features of ductal carcinoma in situ associated with the presence of flat epithelial atypia: an analysis of 543 patients
Flat epithelial atypia is an alteration of mammary terminal duct lobular units that is considered to be a precursor to, or early stage in, the development of some forms of ductal carcinoma in situ. No prior study has systematically evaluated the relationship between various clinico-pathologic features of ductal carcinoma in situ and the presence of coexistent flat epithelial atypia. An understanding of such relationships could provide insight into the connection between flat epithelial atypia and ductal carcinoma in situ. We reviewed slides from 543 ductal carcinoma in situ patients enrolled in a case-control study assessing epidemiologic and pathologic risk factors for local recurrence. We examined the association between the presence of flat epithelial atypia and various clinical factors, pathologic features of the ductal carcinoma in situ, and the presence of coexistent atypical ductal hyperplasia, lobular neoplasia, and non-atypical columnar cell lesions. In univariate analysis, the presence of flat epithelial atypia was significantly related to ductal carcinoma in situ nuclear grade (most common in low grade, least common in high grade; P<0.0001), architectural pattern (most common in micropapillary and cribriform, least common in comedo; P<0.0001), absence of comedo necrosis (P<0.001), absence of stromal desmoplasia (P=0.02) and absence of stromal inflammation (P=0.03). In multivariable analysis, features of ductal carcinoma in situ independently associated with flat epithelial atypia were micropapillary and cribriform patterns and absence of comedo necrosis. Additionally, flat epithelial atypia was significantly associated with the presence of atypical ductal hyperplasia, lobular neoplasia, and columnar cell lesions in both univariate and multivariable analyses. These observations provide support for a precursor-product relationship between flat epithelial atypia and ductal carcinoma in situ lesions that exhibit particular features such as micropapillary and cribriform patterns and absence of comedo necrosis.
Authors: Collins LC; Achacoso NA; Nekhlyudov L; Fletcher SW; Haque R; Quesenberry CP Jr; Alshak NS; Puligandla B; Brodsky GL; Schnitt SJ; Habel LA
Mod Pathol. 2007 Nov;20(11):1149-55. Epub 2007 Aug 31.
Statin use and risk of prostate cancer in the California Men’s Health Study cohort
Statins have known anticarcinogenic effects, however, evidence for long-term statin use as effective chemoprevention for prostate cancer is inconsistent. We examined the association between statin use and risk of prostate cancer among 69,047 eligible participants in the California Men’s Health Study, a prospective cohort of Northern and Southern California Kaiser Permanente (KP) members, ages 45 to 69 years, initiated in 2002. Prostate cancer cases were identified by linkage to the KP California Cancer Registries. Statin exposure, estimated from automated KP outpatient pharmacy records (available since 1991 in Southern California and since 1994 in Northern California), was treated as time-varying and defined as the cumulative days dispensed of any statin from the first dispensing until a prostate cancer diagnosis, radical prostatectomy, termination of membership, or end of study (December 31, 2004). Cox proportional hazards models with age as the time scale were used to estimate rate ratios, while controlling for confounding variables. During follow-up, 888 prostate cancer cases, including 131 advanced cases, were identified. There was no association between ever statin use or <5 years use and prostate cancer. Conversely, >or=5 years use was associated with a 28% lower risk for prostate cancer compared with nonuse (adjusted rate ratio, 0.72; 95% confidence interval, 0.53-0.99). This association did not differ markedly for advanced disease. However, the association did seem to be restricted to those who regularly take nonsteroidal anti-inflammatory drugs. Our findings suggest that long-term statin use might be associated with a reduced risk of prostate cancer but perhaps only among regular nonsteroidal anti-inflammatory drug users.
Authors: Flick ED; Habel LA; Van Den Eeden SK; Quesenberry CP Jr; Sternfeld B; Whitmer RA; Caan BJ; et al.
Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2218-25. Epub 2007 Oct 30.
Obesity and the rising incidence of oesophageal and gastric adenocarcinoma: what is the link?
Authors: Corley DA
Gut. 2007 Nov;56(11):1493-4.
Consumption of animal foods and endometrial cancer risk: a systematic literature review and meta-analysis
This article summarizes and quantifies the current evidence relating dietary intake of animal products and endometrial cancer. Literature searches were conducted to identify peer-reviewed manuscripts published up to December 2006. Twenty-two manuscripts from three cohort studies and 16 case-control studies were identified. One of these cohort studies evaluated only fried meat and another only milk consumption; they were not included in our meta-analyses. The third cohort study identified did not present exposure levels and could not be included in dose-response meta-analysis. This cohort study did not show an association with meat or red meat consumption. Random-effects dose-response summary estimates for case-control studies evaluating these foods were 1.26 (95% CI: 1.03-1.54) per 100 g/day of total meat, 1.51 (95% CI: 1.19-1.93) per 100 g/day of red meat, 1.03 (95% CI: 0.32-3.28) per 100 g/day of poultry, 1.04 (95% CI: 0.55-1.98) per 100 g/day of fish, and 0.97 (95% CI: 0.93-1.01) per serving of dairy. Our meta-analysis, based on case-control data, suggests that meat consumption, particularly red meat, increases endometrial cancer risk. The current literature does not support an association with dairy products, while the evidence is inconsistent for poultry, fish, and eggs. More studies, particularly prospective studies, are needed.
Authors: Bandera EV; Kushi LH; Moore DF; Gifkins DM; McCullough ML
Cancer Causes Control. 2007 Nov;18(9):967-88. Epub 2007 Jul 19.
Medical therapy for diabetes is associated with increased use of lower endoscopy
BACKGROUND: Diabetes mellitus is associated with an increased risk of colorectal neoplasia and diabetes medications may further influence the risk. Observational studies of the effect of diabetes medications on colonic neoplasia may be biased if use of diabetes medications is associated with undergoing lower endoscopy. This study examined the association between diabetes therapies and use of lower endoscopy. METHODS: This retrospective cohort study included patients with diabetes in an integrated, prepaid health plan. The primary exposure variables were use of sulfonylureas, metformin, thiazolidinediones (TZDs), and insulin. The outcome measure was completion of a flexible sigmoidoscopy or colonoscopy. Cox proportional hazards modeling, accounting for the time-varying nature of the medication exposures, was used to generate estimates of the relative hazard (HR) of lower endoscopy with different medications. RESULTS: The study included 44 169 patients followed for a mean duration of 4.2 years (SD = 2.5 years); 34% underwent at least one lower endoscopy. Patients who filled a diabetes medication prescription were more likely to undergo lower endoscopy (HR = 1.13, 95%CI 1.06-1.21). Compared to those taking only sulfonylureas, patients receiving sulfonylureas and metformin (HR = 1.12, 95%CI 1.06-1.18) or metformin alone (HR = 1.17, 95%CI 1.07-1.26) were more likely to undergo lower endoscopy. For all medications, new use was associated with undergoing lower endoscopy (p < 0.05 for all comparisons). CONCLUSIONS: Diabetic patients receiving medications are more likely to undergo lower endoscopy than those on diet control alone, particularly in the first year after initiating a new medication class and if taking metformin.
Authors: Lewis JD; Capra AM; Achacoso NS; Ferrara A; Levin TR; Quesenberry CP Jr; Habel LA
Pharmacoepidemiol Drug Saf. 2007 Nov;16(11):1195-202.
Low-fat dietary pattern and cancer incidence in the Women’s Health Initiative Dietary Modification Randomized Controlled Trial
BACKGROUND: The Women’s Health Initiative Dietary Modification (DM) Randomized Controlled Trial evaluated the effects of a low-fat dietary pattern on chronic disease incidence, with breast cancer and colorectal cancer as primary outcomes. The trial protocol also listed ovarian cancer and endometrial cancer as outcomes that may be favorably affected by the intervention. METHODS: A total of 48,835 postmenopausal women were randomly assigned during 1993-1998 to a DM intervention (n = 19,541) or comparison (usual diet; n = 29,294) group and followed up for an average of 8.1 years. The intervention goal was to reduce total fat intake to 20% of energy and to increase consumption of vegetables, fruits, and grains. Cancer outcomes were verified by pathology report review. We used weighted log-rank tests to compare incidence of invasive cancers of the ovary and endometrium, total invasive cancer, and invasive cancers at other sites between the groups. All statistical tests were two-sided. RESULTS: Ovarian cancer risk was lower in the intervention than in the comparison group (P = .03). Although the overall ovarian cancer hazard ratio (HR) was not statistically significantly less than 1.0, the hazard ratio decreased with increasing intervention duration (P(trend) = .01). For the first 4 years, the risk for ovarian cancer was similar in the intervention and control groups (0.52 cases per 1000 person-years in the intervention group versus 0.45 per 1000 person-years in the comparison group; HR = 1.16, 95% confidence interval [CI] = 0.73 to 1.84); over the next 4.1 years, the risk was lower in the intervention group (0.38 cases per 1000 person-years in the intervention group versus 0.64 per 1000 person-years in the comparison group; HR = 0.60, 95% CI = 0.38 to 0.96). Risk of cancer of the endometrium did not differ between the groups (P = .18). The estimated risk of total invasive cancer was slightly lower in the intervention group than in the control group (HR = 0.95, 95% CI = 0.89 to 1.01; P = .10). CONCLUSIONS: A low-fat dietary pattern may reduce the incidence of ovarian cancer among postmenopausal women.
Authors: Prentice RL; Caan B; Chlebowski RT; et al.
J Natl Cancer Inst. 2007 Oct 17;99(20):1534-43. Epub 2007 Oct 9.
A prospective study of fruits, vegetables, and risk of endometrial cancer
Case-control studies support a lower risk of endometrial cancer associated with greater vegetable consumption but not fruit consumption. One prospective study suggested an inverse association with fruits and vegetables combined. The authors examined associations for vegetables and fruits separately among women in the American Cancer Society’s Cancer Prevention Study II Nutrition Cohort. After exclusions, 41,400 postmenopausal women completed a questionnaire on diet, lifestyle, and medical history at baseline in 1992-1993. Information on diet was updated in 1999; historical dietary information from 1982 was also available. The authors identified 435 eligible cases of endometrial cancer through 2003. In multivariate models, neither fruit consumption (top quintile vs. bottom: rate ratio (RR) = 1.24, 95% confidence interval (CI): 0.90, 1.70; p-trend = 0.30) nor vegetable consumption (RR = 1.21, 95% CI: 0.89, 1.65; p-trend = 0.24) at baseline was associated with risk. Results were similar when diet was cumulatively updated. Only among women who had never used hormone replacement therapy was the risk of endometrial cancer lower in the highest (vs. lowest) tertile of fruit (RR = 0.75, 95% CI: 0.52, 1.07; p-interaction = 0.03, p-trend = 0.11) or vegetable (RR = 0.80, 95% CI: 0.57, 1.13; p-interaction = 0.01, p-trend = 0.29) consumption. This prospective study does not support an association between vegetable or fruit consumption and endometrial cancer.
Authors: McCullough ML; Bandera EV; Patel R; Patel AV; Gansler T; Kushi LH; Thun MJ; Calle EE
Am J Epidemiol. 2007 Oct 15;166(8):902-11. Epub 2007 Aug 9.
Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics
BACKGROUND: One type of fecal occult blood test (FOBT), the unrehydrated guaiac fecal occult blood test (GT), is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs, but it has relatively low sensitivity as a single test for detecting advanced colonic neoplasms (cancer and adenomatous polyps > or = 1 cm in diameter). Thus, improving the sensitivity of FOBT should make colon cancer screening programs that use these tests more effective. METHODS: We assessed prospectively the performance characteristics of two newer FOBTs in 5841 subjects at average risk for colorectal cancer in a large group-model managed care organization. The tests evaluated included a sensitive GT, a fecal immunochemical test (FIT), and the combination of both tests. Patients with positive and negative test results were advised to have colonoscopy and sigmoidoscopy, respectively. Sensitivity and specificity for detecting advanced neoplasms in the left colon within 2 years after the FOBT screening were evaluated for the two tests administered separately and in combination. RESULTS: A total of 139 patients were diagnosed with advanced colorectal neoplasms (n = 14 cancers, n = 128 adenomas) within the 2 years following their initial FOBT screening. Sensitivity for detecting cancer was 81.8% (95% confidence interval [CI] = 47.8% to 96.8%) for the FIT alone and 64.3% (95% CI = 35.6% to 86.0%) for the sensitive GT and the combination test. Sensitivity for detecting advanced colorectal adenomas was 41.3% (95% CI = 32.7% to 50.4%) for the sensitive GT, 29.5% (95% CI = 21.4% to 38.9%) for the FIT, and 22.8% (95% CI =16.1% to 31.3%) for the combination test. Specificity for detecting cancer and adenomas was 98.1% (95% CI = 97.7% to 98.4%) and 98.4% (95% CI = 98.0% to 98.7%), respectively, for the combination test; 96.9% (95% CI = 96.4% to 97.4%) and 97.3% (95% CI = 96.8% to 97.7%), respectively, for the FIT; and 90.1% (95% CI = 89.3% to 90.8%) and 90.6% (95% CI = 89.8% to 91.4%), respectively, for the sensitive GT. CONCLUSIONS: The FIT has high sensitivity and specificity for detecting left-sided colorectal cancer, and it may be a useful replacement for the GT.
Authors: Allison JE; Levin TR; Selby JV; et al.
J Natl Cancer Inst. 2007 Oct 3;99(19):1462-70. Epub 2007 Sep 25.
Telephone counseling helps maintain long-term adherence to a high-vegetable dietary pattern
Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women’s Healthy Eating and Living Study was a multi-institutional randomized trial in 3088 women at risk for breast cancer recurrence. At baseline, the average participant followed a healthy dietary pattern of 7 vegetable and fruit servings, 21 g/d of fiber, and 28.7% energy from fat, although fat intake increased over the enrollment period. Using primarily telephone counseling, the intervention group was encouraged to substantially increase intakes of vegetables, fruits, and fiber while decreasing fat intake. Sets of 24-h dietary recalls were completed on 90% of eligible participants at 1 y and 86% at 4 y. Using a conservative imputation analysis, at 1 y, the intervention group consumed 38% more vegetable servings (100% when including juice) than the comparison group, 20% more fruit, 38% more fiber, 50% more legumes, and 30% more whole grain foods, with a 20% lower intake of energy from fat. At 4 y, the between-group differences were 65% for vegetables (including juice), 25% fruit, 30% fiber, 40% legumes, 30% whole grain foods, and 13% lower intake of energy from fat. The intervention effect on fat intake was similar for early vs. late enrollees. Plasma carotenoid concentrations on a random 28% sample validated self-reported vegetable and fruit intake, with a between-group difference of 66% at 1 y and over 40% at 4 y. This large change will allow testing of hypotheses on the role of dietary change in preventing additional breast cancer events.
Authors: Pierce JP; Caan BJ; Parker BA; et al.
J Nutr. 2007 Oct;137(10):2291-6.
Weight gain and recovery of pre-cancer weight after breast cancer treatments: evidence from the women’s healthy eating and living (WHEL) study
PURPOSE: To examine predictors of weight gain following breast cancer diagnosis and subsequent return to pre-cancer weight. OBJECTIVES: To determine (1) the associations of anti-neoplastic chemotherapy and/or, Tamoxifen((R)) therapy on weight change following breast cancer diagnosis, (2) whether chemotherapy modified the effect of specific demographic and tumor characteristics on weight gain, (3) the proportion and characteristics of women who gained significant weight on chemotherapy and returned to their pre-cancer weight during follow-up. SUBJECTS AND METHODS: Participants were 3088 breast cancer survivors, aged 27-74 years. Weight was measured at baseline and years 1 through 6; pre-cancer weight was self-reported. Cancer stage and treatment modalities were obtained by medical record review; demographic and physical activity data were obtained from questionnaires. Weight gain of >/=5% body weight following cancer diagnosis was considered significant. RESULTS: Chemotherapy was significantly associated with weight gain (OR = 1.65, 95% CI = 1.12, 2.43) and Tamoxifen((R)) was not (OR = 1.03, 95% CI = 0.71, 1.51). Tamoxifen((R)) did not modify the effect of either chemotherapy or its different regimens on weight gain. Both types (anthracycline: OR = 1.63, p-value = 0.01, non-anthracycline: OR = 1.79, p = 0.003) and all regimens of chemotherapy (AC: OR = 1.55, p-value = 0.01, CAF: OR = 1.83, p = 0.003, CMF: OR = 1.76, p = 0.004) were associated with weight gain but the associations were not different from one another. Only 10% of participants returned to their pre-cancer diagnosis weight at the follow-up visits; the degree of initial gain (p for trend <0.0001) predicted that return. CONCLUSION: Chemotherapy was associated with clinically meaningful weight gain, and a return to initial weight following weight gain was unlikely.
Authors: Saquib N; Flatt SW; Natarajan L; Thomson CA; Bardwell WA; Caan B; Rock CL; Pierce JP
Breast Cancer Res Treat. 2007 Oct;105(2):177-86. Epub 2006 Nov 23.
Meta-analysis of antioxidant intake and the risk of esophageal and gastric cardia adenocarcinoma
OBJECTIVE: The incidence of esophageal adenocarcinoma has been increasing rapidly among many countries. Antioxidant intake is a potentially modifiable protective factor, although the results from individual studies are inconclusive. We conducted a systematic review and statistical synthesis of studies that evaluated the associations between vitamin C, vitamin E, or beta-carotene/vitamin A and the risk of esophageal adenocarcinoma or the adjacent gastric cardia (gastroesophageal junction) adenocarcinoma. METHODS: Studies were included if they reported (a) a measure of dietary antioxidant intake; (b) esophageal or cardia adenocarcinoma occurrence; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI), or sufficient data to permit their calculation. RESULTS: We identified 10 studies (1 cohort, 9 case-control; 1,057 esophageal and 644 cardia cases). Summary estimates stratified by cancer site suggested that higher intakes of vitamin C, beta-carotene/vitamin A, and vitamin E were inversely associated with the risk of esophageal adenocarcinoma (vitamin C, OR 0.49, 95% CI 0.39-0.62, P(heterogeneity)= 0.10; beta-carotene, OR 0.46, 95% CI 0.36-0.59, P(heterogeneity)= 0.82; vitamin E intake, OR 0.80, 95% CI 0.63-1.03, P(heterogeneity)= 0.59). Beta-carotene intake was also inversely associated with the risk of cardia adenocarcinoma (OR 0.57, 95% CI 0.46-0.72, P(heterogeneity)= 0.17). Dose effects were observed for most associations. CONCLUSIONS: Pooled results from observational studies suggest that antioxidant intake may be protective against esophageal adenocarcinoma; the data do not support a consistent association between antioxidant intake and the risk of cardia carcinoma. These findings suggest possible etiological differences between these two adjacent malignancies.
Authors: Kubo A; Corley DA
Am J Gastroenterol. 2007 Oct;102(10):2323-30; quiz 2331. Epub 2007 Jun 20.
Education and imaging. Gastrointestinal: glycogenic acanthosis.
Authors: Lee, J K JK; Kum, J J; Ghosh, P P
Journal of gastroenterology and hepatology. 2007 Sep ;22(9):1550. Epub --.
Mammographic density in a multiethnic cohort
OBJECTIVES: To compare mammographic density among premenopausal and early perimenopausal women from four racial/ethnic groups and to examine density and acculturation among Japanese and Chinese women. DESIGN: The study included 391 white, 60 African American, 171 Japanese, and 179 Chinese participants in the Study of Women’s Health Across the Nation, a multisite study of US women transitioning through menopause. Mammograms done when women were premenopausal or early perimenopausal were assessed for area of dense breast tissue and the percent of the breast occupied by dense tissue (percent density). Information on race/ethnicity, acculturation, and other factors was obtained from standardized instruments. Multiple linear regression modeling was used to examine the association between race/ethnicity or acculturation and density measures. RESULTS: Age-adjusted mean percent density was highest for Chinese (52%) and lowest for African American (34%) women. After additional adjustment for body mass index, menopause status, age at first birth, breast-feeding duration, waist circumference, and smoking, African Americans had the highest mean percent density (51%) and Japanese women had the lowest (39%). In contrast, the area of dense tissue was highest for African Americans and similar for white, Japanese, and Chinese women. Less acculturated Chinese and Japanese women tended to have a larger area of density and a higher percent density. CONCLUSIONS: Neither the age-adjusted nor fully adjusted results for percent density or area of dense tissue reflected current differences in breast cancer incidence rates among similarly aged African American, Japanese, Chinese, and white women. In addition, mammographic density was higher in less acculturated Asian women.
Authors: Habel LA; Quesenberry C; Sternfeld B; et al.
Menopause. 2007 Sep-Oct;14(5):891-9.
Dietary lipids and endometrial cancer: the current epidemiologic evidence
BACKGROUND: Because dietary fat has been postulated to affect obesity and estrogen levels, two important risk factors for endometrial cancer, its association with this disease has received some attention. We summarize here the current evidence for several dietary lipids. METHODS: Searches were conducted to identify peer-reviewed manuscripts up to December 2006. Two cohort studies and nine case-control studies were included in meta-analyses. RESULTS: Random-effects summary estimates for case-control studies were 1.24 (95% CI: 1.10, 1.41) per 10% kcal from total fat and 1.28 (95% CI: 1.12, 1.47) per 10 g/1,000 kcal of saturated fat. The only cohort study evaluating total fat and saturated fat did not find an association. We estimated a 35% increased risk (95% CI: 0.96, 1.90) per 150 mg/1,000 kcal of cholesterol intake, based on six case-control studies. For animal fat (per 10 g/1,000 kcal) the summary estimates were 0.78 (95% CI: 0.63, 0.96) and 1.34 (95% CI: 1.06, 1.69) for two cohort and four case-control studies, respectively. CONCLUSIONS: Case-control data suggest an increased risk for total, saturated, and animal fat. However, the limited available cohort data do not support these associations. Additional data, particularly from prospective studies, are needed before conclusions can be drawn.
Authors: Bandera EV; Kushi LH; Moore DF; Gifkins DM; McCullough ML
Cancer Causes Control. 2007 Sep;18(7):687-703. Epub 2007 Jun 16.
Association of childhood and adolescent anthropometric factors, physical activity, and diet with adult mammographic breast density
Early-life exposures may influence the development of breast cancer. The authors examined the association of childhood and adolescent anthropometric factors, physical activity levels, and diet with adult mammographic breast density, a strong risk factor for breast cancer. Women in the Minnesota Breast Cancer Family Study cohort who had undergone mammograms but had not had breast cancer (n=1,893) formed the sample. Information on adolescent exposures, including relative height, weight, and physical activity at ages 7, 12, and 18 years and diet at age 12-13 years, was self-reported during two follow-up studies (1990-2003). Mammographic percent density was estimated using a computer-assisted thresholding program. Statistical analyses were performed using linear mixed-effects models with two-sided tests. Positive associations with height at ages 7 (p<0.001), 12 (p<0.001), and 18 (p<0.001) years and percent density were evident overall and within menopausal status categories. The minimum difference in percent density between the tallest and shortest girls was 3 percent, with a maximum of 7 percent. Weight at age 12 years (p=0.005) and adiposity at age 12 years (p=0.005) were both inversely associated with adult percent density. Adolescent physical activity and diet were unrelated to percent density. These results suggest that adolescent height, a known risk factor for breast cancer, is also associated with mammographic percent density.
Authors: Sellers TA; Vachon CM; Pankratz VS; Janney CA; Fredericksen Z; Brandt KR; Huang Y; Couch FJ; Kushi LH; Cerhan JR
Am J Epidemiol. 2007 Aug 15;166(4):456-64. Epub 2007 Jun 4.
The association between mammographic breast density and bone mineral density in the study of women’s health across the nation
BACKGROUND: Bone mineral density and mammographic breast density are each associated with markers of lifetime estrogen exposure. The association between mammographic breast density and bone mineral density in early perimenopausal women is unknown. METHODS: We analyzed data from a cohort (n = 501) of premenopausal (no change in menstrual regularity) and early perimenopausal (decreased menstrual regularity in past 3 months) participants of African-American, Caucasian, Chinese, and Japanese ethnicity in the Study of Women’s Health Across the Nation. Using multivariable linear regression, we examined the cross-sectional association between percent mammographic density and bone mineral density (BMD). RESULTS: Percent mammographic density was statistically significantly inversely associated with hip BMD and lumbar spine BMD after adjustment (body mass index, ethnicity, age, study site, parity, alcohol intake, cigarette smoking, physical activity, age at first childbirth) in early perimenopausal, but not premenopausal, women. In early perimenopausal women, every 0.1g/cm(2) greater hip BMD predicted a 2% lower percent mammographic density (95% confidence interval -37.0 to -0.6%, p = 0.04). CONCLUSION: Mammographic breast density is inversely associated with BMD in the perimenopausal participants of this community-based cohort. The biological underpinnings of these findings may reflect differential responsiveness of breast and bone mineral density to the steroid milieu.
Authors: Crandall CJ; Zheng Y; Karlamangla A; Sternfeld B; Habel LA; Oestreicher N; Johnston J; Cauley JA; Greendale GA
Ann Epidemiol. 2007 Aug;17(8):575-83. Epub 2007 May 29.
Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet
This study investigated associations between CpG island methylator phenotype (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism and thus, potentially the provision of methyl groups and risk of colon cancer. Data from a large, population-based case-control study (916 incident colon cancer cases and 1,972 matched controls) were used. Candidate polymorphisms in methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), transcobalamin II (TCNII), methionine synthase (MTR), reduced folate carrier (RFC), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated.
Authors: Curtin K; Slattery ML; Ulrich CM; Bigler J; Levin TR; Wolff RK; Albertsen H; Potter JD; Samowitz WS
Carcinogenesis. 2007 Aug;28(8):1672-9. Epub 2007 Apr 21.
NSAIDs and breast cancer recurrence in a prospective cohort study
OBJECTIVE: We examined the association between NSAID use and breast cancer recurrence in a prospective cohort of 2,292 early-stage breast cancer survivors diagnosed from 1997 to 2000 participating in the Life After Cancer Epidemiology (LACE) Study. METHODS: From 2000 to 2002, mailed questionnaires were used to obtain information on aspirin, ibuprofen, and other NSAID use and subsequent breast cancer events. A total of 270 recurrences (local, regional, and distant disease and new primary breast cancers) were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI), adjusting for age at diagnosis, race, cancer stage, tamoxifen treatment, chemotherapy use, body mass index, and cyclooxygenase-2 (COX2) inhibitor use. RESULTS: Current, regular use (at least three days per week at time of questionnaire administration) of ibuprofen (RR, 0.56; 95% CI, 0.32-0.98), but not aspirin (RR, 1.09; 95% CI, 0.74-1.61), was associated with a statistically significant decreased risk of breast cancer recurrence. The combination of ibuprofen and other non-aspirin NSAIDs such as naproxen and sulindac reflected a similar reduction in risk (RR, 0.56; 95% CI, 0.33-0.95). No association was found for the non-NSAID analgesic acetaminophen. CONCLUSION: Our findings provide support for an inverse association between current, regular ibuprofen use and breast cancer recurrence.
Authors: Kwan ML; Habel LA; Slattery ML; Caan B
Cancer Causes Control. 2007 Aug;18(6):613-20. Epub 2007 Apr 3.
Dealing with uncertainty: surveillance colonoscopy after polypectomy
Post-polypectomy surveillance is often done sooner than guideline recommendations. This practice is driven by physician intolerance of uncertainty. The accompanying article by Brenner et al. supports the recommendation to wait 5 years or longer following adenoma removal before performing surveillance colonoscopy. This is particularly true for patients with 1 or 2 small adenomas. Unnecessarily aggressive post-polypectomy surveillance exposes patients to excessive risk of colonoscopy complications without clinical benefit. It also diverts colonoscopy resources away from the more valuable practice of primary screening.
Authors: Levin TR
Am J Gastroenterol. 2007 Aug;102(8):1745-7.
Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) randomized trial
CONTEXT: Evidence is lacking that a dietary pattern high in vegetables, fruit, and fiber and low in total fat can influence breast cancer recurrence or survival. OBJECTIVE: To assess whether a major increase in vegetable, fruit, and fiber intake and a decrease in dietary fat intake reduces the risk of recurrent and new primary breast cancer and all-cause mortality among women with previously treated early stage breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Multi-institutional randomized controlled trial of dietary change in 3088 women previously treated for early stage breast cancer who were 18 to 70 years old at diagnosis. Women were enrolled between 1995 and 2000 and followed up through June 1, 2006. INTERVENTION: The intervention group (n = 1537) was randomly assigned to receive a telephone counseling program supplemented with cooking classes and newsletters that promoted daily targets of 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat. The comparison group (n = 1551) was provided with print materials describing the ‘5-A-Day’ dietary guidelines. MAIN OUTCOME MEASURES: Invasive breast cancer event (recurrence or new primary) or death from any cause. RESULTS: From comparable dietary patterns at baseline, a conservative imputation analysis showed that the intervention group achieved and maintained the following statistically significant differences vs the comparison group through 4 years: servings of vegetables, +65%; fruit, +25%; fiber, +30%, and energy intake from fat, -13%. Plasma carotenoid concentrations validated changes in fruit and vegetable intake. Throughout the study, women in both groups received similar clinical care. Over the mean 7.3-year follow-up, 256 women in the intervention group (16.7%) vs 262 in the comparison group (16.9%) experienced an invasive breast cancer event (adjusted hazard ratio, 0.96; 95% confidence interval, 0.80-1.14; P = .63), and 155 intervention group women (10.1%) vs 160 comparison group women (10.3%) died (adjusted hazard ratio, 0.91; 95% confidence interval, 0.72-1.15; P = .43). No significant interactions were observed between diet group and baseline demographics, characteristics of the original tumor, baseline dietary pattern, or breast cancer treatment. CONCLUSION: Among survivors of early stage breast cancer, adoption of a diet that was very high in vegetables, fruit, and fiber and low in fat did not reduce additional breast cancer events or mortality during a 7.3-year follow-up period. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00003787.
Authors: Pierce JP; Caan BJ; Stefanick ML; et al.
JAMA. 2007 Jul 18;298(3):289-98.
Correlates of screening sigmoidoscopy use among men in a large nonprofit health plan
BACKGROUND: As the majority of patients diagnosed with colorectal cancer have no known risk factors, regular screening is strongly recommended. The authors examined factors associated with screening sigmoidoscopy use among participants in the California Men’s Health Study (CMHS). METHODS: The authors conducted a cross-sectional study over a 5-year period nested within a prospective cohort study. The CMHS enrolled a large multiethnic cohort (n = 84,170) of men from 2 major California health plans. Because screening sigmoidoscopy was the preferred and most commonly used test for patients at average risk of colorectal cancer in the health plans, the authors excluded from the analysis men who completed a barium enema colonoscopy or a fecal occult blood test. RESULTS: Eligible subjects included 39,559 men at average risk for colorectal cancer. Prevalence of screening sigmoidoscopy use decreased with older age and increased with higher education and household income over the 5-year study period. Compared with whites, Asians (adjusted OR, 1.42; 95% CI, 1.30-1.56) and African Americans (adjusted OR, 1.18; 95% CI, 1.08-1.29) were more likely to undergo screening sigmoidoscopy. Screening increased with the number of outpatient visits and with having a primary care provider in internal medicine. Men who did not undergo prostate-specific antigen testing were also less likely to undergo sigmoidoscopy screening. Only 24.5% of current smokers had a screening sigmoidoscopy examination and were 25% less likely to undergo this procedure compared with nonsmokers (adjusted OR, 0.75; 95% CI, 0.69-0.82). CONCLUSIONS: In this insured population for whom financial barriers are minimized, screening sigmoidoscopy use was as low as reported in the general population. However, minority patients were not less likely to be screened.
Authors: Haque R; Quinn VP; Habel LA; Enger SM; Sternfeld B; Van Den Eeden SK; Sadler M; Chiu V; Caan B
Cancer. 2007 Jul 15;110(2):275-81.
Cytoreductive surgery for gynecologic malignancies–new standards of care
Studies on cytoreductive surgery for advanced ovarian and primary peritoneal cancer have consistently shown a strong correlation between cytoreduction and survival, with the best survival observed in patients who have no visible residual disease after successful cytoreductive surgery. Recent data that intraperitoneal chemotherapy further improves survival after optimal cytoreduction adds to the potential benefit of such surgery. More recently, significant survival benefit from optimal cytoreduction has also been shown for patients with recurrent disease and for women with advanced endometrial carcinoma. The selection criteria for patients and critical aspects of the operative technique and timing of cytoreductive surgery are discussed.
Authors: Suh-Burgmann E; Powell CB
Surg Oncol Clin N Am. 2007 Jul;16(3):667-82, x-xi.
Incidental finding of metastatic papillary thyroid carcinoma in a patient with primary hyperparathyroidism.
OBJECTIVE: To report on the management of a patient with the rare concurrence of primary hyperparathyroidism and incidentally found metastatic papillary thyroid carcinoma in an adjacent lymph node.METHODS: We present a case report, including scintigraphic and histologic documentation, and a summary of the related literature. RESULTS: Primary hyperparathyroidism with concomitant occurrence of nonmedullary thyroid carcinoma is rare, occurring in less than 4% of patients. We report a case of a 53-year-old woman with no prior history of endocrine disease with primary hyperparathyroidism and an incidental finding of a concurrent thyroid carcinoma. In this patient, technetium 99m scintigraphy revealed a parathyroid adenoma beneath the inferior pole of the left thyroid bed. Parathyroidectomy was performed successfully with no complications. The final pathology examination showed a large parathyroid adenoma with an incidental finding of a small adjacent lymph node containing metastatic papillary thyroid carcinoma. The patient subsequently underwent total thyroidectomy, and the pathology evaluation revealed papillary thyroid carcinoma, follicular variant. CONCLUSION: To our knowledge, this case of concomitant primary hyperparathyroidism and papillary thyroid cancer is unique in the way in which the diagnosis of metastatic papillary thyroid cancer was made. The presence of parathyroid adenoma should not exclude the diagnosis of thyroid carcinoma; therefore, careful thyroid evaluation should be considered for all patients with primary hyperparathyroidism.
Authors: Lee, Jeffrey K JK; Obrzut, Sebastian L SL; Yi, Eunhee S ES; Deftos, Leonard J LJ; Bouvet, Michael M
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. ;13(4):380-3. Epub --.
Pooled analysis of tobacco use and risk of Parkinson disease
CONTEXT: Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention. OBJECTIVE: To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD. DESIGN, SETTING, AND PARTICIPANTS: We conducted the first ever pooled analysis of PD combining individual-level data from 8 US case-control and 3 cohort studies (Nurses’ Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age- and sex-matched risk sets. MAIN OUTCOME MEASURE: Incident PD. RESULTS: We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (>75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects. CONCLUSIONS: Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.
Authors: Ritz B; Ascherio A; Checkoway H; Marder KS; Nelson LM; Rocca WA; Ross GW; Strickland D; Van Den Eeden SK; Gorell J
Arch Neurol. 2007 Jul;64(7):990-7.
Abdominal obesity and body mass index as risk factors for Barrett’s esophagus
BACKGROUND: Barrett’s esophagus is a strong risk factor for esophageal adenocarcinoma, but little is known about its associations with body mass index (BMI) or abdominal obesity. METHODS: We conducted a case-control study within the Kaiser Permanente Northern California population. Persons with a new diagnosis of Barrett’s esophagus (cases) were matched to subjects with gastroesophageal reflux disease (GERD) without Barrett’s esophagus and to population controls. Subjects completed questionnaires and an anthropometric examination. RESULTS: We interviewed 320 cases, 316 patients with GERD, and 317 controls. There was a general association between Barrett’s esophagus and a larger abdominal circumference (independent of BMI) compared with population controls (odds ratio, 2.24; 95% confidence interval, 1.21-4.15; circumference, >80 cm vs <80 cm). There was a possible risk plateau, with increased risk evident only at circumferences >80 cm and no significant trend for further increases in circumference. There was a trend for association compared with patients with GERD (test for trend, P = .03). There was no association between Barrett’s esophagus and BMI. Abdominal circumference was associated with GERD symptom severity (odds ratio, 1.86; 95% confidence interval, 1.03-3.38; risk of severe weekly GERD, per 10-cm circumference); adjustment for GERD partially attenuated the association between Barrett’s esophagus and circumference. CONCLUSIONS: Waist circumference, but not BMI, had some modest independent associations with the risk of Barrett’s esophagus. The findings provide partial support for the hypothesis that abdominal obesity contributes to GERD, which may in turn increase the risk of Barrett’s esophagus.
Authors: Corley DA; Kubo A; Levin TR; Block G; Habel L; Zhao W; Leighton P; Quesenberry C; Rumore GJ; Buffler PA
Gastroenterology. 2007 Jul;133(1):34-41; quiz 311. Epub 2007 Apr 25.
Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity
PURPOSE: Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. PATIENTS AND METHODS: A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. RESULTS: In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor-positive cancers. CONCLUSION: A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival.
Authors: Pierce JP; Madlensky L; Rock CL; Rock CL; et al.
J Clin Oncol. 2007 Jun 10;25(17):2345-51.
Serum ghrelin levels and risk of subsequent adenocarcinoma of the esophagus
OBJECTIVE: Several large studies have shown a negative association between Helicobacter pylori (H. pylori) infection and esophageal adenocarcinoma. Diminution of gastric ghrelin secretion by H. pylori could protect against esophageal malignancy by decreasing appetite, food intake, and acid production, thereby decreasing weight and gastroesophageal reflux. METHODS: We evaluated the association of ghrelin with esophageal adenocarcinoma using a population from a previous nested case-control study. Among 128,992 enrolled in a multiphasic health checkup (MHC) between 1964 and 1969, 52 patients developed esophageal adenocarcinoma by the year 2000. Three random controls from the MHC cohort were matched to each case by age, sex, race, and the date and site of their MHC. Serum samples collected at the MHC had been previously tested for IgG antibodies against H. pylori and the CagA protein. Serum ghrelin concentrations were determined by a commercial EIA on 52% of the initial subjects (31 cases and 79 controls). RESULTS: A concentration of ghrelin greater than 3,200 pg/mL at MHC (fourth quartile) was associated with a lower risk of esophageal cancer (H. pylori and body mass index [BMI] adjusted OR=0.18 [CI 0.04-0.78]). This inverse association was seen only in overweight subjects (BMI>or=25, P value for interaction=0.09). The effects of H. pylori and ghrelin were independent. CONCLUSION: Contrary to the original hypothesis, high rather than low serum ghrelin was associated with protection against esophageal adenocarcinoma but only among overweight subjects.
Authors: de Martel C; Haggerty TD; Corley DA; Vogelman JH; Orentreich N; Parsonnet J
Am J Gastroenterol. 2007 Jun;102(6):1166-72. Epub 2007 Mar 22.
Effect of non-steroidal anti-inflammatory medications on the risk of amyotrophic lateral sclerosis
Inflammatory processes may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). We examined the association of non-steroidal anti-inflammatory drugs (NSAIDs) with the risk of ALS in case-control study of incident cases (n = 111) conducted within the Kaiser Permanente Medical Care Program of Northern California during the years 1996-2000. Controls (n = 258) randomly selected from the same population were frequency matched by age and gender to the ALS cases. Information regarding use of NSAIDs (non-aspirin and aspirin) and three classes of ‘control’ medications was collected by in-person structured interview. Subjects who used medication at least twice a week for at least a month were classified as ‘ever users’. Multivariable logistic regression models were adjusted for age, gender, history of osteoarthritis/rheumatoid arthritis and pain, and other medication use. Overall, there was no association between NSAID use and ALS; however, some sex differences were noted for non-aspirin NSAID use. Among men, non-aspirin NSAID use was associated with a two-fold increased risk of ALS (adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.0-3.9), whereas among women, non-aspirin NSAID use was not associated with increased ALS risk (adjusted OR 0.5, 95% CI 0.2-1.2). ALS risk was not associated with aspirin use or with ‘control’ medications. This study did not find any evidence to suggest that NSAID use reduces the risk of ALS. The observed sex differences with non-aspirin NSAID use could be due to chance or an unmeasured confounder.
Authors: Popat RA; Tanner CM; Van Den Eeden SK; Bernstein AL; Bloch DA; Leimpeter A; McGuire V; Nelson LM
Amyotroph Lateral Scler. 2007 Jun;8(3):157-63.
Abdominal obesity, ethnicity and gastro-oesophageal reflux symptoms
OBJECTIVE: To evaluate the associations between abdominal obesity and gastro-oesophageal reflux disease (GORD), and their interactions with ethnicity and gender. DESIGN: A cross-sectional study. Participants completed detailed symptom questionnaires and underwent a standardised examination, including anthropometric measurements. SETTING: A large integrated healthcare system. PATIENTS: 80 110 members of the Kaiser Permanente multiphasic health check-up cohort. MAIN OUTCOME MEASURES: Gastro-oesophageal reflux-type symptoms. RESULTS: Recent reflux-type symptoms were present in 11% of the population. The multivariate OR for symptoms with an abdominal diameter (adjusted for body mass index (BMI)) of >/=26 vs <16.3 cm was 1.85 (95% CI 1.55 to 2.21) for the white population, 0.95 (95% CI 0.61 to 1.48) for the black population and 0.64 (95% CI 0.18 to 2.30) for Asians. The mean abdominal diameter was greater in men (22.0 cm, 95% CI 21.9 to 22.0) than in women (20.1 cm, 95% CI 20.0 to 20.1, p<0.01), but the risk of symptoms for any given diameter did not differ markedly by gender. The association between increasing BMI and symptoms was also much stronger among the white population than among the black population. The association between BMI and reflux-type symptoms was partially mediated through abdominal diameter. CONCLUSIONS: There was a consistent association between abdominal diameter (independent of BMI) and reflux-type symptoms in the white population, but no consistent associations in the black population or Asians. The BMI association was also strongest among the white population. These findings, combined with the increased prevalence of abdominal obesity in male subjects, suggest that an increased obesity may disproportionately increase GORD-type symptoms in the white population and in male subjects.
Authors: Corley DA; Kubo A; Zhao W
Gut. 2007 Jun;56(6):756-62. Epub 2006 Oct 17.
Thymidylate synthase polymorphisms and colon cancer: associations with tumor stage, tumor characteristics and survival
Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. We investigated the role of functional polymorphisms in the TS 5′-UTR promoter enhancer region (TSER, 3 or 2 repeats of a 28-bp sequence) and the 3′-UTR (1494delTTAAAG) and their association with colon tumor characteristics, including tumor stage and acquired mutations in p53, Ki-ras and microsatellite instability. Data from a population-based incident case-control colon cancer study in northern California, Utah and Minnesota (1,206 cases, 1,962 controls) was analyzed using unordered polytomous logistic regression models. In both men and women, individuals with variant TS alleles were at reduced risk of having an advanced stage tumor (metastatic disease: OR = 0.35, 95% CI: 0.2-0.6 vs. wildtype TSER and 3′-UTR). Stage-adjusted survival did not differ by genotype. Men with 1 or 2 variant alleles in both the TSER and 3′-UTR genotypes had a 50% reduced risk of a p53-positive tumor (OR = 0.5, 95% CI: 0.3-0.9 vs. homozygous wildtype TSER and 3′-UTR). Women with 1 or 2 variant alleles for either the TSER or 3′-UTR polymorphism had reduced risk of having any colon tumor that did not vary by mutation status. This study provides some support for associations between TS genotype and colon cancer tumor characteristics.
Authors: Curtin K; Ulrich CM; Samowitz WS; Bigler J; Caan B; Potter JD; Slattery ML
Int J Cancer. 2007 May 15;120(10):2226-32.
Standardized colonoscopy reporting and data system: report of the Quality Assurance Task Group of the National Colorectal Cancer Roundtable
BACKGROUND: Standardized reporting systems for diagnostic and screening tests facilitate quality improvement programs and clear communication among health care providers. Although colonoscopy is commonly used for screening, diagnosis, and therapy, no standardized reporting system for this procedure currently exists. The Quality Assurance Task Group of the National Colorectal Cancer Roundtable developed a reporting and data system for colonoscopy based on continuous quality improvement indicators. DESIGN: The Task Group systematically reviewed quality indicators recommended by the Multi-Society Task Force on Colorectal Cancer and developed consensus-based terminology for reporting and data systems to capture these data elements. The Task Group included experts in several disciplines: gastroenterology, primary care, diagnostic imaging, and health care delivery. RESULTS AND CONCLUSIONS: The standardized colonoscopy reporting and data system provides a tool that can be used for efforts in continuous quality improvement within and across practices that use colonoscopy.
Authors: Lieberman D; Levin TR; Winawer S; et al.
Gastrointest Endosc. 2007 May;65(6):757-66.
Dietary intake of folate and co-factors in folate metabolism, MTHFR polymorphisms, and reduced rectal cancer
Little is known about the contribution of polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) and the folate metabolism pathway in rectal cancer alone. Data were from participants in a case-control study conducted in Northern California and Utah (751 cases and 979 controls). We examined independent associations and interactions of folate, B vitamins, methionine, alcohol, and MTHFR polymorphisms (MTHFR C677T and A1298C) with rectal cancer. Dietary folate intake was associated with a reduction in rectal cancer OR 0.66, 95% CI 0.48-0.92 (>475 mcg day compared to < or = 322 mcg) as was a combination of nutrient intakes contributing to higher methyl donor status (OR 0.79, 95% CI 0.66-0.95). Risk was reduced among women with the 677 TT genotype (OR 0.54, 95% CI 0.30-0.9), but not men (OR 1.11, 95% CI 0.70-1.76) and with the 1298 CC genotype in combined gender analysis (OR 0.67, 95% CI 0.46-0.98). These data are consistent with a protective effect of increasing dietary folate against rectal cancer and suggest a protective role of the MTHFR 677 TT genotype in women and 1298 CC in men and women. Folate intake, low methyl donor status, and MTHFR polymorphisms may play independent roles in the etiology of rectal cancer.
Authors: Murtaugh MA; Curtin K; Sweeney C; Wolff RK; Holubkov R; Caan BJ; Slattery ML
Cancer Causes Control. 2007 Mar;18(2):153-63. Epub 2007 Jan 23.
Change in body size and the risk of colorectal adenomas
Adiposity has been recognized as a risk factor for colorectal adenoma, but the influence of weight gain, adipose tissue distribution, and possible differences between ethnic/racial and gender groups remains unanswered. The aim of this prospective study was to examine the association between adiposity and weight change and colorectal adenoma risk. Over approximately 10-year period, anthropometric measures and other risk factors were measured at three time points in the multicenter multiethnic Insulin Resistance Atherosclerosis Study cohort. Colonoscopies were then conducted on 600 cohort participants regardless of symptoms whose mean age at colonoscopy was 64 years. Multivariate logistic regression analyses were used to assess the association between colorectal adenomas and measures of adiposity and weight change over the approximately 10-year period before colonoscopy. Obesity was positively associated with risk of colorectal adenomas at the time of colonoscopy [adjusted odds ratio (OR(adj)), 2.16; 95% confidence interval (95% CI), 1.13-4.14] and was stronger in women (OR(adj), 4.42; 95% CI, 1.53-12.78) than in men (OR(adj), 1.26; 95% CI, 0.52-3.07). The risk of adenomas increased among participants who gained weight compared with those who maintained weight over the approximately 5 years (OR(adj), 2.30; 95% CI, 1.25-4.22) and approximately 10 years (OR(adj), 2.12; 95% CI, 1.25-3.62). These associations were similar for both advanced and nonadvanced adenomas. These results suggest a positive association between obesity, weight gain, and colorectal adenoma risk. Stronger associations were observed when obesity was measured at the time of colonoscopy, suggesting that obesity may be a promoting factor in the growth of colorectal adenomas.
Authors: Sedjo RL; Byers T; Levin TR; Haffner SM; Saad MF; Tooze JA; D'Agostino RB Jr
Cancer Epidemiol Biomarkers Prev. 2007 Mar;16(3):526-31.
Pregnancy plasma glucose levels exceeding the American Diabetes Association thresholds, but below the National Diabetes Data Group thresholds for gestational diabetes mellitus, are related to the risk of neonatal macrosomia, hypoglycaemia and hyperbilirubinaemia
AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a risk factor for perinatal complications. In several countries, the criteria for the diagnosis of GDM have been in flux, the American Diabetes Association (ADA) thresholds recommended in 2000 being lower than those of the National Diabetes Data Group (NDDG) that have been in use since 1979. We sought to determine the extent to which infants of women meeting only the ADA criteria for GDM are at increased risk of neonatal complications. MATERIALS AND METHODS: In a multiethnic cohort of 45,245 women who did not meet the NDDG criteria and were not treated for GDM, we conducted nested case-control studies of three complications of GDM that occurred in their infants: macrosomia (birthweight >4,500 g, n = 494); hypoglycaemia (plasma glucose <2.2 mmo/l, n = 488); and hyperbilirubinaemia (serum bilirubin > or =342 micromol/l (20 mg/dl), n = 578). We compared prenatal glucose levels of the mothers of these infants and mothers of 884 control infants. RESULTS: Women with GDM by ADA criteria only (two or more glucose values exceeding the threshold) had an increased risk of having an infant with macrosomia (odds ratio OR = 3.40, 95% CI = 1.55-7.43), hypoglycaemia (OR = 2.61, 95% CI = 0.99-6.92) or hyperbilirubinaemia (OR = 2.22, 95% CI = 0.98-5.04). Glucose levels 1 h after the 100-g glucose challenge that exceeded the ADA threshold were particularly strongly associated with each complication. CONCLUSIONS/INTERPRETATION: These results lend support to the ADA recommendations and highlight the importance of the 1-h glucose measurement in a diagnostic test for GDM.
Authors: Ferrara A; Weiss NS; Hedderson MM; Quesenberry CP Jr; Selby JV; Ergas IJ; Peng T; Escobar GJ; Pettitt DJ; Sacks DA
Diabetologia. 2007 Feb;50(2):298-306. Epub 2006 Nov 14.
Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer
It has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population-based case-control study of incident colon cancer were used to evaluate whether intake of dietary, obesity, physical activity and nonsteroidal antiinflammatory drugs are associated with a CpG island methylator phenotype (CIMP). The BRAF V600E mutation and 5 CpG island markers (MINT1, MINT2, MINT31, p16 and hMLH1) were assessed in 1154 cases of colon cancer. We hypothesized that dietary factors involved in DNA methylation, cruciferous vegetables and use of aspirin/NSAIDs would be associated with CIMP-high tumors. Dietary folate, vitamins B(6) and B(12), methionine and alcohol were not associated with increased likelihood of colon tumors with the CIMP-high (2 or more markers methylated) phenotype. Dietary fiber, physical activity and aspirin and other nonsteroidal antiinflammatory drugs were inversely associated with both CIMP-low and CIMP-high tumors. Our results also suggested non-CIMP pathways as well. Obese individuals were at 2-fold increased risk of having a CIMP-low tumor. Alcohol was associated with an increased risk of tumors that were MSI+ and CIMP-low. In the presence of smoking 20 or more cigarettes per day, use of NSAIDs did not protect against a BRAF mutation. Our data suggest multiple pathways to colon cancer. They do not support a unique role for dietary folate, alcohol, vitamins B(6) and B(12) and methionine in a CpG island methylator phenotype.
Authors: Slattery ML; Curtin K; Sweeney C; Levin TR; Potter J; Wolff RK; Albertsen H; Samowitz WS
Int J Cancer. 2007 Feb 1;120(3):656-63.
Increase in cruciferous vegetable intake in women previously treated for breast cancer participating in a dietary intervention trial
Consumption of cruciferous vegetables has been associated with reduced breast cancer risk mechanistically and in population-based studies, although evidence has been inconsistent. This inconsistency may be related to limitations in quantifying and qualifying cruciferous vegetable exposure using standard instruments for dietary assessment (for example, food-frequency questionnaires, FFQs) or due to low levels of intake demonstrated among U.S. population samples. Cruciferous vegetable intake data are presented from a longitudinal study of a high-vegetable dietary intervention to reduce breast cancer recurrence among breast cancer survivors (n=1,156; 536 intervention and 620 comparison group subjects). Intake was assessed using repeat administration of an FFQ and cross-sectional administration of a cruciferous vegetable-specific FFQ (CVFFQ). Mean intake in the intervention group assessed using the standard FFQ was 37.7 g/day at baseline and increased to 57.1 g/day at 12 mo (P=0.0001) and was sustained through 48 mo. Broccoli and cabbage were the most commonly consumed cruciferous vegetables, regardless of the instrument used to assess intake. Differences in intake by group assignment were shown for raw cruciferous vegetables (30.2 g/day vs. 24.6 g/day, assessed using the CVFFQ), suggesting increased exposure to biologically active, cancer-preventive food constituents. These data suggest that this study population will be the first U.S. population sample to provide ample quantity and variety in cruciferous intake to examine whether these vegetables are protective against breast cancer recurrence.
Authors: Thomson CA; Rock CL; Caan BJ; Flatt SW; Al-Delaimy WA; Newman VA; Hajek RA; Chilton JA; Pierce JP
Nutr Cancer. 2007;57(1):11-9.
Pilot study of urinary biomarkers of phytoestrogens, phthalates, and phenols in girls
BACKGROUND: Hormonally active environmental agents have been measured among U.S. children using exposure biomarkers in urine. However, little is known about their variation by race, age, sex, and geography, and no data exist for newly developed biomarkers. OBJECTIVE: Our goal was to characterize relevant, prevalent exposures for a study of female pubertal development. METHODS: In a pilot study among 90 girls from New York City, New York, Cincinnati, Ohio, and northern California, we measured 25 urinary analytes representing 22 separate agents from three chemical families: phytoestrogens, phthalates, and phenols. Exposures occur chiefly from the diet and from household or personal care products. RESULTS: Participants represented four racial/ethnic groups (Asian, black, Hispanic, white), with mean age of 7.77 years. Most analytes were detectable in > 94% of samples. The highest median concentrations for individual analytes in each family were for enterolactone (298 microg/L), monoethylphthalate (MEP; 83.2 microg/L), and benzophenone-3 (BP3; 14.7 microg/L). Few or no data have been reported previously for four metabolites: mono(2-ethyl-5-carboxypentyl) phthalate, tridosan, bisphenol A (BPA), and BP3; these were detected in 67-100% of samples with medians of 1.8-53.2 microg/L. After multivariate adjustment, two analytes, enterolactone and BPA, were higher among girls with body mass index < 85th reference percentile than those at or above the 85th percentile. Three phthalate metabolites differed by race/ethnicity [MEP, mono(2-ethylhexyl) phthalate, and mono-3-carboxypropylphthalate]. CONCLUSIONS: A wide spectrum of hormonally active exposure biomarkers were detectable and variable among young girls, with high maximal concentrations (> 1,000 microg/L) found for several analytes. They varied by characteristics that may be relevant to development.
Authors: Wolff MS; Teitelbaum SL; Windham G; Pinney SM; Britton JA; Chelimo C; Godbold J; Biro F; Kushi LH; Pfeiffer CM; Calafat AM
Environ Health Perspect. 2007 Jan;115(1):116-21.
Lifestyle factors and survival in women with breast cancer
With increasing longevity and more effective cancer therapies, the population of cancer survivors is increasing. For example, it is estimated that there are over 2 million breast cancer survivors in the United States. Among cancer survivors and their families, there is substantial interest in whether there is anything that they can do beyond conventional therapy to improve their prognosis. Chief among these is interest in diet and use of complementary and alternative therapies. Despite this interest, there is surprisingly little that is known about the effects of these factors on cancer survival. This is in part because of the usual approach to research on diet and breast cancer in human populations. Studies that have had food and nutrition as a main interest have focused almost exclusively on cancer etiology and prevention; there are literally hundreds of such studies. Meanwhile, studies of populations after a breast cancer diagnosis have rarely considered lifestyle factors. Such studies have focused largely on therapeutics, such as effects of different chemotherapy regimens, or prognostic factors, such as the effects of stage of disease, hormone receptor status, or gene expression signatures on prognosis. To the extent that lifestyle factors have been a focus of cancer prognosis studies, they have often been aimed at the question of whether they impact quality of life, and not on whether they influence cancer survival or recurrence. There have been a handful of studies that have had lifestyle factors such as diet and physical activity as a principal focus. In addition to 2 randomized trials, the Women’s Intervention Nutrition Study (WINS) and the Women’s Healthy Eating and Living Study, there are at least 5 ongoing prospective cohort studies in breast cancer survivors that have diet as a main focus. Although these studies differ in various aspects, they are all aimed at examining whether differences in diet may result in differences in recurrence and mortality rates. One such study, the Pathways Study, is a prospective cohort study that began recruitment of study participants in early 2006. This study is unique in that it is enrolling women as soon after breast cancer diagnosis as is practical, whereas other studies have generally enrolled women after completion of adjuvant therapy or later. This and other studies promise to provide some of the first objective information regarding diet and breast cancer prognosis and serve as models for studies of diet and prognosis of other cancers.
Authors: Kushi LH; Kwan ML; Lee MM; Ambrosone CB
J Nutr. 2007 Jan;137(1 Suppl):236S-242S.
Maternal illness and drug/medication use during the period surrounding pregnancy and risk of childhood leukemia among offspring
Maternal illness and drug/medication use (prescription, over-the-counter, and illicit) during pregnancy might be related to childhood leukemia risk. These issues were evaluated using data (1995-2002) from the Northern California Childhood Leukemia Study. The authors selected 365 children under age 15 years who had been diagnosed with incident leukemia and birth certificate controls who were matched to them on age, sex, Hispanic ethnicity, and maternal race. Data on maternal illnesses and drug use from before pregnancy through breastfeeding were obtained by interview with the biologic mother and were analyzed by conditional logistic regression. Maternal history of influenza/pneumonia was associated with a statistically significant increased risk of acute lymphoblastic leukemia (ALL) in the offspring (odds ratio (OR) = 1.89, 95% confidence interval (CI): 1.24, 2.89), although the risk was nonsignificant for common ALL (OR = 1.41, 95% CI: 0.75, 2.63). A similar pattern of increased risk was found for history of sexually transmitted disease. Use of iron supplements was indicative of decreased ALL risk (OR = 0.67, 95% CI: 0.47, 0.94). Observing an increased risk of leukemia in children of mothers reporting a history of influenza/pneumonia and sexually transmitted disease around the time of pregnancy suggests that maternal infection might contribute to the etiology of leukemia. Furthermore, maternal iron supplement use may be protective against childhood leukemia.
Authors: Kwan ML; Metayer C; Crouse V; Buffler PA
Am J Epidemiol. 2007 Jan 1;165(1):27-35. Epub 2006 Oct 11.
Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study
BACKGROUND: Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management. METHODS: A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided. RESULTS: Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status. CONCLUSIONS: A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.
Authors: Chlebowski RT; Caan B; Elashoff RM; et al.
J Natl Cancer Inst. 2006 Dec 20;98(24):1767-76.
Complications of colonoscopy in an integrated health care delivery system
BACKGROUND: Information about colonoscopy complications, particularly postpolypectomy bleeding, is limited. OBJECTIVE: To quantify the magnitude and severity of colonoscopy complications. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente of Northern California. PATIENTS: 16, 318 members 40 years of age or older undergoing colonoscopy between January 1994 and July 2002. MEASUREMENTS: Electronic records reviewed for serious complications, including hospital admission within 30 days of colonoscopy for colonic perforation, colonic bleeding, diverticulitis, the postpolypectomy syndrome, or other serious illnesses directly related to colonoscopy. RESULTS: 82 serious complications occurred (5.0 per 1000 colonoscopies [95% CI, 4.0 to 6.2 per 1000 colonoscopies]). Serious complications occurred in 0.8 per 1000 colonoscopies without biopsy or polypectomy and in 7.0 per 1000 colonoscopies with biopsy or polypectomy. Perforations occurred in 0.9 per 1000 colonoscopies (CI, 0.5 to 1.5 per 1000 colonoscopies) (0.6 per 1000 without biopsy or polypectomy and 1.1 per 1000 with biopsy or polypectomy). Postbiopsy or postpolypectomy bleeding occurred in 4.8 per 1000 colonoscopies with biopsy (CI, 3.6 to 6.2 per 1000 colonoscopies). Biopsy or polypectomy was associated with an increased risk for any serious complication (rate ratio, 9.2 [CI, 2.9 to 29.0] vs. colonoscopy without biopsy). Ten deaths (1 attributable to colonoscopy) occurred within 30 days of the colonoscopy. LIMITATIONS: 99.3% (16 204) of colonoscopies were nonscreening examinations. The rate of complications may be lower in a primary screening sample. The small number of observed adverse events limited power to detect risk factors for complications. CONCLUSIONS: Colonoscopy with biopsy or polypectomy is associated with increased risk for complications. Perforation may also occur during colonoscopies without biopsies.
Authors: Levin TR; Zhao W; Conell C; Seeff LC; Manninen DL; Shapiro JA; Schulman J
Ann Intern Med. 2006 Dec 19;145(12):880-6.
Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer
BACKGROUND: Cigarette smoking has been associated with microsatellite instability in sporadic colon cancer. Most microsatellite-unstable colon cancers have widespread methylation of CpG islands (i.e., the CpG island methylator phenotype [CIMP]), and many of these tumors harbor the V600E BRAF mutation. We investigated whether the association between smoking and all colon cancers could be explained through induction of CIMP and/or BRAF mutations. METHODS: We evaluated 1315 case patients with colon cancer and 2392 control subjects in a population-based study. Demographic information, including smoking history, was obtained in an interview. Microsatellite instability was determined primarily by evaluation of the mononucleotide repeat BAT-26. CIMP was determined by sodium bisulfite modification of DNA followed by methylation-specific polymerase chain reaction amplification of CpG islands in hMLH1, p16, and MINTS1, -2, and -31. Tumors were scored as CIMP high (i.e., > or = 2 CpG islands methylated) or CIMP low (i.e., < 2 CpG islands methylated). BRAF V600E mutations were identified by sequencing. Logistic regression was used to quantify relationships among smoking, CIMP, and BRAF. All statistical tests were two-sided. RESULTS: Heavy smoking (i.e., > 20 cigarettes per day), compared with nonsmoking, was associated with an increased risk of CIMP-high colon cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.43 to 2.97) and also with BRAF V600E mutations (OR = 3.16, 95% CI = 1.80 to 5.54). The association between cigarette smoking and the risk of colon cancer was limited to the minority of tumors that were CIMP high and BRAF wild type or CIMP high and BRAF mutated (for heavy smokers, OR = 1.91, 95% CI = 1.23 to 2.97, and OR = 2.85, 95% CI = 1.53 to 5.29, respectively). All relationships above showed a statistically significant relationship to amount smoked (P(trend) < .001 for all, except that relationship with tumors that were CIMP high and BRAF wild type, for which P(trend) = .008) and were independent of microsatellite instability. CONCLUSIONS: Previously identified associations between smoking and colon cancer, whether microsatellite unstable or stable, appear to be explained by the association of smoking with CIMP and BRAF mutations.
Authors: Samowitz WS; Albertsen H; Sweeney C; Herrick J; Caan BJ; Anderson KE; Wolff RK; Slattery ML
J Natl Cancer Inst. 2006 Dec 6;98(23):1731-8.
Recent declines in hormone therapy utilization and breast cancer incidence: clinical and population-based evidence
Authors: Clarke CA; Glaser SL; Uratsu CS; Selby JV; Kushi LH; Herrinton LJ
J Clin Oncol. 2006 Nov 20;24(33):e49-50.
New-onset diabetes and pancreatic cancer
BACKGROUND & AIMS: Although many individuals with pancreatic cancer have diabetes, the association between new-onset diabetes mellitus and the subsequent incidence of pancreatic cancer is unclear. METHODS: We conducted a retrospective cohort study to estimate the incidence of pancreatic cancer subsequent to a new diabetes diagnosis and to evaluate factors associated with a subsequent pancreatic cancer diagnosis. We used the Veterans Health Administration National Patient Care Database to assemble a cohort of 1,421,794 US veterans without prior diabetes or pancreatic cancer diagnoses. We recorded coding for new diabetes diagnoses (> or =2 International Classification of Diseases-9 codes for diabetes within a 12-month period), pancreatic cancer, age, sex, race, and common gastrointestinal symptoms. RESULTS: A total of 36,631 (2.6%) of the 1,421,794 veterans were diagnosed with new-onset diabetes in 1999; 149 subsequently received a diagnosis of pancreatic cancer. Pancreatic cancer incidence in patients with new-onset diabetes (83.8/100,000 person-years) was 2.2-fold higher (95% confidence interval, 1.84-2.56) than in nondiabetics, and was highest during the first 2 years after diabetes diagnosis. One additional pancreatic cancer was diagnosed for every 332 new diabetics over 6 years. A subsequent pancreatic cancer diagnosis (among new-onset diabetics) was associated independently with younger age groups, changes in bowel habits, constipation, epigastric pain, and malnutrition. CONCLUSIONS: New-onset diabetes was associated with a significantly increased rate of pancreatic cancer diagnosis, particularly in the first 2 years after diabetes diagnosis. Factors associated with pancreatic cancer diagnosis included younger age groups and the presence of gastrointestinal symptoms. The absolute incidence of pancreatic cancer was low.
Authors: Gupta S; Vittinghoff E; Bertenthal D; Corley D; Shen H; Walter LC; McQuaid K
Clin Gastroenterol Hepatol. 2006 Nov;4(11):1366-72; quiz 1301. Epub 2006 Sep 1.
Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson’s disease: a large-scale international study
BACKGROUND: A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson’s disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. METHODS: Investigators from three Michael J Fox Foundation for Parkinson’s Research-funded genetics consortia-comprising 14 teams-contributed DNA samples from 5526 patients with Parkinson’s disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. FINDINGS: In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0.89 to 1.09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0.95 to 1.08); there was little heterogeneity except for SNP rs7520966. INTERPRETATION: Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson’s disease.
Authors: Elbaz A; Van Den Eeden SK; Trikalinos TA; et al.
Lancet Neurol. 2006 Nov;5(11):917-23.
New developments in the epidemiology of cancer prognosis: traditional and molecular predictors of treatment response and survival
Authors: Ambrosone CB; Rebbeck TR; Morgan GJ; Albain KS; Calle EE; Evans WE; Hayes DF; Kushi LH; McLeod HL; Rowland JH; Ulrich CM
Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2042-6.
Antibiotics and risk of breast cancer: up to 9 years of follow-up of 2.1 million women
Antibiotic use has been associated with risk of breast cancer in previous reports. Using Cox proportional hazards analysis, we evaluated this association in 2,130,829 adult female subscribers of a health care program according to their receipt of prescriptions of antibiotics from outpatient pharmacies. Hormone use was taken into account. Altogether, 18,521 women developed breast cancer in up to 9.4 years of follow-up. Use of any antibiotic was associated with slightly increased risk [hazard ratio (HR), 1.14; 95% confidence interval (95% CI), 1.10-1.18] but there was little, if any, evidence of dose response, with HR of 1.17 (95% CI, 0.97-1.42) for >1,000 days of use compared with no use. The only two weakly associated antibiotic groups (HR >1.10 for >100 days of use) were tetracyclines and macrolides with HRs (95% CI) of 1.23 (1.11-1.36) and 1.16 (0.98-1.36), respectively. An association of lincosamides with breast cancer in an earlier, smaller database was not confirmed, but follow-up was too short in the present data for adequate evaluation. Medical record review suggested that acne and/or rosacea could be the underlying factor, associated with long-term antibiotic therapy and found by others to be associated with risk of breast cancer. Although causality cannot be ruled out, the observed associations of antibiotics overall, tetracyclines, and macrolides with breast cancer were weak and could be explained by uncontrolled confounding by the diseases being treated or by other factors.
Authors: Friedman GD; Oestreicher N; Chan J; Quesenberry CP Jr; Udaltsova N; Habel LA
Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2102-6.
Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis
BACKGROUND: Gastroesophageal reflux disease (GERD) is a common cause of morbidity and health-care utilization in many countries. Obesity is a potentially modifiable risk factor, but existing studies have conflicting results, possibly due to differences in study design, definitions, or populations. METHODS: We performed a systematic review and meta-analysis of studies identified using MEDLINE, the Web of Science electronic database, manual literature review, and a review of expert bibliographies. Studies were included if they: (1) evaluated obesity, body mass index (BMI), or another measure of body size; (2) included data on reflux symptoms, esophagitis, or a GERD-related hospitalization; and (3) reported a relative risk or odds ratio (OR) with confidence intervals or provided sufficient data to permit their calculation. RESULTS: We identified 20 studies that included 18,346 patients with GERD. Studies from the United States demonstrated an association between increasing BMI and the presence of GERD (95% confidence interval [CI]= 1.36-1.80, overweight, OR = 1.57, P value homogeneity = 0.51, 95% CI = 1.89-2.45, obese, OR = 2.15, P= 0.10). Studies from Europe provided heterogeneous results despite stratification for several factors; individual studies demonstrated both positive associations and no association. CONCLUSIONS: This analysis demonstrates a positive association between increasing BMI and the presence of GERD within the United States; this relationship became apparent only after stratification by country and level of BMI. These results support the evaluation of weight reduction as a potential therapy for GERD. Further studies are needed to evaluate potential mechanisms and any differences in this relationship among different study populations.
Authors: Corley DA; Kubo A
Am J Gastroenterol. 2006 Nov;101(11):2619-28. Epub 2006 Sep 4.
Increases in plasma carotenoid concentrations in response to a major dietary change in the women’s healthy eating and living study
BACKGROUND: Cohort studies suggest that higher circulating carotenoid concentrations through food sources may reduce breast cancer events. Other intervention studies have not achieved the level of change in circulating carotenoids required to properly test this hypothesis. METHODS: In a randomized trial of 2,922 breast cancer survivors, we examined blood and self-reported diet at baseline and 1 year. Intensive telephone counseling encouraged a plant-based diet in the intervention group. Diet was measured via 24-hour recalls, and a panel of plasma carotenoid concentrations was assessed at both time points. RESULTS: The study intervention was associated with a 51% increase in total carotenoid concentration, from 2.272 +/- 1.294 to 3.440 +/- 2.320 micromol/L, achieved mainly by marked increases in targeted carotenoids: alpha-carotene, beta-carotene, and lutein. For each of these targeted carotenoids, the proportion of the intervention sample remaining below the cutpoint for the lowest baseline quartile decreased by one third to one half. After 1 year of study, half of the intervention group was in the highest baseline quartile. No change in distribution was observed in comparison group. Intervention participants achieved this change by both dietary pattern and vegetable juice consumption. Participants who chose to change dietary pattern without consuming significant quantities of vegetable juice achieved 75% of the level of change observed in other intervention participants. CONCLUSIONS: Innovative telephone counseling intervention and dietary targets in the Women’s Healthy Eating and Living study were associated with the level of change in circulating carotenoid concentration necessary to test the diet and breast cancer hypothesis suggested by cohort studies.
Authors: Pierce JP; Caan BJ; Women's Healthy Eating and Living Study Group; et al.
Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1886-92.
Attention-deficit/hyperactivity disorder in children: excess costs before and after initial diagnosis and treatment cost differences by ethnicity
OBJECTIVES: To estimate the excess costs for children in the years surrounding initial diagnosis of attention-deficit/hyperactivity disorder (ADHD) and to estimate differences in treatment costs by ethnicity. DESIGN: We identified children diagnosed with ADHD and estimated their health service costs in the 2 years before and 2 years after initial diagnosis of ADHD. Costs were compared with those for children without ADHD. We adjusted for age, sex, ethnicity, pharmacy co-pay, estimated family income, coexisting mental health disorders, and chronic medical conditions. SETTING: Nonprofit, integrated health care delivery system in northern California from January 1, 1996, to December 31, 2004. PARTICIPANTS: Children aged 2 to 10 years with (n = 3122) and without (n = 15 899) ADHD. Main Exposure Attention-deficit/hyperactivity disorder. MAIN OUTCOME MEASURES: Health care costs and use in the years before and after initial ADHD diagnosis as well as costs of ADHD-related services. RESULTS: Compared with children without ADHD, children with ADHD had mean costs that were $488 more in the second year before their ADHD diagnosis, $678 more in the year before their diagnosis, $1328 more in the year after their diagnosis, and $1040 more in the second year after their diagnosis. Asian Americans diagnosed with ADHD had lower total ADHD-related mean costs per year than white Americans diagnosed with ADHD ($221 lower), and Asian Americans, African Americans, and Hispanic Americans all had lower ADHD-related pharmacy mean costs than white Americans ($95, $63, and $77 lower, respectively). CONCLUSIONS: Children with ADHD use significantly more health services before and after their diagnosis than children without ADHD. Among children diagnosed with ADHD, nonwhite Americans (especially Asian Americans) use fewer ADHD-related services than white Americans.
Authors: Ray GT; Levine P; Croen LA; Bokhari FA; Hu TW; Habel LA
Arch Pediatr Adolesc Med. 2006 Oct;160(10):1063-9.
Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen plus progestin
OBJECTIVES: To assess the extent to which prior hormone therapy modifies the breast cancer risk found with estrogen plus progestin (E+P) in the Women’s Health Initiative (WHI) randomized trial. METHODS: Subgroup analyses of prior hormone use on invasive breast cancer incidence in 16,608 postmenopausal women in the WHI randomized trial of E+P over an average 5.6 years of follow-up. RESULTS: Small but statistically significant differences were found between prior HT users and non-users for most breast cancer risk factors but Gail risk scores were similar. Duration of E+P use within the trial (mean 4.4 years, S.D. 2.0) did not vary by prior use. Among 4311 prior users, the adjusted hazard ratio (HR) for E+P versus placebo was 1.96 (95% confidence interval [CI]: 1.17-3.27), significantly different (p=0.03) from that among 12,297 never users (HR 1.02; 95% CI: 0.77-1.36). The interaction between study arm and follow-up time was significant overall (p=0.01) and among never users (p=0.02) but not among prior users (p=0.10). The cumulative incidence over time for the E+P and placebo groups appeared to cross after about 3 years in prior users, and after about 5 years in women with no prior use. No interaction was found with duration (p=0.08) or recency of prior use (p=0.17). Prior hormone use significantly increased the E+P hazard ratio for larger, more advanced tumors. CONCLUSION: A safe interval for combined hormone use could not be reliably defined with these data. However, the significant increase in breast cancer risk in the trial overall after only 5.6 years of follow-up, initially concentrated in women with prior hormone exposure, but with increasing risk over time in women without prior exposure, suggests that durations only slightly longer than those in the WHI trial are associated with increased risk of breast cancer. Longer-term exposure and follow-up data are needed.
Authors: Anderson GL; Khandekar J; Ritenbaugh C; et al.
Maturitas. 2006 Sep 20;55(2):103-15. Epub 2006 Jul 11.
The association between aspirin use and the incidence of colorectal cancer in women
The purpose of this study was to test the hypothesis that aspirin use is associated with a decreased risk of incident colorectal cancer. From the Women’s Health Initiative, 91,574 participants between the ages of 50 and 79 years at baseline in 1993-1998 provided details on aspirin use via interview using a standardized questionnaire and were subsequently followed annually for incident colorectal cancer during a period of over 6 years. For those persons who reported aspirin use, the type of compound, dose, and duration of use were recorded. Medical histories suggestive of colorectal cancers at the annual update were verified by medical record and pathology report review by trained local physician adjudicators. There were 631 confirmed cases of invasive cancer of the colon or rectum. There was no significant association between any aspirin use and risk for incident colorectal cancer (hazard ratio = 0.96, 95% confidence interval: 0.8, 1.2). Moreover, with no aspirin use as the referent category, there were no significant associations for duration of aspirin intake by category (< 1, 1- < 2, 2- < 3, 3- < 4, 4- < 5, and > or = 5 years) or for daily dosage by category (< 165, 165- < 300, 300- < 495, or > or = 495 mg).
Authors: Allison M; Garland C; Chlebowski R; Criqui M; Langer R; Wu L; Roy H; McTiernan A; Kuller L; Women's Health Initiative Investigators
Am J Epidemiol. 2006 Sep 15;164(6):567-75. Epub 2006 Jul 17.
Risk of fracture in women with type 2 diabetes: the Women’s Health Initiative Observational Study
CONTEXT: Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes. OBJECTIVE: The objective of the study was to determine the risk of fracture in postmenopausal women with type 2 diabetes and determine whether risk varies by fracture site, ethnicity, and baseline bone density. DESIGN, SETTING, AND PARTICIPANTS: Women with clinically diagnosed type 2 diabetes at baseline in the Women’s Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined. MAIN OUTCOME MEASURES: All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD) in a subset also was measured. RESULTS: The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controlling for multiple risk factors including frequency of falls [adjusted relative risk (RR) 1.20, 95% confidence interval (CI) 1.11-1.30]. In a subsample of women with baseline BMD scores, women with diabetes had greater hip and spine BMD. The elevated fracture risk was found at multiple sites (hip/pelvis/upper leg; foot; spine/tailbone) among black women (RR 1.33, 95% CI 1.00-1.75) and women with increased baseline bone density (RR 1.26, 95% CI 0.96-1.66). CONCLUSION: Women with type 2 diabetes are at increased risk for fractures. This risk is also seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).
Authors: Bonds DE; Larson JC; Schwartz AV; Strotmeyer ES; Robbins J; Rodriguez BL; Johnson KC; Margolis KL
J Clin Endocrinol Metab. 2006 Sep;91(9):3404-10. Epub 2006 Jun 27.
American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity
The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services’ 2005 Dietary Guidelines for Americans.
Authors: Kushi LH; Byers T; Doyle C; Bandera EV; McCullough M; McTiernan A; Gansler T; Andrews KS; Thun MJ; American Cancer Society 2006 Nutrition and Physical Activity Guidelines Advisory Committee
CA Cancer J Clin. 2006 Sep-Oct;56(5):254-81; quiz 313-4.
Post-diagnosis weight gain and breast cancer recurrence in women with early stage breast cancer
PURPOSE: To examine whether weight gain after diagnosis of breast cancer affects the risk of breast cancer recurrence. PATIENT AND METHODS: Patients included 3215 women diagnosed with early stage breast cancer (Stage I >1 cm., II, and IIIA) who were enrolled either in an observational cohort of breast cancer survivors or were part of the comparison group of a dietary intervention trial to prevent breast cancer recurrence. We computed weight change from 1 year prior to diagnosis to study enrollment. Delayed entry Cox proportional hazards models were used to evaluate associations of categories of weight change with time to recurrence, controlling for known prognostic factors. RESULTS: Neither moderate (5-10%) nor large (> 10%) weight gain (HR 0.8, 95% CI, 0.6-1.1; HR 0.9, 95% CI, 0.7-1.2, respectively) after breast cancer diagnosis was associated with an increased risk of breast cancer recurrence in the early years post-diagnosis (median time of 73.7 months from diagnosis). CONCLUSION: Our research provides evidence that weight gain commonly seen in the first several years following a breast cancer diagnosis does not increase a woman’s risk for breast cancer recurrence in the first 5-7 years post-diagnosis. However, this research does not address the effects of weight gain on overall survival or on the risk of other new cancers, other prognostic outcomes of concern to the breast cancer survivor.
Authors: Caan BJ; Gunderson EP; Habel L; Sternfeld B; Pierce JP; et al.
Breast Cancer Res Treat. 2006 Sep;99(1):47-57. Epub 2006 Mar 16.
A comparison of two dietary instruments for evaluating the fat-breast cancer relationship
BACKGROUND: Previous research suggests food diaries may be more efficient than food frequency questionnaires (FFQ) in detecting a dietary fat-breast cancer relationship. We assessed this further using 4 day food records (FRs) and FFQs in a large sample. METHODS: Participants were from the non-intervention group of the dietary modification component of the Women’s Health Initiative Clinical Trial: 603 breast cancer cases and 1206 controls matched on age, clinic, and length of follow-up. Relative risks (RRs) were estimated using unconditional logistic regression, adjusted for confounders and for the selection into the trial of women with an FFQ report exceeding 32% calories from fat. Direct comparison of the statistical power of the two instruments used the standardized log RR. An alternative analysis after removing subjects with missing covariate data was also conducted. RESULTS: The RR estimate for breast cancer in the top quintile of total fat intake, adjusted for confounders and total energy, was 1.82 (P for trend 0.02) for the FR but 0.67 for the FFQ (P for trend 0.24). Following adjustment for selection, estimates were 2.09 (P for trend 0.008) for the FR (alternative: 2.54, P for trend 0.006) and 1.71 (P for trend 0.18) for the FFQ (alternative: 1.24, P for trend 0.41). Similar results were seen for fat subtypes, particularly unsaturated fats. Comparisons showed higher statistical power for the FR than the FFQ (e.g. total fat, P = 0.08: alternative P = 0.01). CONCLUSIONS: Alternative instruments, such as FRs, may be preferable to FFQs for evaluating diet-disease relationships in cohort studies. The results support a positive association between dietary fat and breast cancer.
Authors: Freedman LS; Potischman N; Kipnis V; Midthune D; Schatzkin A; Thompson FE; Troiano RP; Prentice R; Patterson R; Carroll R; Subar AF
Int J Epidemiol. 2006 Aug;35(4):1011-21. Epub 2006 May 3.
Twins of mistaken zygosity (TOMZ): evidence for genetic contributions to dietary patterns and physiologic traits
Twin designs, comparing correlations in monozygotic (MZ) versus dizygotic (DZ) twins, have an extensive history. One major confounder in such studies is that MZ twins may share postnatal environmental influences more so than do DZ twins. To avoid such confounding, twins separated at or soon after birth have been studied, but their scarcity often makes this approach impractical. Another method has been to measure the degree of contact twins have maintained over time, and adjust the observed correlations. Here, we remove confounding by utilizing the discrepancy between biological and self-perceived zygosity to separate environmental from genetic sources of twin similarity. We analyzed dietary patterns and physiologic traits in 350 female twin pairs of the 1988 Kaiser Permanente Twin Registry. Among twin pairs, 175 were MZ by self-report and genetic testing (MZC), 136 were DZ by self-report and genetic testing (DZC), 30 were MZ by genetic testing but not by self-report (MZW), and 9 were DZ by genetic testing but not by self-report (DZW) but were excluded due to small sample size. For healthy food patterns, MZC and MZW intraclass correlations were similar and greater than for DZC, yielding positive and significant heritability estimates. For unhealthy food patterns, the MZC, MZW and DZC correlations were similar with no significant heritability. For physiologic traits, MZC and MZW correlations were similar and higher than those for DZC, indicating significant heritability, except for insulin for which MZW and DZC were similar and which showed modest heritability. Twins of mistaken zygosity (TOMZ) provides a useful approach to robust determination of heritability.
Authors: Gunderson EP; Tsai AL; Selby JV; Caan B; Mayer-Davis EJ; Risch N
Twin Res Hum Genet. 2006 Aug;9(4):540-9.
Mortality and cardiac and vascular outcomes in extremely obese women
CONTEXT: Obesity, typically measured as body mass index of 30 or higher, has 3 subclasses: obesity 1 (30-34.9); obesity 2 (35-39.9); and extreme obesity (> or =40). Extreme obesity is increasing particularly rapidly in the United States, yet its health risks are not well characterized. OBJECTIVE: To determine how cardiovascular and mortality risks differ across clinical weight categories in women, with a focus on extreme obesity. DESIGN, SETTING, AND PARTICIPANTS: We examined incident mortality and cardiovascular outcomes by weight status in 90,185 women recruited from 40 US centers for the Women’s Health Initiative Observational Study and followed up for an average of 7.0 years (October 1, 1993 to August 31, 2004). MAIN OUTCOME MEASURES: Incidence of mortality, coronary heart disease, diabetes, and hypertension. RESULTS: Extreme obesity prevalence differed with race/ethnicity, from 1% among Asian and Pacific Islanders to 10% among black women. All-cause mortality rates per 10,000 person-years were 68.39 (95% confidence interval [CI], 65.26-71.68) for normal body mass index, 71.16 (95% CI, 67.68-74.82) for overweight, 84.47 (95% CI, 78.90-90.42) for obesity 1, 102.85 (95% CI, 92.90-113.86) for obesity 2, and 116.85 (95% CI, 103.36-132.11) for extreme obesity. Analyses adjusted for age, smoking, educational achievement, US region, and physical activity levels showed that weight-related risk for all-cause mortality, coronary heart disease mortality, and coronary heart disease incidence did not differ by race/ethnicity. Adjusted analyses among white and black participants showed positive trends in all-cause mortality and coronary heart disease incidence with increasing weight category. Much of the obesity-related mortality and coronary heart disease risk was mediated by diabetes, hypertension, and hyperlipidemia. In white women, weight-related all-cause mortality risk was modified by age, with obesity conferring less risk among older women. CONCLUSIONS: Considering obesity as a body mass index of 30 or higher may lead to misinterpretation of individual and population risks. Escalating extreme obesity may exacerbate health effects and costs of the obesity epidemic.
Authors: McTigue K; Larson JC; Valoski A; Burke G; Kotchen J; Lewis CE; Stefanick ML; Van Horn L; Kuller L
JAMA. 2006 Jul 5;296(1):79-86.
High dry bean intake and reduced risk of advanced colorectal adenoma recurrence among participants in the polyp prevention trial
Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial-based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18-0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial-based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence.
Authors: Lanza E; Caan B; Schatzkin A; et al.
J Nutr. 2006 Jul;136(7):1896-903.
Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention
BACKGROUND AND AIMS: Variant genotypes of uridine diphosphate glucuronsyltransferase isoenzyme 1A6 (UGT1A6) associated with decreased metabolic activity have been associated with an enhanced protective effect of aspirin on the development of colorectal adenomas. However, interactions between UGT1A6 variants or variants of another enzyme that metabolizes nonsteroidal anti-inflammatory drugs (NSAIDs), cytochrome P4502C9 (CYP2C9), and NSAIDs in the prevention of colorectal cancer have not been studied extensively. METHODS: UGT1A6 and CYP2C9 genotypes were determined in 2295 individuals with colorectal cancer and 2903 controls. Interactions between these genotypes, aspirin or ibuprofen use, and colorectal cancer risk were determined. RESULTS: Variant CYP2C9 genotypes enhanced the protective effect of ibuprofen on the prevention of colorectal cancer, and a dose-response relationship with respect to increasing numbers of variant alleles was seen (P interaction = .02). CYP2C9 variants were more effective in individuals with wild-type rather than variant UGT1A6 (P interaction < .007). Variant CYP2C9 genotypes showed no interaction with aspirin usage, and variant UGT1A6 genotypes showed no interaction with either NSAID with respect to colorectal cancer protection. CONCLUSIONS: In this study, the major effect seen was an enhancement by slower-metabolizing CYP2C9 variants of the chemopreventive activity of ibuprofen against colorectal cancer.
Authors: Samowitz WS; Wolff RK; Curtin K; Sweeney C; Ma KN; Andersen K; Levin TR; Slattery ML
Clin Gastroenterol Hepatol. 2006 Jul;4(7):894-901. Epub 2006 Jun 22.
Long-term outcomes following conservative surgery for borderline tumor of the ovary: a large population-based study
OBJECTIVES: To examine outcomes in women treated with conservative surgery for borderline ovarian tumor in a large population-based cohort with long-term follow-up. METHODS: Women treated by conservative surgery for borderline tumor of the ovary from 1982-2004 within a large HMO setting were identified using electronic and tumor registry data. Chart review was performed when electronic data were incomplete. The indications for and outcomes from any subsequent gynecologic surgery and the risk of recurrent ovarian borderline and malignant tumor were determined. Risk factors for recurrence were analyzed using multivariate regression. RESULTS: Among one hundred and ninety-three patients identified, the average age was 33 (12-95), with 97% having apparent Stage I disease. Patients were followed with remaining ovarian tissue in situ for a mean of 6.9 years, with 59 women having 10 or more years of such observation. There were 21 recurrences with borderline tumor (11%) with a median time to first recurrence of 4.7 years; women treated by cystectomy recurred three times more often compared to women treated by oophorectomy (23% versus 7%). Two patients (1%) recurred with malignant disease involving remaining ovarian tissue, both within the first 3 years after surgery, with one death due to recurrence. During long-term follow-up, 19% of patients eventually underwent complete removal of ovarian tissue: in 8%, the surgery was prophylactic, in 5%, surgery was done for benign pathology, and in 6% for recurrent disease. CONCLUSIONS: In this population-based HMO setting, 11% of women treated with conservative surgery for borderline tumor recurred; however, half of these recurrences were successfully managed by repeat conservative surgery, with only 6% of women overall needing eventual complete removal of ovaries for recurrent disease. Patients treated by cystectomy were three times more likely to recur than those treated by oophorectomy. Malignant recurrences were rare, and while borderline recurrences often occurred more than 3 years after initial surgery, late malignant recurrences were not observed. These favorable long-term outcomes provide support for conservative surgery for these women.
Authors: Suh-Burgmann E
Gynecol Oncol. 2006 Dec;103(3):841-7. Epub 2006 Jun 21.
Associations between vitamin D, vitamin D receptor gene and the androgen receptor gene with colon and rectal cancer
The transcriptional activity of the vitamin D receptor (VDR) gene is regulated, at least in part, by the androgen receptor (AR) gene. We evaluate how the number of polyglutamine (CAG) repeats of the AR gene influence colorectal cancer in conjunction with vitamin D, sunshine exposure and VDR. Studies of colon (1,580 cases and 1,968 controls) and rectal (797 cases and 1,016 controls) cancer were used. Vitamin D intake and average hours of sunshine exposure interacted with AR genotype in men. Men with low vitamin D intake or low levels of sunshine exposure who had 23+ CAG repeats of the AR gene had the greatest risk of colon cancer. ORs for men with 23 or more CAG repeats of the AR gene and in the lowest tertile of vitamin D intake or sunshine exposure were 1.71 (95% CI 1.14, 2.56) and 1.51 (95% CI 1.09, 2.09). Men with high levels of sunshine exposure were at reduced risk of developing rectal cancer if they had 23 or more CAG repeats (OR 0.62 95% CI 0.39, 0.97) than if they had fewer than 23 CAG repeats. The FF genotype of the Fok1 VDR gene was associated with reduced risk of colon cancer among women with any allele of 23+ CAG repeats (OR 0.62 95% CI 0.44, 0.88), whereas men with the LL/bb VDR genotypes were at reduced risk of rectal cancer if they also had 23+ CAG repeats (OR 0.71 95% CI 0.48, 1.05) relative to men with fewer than 23 CAG repeats of the AR gene. These data provide support for the role of vitamin D and sunshine exposure in the etiology of colorectal cancer and suggest that AR gene may modulate the association.
Authors: Slattery ML; Sweeney C; Murtaugh M; Ma KN; Caan BJ; Potter JD; Wolff R
Int J Cancer. 2006 Jun 15;118(12):3140-6.
Development of a glycemic index database for food frequency questionnaires used in epidemiologic studies
Consumption of foods with a high glycemic index (GI) or glycemic load (GL) is hypothesized to contribute to insulin resistance, which is associated with increased risk of diabetes mellitus, obesity, cardiovascular disease, and some cancers. However, dietary assessment of GI and GL is difficult because values are not included in standard food composition databases. Our objective was to develop a database of GI and GL values that could be integrated into an existing dietary database used for the analysis of FFQ. Food GI values were obtained from published human experimental studies or imputed from foods with a similar carbohydrate and fiber content. We then applied the values to the Women’s Health Initiative (WHI) FFQ database and tested the output in a random sample of previously completed WHI FFQs. Of the 122 FFQ line items (disaggregated into 350 foods), 83% had sufficient carbohydrate (>5 g/serving) for receipt of GI and GL values. The foods on the FFQ food list with the highest GL were fried breads, potatoes, pastries, pasta, and soft drinks. The fiber content of foods had very little influence on calculated GI or GL estimates. The augmentation of this FFQ database with GI and GL values will enable etiologic investigations of GI and GL with numerous disease outcomes in the WHI and other epidemiologic studies that utilize this FFQ.
Authors: Neuhouser ML; Tinker LF; Thomson C; Caan B; Horn LV; Snetselaar L; Parker LM; Patterson RE; Robinson-O'Brien R; Beresford SA; Shikany JM
J Nutr. 2006 Jun;136(6):1604-9.
Statin use and breast cancer: prospective results from the Women’s Health Initiative
BACKGROUND: Despite experimental observations suggesting that 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) have antitumor activity, clinical studies have reached mixed conclusions about the relationship between statin use and breast cancer risk. METHODS: To investigate associations between potency, duration of use, and type of statin used and risk of invasive breast cancer, we examined data for 156,351 postmenopausal women who were enrolled in the Women’s Health Initiative. Information was collected on breast cancer risk factors and on the use of statins and other lipid-lowering drugs. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical tests were two-sided. RESULTS: Over an average follow-up of 6.7 years, 4383 invasive breast cancers were confirmed by medical record and pathology report review. Statins were used by 11,710 (7.5%) of the cohort. Breast cancer incidence was 4.09 per 1000 person-years (PY) among statin users and 4.28 per 1000 PY among nonusers. In multivariable models, the hazard ratio of breast cancer among users of any statin, compared with nonusers, was 0.91 (95% CI = 0.80 to 1.05, P = .20). There was no trend in risk by duration of statin use, with HR = 0.80 (95% CI = 0.63 to 1.03) for < 1 year of use, HR = 0.99 (95% CI = 0.80 to 1.23) for 1- < 3 years of use, and HR = 0.94 (95% CI = 0.75 to 1.18) for > or = 3 years of use. Hydrophobic statins (i.e., simvastatin, lovastatin, and fluvastatin) were used by 8106 women, and their use was associated with an 18% lower breast cancer incidence (HR = 0.82, 95% CI = 0.70 to 0.97, P = .02). Use of other statins (i.e., pravastatin and atorvastatin) or nonstatin lipid-lowering agents was not associated with breast cancer incidence. CONCLUSIONS: Overall statin use was not associated with invasive breast cancer incidence. Our finding that use of hydrophobic statins may be associated with lower breast cancer incidence suggests possible within-class differences that warrant further evaluation.
Authors: Cauley JA; McTiernan A; Rodabough RJ; LaCroix A; Bauer DC; Margolis KL; Paskett ED; Vitolins MZ; Furberg CD; Chlebowski RT; Women's Health Initiative Research Group
J Natl Cancer Inst. 2006 May 17;98(10):700-7.
Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer
Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stages II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double-contrast barium enema or computed tomography colonography should be performed preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that examination is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see ‘Guidelines for Colonoscopy Surveillance After Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society’). Shorter intervals also are indicated if the patient’s age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence compared with those with colon cancer. Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6-month intervals for the first 2 years after resection can be considered for the purpose of detecting a surgically curable recurrence of the original rectal cancer.
Authors: Rex DK; Levin TR; US Multi-Society Task Force on Colorectal Cancer; et al.
Gastroenterology. 2006 May;130(6):1865-71.
Barrett’s esophagus and medications that relax the lower esophageal sphincter
OBJECTIVES: Medications that may increase gastroesophageal reflux could be risk factors for esophageal adenocarcinoma; however, epidemiologic studies present conflicting results. We evaluated patients with a high-risk condition, Barrett’s esophagus, to identify risk factors that may act early in the carcinogenic process. METHODS: We conducted a nested case-control study within a large integrated health-services organization. Electronic databases were used to identify incident diagnoses of Barrett’s esophagus (cases); two controls were matched to each case. Electronic databases provided information on the use of medications that may induce reflux (nitrates, calcium channel blockers, xanthines, benzodiazepines, and beta agonists) and potential confounders. A supplemental mailed questionnaire evaluated additional potential confounders. RESULTS: We identified 421 cases and selected 842 controls. The association between any medication use and a Barrett’s esophagus diagnosis was modified by age; an increased risk was observed only among subjects <70 yr of age (adjusted odds ratio [OR] = 2.6; 95% confidence interval [CI] 1.5-4.6). A Barrett's esophagus diagnosis was associated with asthma medication use (OR 5.8; 95% CI 2.2, 14.9), but not with the other medications studied. Subgroup analyses suggested that medication use was not independently associated with reflux symptoms and that adjustment for asthma symptoms substantially reduced the association between medication use and a Barrett's esophagus diagnosis. CONCLUSION: The use of medications that may induce reflux was associated with a Barrett's esophagus diagnosis among younger persons. This association was only observed with asthma medications; the analyses suggested the possibility of confounding by indication, whereby reflux may cause both asthma and Barrett's esophagus.
Authors: Corley DA; Levin TR; Habel LA; Buffler PA
Am J Gastroenterol. 2006 May;101(5):937-44.
Body mass index and adenocarcinomas of the esophagus or gastric cardia: a systematic review and meta-analysis
BACKGROUND: The incidence of esophageal adenocarcinoma has increased markedly in recent decades in many countries. Obesity is a potential risk factor, although the results of individual studies differ. We did a systematic review and statistical synthesis of studies that evaluated the association between body mass index (BMI) and the risk of esophageal adenocarcinoma or the adjacent gastric cardia adenocarcinoma. METHODS: We identified potential studies using Medline, the Web of Science database, a manual review of the literature and expert bibliographies. Studies were included if they reported (a) a measure of body mass; (b) the occurrence of esophageal or cardia adenocarcinoma diagnosis; and (c) a relative risk or odds ratio (OR) with confidence intervals (CI) or provided sufficient data to permit their calculation. RESULTS: We identified 14 studies (2 cohort, 12 case-control; 2,488 esophageal and 2,509 cardia adenocarcinomas). A high BMI (>25) was associated with an increased risk of esophageal adenocarcinoma (males, OR, 2.2; 95% CI, 1.7-2.7; females, OR, 2.0; 95% CI, 1.4-2.9). Higher levels of BMI were associated with increased risk (overweight males, OR, 1.8; 95% CI, 1.5-2.2; obese males, OR, 2.4; 95% CI, 1.9-3.2). The overall associations with cardia cancer were heterogeneous, although stratification by study location provided homogeneous results for populations from the United States or Europe. A high BMI was weakly associated with the risk of cardia adenocarcinoma (OR, 1.5; 95% CI, 1.3-1.8; P(heterogeneity) = 0.38). CONCLUSIONS: Pooled results from observational studies support a positive association between high BMI and the risk for esophageal and possibly for cardia adenocarcinoma.
Authors: Kubo A; Corley DA
Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):872-8.
Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society
Adenomatous polyps are the most common neoplastic findings uncovered in people who undergo colorectal screening or have a diagnostic workup for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas as well as missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which demonstrated clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance be 3 years after polypectomy for most patients. In 2003, these guidelines were updated, colonoscopy was recommended as the only follow-up examination, and stratification at baseline into lower and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have demonstrated that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present paper, a careful analytic approach was designed addressing all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be more definitely stratified at their baseline colonoscopy into those at lower or increased risk for a subsequent advanced neoplasia. People at increased risk have either three or more adenomas, or high-grade dysplasia, or villous features, or an adenoma > or =1 cm in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have one or two small (< 1 cm) tubular adenomas with no high-grade dysplasia can have a follow-up in 5 to 10 years, whereas people with hyperplastic polyps only should have a 10-year follow-up as average-risk people. Recent papers have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians' concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase utilization of the recommendations by endoscopists. Adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.
Authors: Winawer SJ; Levin TR; Rex DK; et al.
CA Cancer J Clin. 2006 May-Jun;56(3):143-59; quiz 184-5.
Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy
CONTEXT: The Women’s Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis. OBJECTIVE: To determine the effects of CEE on breast cancers and mammographic findings. DESIGN, SETTING, AND PARTICIPANTS: Following breast cancer risk assessment, 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included. INTERVENTION: A dose of 0.625 mg/d of CEE or an identical-appearing placebo. MAIN OUTCOME MEASURES: Breast cancer incidence, tumor characteristics, and mammogram findings. RESULTS: After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up. CONCLUSIONS: Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.
Authors: Stefanick ML; Paskett ED; WHI Investigators; et al.
JAMA. 2006 Apr 12;295(14):1647-57.
PPARgamma and colon and rectal cancer: associations with specific tumor mutations, aspirin, ibuprofen and insulin-related genes (United States)
We hypothesize that the peroxisome proliferator-activated receptor-gamma (PPARgamma) is associated with colorectal cancer given its association with insulin, diabetes, obesity, and inflammation. In this study, we evaluated the association between colorectal cancer and specific tumor mutations and the Pro12Ala (P12A) PPARgamma polymorphism. We also evaluated interactions between the PPARgamma gene and other insulin-related genes and use of aspirin and non-steroidal anti-inflammatory drug use. Data were available from 1,577 cases of colon cancer that were matched to 1,971 population-based controls and 794 cases of rectal cancer that were matched to 1,001 population-based controls. Colon tumors from the case subjects were evaluated for p53 and Ki-ras mutations and microsatellite instability (MSI). Insulin-related genes evaluated were the Bsm1, polyA, and Fok1 polymorphisms of the VDR gene; the G972R IRS1 polymorphism; the G1057D IRS2 polymorphism; the 19CA repeat polymorphism of the IGF1 gene; and the -200A>C IGFBP3 polymorphism. The odds ratio (OR) between the PA/AA genotypes and proximal tumors was 0.83 (95% CI: 0.69-1.01); for distal tumors was 1.00 (95% CI: 0.83-1.21); and for rectal tumors was 1.04 (95% CI: 0.86-1.25). Evaluation of specific types of tumor mutations showed that colon cancer cases with the PA or AA genotypes were less likely to have p53 tumor mutations (OR 0.78; 95% CI: 0.62-0.99), specifically transition mutations (OR 0.74; 95% CI: 0.56-0.97). Colon cancer cases also were less likely to have a tumor with MSI if they had the PA or AA PPARgamma genotype (OR 0.68; 95% CI: 0.47-0.98); differences in Ki-ras mutations were not seen in colon tumors by PPARgamma genotype. Those who did not take ibuprofen-type drugs and had the PA or AA genotypes were at a significantly greater risk of rectal cancer (OR 2.11; 95% CI: 1.52-2.92; p interaction 0.03) than people with the PP genotype regardless of ibuprofen-type drug use. There was a significant interaction between the -200A>C IGFBP3 polymorphism and the Pro12Ala PPARgamma polymorphism and risk of colon cancer (p for interaction = 0.02) with individuals being at significantly lower risk if they had both the CC IGFBP3 genotype and the PA/AA PPARgamma genotype. For rectal cancer there was a significant interaction between the Bsm1/polyA polymorphisms (p = 0.001) of the VDR gene and the PA/AA Pro12Ala PPARgamma polymorphism with the highest risk group being those with both the PA/AA Pro12Ala PPARgamma and the BB/SS VDR genotypes. These data suggest that PPARgamma may be associated with many aspects of colorectal cancer including insulin- and inflammation-related mechanisms.
Authors: Slattery ML; Curtin K; Wolff R; Ma KN; Sweeney C; Murtaugh M; Potter JD; Levin TR; Samowitz W
Cancer Causes Control. 2006 Apr;17(3):239-49.
Haplotype analysis of common vitamin D receptor variants and colon and rectal cancers
Inherited variants of the vitamin D receptor (VDR) gene may influence cancer risk by altering the effect of vitamin D on cell growth and homeostasis. Studies have examined genotypes for common VDR polymorphisms, including a single nucleotide polymorphism (SNP) detected by Bsm1, a polyadenosine [poly(A)] repeat polymorphism, and a SNP detected by Fok1, as candidates for susceptibility to cancer, but most have not evaluated haplotypes for these markers. We investigated haplotypes for these polymorphisms in case-control studies of colon cancer (1,811 cases and 1,451 controls) and rectal cancer (905 cases and 679 controls). We used the expectation-maximization algorithm to estimate haplotypes for White, Hispanic, African-American, and Asian subjects, tested for differences in VDR haplotype distribution, and calculated odds ratios (OR) for association between haplotype and cancer. The distribution of haplotypes differed by race or ethnic group, but four common haplotypes accounted for the majority of alleles in all groups. VDR haplotype distributions differed between colon cancer cases and controls (P = 0.0004). The common haplotype bLF, containing Bsm1 b (Bsm1 restriction site present), poly(A) long (18-22 repeats), and Fok1 F (restriction site absent) was associated with increased risk of colon cancer, OR 1.15 (95% confidence interval, 1.03-1.28), as was the rare haplotype BLF, containing Bsm1 B (restriction site absent), poly(A) long, and Fok1 F (OR, 2.40; 95% confidence interval, 1.43-4.02). No case-control differences were detected for rectal cancer. In this analysis, haplotypes of the VDR influenced risk of colon cancer, but haplotype variables had only slightly better ability to explain case-control differences than genotype variables.
Authors: Sweeney C; Curtin K; Murtaugh MA; Caan BJ; Potter JD; Slattery ML
Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):744-9.
Sexual activity and function in middle-aged and older women
OBJECTIVE: Data on the sexual activity of middle-aged and older women are scant and vary widely. This analysis estimates the prevalence and predictors of sexual activity and function in a diverse group of women aged 40-69 years. METHODS: The Reproductive Risk Factors for Incontinence Study at Kaiser (RRISK) was a population-based study of 2,109 women aged 40-69 years who were randomly selected from long-term Kaiser Permanente members. Women completed self-report questionnaires on sexual activity, comorbidities, and general quality of life. Logistic and linear regression and proportional odds models were used when appropriate to identify correlates of sexual activity, frequency, satisfaction, and dysfunction. RESULTS: Mean age was 55.9 (+/- 8) years and nearly three fourths of the women were sexually active. Of the sexually active women, 60% had sexual activity at least monthly, approximately two thirds were at least somewhat satisfied, and 33% reported a problem in one or more domains. Monthly or more frequent sexual activity was associated with younger age, higher income, being in a significant relationship, a history of moderate alcohol use, and lower body mass index (BMI) (all P < .05). Satisfaction with sexual activity was associated with African-American race, lower BMI, and higher mental health score (all P < .05). More sexual dysfunction was associated with having a college degree or greater, poor health, being in a significant relationship, and a low mental health score (all P < .05). CONCLUSION: Middle-aged and older women engage in satisfying sexual activity, and one third reported problems with sexual function. Demographic factors as well as some issues associated with aging can adversely affect sexual frequency, satisfaction, and function. LEVEL OF EVIDENCE: II-3.
Authors: Addis IB; Van Den Eeden SK; Wassel-Fyr CL; Vittinghoff E; Brown JS; Thom DH; Reproductive Risk Factors for Incontinence Study at Kaiser Study Group
Obstet Gynecol. 2006 Apr;107(4):755-64.
Social networks, social support, and survival after breast cancer diagnosis
PURPOSE: We prospectively examined social ties and survival after breast cancer diagnosis.PATIENTS AND METHODS: Participants included 2,835 women from the Nurses’ Health Study who were diagnosed with stages 1 to 4 breast cancer between 1992 and 2002. Of these women, 224 deaths (107 of these related to breast cancer) accrued to the year 2004. Social networks were assessed in 1992, 1996, and 2000 with the Berkman-Syme Social Networks Index. Social support was assessed in 1992 and 2000 as the presence and availability of a confidant. Cox proportional hazards models were used in prospective analyses of social networks and support, both before and following diagnosis, and subsequent survival.RESULTS: In multivariate-adjusted analyses, women who were socially isolated before diagnosis had a subsequent 66% increased risk of all-cause mortality (HR = 1.66; 95% CI, 1.04 to 2.65) and a two-fold increased risk of breast cancer mortality (HR = 2.14; 95% CI, 1.11 to 4.12) compared with women who were socially integrated. Women without close relatives (HR = 2.65; 95% CI, 1.03 to 6.82), friends (HR = 4.06; 95% CI, 1.40 to 11.75), or living children (HR = 5.62; 95% CI, 1.20 to 26.46) had elevated risks of breast cancer mortality and of all-cause mortality compared with those with the most social ties. Neither participation in religious or community activities nor having a confidant was related to outcomes. Effect estimates were similar in analyses of postdiagnosis networks.CONCLUSION: Socially isolated women had an elevated risk of mortality after a diagnosis of breast cancer, likely because of a lack of access to care, specifically beneficial caregiving from friends, relatives, and adult children.
Authors: Kroenke CH; Kubzansky LD; Schernhammer ES; Holmes MD; Kawachi I;
J Clin Oncol. 2006 Mar 1;24(7):1105-11.
Use of raloxifene among women with a history of breast cancer
PURPOSE: To examine raloxifene use among women with a history of breast cancer. METHODS: Kaiser Permanente tumor registry and membership files were used to identify women diagnosed with breast cancer after 1994 who were health plan members in 1998 or later, when raloxifene became available. Information on raloxifene treatment was obtained from computerized pharmacy records. Treatment patterns were examined and the characteristics of those who did and did not receive raloxifene were compared. RESULTS: Among the 17,968 women with a history of breast cancer, 711 (4.0%) had at least one prescription for raloxifene. Use among these women was more common than among similarly aged women in the health plan without a history of breast cancer, especially among those less than age 60 years. Among women with a history of breast cancer, raloxifene users were more than twice as likely as non-users to have had a bone mineral density test (60 versus 26%, p<0.0001) and, if tested, were more likely to have osteopenia or osteoporosis (80 versus 63%, p<0.0001). Compared to non-users, users had earlier stage breast cancer at diagnosis (80% versus 71% with local disease, p<0.0001). Raloxifene use was largely restricted to women whose initial breast cancer had not been treated with adjuvant tamoxifen or who had received less than 5 years of tamoxifen therapy. CONCLUSION: In this setting, raloxifene use among women with a history of breast cancer is related to stage at diagnosis and bone mineral density and is rare among women who have completed a 5-year course of adjuvant tamoxifen.
Authors: Habel LA; Pressman A; Ettinger B; Sidney S; Suh-Burgmann B; Fehrenbacher L; Quesenberry CP
Breast Cancer Res Treat. 2006 Mar;96(2):123-9.
Epidemiologic research on the obesity epidemic: a socioenvironmental perspective
Authors: Kushi LH
Epidemiology. 2006 Mar;17(2):131-3.
Conjugated equine estrogens and coronary heart disease: the Women’s Health Initiative
BACKGROUND: In recent randomized trials, conjugated equine estrogens (CEE) with continuous medroxyprogesterone acetate provided no protection against coronary heart disease in postmenopausal women and may have increased cardiac risk. These trials did not address the role of unopposed estrogen for coronary protection. METHODS: A total of 10 739 women aged 50 to 79 years at baseline (mean age, 63.6 years) who had previously undergone hysterectomy were randomized to receive CEE, 0.625 mg/d, or placebo at 40 US clinical centers beginning in 1993. The trial was terminated early after 6.8 years of follow-up (planned duration, 8.5 years). This report includes final, centrally adjudicated results for the primary efficacy outcome (myocardial infarction or coronary death), secondary coronary outcomes, and subgroup analyses. RESULTS: During the active intervention period, 201 coronary events were confirmed among women assigned to receive CEE compared with 217 events among women assigned to receive placebo (hazard ratio, 0.95; nominal 95% confidence interval, 0.79-1.16). Among women aged 50 to 59 years at baseline, the hazard ratio for the primary outcome was 0.63 (nominal 95% confidence interval, 0.36-1.08). In that age group, coronary revascularization was less frequent among women assigned to receive CEE (hazard ratio, 0.55; nominal 95% confidence interval, 0.35-0.86), as were several composite outcomes, which included the primary outcome and coronary revascularization (hazard ratio, 0.66; nominal 95% confidence interval, 0.44-0.97). CONCLUSIONS: Conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death in generally healthy postmenopausal women during a 7-year period of use. There was a suggestion of lower coronary heart disease risk with CEE among women 50 to 59 years of age at baseline.
Authors: Hsia J; Women's Health Initiative Investigators; et al.
Arch Intern Med. 2006 Feb 13;166(3):357-65.
Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial
CONTEXT: The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial. OBJECTIVE: To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence. DESIGN AND SETTING: A randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005. PARTICIPANTS: A total of 48,835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled. INTERVENTIONS: Women were randomly assigned to the dietary modification intervention group (40% [n = 19,541]) or the comparison group (60% [n = 29,294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes. MAIN OUTCOME MEASURE: Invasive breast cancer incidence. RESULTS: Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor. CONCLUSIONS: Among postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.
Authors: Prentice RL; Caan B; Henderson MM; et al.
JAMA. 2006 Feb 8;295(6):629-42.
Low-fat dietary pattern and risk of colorectal cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial
CONTEXT: Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial. OBJECTIVE: To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: The Women’s Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States. INTERVENTIONS: Participants were randomly assigned to the dietary modification intervention (n = 19,541; 40%) or the comparison group (n = 29,294; 60%). The intensive behavioral modification program aimed to motivate and support reductions in dietary fat, to increase consumption of vegetables and fruits, and to increase grain servings by using group sessions, self-monitoring techniques, and other tailored and targeted strategies. Women in the comparison group continued their usual eating pattern. MAIN OUTCOME MEASURE: Invasive colorectal cancer incidence. RESULTS: A total of 480 incident cases of invasive colorectal cancer occurred during a mean follow-up of 8.1 (SD, 1.7) years. Intervention group participants significantly reduced their percentage of energy from fat by 10.7% more than did the comparison group at 1 year, and this difference between groups was mostly maintained (8.1% at year 6). Statistically significant increases in vegetable, fruit, and grain servings were also made. Despite these dietary changes, there was no evidence that the intervention reduced the risk of invasive colorectal cancer during the follow-up period. There were 201 women with invasive colorectal cancer (0.13% per year) in the intervention group and 279 (0.12% per year) in the comparison group (hazard ratio, 1.08; 95% confidence interval, 0.90-1.29). Secondary analyses suggested potential interactions with baseline aspirin use and combined estrogen-progestin use status (P = .01 for each). Colorectal examination rates, although not protocol defined, were comparable between the intervention and comparison groups. Similar results were seen in analyses adjusting for adherence to the intervention. CONCLUSION: In this study, a low-fat dietary pattern intervention did not reduce the risk of colorectal cancer in postmenopausal women during 8.1 years of follow-up. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT00000611.
Authors: Beresford SA; Caan B; Whitlock E; et al.
JAMA. 2006 Feb 8;295(6):643-54.
Vitamin D receptor gene polymorphisms, dietary promotion of insulin resistance, and colon and rectal cancer
Modifiable risk factors in colorectal cancer etiology and their interactions with genetic susceptibility are of particular interest. Functional vitamin D receptor (VDR) gene polymorphisms may influence carcinogenesis through modification of cell growth, protection from oxidative stress, cell-cell matrix effects, or insulin and insulin-like growth factor pathways. We investigated interactions between foods (dairy products, red and processed meat, and whole and refined grains) and dietary patterns (sucrose-to-fiber ratio and glycemic index) associated with insulin resistance with the FokI polymorphism of the VDR gene and colon and rectal cancer risk. Data (diet, anthropometrics, and lifestyle) and DNA came from case-control studies of colon (1,698 cases and 1,861 controls) and rectal cancer (752 cases and 960 controls) in northern California, Utah, and the Twin Cities metropolitan area, Minnesota (colon cancer study only). Unconditional logistic regression models were adjusted for smoking, race, sex, age, body mass index, physical activity, energy intake, dietary fiber, and calcium. The lowest colon cancer risk was observed with the Ff/ff FokI genotypes and a low sucrose-to-fiber ratio. Rectal cancer risk decreased with greater consumption of dairy products and increased with red or processed meat consumption and the FF genotype. Modifiable dietary risk factors may be differentially important among individuals by VDR genotype and may act through the insulin pathway to affect colon cancer risk and through fat, calcium, or other means to influence rectal cancer risk.
Authors: Murtaugh MA; Sweeney C; Ma KN; Potter JD; Caan BJ; Wolff RK; Slattery ML
Nutr Cancer. 2006;55(1):35-43.
Reducing unnecessary surveillance colonoscopies: a mandate for endoscopists
Authors: Levin TR
Gastrointest Endosc. 2006 Jan;63(1):104-6.
A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients
INTRODUCTION: The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. METHODS: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. RESULTS: After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7-3.9%), 10.7% (95% CI 6.3-14.9%), and 15.5% (95% CI 7.6-22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5-7.9%), 17.8% (95% CI 11.8-23.3%), and 19.9% (95% CI 14.2-25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. CONCLUSION: In this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients.
Authors: Habel LA; Quesenberry CP; et al.
Breast Cancer Res. 2006;8(3):R25. Epub 2006 May 31.
California Men’s Health Study (CMHS): a multiethnic cohort in a managed care setting
BACKGROUND: We established a male, multiethnic cohort primarily to study prostate cancer etiology and secondarily to study the etiologies of other cancer and non-cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old males who were members of a large, prepaid health plan in California. Participants completed two surveys on-line or on paper in 2002-2003. Survey content included demographics; family, medical, and cancer screening history; sexuality and sexual development; lifestyle (diet, physical activity, and smoking); prescription and non-prescription drugs; and herbal supplements. We linked study data with clinical data, including laboratory, hospitalization, and cancer data, from electronic health plan files. We recruited 84,170 participants, approximately 40% from minority populations and over 5,000 who identified themselves as other than heterosexual. We observed a wide range of education (53% completed less than college) and income. PSA testing rates (75% overall) were highest among black participants. Body mass index (BMI) (median 27.2) was highest for blacks and Latinos and lowest for Asians, and showed 80.6% agreement with BMI from clinical data sources. The sensitivity and specificity can be assessed by comparing self-reported data, such as PSA testing, diabetes, and history of cancer, to health plan data. We anticipate that nearly 1,500 prostate cancer diagnoses will occur within five years of cohort inception. DISCUSSION: A wide variety of epidemiologic, health services, and outcomes research utilizing a rich array of electronic, biological, and clinical resources is possible within this multiethnic cohort. The California Men’s Health Study and other cohorts nested within comprehensive health delivery systems can make important contributions in the area of men’s health.
Authors: Enger SM; Van Den Eeden SK; Sternfeld B; Loo RK; Quesenberry CP Jr; Rowell S; Sadler MC; Schaffer DM; Habel LA; Caan BJ
BMC Public Health. 2006 Jun 30;6:172.
Alcohol and cancer
Authors: Bandera EV; Kushi LH
In: Heber D, editor. Nutritional oncology. 2nd edition. Amsterdam: Elsevier-Academic Press, 2006.
Associations between ERalpha, ERbeta, and AR genotypes and colon and rectal cancer
Estrogen and androgens are thought to be involved in the etiology of colorectal cancer. We evaluate genetic variants of the estrogen receptor genes (ERalpha and ERbeta) and the androgen receptor gene (AR). We use data from two large case-control studies of colon (n = 1,580 cases and 1,968 controls) and rectal (n = 797 cases and 1,016 controls) cancer. We evaluated the 351A >G XbaI polymorphism of ERalpha, the 1,082 G >A and CA repeat polymorphisms of ERbeta, and the CAG repeat of AR. Having two 25 or more CA repeats in ERbeta was associated with an increased relative risk of colon cancer in women [odds ratio (OR), 2.13; 95% confidence interval (95% CI), 1.24-3.64] but not in men (P(interaction) relative excess risk from interaction < 0.01; multiplicative = 0.03). Increasing number of AR CAG repeats was directly associated with colon cancer among men (OR, 1.28; 95% CI, 1.06-1.54), but not women (OR, 0.83; 95% CI, 0.68-1.02); the interaction P value for AR gene x sex was <0.01. Taking hormone replacement therapy (HRT) was associated with a reduced risk of colon cancer in the presence of the R allele of the ERbeta gene, whereas an R allele was associated with increased risk among postmenopausal women who did not take HRT. Postmenopausal women not using HRT who had > or =25 CA repeats of the ERbeta gene had over a 6-fold increased risk of colon cancer (OR, 6.71; 95% CI, 2.89-15.6). Our results suggest that the ERbeta gene is more important than ERalpha in the etiology of colorectal cancer.
Authors: Slattery ML; Sweeney C; Murtaugh M; Ma KN; Wolff RK; Potter JD; Caan BJ; Samowitz W
Cancer Epidemiol Biomarkers Prev. 2005 Dec;14(12):2936-42.
The association between cigarette smoking and colorectal polyp recurrence (United States)
OBJECTIVE: Although evidence exists linking smoking to precancerous colorectal adenomatous polyps, few studies have examined the association between cigarette smoking and recurrence of colorectal polyps. This association was investigated prospectively with data from the Polyp Prevention Trial. METHODS: Cigarette smoking data were collected through baseline interviews. The study was completed by 1872 men and women with presence of adenomas at baseline colonoscopy. Multiple logistic regression analysis was used to examine the association between cigarette smoking and polyp recurrence (adenomatous and hyperplastic) up to four years from baseline. RESULTS: Adenoma recurrence was not related to cigarette smoking. Current smokers had increased odds of hyperplastic polyps at follow-up compared to never smokers (OR 2.88, 95% CI 2.06-4.01). Current smoking was associated with subsequent distal (OR 3.44, 95% CI 2.38-4.95) and rectal (OR 3.53, 95% CI 2.15-5.78) hyperplastic polyps, but not subsequent proximal hyperplastic polyps. Cigarette smoking was associated with subsequent multiple and small size (4 mm) hyperplastic polyps. Significant linear trends were observed between development of subsequent hyperplastic polyps and all smoking variables. CONCLUSIONS: Although no association with recurrent adenomas was observed, cigarette smoking was significantly associated with hyperplastic polyp development, except for those in the proximal colon. This prospective study confirms that cigarette smoking has a significant effect on the development of hyperplastic colorectal polyps.
Authors: Paskett ED; Caan B; Polyp Prevention Trial Study Group; et al.
Cancer Causes Control. 2005 Nov;16(9):1021-33.
Polymorphisms in the reduced folate carrier, thymidylate synthase, or methionine synthase and risk of colon cancer
Folate metabolism supports the synthesis of nucleotides as well as the transfer of methyl groups. Polymorphisms in folate-metabolizing enzymes have been shown to affect risk of colorectal neoplasia and other malignancies. Using data from a population-based incident case-control study (1,600 cases and 1,962 controls), we investigated associations between genetic variants in the reduced folate carrier (RFC), thymidylate synthase (TS), methionine synthase (MTR), and 5,10-methylenetetrahydrofolate reductase (MTHFR) and colon cancer risk. The TS enhancer region (TSER) variant was associated with a reduced risk among men [2rpt/2rpt versus 3rpt/3rpt wild-type; odds ratio (OR), 0.7; 95% confidence interval, 0.6-0.98] but not women. When combined genotypes for both TS polymorphisms (TSER and 3′-untranslated region 1494delTTAAAG) were evaluated, ORs for variant genotypes were generally below 1.0, with statistically significantly reduced risks among women. Neither MTR D919G nor RFC 80G>A polymorphisms were associated with altered colon cancer risk. Because folate metabolism is characterized by interrelated reactions, we evaluated gene-gene interactions. Genotypes resulting in reduced MTHFR activity in conjunction with low TS expression were associated with a reduced risk of colon cancer. When dietary intakes were taken into account, individuals with at least one variant TSER allele (3rpt/2rpt or 2rpt/2rpt) were at reduced risk in the presence of a low folate intake. This study supports findings from adenoma studies indicating that purine synthesis may be a relevant biological mechanism linking folate metabolism to colon cancer risk. A pathway-based approach to data analysis is needed to help discern the independent and combined effects of dietary intakes and genetic variability in folate metabolism.
Authors: Ulrich CM; Curtin K; Potter JD; Bigler J; Caan B; Slattery ML
Cancer Epidemiol Biomarkers Prev. 2005 Nov;14(11 Pt 1):2509-16.
MTHFR variants reduce the risk of G:C->A:T transition mutations within the p53 tumor suppressor gene in colon tumors
5,10-Methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme in folate-mediated 1-carbon metabolism. Reduced MTHFR activity has been associated with genomic DNA hypomethylation. Methylated cytosines at CpG sites are easily mutated and have been implicated in G:C–>A:T transitions in the p53 tumor suppressor gene. We investigated 2 polymorphisms in the MTHFR gene (C677T and A1298C) and their associations with colon tumor characteristics, including acquired mutations in Ki-ras and p53 genes and microsatellite instability (MSI). The study population comprised 1248 colon cancer cases and 1972 controls, who participated in a population-based case-control study and had been analyzed previously for MSI, acquired mutations in Ki-ras, p53, and germline MTHFR polymorphisms. Multivariable-adjusted odds ratios are presented. Overall, MTHFR genotypes were not associated with MSI status or the presence of any p53 or Ki-ras mutation. Individuals with homozygous variant MTHFR genotypes had a significantly reduced risk of G:C–>A:T transition mutations within the p53 gene, yet, as hypothesized, only at CpG-associated sites [677TT vs. 677CC (referent group) OR = 0.4 (95% CI: 0.1-0.8) for CpG-associated sites; OR = 1.5 (0.7-3.6) for non-CpG associated sites]. Genotypes conferring reduced MTHFR activity were associated with a decreased risk of acquired G:C–>A:T mutations within the p53 gene occurring at CpG sites. Consistent with evidence on the phenotypic effect of the MTHFR C677T variant, we hypothesize that this relation may be explained by modestly reduced genomic DNA methylation, resulting in a lower probability of spontaneous deamination of methylated cytosine to thymidine. These results suggest a novel mechanism by which MTHFR polymorphisms can affect the risk of colon cancer.
Authors: Ulrich CM; Curtin K; Samowitz W; Bigler J; Potter JD; Caan B; Slattery ML
J Nutr. 2005 Oct;135(10):2462-7.
Plasma carotenoids and recurrence-free survival in women with a history of breast cancer
PURPOSE: Previous studies suggest that diet may affect recurrence or survival rates in women who have been diagnosed with breast cancer. The purpose of this study was to examine the relationship between plasma carotenoid concentration, as a biomarker of vegetable and fruit intake, and risk for a new breast cancer event in a cohort of women with a history of early-stage breast cancer. METHODS: Participants were 1,551 women previously treated for breast cancer who were randomly assigned to the control arm of a diet intervention trial between March 1995 and November 2000. Outcome events were probed during semiannual interviews and verified by medical record review. During the period under study, 205 women had a recurrence or new primary breast cancer. Plasma carotenoid concentrations were measured in baseline blood samples. Hazard ratios (HR) and 95% CIs by quartiles of plasma carotenoids were computed, controlling for tumor stage, grade, and hormone receptor status; chemotherapy and tamoxifen therapy; clinical site; age at diagnosis; body mass index; and plasma cholesterol concentration. RESULTS: Women in the highest quartile of plasma total carotenoid concentration had significantly reduced risk for a new breast cancer event (HR, 0.57; 95% CI, 0.37 to 0.89), controlled for covariates influencing breast cancer prognosis. CONCLUSION: Plasma carotenoids are a biologic marker of intake of vegetables and fruit, so this observation supports findings from previous studies that have linked increased vegetable and fruit intake with greater likelihood of recurrence-free survival in women who have been diagnosed with early-stage breast cancer.
Authors: Rock CL; Flatt SW; Natarajan L; Thomson CA; Bardwell WA; Newman VA; Hollenbach KA; Jones L; Caan BJ; Pierce JP
J Clin Oncol. 2005 Sep 20;23(27):6631-8.
Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer
BACKGROUND & AIMS: The concept of a CpG island methylator phenotype (CIMP), especially in microsatellite stable colon cancer, is not accepted universally. We therefore evaluated a large population-based sample of individuals with colon cancer and used univariate and multivariate analyses of CIMP with clinicopathologic variables and tumor mutations to determine the biologic relevance of this phenotype. METHODS: A total of 864 tumors from individuals with colon cancer from Utah and Northern California were evaluated by methylation-specific polymerase chain reaction of CpG islands in hMLH1, methylated in tumors (MINT) 1, MINT 2, MINT 31, and CDKN2A (p16). CIMP high was defined as methylation at 2 or more of these loci. The BRAF V600E mutation was determined by sequencing. Microsatellite instability had been determined previously. RESULTS: In a multivariate analysis of microsatellite stable tumors, CIMP high was related significantly to the V600E BRAF mutation (odds ratio, 39.52; 95% confidence interval, 11.44-136.56), KRAS2 mutations (odds ratio, 2.22; 95% confidence interval, 1.48-3.34), older age (P trend = .03), and increased stage (P trend = .03), and these tumors were less likely to be located in the distal colon (odds ratio, .42; 95% confidence interval, .27-.65). CIMP-high unstable tumors also were more likely to have the V600E BRAF mutation, be located proximally, and occur in older individuals (in univariate analyses). However, CIMP-high unstable tumors were significantly more likely than their stable counterparts to be KRAS2 wild type, TP53 wild type, poorly differentiated, proximally located, occur at lower stages, and have the BRAF V600E mutation (64.1% vs 17.6%). CONCLUSIONS: The evaluation of a large, population-based sample strongly supports the biologic relevance of CIMP in colon cancer. However, the presence or absence of microsatellite instability has a major effect on the expression of this phenotype.
Authors: Samowitz WS; Albertsen H; Herrick J; Levin TR; Sweeney C; Murtaugh MA; Wolff RK; Slattery ML
Gastroenterology. 2005 Sep;129(3):837-45.
Incomplete screening flexible sigmoidoscopy associated with female sex, age, and increased risk of colorectal cancer
BACKGROUND: Several previous studies have found that females and older individuals are at greater risk of having incomplete flexible sigmoidoscopy. However, no prior study has reported the subsequent risk of colorectal cancer (CRC) following incomplete sigmoidoscopy. METHODS: Using data from 55 791 individuals screened as part of the Colon Cancer Prevention (CoCaP) programme of Kaiser Permanente of Northern California, we evaluated the likelihood of having an inadequate (<40 cm) examination by age and sex, and estimated the risk of distal CRC according to depth of sigmoidoscope insertion at the baseline screening examination. Multivariate estimation of risks was performed using Poisson regression. RESULTS: Older individuals were at a much greater risk of having an inadequate examination (relative risk (RR) for age 80+ years compared with 50-59 years 2.6 (95% confidence interval (CI) 2.3-3.0)), as were females (RR 2.3 (95% CI 2.2-2.5)); these associations were attenuated but remained strong if Poisson models were further adjusted for examination limitations (pain, stool, and angulation). There was an approximate threefold increase in the risk of distal CRC if the baseline sigmoidoscopy did not reach a depth of at least 40 cm; a smaller increase in risk was observed for examinations that reached 40-59 cm. CONCLUSIONS: Older individuals and women are at an increased risk of having inadequate sigmoidoscopy. Because inadequate sigmoidoscopy results in an increased risk of subsequent CRC, physicians should consider steps to maximise the depth of insertion of the sigmoidoscope or, failing this, should consider an alternative screening test.
Authors: Doria-Rose VP; Newcomb PA; Levin TR
Gut. 2005 Sep;54(9):1273-8. Epub 2005 May 4.
Effect of reproductive factors and postmenopausal hormone use on the risk of Parkinson disease
OBJECTIVE: Parkinson disease (PD) is less common in women possibly because of hormonal or reproductive influences. The objective of this study was to evaluate the associations of reproductive factors and postmenopausal hormone use with the risk of PD among postmenopausal women. METHODS: Incident cases (n = 178) and randomly selected age-matched controls (n = 189) who were members of the Kaiser Permanente Medical Care Program (KPMCP) of Northern California participated in the study conducted during the years 1994 to 1995. Statistical analyses were carried out using logistic regression. RESULTS: The association of postmenopausal hormone use with PD risk depended on the type of menopause. Among women with history of a hysterectomy with or without an oophorectomy, estrogen use alone was associated with a 2.6-fold increased risk (adjusted odds ratio (OR) 2.6, 95% CI: 1.1 to 6.1) and significant trends in the risk of PD were observed with increasing duration of estrogen use, but disease risk was not influenced by recency of use. In contrast, among women with natural menopause, no increased risk of PD was observed with hormone use (estrogen alone or a combined estrogen-progestin regimen). Early age at final menstrual period (44 years or younger) was associated with reduction in risk (adjusted OR 0.5, 95% CI: 0.3 to 1.0). Age at menarche and parity were not associated with the risk of PD. CONCLUSION: Postmenopausal use of estrogen alone may increase the risk of Parkinson disease (PD) among women with a hysterectomy. Among women with natural menopause for whom the usual treatment is combined estrogen-progestin therapy, no increased risk of PD was observed.
Authors: Popat RA; Van Den Eeden SK; Tanner CM; McGuire V; Bernstein AL; Bloch DA; Leimpeter A; Nelson LM
Neurology. 2005 Aug 9;65(3):383-90.
Body size changes in relation to postmenopausal breast cancer among women on Long Island, New York
To examine effects of body size change on postmenopausal breast cancer, the authors conducted a population-based case-control study among 990 cases and 1,006 controls participating in the Long Island Breast Cancer Study Project in 1996-1997. Women who had gained more than 15 kg (33 pounds) since age 20 years were at a 1.6-fold increased risk of breast cancer (95% confidence interval (CI): 1.11, 2.26) relative to their counterparts with stable (+/-3 kg) weight. Subjects who had gained more than 11 kg (24 pounds) during the peri- and postmenopausal years (since age 50 years) had 1.62 times the risk of breast cancer of those whose weight remained unchanged during this time period. This effect of peri- and postmenopausal body size gain was present only among never users of hormone replacement therapy (odds ratio (OR) = 2.02 (95% CI: 1.35, 3.02) as opposed to 0.81 (95% CI: 0.43, 1.53) for ever users; multiplicative interaction: p < 0.01) and was more pronounced among women with estrogen receptor-positive/progesterone receptor-positive breast cancer (OR = 2.17, 95% CI: 1.38, 3.42). Weight loss over the lifetime was associated with decreased risk of postmenopausal breast cancer (OR = 0.55, 95% CI: 0.32, 0.96). These results add to the literature by focusing on the perimenopausal weight trajectory and support efforts urging women to avoid weight gain as they age.
Authors: Eng SM; Gammon MD; Terry MB; Kushi LH; Teitelbaum SL; Britton JA; Neugut AI
Am J Epidemiol. 2005 Aug 1;162(3):229-37. Epub 2005 Jun 29.
Associations between apoE genotype and colon and rectal cancer
Apolipoprotein E (apoE) plays a major role in the metabolism of bile acids, cholesterol and triglycerides, and has recently been proposed as being involved in the carcinogenic process. Given the potential role of bile acids in colorectal cancer etiology, it is reasonable that colorectal cancer risk might be modified by apoE genotype. We used data collected from a case-control study of colon cancer (n=1556 cases and 1948 controls) and rectal cancer (n=777 cases and 988 controls). The absence of an e3 apoE allele significantly increased the risk of colon cancer (OR=1.37 95% CI 1.00-1.87), particularly among those diagnosed when older than 64 years (OR=1.88 95% CI 1.17-3.04; P interaction between age and apoE genotype equal to 0.05). A significant three-way interaction was detected for family history of colorectal cancer, age at diagnosis and apoE genotype (P = 0.05), in those diagnosed when older, not having an e3 allele and having a significantly increased risk of colon cancer with family history of colorectal cancer (OR=3.93 95% CI 1.23-12.6). This was compared with the risk associated with family history of colorectal cancer among those diagnosed when older, with an e3 allele of 1.61 (95% CI 1.17-2.23) or those diagnosed when younger without an e3 allele (OR=2.40 95% CI 0.56-10.3). Among those diagnosed when older than 64 years, associations of BMI and prudent diet with colon cancer were stronger among individuals without an e3 allele, although the P for interaction was not significant. We did not detect any significant associations between apoE genotype and rectal cancer, survival after diagnosis with colorectal cancer, stage of disease at diagnosis or type of tumor mutation. These findings suggest those apoE genotypes that do not include the e3 allele, the same genotypes that are associated with increased risk of coronary heart disease, may influence development of colon cancer among those who are older at diagnosis.
Authors: Slattery ML; Sweeney C; Murtaugh M; Ma KN; Potter JD; Levin TR; Samowitz W; Wolff R
Carcinogenesis. 2005 Aug;26(8):1422-9. Epub 2005 Apr 7.
Insulin-like growth factor pathway polymorphisms associated with body size in Hispanic and non-Hispanic white women
Polymorphisms affecting insulin-like growth factors (IGF), their binding proteins (IGFBP), insulin receptor substrates (IRS), and other IGF regulatory molecules may affect growth, obesity, and obesity-related diseases, including cancer. The objective of this study was to better describe the associations between several IGF pathway variants and body size. Hispanic (n = 462) and non-Hispanic White (n = 1,702) women were recruited as controls in collaborative population-based case-control studies in Arizona, New Mexico, Colorado, Utah, and California. Body size measurements were taken by trained interviewers; genotypes were determined for the IGF1 CA repeat, the IGFBP3 -202 C > A substitution, the IRS1 G972R and IRS2 G1057D substitutions, and the vitamin D receptor (VDR) BsmI and FokI polymorphisms. Two associations were observed that were consistent in both Hispanics and non-Hispanic Whites: IGF1 CA repeat alleles of length other than 19 were associated with higher mean waist-to-hip ratios (WHR), P = 0.01, and women who carried an IGFBP3 A allele, compared with women with the CC genotype, more often reported high birthweight (odds ratio, 1.9; 95% confidence interval, 1.1-3.2). We observed trends for associations between IGFBP3 A allele and taller height, IRS1R allele, and smaller WHR, and VDR FokI ff genotype and larger WHR; each of these trends was present in only one ethnic group, and heterogeneity of effect by ethnicity was detected. These results provide evidence that IGF pathway polymorphisms have functional effects on growth and central obesity and indicate that genotype-phenotype relationships are ethnic specific.
Authors: Sweeney C; Murtaugh MA; Baumgartner KB; Byers T; Giuliano AR; Herrick JS; Wolff R; Caan BJ; Slattery ML
Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1802-9.
Quality in the technical performance of screening flexible sigmoidoscopy: recommendations of an international multi-society task group
BACKGROUND: Flexible sigmoidoscopy (FS) is a complex technical procedure performed in a variety of settings, by examiners with diverse professional backgrounds, training, and experience. Potential variation in technical quality may have a profound impact on the effectiveness of FS on the early detection and prevention of colorectal cancer. AIM: We propose a set of consensus and evidence based recommendations to assist the development of continuous quality improvement programmes around the delivery of FS for colorectal cancer screening. RECOMMENDATIONS: These recommendations address the intervals between FS examinations, documentation of results, training of endoscopists, decision making around referral for colonoscopy, policies for antibiotic prophylaxis and management of anticoagulation, insertion of the FS endoscope, bowel preparation, complications, the use of non-physicians as FS endoscopists, and FS endoscope reprocessing. For each of these areas, continuous quality improvement targets are recommended, and research questions are proposed.
Authors: Levin TR; Rex DK; et al.
Gut. 2005 Jun;54(6):807-13.
Life After Cancer Epidemiology (LACE) Study: a cohort of early stage breast cancer survivors (United States)
The Life After Cancer Epidemiology (LACE) Study, a cohort of 2321 early stage breast cancer survivors, was established in 2000 to examine how modifiable behavioral risk factors affect quality of life and long-term survival. Women were recruited primarily from the Kaiser Permanente Northern California Cancer Registry (KPNCAL) and the Utah cancer registry (UCR), United States. Baseline data were collected, on average, at two years post-diagnosis through self-administered questionnaires that included information on demographics, medical history, anthropometry, diet, supplements, physical activity and quality of life. The purpose of this paper is to describe the creation and baseline characteristics of the cohort. Forty-six percent of women to whom questionnaires were mailed agreed to participate. The cohort which is 80% white, was diagnosed predominantly with Stage I and II breast cancer (93%), and will have been followed for 5.6 years post-diagnosis, on average, by the end of 2004. Women reported slightly over four daily servings of fruit and vegetables, well below the suggested 5-A-Day national guidelines. Compared to women free of cancer, physical activity patterns were similar, while weight gain, especially in younger women, was higher than is typical. These data suggest that in the early years post-diagnosis, breast cancer survivors exhibit similar patterns to the general population in many health behaviors.
Authors: Caan B; Sternfeld B; Gunderson E; Coates A; Quesenberry C; Slattery ML
Cancer Causes Control. 2005 Jun;16(5):545-56.
Energy balance, insulin-related genes and risk of colon and rectal cancer
Energy balance, or the ability to maintain body weight by balancing energy intake with energy expenditure, appears to be important in the etiology of colon cancer. One possible mechanism whereby energy balance may be associated with colorectal cancer is through its association with insulin. In our study, we evaluate the interaction between polymorphisms in 4 genes thought to be involved in insulin-related functions and components of energy balance with risk of colorectal cancer. Data from 2 population-based case-control studies of colon and rectal cancer conducted in Utah and Northern California were used to evaluate associations between body mass index (BMI), physical activity, energy intake and sucrose-to-fiber ratio and a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide -202 of the IGFBP3, the G972R polymorphism of the IRS1 gene and the G1057D polymorphism of the IRS2 gene. A total of 1,346 incident colon cancer cases and 1,544 population-based controls and 952 incident rectal cancer cases and 1,205 controls were available for analysis. Inconsistent associations were identified between BMI, physical activity, energy intake and insulin-related genes. The 192/192 IGF1 genotype was associated with significant reduction in colon cancer risk among those with high physical activity (odds ratio [OR] 0.57; 95% confidence interval [CI] 0.39-0.83; p interaction 0.01). Although there was no significant pattern of interaction between either BMI or energy intake and polymorphisms assessed, specific sources of energy did appear to be more related to colon cancer risk in the presence of specific IRS2 and IGF1 genotypes. A high sucrose-to-fiber ratio increased risk of colon cancer in men who had the IRS2 DD genotype and among men who did not have the 192/192 IGF1 genotype. In summary, these data support the importance of components of energy balance in risk of colorectal cancer. Obesity, physical activity and energy intake appear to alter risk of colorectal cancer; however, the risk appears to be minimally influenced by genetic variants evaluated.
Authors: Slattery ML; Murtaugh M; Caan B; Ma KN; Neuhausen S; Samowitz W
Int J Cancer. 2005 May 20;115(1):148-54.
Microsomal epoxide hydrolase polymorphisms are not associated with colon cancer risk
Authors: Robien K; Curtin K; Ulrich CM; Bigler J; Samowitz W; Caan B; Potter JD; Slattery ML
Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1350-2.
Interactions of peroxisome proliferator-activated receptor {gamma} and diet in etiology of colorectal cancer
The peroxisome proliferator-activated receptor gamma (PPARgamma) is one of a group of ligand-activated nuclear receptors responsible for regulation of glucose, lipid homeostasis, cell differentiation, and apoptosis. The 12 proline-to-alanine (Pro12Ala) substitution polymorphism in PPARgamma produces proteins with lower activity. Variation in PPARgamma expression in the bowel and the role of dietary fatty acids as ligands for PPARgamma led investigation of whether the associations of diet with colon and rectal cancer risk were modified by PPARgamma genotype. Data (diet, lifestyle, and DNA) came from case-control studies of colon (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls) conducted in Northern California, Utah, and the Twin City, Minnesota Metropolitan area (colon cancer study only). Unconditional logistic regression models were adjusted for age at selection, body mass index, physical activity, energy intake, dietary fiber, and calcium. We found no significant interactions between macronutrient (fat, protein, and carbohydrate) and colorectal cancer. High lutein intake [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.44-0.89], low refined grain intake (OR, 0.70; 95% CI, 0.53-0.94), or a high prudent diet score (OR, 0.66; 95% CI, 0.49-0.89) and PA/AA PPARgamma genotype were associated with reduced colon cancer risk. Risk of rectal cancer was increased among those with the PA/AA PPARgamma genotype and a high mutagen index (OR, 1.63; 95% CI, 1.12, 2.36). Its unclear whether the alterations in risk in those with the less active phenotype for PPARgamma is related to activation of PPARgamma by nutrients or dietary patterns acting as ligands or direct influences of these nutrients on colon and rectal cancer processes that are important with lower PPARgamma activity.
Authors: Murtaugh MA; Ma KN; Caan BJ; Sweeney C; Wolff R; Samowitz WS; Potter JD; Slattery ML
Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1224-9.
Screening by prostate-specific antigen and digital rectal examination in relation to prostate cancer mortality: a case-control study
BACKGROUND: The potential role of prostate cancer screening in reducing mortality is uncertain. To examine whether screening with the prostate-specific antigen (PSA) test or digital rectal examination is associated with reduced prostate cancer mortality, we conducted a population-based case-control study in 4 health maintenance organizations. METHODS: Cases were 769 health plan members who died because of prostate adenocarcinoma during the years 1997-2001. We randomly selected 929 controls from the health plan membership and matched them to cases on health plan, age, race, and membership history. Medical records were used to document all screening tests in the 10 years before and including the date on which prostate cancer was first suspected. RESULTS: Among white participants, 62% of cases and 69% of controls had a least 1 screening PSA test or digital rectal examination (odds ratio = 0.73; 95% confidence interval = 0.55-0.97). The corresponding proportions for blacks were 59% and 61% (1.0; 0.59-1.4). Most screening tests were digital rectal examinations; therefore, in the subgroup with no history of PSA screening, the association between digital rectal screening and prostate cancer mortality was similar to the overall association (0.65 [0.48-0.88] among whites; 0.86 [0.53-1.4] among blacks). Very few men received screening PSA without screening digital rectal examination (6% of cases and 7% of controls among whites). CONCLUSIONS: Digital rectal screening was associated with a reduced risk of death due to prostate cancer in our population. Because of several data limitations, this study could not accurately estimate the effect of PSA screening separate from digital rectal examination.
Authors: Weinmann S; Richert-Boe KE; Van Den Eeden SK; Enger SM; Rybicki BA; Shapiro JA; Weiss NS
Epidemiology. 2005 May;16(3):367-76.
Weight, weight gain, and survival after breast cancer diagnosis.
PURPOSE: To determine whether weight prior to diagnosis and weight gain after diagnosis are predictive of breast cancer survival.METHODS: Patients included 5,204 Nurses’ Health Study participants diagnosed with incident, invasive, nonmetastatic breast cancer between 1976 and 2000; 860 total deaths, 533 breast cancer deaths, and 681 recurrences (defined as secondary lung, brain, bone, or liver cancer, and death from breast cancer) accrued to 2002. We computed the change in body mass index (BMI) from before to the first BMI reported > or = 12 months after the date of diagnosis. Cox proportional hazards models were used to evaluate associations of categories of BMI before diagnosis and of BMI change with time to event. We stratified by smoking, menopausal status, and breast cancer-related variables.RESULTS: In multivariate-adjusted analyses, weight before diagnosis was positively associated with breast cancer recurrence and death, but this was apparent only in never smokers. Similarly, among never-smoking women, those who gained between 0.5 and 2.0 kg/m(2) (median gain, 6.0 lb; relative risk [RR], 1.35; 95% CI, 0.93 to 1.95) or more than 2.0 kg/m(2) (median gain, 17.0 lb; RR, 1.64; 95% CI, 1.07 to 2.51) after diagnosis had an elevated risk of breast cancer death during follow-up (median, 9 years), compared with women who maintained their weight (test for linear trend, P = .03). Associations with weight were stronger in premenopausal than in postmenopausal women. Similar findings were noted for breast cancer recurrence and all-cause mortality.CONCLUSION: Weight and weight gain were related to higher rates of breast cancer recurrence and mortality, but associations were most apparent in never-smoking women.
Authors: Kroenke CH1; Chen WY; Rosner B; Holmes MD;
J Clin Oncol. 2005 Mar 1;23(7):1370-8. Epub 2005 Jan 31.
Achieving substantial changes in eating behavior among women previously treated for breast cancer–an overview of the intervention
OBJECTIVE: To describe the intervention in a clinical trial examining the effect of a plant-based diet on breast cancer recurrence. To report baseline to 12-month dietary change and investigate whether cooking-class attendance influenced adherence to the study’s dietary targets. DESIGN: A descriptive analysis of baseline and 12-month dietary intake data and other variables from a subcohort of participants in the Women’s Healthy Eating and Living Study. SUBJECTS/SETTING: Seven hundred thirty-nine women (primarily non-Hispanic white and well educated) who had been treated for early stage breast cancer. All were intervention group participants and had adhered to the Women’s Healthy Eating and Living Study counseling and dietary assessment protocols. Mean age at study entry was 54 years, and mean body mass index was 26.7. INTERVENTION: Telephone counseling, complemented by an orientation meeting, cooking classes, and newsletters. MAIN OUTCOME MEASURES: The change in intake of vegetables, vegetable juice, fruit, fiber, and fat between baseline and 12 months is reported, and the association between cooking classes attended and overall dietary adherence is examined. STATISTICAL ANALYSES PERFORMED: Mean intake for vegetables, vegetable juice, fruit, fiber, and fat were calculated. Percentage of women meeting select Healthy People 2010 objectives were tabulated. RESULTS: Total daily vegetable, vegetable juice, fruit, and fiber intake increased significantly (P <.01), while fat decreased significantly (P <.01). The percentage of women meeting the Healthy People 2010 fruit and vegetable objectives increased substantially. Overall dietary adherence was associated with increased cooking-class attendance (P for trend <.01). CONCLUSIONS: A multimodal approach to dietary modification, based largely on individualized telephone counseling, can substantially change the overall dietary pattern of women previously treated for breast cancer.
Authors: Newman VA; Thomson CA; Rock CL; Flatt SW; Kealey S; Bardwell WA; Caan BJ; Pierce JP; Women's Healthy Eating and Living (WHEL) Study Group
J Am Diet Assoc. 2005 Mar;105(3):382-91; quiz 488.
The association of calcium and vitamin D with risk of colorectal adenomas
The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel. Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants. We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group, age, gender, nonsteroidal anti-inflammatory drug use, total energy intake, and the interaction of gender and intervention group. Vitamin D models were also adjusted for the location of the clinic site. Dietary variables were adjusted for total energy intake via the residual method. There were no overall significant associations between adenoma recurrence and dietary calcium intake [odds ratio (OR) for the 5th compared with the lowest quintile = 0.91; 95% CI = 0.67-1.23; P-trend = 0.68], total calcium intake (OR = 0.86; 95% CI = 0.62-1.18; P-trend = 0.20), or dietary vitamin D intake (OR = 0.93; 95% CI = 0.69-1.25; P-trend = 0.43) averaged over follow-up. Total vitamin D intake was weakly inversely associated with adenoma recurrence (OR = 0.84; 95% CI = 0.62-1.13; P-trend = 0.03). Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence (OR for any compared with no use = 0.82; 95% CI = 0.68-0.99; and OR = 0.82; 95% CI = 0.68-0.99; for calcium and vitamin D, respectively). Slightly stronger associations were noted for the prevention of multiple recurrences. Our analyses did not suggest a significant effect modification between total calcium and total vitamin D intake (P = 0.14) on risk for adenoma recurrence. This trial cohort provides some evidence that calcium and vitamin D may be inversely associated with adenoma recurrence.
Authors: Hartman TJ; Caan B; Polyp Prevention Study Group; et al.
J Nutr. 2005 Feb;135(2):252-9.
The CYP1A1 genotype may alter the association of meat consumption patterns and preparation with the risk of colorectal cancer in men and women
We hypothesized that the risk of colorectal cancer associated with meat preparation methods producing heterocyclic amines or polycyclic aromatic hydrocarbons is modified by the CYP1A1 genotype alone or in combination with the GSTM1 genotype or the NAT2 imputed phenotype. A total of 952 rectal cancer cases and 1205 controls (between September 1997 and February 2002) and 1346 colon cancer cases and 1544 controls (between October 1991 and September 1994) from Utah and Northern California were recruited from a population-based case-control study. Detailed interviews ascertained lifestyle, medical history, and diet and we extracted DNA from whole blood. Risk of colorectal cancer decreased among men with the CYP1A1 *2 any variant genotype and the lowest intake of poultry and men and women with high use of white meat drippings. Risk increased among men with the CYP1A1 *1 (no variant) allele and high white meat mutagen index, but decreased among those with the CYP1A1 *2 genotype. Risk increased with a high white meat mutagen index among women with the CYP1A1 *2 genotype and the GSTM1 present genotype. Risk of colorectal cancer decreased with the CYP1A1 *2 genotype, the NAT2 slow phenotype, and the use of white meat or its drippings. The association of risk for colorectal cancer and selected red and white meat mutagen indices and the use of white meat drippings, or fried white meat variables was more evident within select combinations of the CYP1A1 genotype and either the GSTM1 genotype or NAT2 than with the CYP1A1 alone. Genetic susceptibility may modify the associations of some meat or meat preparation factors with the risk of colorectal cancer.
Authors: Murtaugh MA; Sweeney C; Ma KN; Caan BJ; Slattery ML
J Nutr. 2005 Feb;135(2):179-86.
Urologic complications of diabetes
Authors: Brown JS; Wessells H; Chancellor MB; Howards SS; Stamm WE; Stapleton AE; Steers WD; Van Den Eeden SK; McVary KT
Diabetes Care. 2005 Jan;28(1):177-85.
PPARgamma, energy balance, and associations with colon and rectal cancer
Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been hypothesized as being involved in colorectal cancer given its role in adipocyte development and insulin resistance. In this study we evaluated the association between the Pro12Ala (P12A) PPARgamma polymorphism and body mass index (BMI), waist-to-hip ratio (WHR), physical activity level, and energy intake and risk of colorectal cancer using data from a population-based, case-control study of colon cancer (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001 controls). We further evaluated how the P12A PPARgamma polymorphism is associated with obesity and fat pattern in the control population. The odd ratio for PPARgamma PA or AA genotype relative to the PP genotype for colon cancer was 0.9 (95% confidence interval, CI=0.8-1.0) and for rectal cancer was 1.2 (95% CI=1.0-1.5) adjusting for race, age, and sex. P12A PPARgamma did not significantly interact with BMI, WHR, energy intake, and energy expenditure to alter risk of colon or rectal cancer. Furthermore, the P12A PPARgamma polymorphism was not associated with obesity or WHR in the control population; it did not interact with energy intake or energy expenditure to alter risk of obesity or large WHR. These data do not support the hypothesis that the P12A PPARgamma polymorphism is associated with colon or rectal cancer through regulation of energy balance.
Authors: Slattery ML; Murtaugh MA; Sweeney C; Ma KN; Potter JD; Caan BJ; Samowitz W
Nutr Cancer. 2005;51(2):155-61.
Colonoscopy capacity: Can we build it? Will they come?
Authors: Levin TR
Gastroenterology. 2004 Dec;127(6):1841-4.
Associations between BMI, energy intake, energy expenditure, VDR genotype and colon and rectal cancers (United States)
Components of energy balance are important elements associated with colorectal cancer risk. In this study we examine the association between VDR genotypes, BMI, physical activity, and energy intake and risk of colorectal cancer. Data from a population-based case-control study of colon (1174 cases and 1174 controls) and rectal (785 cases and 1000 controls) cancer was used to evaluate the associations. The Bsm1, polyA, and Fok1 VDR polymorphisms were evaluated. For colon cancer, those who are obese were at greater risk of colon cancer if they had the SS or BB (OR = 3.50; 95% CI = 1.75-7.03; p interaction 0.03) or ff (OR = 2.62; 95% CI = 1.15-5.99; p interaction 0.12/) VDR genotypes. On the other hand, those who were least physically active were at greater risk of colon cancer if they had the ff VDR genotype (OR = 3.46; 95% CI = 1.58-7.58; p interaction 0.05). The association between energy intake and colon cancer appears to be driven more by energy intake than Bsm1 or polyA VDR genotypes, although there was a significant interaction between the Fok1 VDR polymorphism and energy intake and risk of both colon and rectal cancer (p interaction 0.01 for colon and 0.04 for rectal). These data suggest a relationship between VDR genotype and factors related to energy balance in modifying colorectal cancer risk.
Authors: Slattery ML; Murtaugh M; Caan B; Ma KN; Wolff R; Samowitz W
Cancer Causes Control. 2004 Nov;15(9):863-72.
Mammographic density and breast cancer after ductal carcinoma in situ
Women with ductal carcinoma in situ (DCIS) are at substantially increased risk for a second breast cancer, but few strong predictors for these subsequent tumors have been identified. We used Cox regression modeling to examine the association between mammographic density at diagnosis of DCIS of 504 women from the National Surgical Adjuvant Breast and Bowel Project B-17 trial and risk of subsequent breast cancer events. In this group of patients, mostly 50 years old or older, approximately 6.6% had breasts categorized as highly dense (i.e., > or =75% of the breast occupied by dense tissue). After adjusting for treatment with radiotherapy, age, and body mass index, women with highly dense breasts had 2.8 (95% confidence interval [CI] = 1.3 to 6.1) times the risk of subsequent breast cancer (DCIS or invasive), 3.2 (95% CI = 1.2 to 8.5) times the risk of invasive breast cancer, and 3.0 (95% CI = 1.2 to 7.5) times the risk of any ipsilateral breast cancer, compared with women with less than 25% of the breast occupied by dense tissue. Our results provide initial evidence that the risk of second breast cancers may be increased among DCIS patients with highly dense breasts.
Authors: Habel LA; Dignam JJ; Land SR; Salane M; Capra AM; Julian TB
J Natl Cancer Inst. 2004 Oct 6;96(19):1467-72.
Influence of site classification on cancer incidence rates: an analysis of gastric cardia carcinomas
BACKGROUND: Recent reports suggest that the incidences of cardia and gastroesophageal junction carcinomas have increased markedly. The influence of improvements in cancer site classification (i.e., from no specific site to a specific site) on these incidence rates is unknown. METHODS: We analyzed data for all gastric cancers reported to the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer registries from 1974 through 1998. We compared incidence figures adjusted for improvements in site classification with the standard unadjusted incidence rates traditionally reported from SEER data. All analyses used two-sided statistical tests. RESULTS: Among white males, the proportion of gastric cancers with an unspecified location decreased from 38% from 1974 to 1976 to 14% in 1996 to 1998. Between 1974-1976 and 1996-1998, the adjusted cardia cancer incidence rate for white males was unchanged (5.3% increase, from 3.6 to 3.8 per 100,000 population/year, respectively; P =.59), whereas the unadjusted cardia cancer incidence rate underwent a statistically significant increase (77% increase, from 1.9 to 3.4 per 100 000 population/year, respectively; P<.001). During the same period, the adjusted noncardia gastric cancer incidence rate in white males decreased from 6.8 to 3.8 per 100,000 population/year (P<.001), an absolute decrease more than twice as large as that seen using standard unadjusted SEER data (from 4.5 to 3.2 per 100,000 population/year; P<.001). Similar findings were observed for black males. CONCLUSIONS: Improved specification of gastric cancer sites may largely account for the purported increase in cardia cancer incidence in recent decades. Noncardia gastric cancer incidence may be decreasing much more rapidly than previously appreciated. These results illustrate the potentially large influence of changes in site classification on some cancer incidence rates.
Authors: Corley DA; Kubo A
J Natl Cancer Inst. 2004 Sep 15;96(18):1383-7.
The incidence of colorectal cancer following a negative screening sigmoidoscopy: implications for screening interval
BACKGROUND & AIMS: Current guidelines recommend a 5-year interval for colorectal cancer (CRC) screening by sigmoidoscopy. However, the optimal screening interval is uncertain. We estimated the annual incidence of distal and proximal CRC in the first 5 years following a negative sigmoidoscopy examination to gauge the potential benefit of rescreening in <5 years. METHODS: A cohort of 72,483 participants in the Colon Cancer Prevention program of Kaiser Permanente of Northern California (KP) was defined using computerized databases. Men and women aged 50 years and older who had a negative screening flexible sigmoidoscopy examination between 1994 and 1996 and were considered not to be at high risk for developing CRC were included. Subjects were censored at the time of diagnosis (for cases), death, termination of KP membership, or subsequent colon examination. RESULTS: Thirty cases of distal and 80 cases of proximal CRC occurred. Age-adjusted incidence rates of distal CRC ranged from a low of 2.8 per 100,000 person-years in the first year of follow-up to a high of 13.0 per 100,000 in the fourth year (rate difference, 10.2; 95% confidence interval, 1.1-19.3). However, for the entire follow-up period, incidence of distal CRC remained much lower than age-adjusted rates of 70.6 in the general population (Surveillance, Epidemiology, and End Results registry). The incidence of proximal CRC was also decreased modestly over population rates of disease. CONCLUSIONS: Screening by sigmoidoscopy more frequently than every 5 years would likely lead, at best, to only modest improvements as compared with a 5-year screening interval.
Authors: Doria-Rose VP; Levin TR; Selby JV; Newcomb PA; Richert-Boe KE; Weiss NS
Gastroenterology. 2004 Sep;127(3):714-22.
Adherence to the AICR cancer prevention recommendations and subsequent morbidity and mortality in the Iowa Women’s Health Study cohort
In 1997, the American Institute for Cancer Research (AICR) published 14 recommendations related to diet for individuals to reduce cancer incidence on a global basis; smoking was also discouraged. We operationalized these into nine recommendations that are particularly relevant to western populations in a cohort of 29,564 women ages 55 to 69 years at baseline in 1986 who had no history of cancer or heart disease. The cohort was followed through 1998 for cancer incidence (n = 4,379), cancer mortality (n = 1,434), cardiovascular disease (CVD) mortality (n = 1,124), and total mortality (n = 3,398). The median number (range) of recommendations followed was 4 (0-8), and 33% of the cohort had ever smoked. Women who followed no or one recommendation compared with six to nine recommendations were at an increased risk of cancer incidence [relative risk (RR) 1.35, 95% confidence interval (CI) 1.15-1.58] and cancer mortality (RR 1.43, 95% CI 1.11-1.85), but there was no association with CVD mortality (RR 1.06, 95% CI 0.78-1.43). We calculated the population attributable risk (PAR) to estimate the proportion of cancer incidence, cancer mortality, and CVD mortality that theoretically would have been avoidable if the entire cohort had never smoked, had followed six to nine recommendations, or had done both. The PARs for smoking were 11% (95% CI 10-13) for cancer incidence, 21% (95% CI 17-24) for cancer mortality, and 20% (95% CI 16-23) for CVD mortality. The PARs for not following six to nine recommendations were 22% (95% CI 12-30) for cancer incidence, 11% (95% CI -5 to 24) for cancer mortality, and 4% (95% CI -20 to 19) for CVD mortality. When smoking and the operationalized AICR recommendations were combined together, the PARs were 31% (95% CI 19-37) for cancer incidence, 30% (95% CI 15-40) for cancer mortality, and 22% (95% CI 4-36) for CVD mortality. These data suggest that the adherence to the AICR recommendations, independently and in conjunction with not smoking, is likely to have a substantial public health impact on reducing cancer incidence and, to a lesser degree, cancer mortality at the population level.
Authors: Cerhan JR; Potter JD; Gilmore JM; Janney CA; Kushi LH; Lazovich D; Anderson KE; Sellers TA; Folsom AR
Cancer Epidemiol Biomarkers Prev. 2004 Jul;13(7):1114-20.
The evolution to stool DNA testing for colorectal cancer
Despite a variety of screening strategies and recent trends showing death rate stabilization, colorectal cancer still remains the second leading cause of overall cancer death. Current screening tools suffer from performance limitations, low patient acceptability, and marginal reliable access within the health care system. Noninvasive strategies present the lowest risk with the highest potential for patient satisfaction. However, serious implementation barriers exist requiring consistent programmatic screening, strict patient adherence, and poor sensitivity for adenomas. Colonoscopy remains an invasive screening test with the best sensitivity and specificity, but faces large financial costs, manpower requirements, patient access and adherence. Development of advanced molecular techniques identifying altered DNA markers in exfoliated colonocytes signify early or precancerous growth. Stool-based DNA testing provides an entirely noninvasive population-based screening strategy which patients can perform easier than faecal occult blood testing (FOBT). Large-scale prospective randomized control trials currently pending should help characterize accurate test performance, screening intervals, cost-effectiveness, direct comparison to FOBT and analysis of patient adherence. As tumour development pathways and potential target genes are further elucidated, refinements in multi-assay stool-based DNA testing portend enhanced test characteristics to detect and treat this genetically heterogeneous disease.
Authors: Tagore KS; Levin TR; Lawson MJ
Aliment Pharmacol Ther. 2004 Jun 15;19(12):1225-33.
The risk for malignant primary adult-onset glioma in a large, multiethnic, managed-care cohort: cigarette smoking and other lifestyle behaviors
PURPOSE: To determine the risk for malignant primary adult-onset glioma (MPAG) associated with cigarette smoking and other lifestyle behaviors in a large, multiethnic, managed-care cohort. METHODS: The study population included a cohort of 133,811 subscribers to the Kaiser Permanente Medical Care Program of Northern California who had received a multiphasic health checkup and questionnaire between 1977 and 1985, were at least 25 years old at their start of follow-up, and had no prior history of benign or malignant brain tumors. In this cohort, patients were followed for up to 21 years for the development of MPAG. RESULTS: Risk for MPAG among women increased with increasing packs of cigarettes smoked per day (p-for-trend = 0.04), adjusting for cigar and pipe smoking, patient age, sex, race, education, alcohol use and coffee consumption. A similar pattern was not observed for men. Individuals who smoked marijuana at least once a month, adjusting for cigarette smoking (packs smoked per day) and for the factors noted above, had a 2.8-fold (CI = 1.3-6.2) increased risk for MPAG. Relative risk for MPAG increased with increasing consumption of coffee (p-for-trend = 0.05). CONCLUSIONS: Cigarette smoking was associated with an increased risk for MPAG among women but not among men. Individuals who smoked marijuana at least once a month had an increased risk for MPAG, although no dose-response relation was observed. Drinkers of >7 cups of coffee per day had a 70% increased risk for MPAG and smaller risk elevation for lower consumption. Alcohol usage was not associated with an increased risk for MPAG.
Authors: Efird JT; Friedman GD; Sidney S; Klatsky A; Habel LA; Udaltsova NV; Van den Eeden S; Nelson LM
J Neurooncol. 2004 May;68(1):57-69.
Screening in liver disease: report of an AASLD clinical workshop
This report summarizes an AASLD Clinical Workshop that was presented at Digestive Diseases Week 2003 on screening in liver diseases. As newer diagnostic tests become available, many liver diseases and complications of liver disease can be detected at an early asymptomatic stage. In many cases, early detection can lead to earlier treatment and an improved outcome. However, screening for liver diseases in asymptomatic persons has the potential for adverse consequences, including discrimination and stigmatization. The cost of screening programs is significant, and access to screening tests varies in different countries. Future screening programs require careful planning and implementation to balance the benefits, risks, and cost-effectiveness. This review outlines the concepts of screening and their application to a broad range of liver diseases.
Authors: Adams PC; Arthur MJ; Boyer TD; DeLeve LD; Di Bisceglie AM; Hall M; Levin TR; Provenzale D; Seeff L
Hepatology. 2004 May;39(5):1204-12.
Meat consumption patterns and preparation, genetic variants of metabolic enzymes, and their association with rectal cancer in men and women
Meat consumption, particularly of red and processed meat, is one of the most thoroughly studied dietary factors in relation to colon cancer. However, it is not clear whether meat, red meat, heterocyclic amines (HCA), or polycyclic aromatic hydrocarbons (PAH) are associated with the risk for rectal cancer. Rectal cancer cases (n = 952) and controls (n = 1205) from Utah and Northern California were recruited from a population-based case-control study between September 1997 and February 2002. Detailed in-person interviews regarding lifestyle, medical history, and diet were conducted. DNA was extracted from peripheral lymphocytes obtained from whole-blood samples, and glutathione S-transferase (GST)M1 enzyme and N-acetyl transferase (NAT)2 enzyme genotypes were assessed. Although energy and cholesterol intakes were higher among cases than controls, adjustment for confounders accounted for the differences. Increased consumption of well-done red meat [odds ratio (OR) 1.33 95% CI 0.98, 1.79] was associated with an (P = 0.04) increase in risk for rectal cancer among men. The mutagen index, calculated on the bases of reported amount, doneness, and method of cooking meat, was also positively but not significantly (P = 0.24) associated with risk of rectal cancer for men (OR 1.37 95% CI 0.98, 1.92). NAT2-imputed phenotype and GSTM1 did not consistently modify rectal cancer risk associated with meat intake. These data suggest that mutagens such as HCA that form when meat is cooked may be culpable substances in rectal cancer risk, not red meat itself.
Authors: Murtaugh MA; Ma KN; Sweeney C; Caan BJ; Slattery ML
J Nutr. 2004 Apr;134(4):776-84.
Marked multi-ethnic variation of esophageal and gastric cardia carcinomas within the United States
OBJECTIVE: No prior studies have contrasted esophageal and gastric cardia carcinoma incidence rates among multiple ethnicities. We evaluated whether these adjacent cancers differ; such detailed demographic analyses would inform risk factor, screening, and intervention studies. METHODS: We contrasted incidence rates and temporal trends from the Surveillance, Epidemiology, and End Results (SEER) cancer registry data between 1992 and 1998 for five groups: non-Hispanic whites (Caucasians), white Hispanics (Hispanics), blacks, Asians/Pacific Islanders (Asians/PI), and Native Americans (NA). RESULTS: Caucasian males’ esophageal adenocarcinoma rate (4.2 per 100,000 population/yr) was double that of Hispanics and four-fold higher than those of blacks, Asians/PI, and NA (p < 0.01). Female rates were much lower than male rates for all ethnicities. Similar to esophageal adenocarcinoma, cardia adenocarcinoma rates were highest in Caucasian males (3.4 per 100,000 population/yr); however, the ethnic differences were much less and female rates were comparable for all almost all ethnicities (range 0.6-0.7 per 100,000 population/yr) except NA. Esophageal adenocarcinoma incidence rates increased significantly only in Caucasians (males 5.6%/yr, females 9%/yr; p < 0.05) and cardia cancer rates did not increase for any ethnicity during this period. In contrast, esophageal squamous cell carcinoma incidence rates were highest in blacks (8.8 per 100,000 population/yr) and Asians/PI (3.9 per 100,000 population/yr) and rates were stable or declined for all ethnicities between 1992 and 1998. CONCLUSIONS: Esophageal and cardia carcinoma incidence rates vary much more markedly by ethnicity and gender than previously reported and the two sites differ from each other. Current putative risk factors do not adequately explain these large differences. These data have implications for risk factor, screening, and intervention studies.
Authors: Kubo A; Corley DA
Am J Gastroenterol. 2004 Apr;99(4):582-8.
Estrogen plus progestin and colorectal cancer in postmenopausal women
BACKGROUND: Although the Women’s Health Initiative (WHI) trial of estrogen plus progestin in postmenopausal women identified more overall health risks than benefits among women in the hormone group, the use of estrogen plus progestin was associated with a significant decrease in the risk of colorectal cancer. We analyzed features of the colorectal cancers that developed and their relation to the characteristics of the participants. METHODS: In the WHI trial, 16,608 postmenopausal women who were 50 to 79 years of age and had an intact uterus were randomly assigned to a combination of conjugated equine estrogens (0.625 mg per day) plus medroxyprogesterone acetate (2.5 mg per day) or placebo. The main outcome measures were the incidence, stages, and types of colorectal cancer, as determined by blinded central adjudication. RESULTS: There were 43 invasive colorectal cancers in the hormone group and 72 in the placebo group (hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.81; P=0.003). The invasive colorectal cancers in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean +/-SD, 3.2+/-4.1 vs. 0.8+/-1.7; P=0.002) and were more advanced (regional or metastatic disease, 76.2 percent vs. 48.5 percent; P=0.004). In exploratory analyses, women in the hormone group with antecedent vaginal bleeding had colorectal cancers with a greater number of positive nodes than women in the hormone group who did not have vaginal bleeding (3.8+/-4.3 vs. 0.7+/-1.5 nodes, P=0.006). CONCLUSIONS: Relatively short-term use of estrogen plus progestin was associated with a decreased risk of colorectal cancer. However, colorectal cancers in women who took estrogen plus progestin were diagnosed at a more advanced stage than those in women who took placebo.
Authors: Chlebowski RT; Ascensao J; Women's Health Initiative Investigators; et al.
N Engl J Med. 2004 Mar 4;350(10):991-1004.
Low energy reporting may increase in intervention participants enrolled in dietary intervention trials
OBJECTIVE: To examine differences in low energy intake reporting between intervention and control groups during a dietary intervention trial. DESIGN: Retrospective data analysis from a subcohort of participants in the Polyp Prevention Trial (PPT), a 4-year, multisite, randomized, controlled dietary intervention trial. Intervention consisted of educational material and counseling sessions supporting a low-fat, high-fiber diet. Baseline and annual demographics, behavioral characteristics, energy intake (EI) based on self-reported 4-day food records, and height and weight of participants were collected at baseline and annually. Basal metabolic rate (BMR) was estimated (using the Schofield equation) to calculate EI/BMR. SUBJECTS: Of the 443 participants (302 male, 141 female) at baseline, 195 (43.3%) were younger than 60 years, and 394 (91%) were white. At Year 4, 383 participants remained: 186 (122 men, 64 women) in the intervention group, and 197 (133 men, 64 women) in the control group. STATISTICAL ANALYSES: Using either paired t tests or analysis of variance, the differences between the means for EI, weight, and EI/BMR were compared at baseline, Year 1, and Year 4 for the participants who remained at Year 4. The Goldberg EI/BMR cutoff value of 1.06 (for plausible EI) identified participants who reported low EI. Linear regression was used to quantify the association of various risk factors to EI/BMR and for multivariate analyses within groups. chi(2) contingency table analysis quantified differences of low energy reporting within groups. RESULTS: At baseline, 46.8% of women and 11.6% of men reported lower than plausible EI. Only men had a significant increase in low energy reporting after randomization. At Year 1, 18.9% of intervention group men reported low EI compared with 9.8% of control group men (P<.05). At Year 4, 23.0% of intervention group men reported low EI compared with 12.8% of control group men (P<.05). CONCLUSIONS/APPLICATIONS: Difference in low EI reporting between intervention and control groups could distort results from dietary intervention trials; interpretation of findings from dietary trials must include this potential bias. Intervention study design should include dietary intake data collection methods that are not subject to such bias (ie, biomarkers and performance criteria) to measure intervention compliance.
Authors: Caan B; Lanza E; et al.
J Am Diet Assoc. 2004 Mar;104(3):357-66; quiz 491.
Factors associated with colorectal cancer screening in a population-based study: the impact of gender, health care source, and time
INTRODUCTION: The effectiveness of colorectal cancer screening in reducing incident colorectal cancer and the risk of death has been shown. Despite campaigns to promote the benefits of and use of colorectal cancer screening, most people are not participating in screening. In this paper, we examine factors associated with screening behavior over time, by health care provider, and by gender and report associations between screening and development of colorectal cancer after adjusting for diet and lifestyle factors. METHODS: Data from two population-based case-control studies of colorectal cancer were used to examine risk associations with nonparticipation in colorectal cancer screening. Study participants were identified for the first study between 1991 and 1994 (N = 1,346 cases and 1,544 controls) and for the second between 1997 and 2001 (N = 952 cases and 1,205 controls) and were asked to complete a detailed in-person interviewer-administered diet and lifestyle questionnaire. The control population is used to examine changes in screening behavior and associations with screening over time. RESULTS: Significantly, fewer people reported fecal occult blood test (FOBT) in 1997-2001 than in 1991-1994 (62.5% in 1991-1994 vs. 47.2% in 1997-2001); a slight nonsignificant increase in sigmoidoscopy screening was reported for these periods among controls (33.9% vs. 36.6%). In the control population, during these periods, there was a statistically significant increase in the number of people who reported having had a sigmoidoscopy for screening rather than for problems (72.6% in 1997-2001 vs. 63.8% in 1991-1994). There were differences in factors associated with screening behavior by time, by sex, and by health care provider, although having a family history of colorectal cancer, having more education, and being male was associated with more screening in all settings. After adjusting for diet and lifestyle factors, we observed that non-sigmoidoscopy screening significantly influenced risk of incident cancer (rectal OR: 2.9; 95% CI, 2.3-3.7; distal tumor OR: 1.8; 95% CI, 1.4-2.3); proximal tumor: 1.4; 95% CI, 1.1-1.8). Nonuse of FOBT also was associated significantly with tumors in the rectal (OR: 1.6; 95% CI, 1.3-1.9) and distal (OR: 1.4; 95% CI, 1.1-1.8) sites. SUMMARY: These data reinforce the importance of screening to reduce risk of colorectal cancer development. However, flexible sigmoidoscopy screening is increasing only modestly over time, and primarily in settings where a significant investment in screening has been made. FOBT screening, which is effective for rectal cancer prevention, is actually decreasing.
Authors: Slattery ML; Kinney AY; Levin TR
Prev Med. 2004 Mar;38(3):276-83.
Telephone counseling intervention increases intakes of micronutrient- and phytochemical-rich vegetables, fruit and fiber in breast cancer survivors
Although a large body of evidence suggests that diet may play an important role in cancer prevention, randomized controlled trials reported to date have not achieved sufficient increases in protective micronutrients and phytochemicals to adequately test the hypothesis that diet can reduce cancer risk. The Women’s Healthy Eating and Living (WHEL) Study, a randomized controlled trial of the role diet modification may play in future breast cancer events, introduced an innovative theory-based telephone counseling intervention to teach participants to consume a high fiber, low fat diet emphasizing vegetables and fruits rich in carotenoids and other potentially protective phytochemicals. This report examines the baseline to 12-mo changes in dietary intakes of 2970 participants, assessed through 24-h recalls and validated with plasma carotenoid concentrations. At 12 mo, the intervention group reported a significantly increased daily vegetable intake (+vegetable juice) of 7.1 servings (+82%) and fruit intake of 3.9 servings (+18%). Fiber intake increased from 3.04 to 4.16 g/(MJ. d), whereas energy from fat decreased significantly from 28.6 to 23.7%. Plasma carotenoid concentrations increased significantly, i.e., alpha-carotene (+223%); beta-carotene (+87%); lutein (+29%); and lycopene (+17%). In the comparison group, dietary intake and plasma carotenoid concentrations were essentially identical to those of the intervention group at baseline and were unchanged at 12 mo. The WHEL Study showed that a telephone counseling intervention can achieve major increases in micronutrient- and phytochemical-rich vegetables, fruit and fiber intakes, enabling an investigation of the potential cancer preventive effects of these food components.
Authors: Pierce JP; Caan BJ; Women's Healthy Eating and Living (WHEL) Study Group; et al.
J Nutr. 2004 Feb;134(2):452-8.
MTHFR C677T and A1298C polymorphisms: diet, estrogen, and risk of colon cancer
5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism, diverting metabolites toward methylation reactions or nucleotide synthesis. Using data from an incident case-control study (1608 cases and 1972 controls) we investigated two polymorphisms in the MTHFR gene, C677T and A1298C, and their associations with risk of colon cancer. All of the combined genotypes were evaluated separately, and the 1298AA/677CC (wild-type/wild-type) group was considered the reference group. Among both men and women, the 677TT/1298AA (variant/wild-type) genotype was associated with a small reduction in risk [men: odds ratio (OR), 0.7, 95% confidence interval (CI), 0.5-1.0; women: OR, 0.8, 95% CI, 0.5-1.2]. However, the 677CC/1298CC (wild-type/variant) genotype was associated with a statistically significant lower risk among women (OR, 0.6; 95% CI, 0.4-0.9) but not men. When the polymorphisms were considered individually, for A1298C a significant risk reduction associated with the homozygous variant CC genotype was seen among women only (OR, 0.6; 95% CI, 0.5-0.9), and nonstatistically significant reduced risks were observed for the variant 677 TT genotypes among both men and women. Stratification by nutrient intakes showed inverse associations with higher intakes of folate, vitamin B(2), B(6), B(12), and methionine among women with the MTHFR 677CC/1298AA genotypes, but not those with 677TT/1298AA. We observed opposite risk trends for both MTHFR variants, depending on whether women used hormone-replacement therapy or not (P for interaction = <.01). In summary, this study supports recent findings that the MTHFR A1298C polymorphism may be a predictor of colon cancer risk and have functional relevance. The possible interaction with hormone-replacement therapy warrants additional investigation.
Authors: Curtin K; Bigler J; Slattery ML; Caan B; Potter JD; Ulrich CM
Cancer Epidemiol Biomarkers Prev. 2004 Feb;13(2):285-92.
Antioxidants, carotenoids, and risk of rectal cancer
Numerous properties suggest that antioxidants and carotenoids may be valuable chemopreventive agents. A population-based case-control study of 952 rectal cancer cases and 1,205 controls from Northern California and Utah was conducted between September 1997 and February 2002. Detailed diet history, medical history, and lifestyle factors interviews were conducted. Dietary antioxidants were not associated with rectal cancer risk in men. For women, relative to the highest level of intake, low intake of dietary lycopene (odds ratio (OR) = 1.7, 95% confidence interval (CI): 1.0, 2.8) or vitamin E (OR = 2.2, 95% CI: 1.1, 4.3) was associated with an increased risk of rectal cancer. Alpha-, beta-, and gamma-tocopherol were associated with an approximate twofold increased risk of rectal cancer in women. Associations were stronger for women aged > or = 60 years for vitamin E and tocopherols (alpha-tocopherol OR = 3.6, 95% CI: 1.4, 9.4; gamma-tocopherol OR = 5.3, 95% CI: 2.1, 13.2; delta-tocopherol OR = 1.9, 95% CI: 0.9, 4.0), except for beta-tocopherol, for which risk increased twofold for all women. Associations differed by estrogen status for beta-carotene, lycopene, and vitamin E. These results suggest that vitamin E and lycopene may modestly reduce the risk of rectal cancer in women.
Authors: Murtaugh MA; Ma KN; Benson J; Curtin K; Caan B; Slattery ML
Am J Epidemiol. 2004 Jan 1;159(1):32-41.
Family history and colorectal cancer: predictors of risk
INTRODUCTION: While the association between family history of colorectal cancer in first-degree relatives and risk of developing colon cancer has been well defined, the association with rectal cancer is much less clear. The purpose of this study is to define rectal cancer risk associated with family history of colorectal cancer in first-degree relatives. We also evaluate diet and lifestyle factors associated with developing colorectal cancer among participants with a positive family history. METHODS: Data were available from two population-based case–control studies of colon and rectal cancer. Participants were members of the Kaiser Permanente Medical Care Program (KPMCP) or residents of the state of Utah. Cases were first primary colon cancer diagnosed between 1991 and 1994 (n = 1308 cases and 1544 controls) or rectal cancer diagnosed between 1997 and 2001 (n = 952 cases and 1205 controls). RESULTS: A family history of colorectal cancer in any first-degree relatives slightly increased risk of rectal cancer (OR: 1.37 95% CI: 1.02-1.85). Family history of colorectal cancer was associated with the greatest risk among those diagnosed at age 50 or younger (OR: 2.09 95% CI: 0.94-4.65 for rectal tumors; OR: 3.00 95% CI: 0.98-9.20 for distal colon tumors; and OR: 7.88 95% CI: 2.62-23.7 for proximal colon tumors). Factors significantly associated with cancer risk among those with a family history of colorectal cancer, included not having a sigmoidoscopy (OR: 2.81 95% CI: 1.86-4.24): a diet not Prudent, i.e. high in fruits, vegetables, whole grains, fish and poultry, (OR: 2.79 95% CI: 1.40-5.56); smoking cigarettes (OR: 1.68 95% CI: 1.12-2.53), and eating a Western diet, i.e. a diet high in meat, refined grains, high-fat foods, and fast foods, (OR: 2.15 95% CI: 1.06-4.35). Physical inactivity was not associated with increased cancer risk among those with a positive family history of colorectal cancer. SUMMARY: These results confirm observations reported by others that a family history of colorectal cancer increases risk of cancer among those diagnosed at a younger age. Associations with family history are weakest for rectal cancer and strongest for proximal colonic tumors. Since several diet and lifestyle factors influence development of cancer among those with a family history of the disease, there appears to be practical approaches for individuals with a family history of colorectal cancer to reduce their cancer risk.
Authors: Slattery ML; Levin TR; Ma K; Goldgar D; Holubkov R; Edwards S
Cancer Causes Control. 2003 Nov;14(9):879-87.
What does sigmoidoscopy really miss?
Authors: Levin TR
Am J Gastroenterol. 2003 Oct;98(10):2326-7.
Improvement of gastroesophageal reflux symptoms after radiofrequency energy: a randomized, sham-controlled trial
BACKGROUND & AIMS: Gastroesophageal reflux disease is a prevalent disorder that often requires long-term medical therapy or surgery. The United States Food and Drug Administration recently cleared new endoluminal gastroesophageal reflux disease treatments; however, no controlled trials exist. METHODS: We randomly assigned 64 gastroesophageal reflux disease patients to radiofrequency energy delivery to the gastroesophageal junction (35 patients) or to a sham procedure (29 patients). Principal outcomes were reflux symptoms and quality of life. Secondary outcomes were medication use and esophageal acid exposure. After 6 months, interested sham patients crossed over to active treatment. RESULTS: At 6 months, active treatment significantly and substantially improved patients’ heartburn symptoms and quality of life. More active vs. sham patients were without daily heartburn symptoms (n = 19 [61%] vs. n = 7 [33%]; P = 0.05), and more had a >50% improvement in their gastroesophageal reflux disease quality of life score (n = 19 [61%] vs. n = 6 [30%]; P = 0.03). Symptom improvements persisted at 12 months after treatment. At 6 months, there were no differences in daily medication use after a medication withdrawal protocol (n = 17 [55%] vs. n = 14 [61%]; P = 0.67) or in esophageal acid exposure times. There were no perforations or deaths. CONCLUSIONS: Radiofrequency energy delivery significantly improved gastroesophageal reflux disease symptoms and quality of life compared with a sham procedure, but it did not decrease esophageal acid exposure or medication use at 6 months. This procedure represents a new option for selected symptomatic gastroesophageal reflux disease patients who are intolerant of, or desire an alternative to, traditional medical therapies.
Authors: Corley DA; Katz P; Wo JM; Stefan A; Patti M; Rothstein R; Edmundowicz S; Kline M; Mason R; Wolfe MM
Gastroenterology. 2003 Sep;125(3):668-76.
How should we select health professionals for studies?
The investigation of healthcare professionals’ practice patterns has increased sharply, in part driven by the development of practice guidelines; however, the optimal way to select providers is not known. We evaluated three distinct sources of physician specialists for completeness and potential biases. Professional society directories, which are frequently used to identify providers, provided biased populations. A national registry, the American Medical Association master file, produced the most comprehensive, least-biased single source.
Authors: Verma R; Corley DA
Outcomes Manag. 2003 Jul-Sep;7(3):129-33.
Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity
The goal of this study was to estimate the incidence of Parkinson’s disease by age, gender, and ethnicity. Newly diagnosed Parkinson’s disease cases in 1994-1995 were identified among members of the Kaiser Permanente Medical Care Program of Northern California, a large health maintenance organization. Each case met modified standardized criteria/Hughes diagnostic criteria as applied by a movement disorder specialist. Incidence rates per 100,000 person-years were calculated using the Kaiser Permanente membership information as the denominator and adjusted for age and/or gender using the direct method of standardization. A total of 588 newly diagnosed (incident) cases of Parkinson’s disease were identified, which gave an overall annualized age- and gender-adjusted incidence rate of 13.4 per 100,000 (95% confidence interval (CI): 11.4, 15.5). The incidence rapidly increased over the age of 60 years, with only 4% of the cases being under the age of 50 years. The rate for men (19.0 per 100,000, 95% CI: 16.1, 21.8) was 91% higher than that for women (9.9 per 100,000, 95% CI: 7.6, 12.2). The age- and gender-adjusted rate per 100,000 was highest among Hispanics (16.6, 95% CI: 12.0, 21.3), followed by non-Hispanic Whites (13.6, 95% CI: 11.5, 15.7), Asians (11.3, 95% CI: 7.2, 15.3), and Blacks (10.2, 95% CI: 6.4, 14.0). These data suggest that the incidence of Parkinson’s disease varies by race/ethnicity.
Authors: Van Den Eeden SK; Tanner CM; Bernstein AL; Fross RD; Leimpeter A; Bloch DA; Nelson LM
Am J Epidemiol. 2003 Jun 1;157(11):1015-22.
A randomized controlled trial of test-and-treat strategy for Helicobacter pylori: clinical outcomes and health care costs in a managed care population receiving long-term acid suppression therapy for physician-diagnosed peptic ulcer disease
BACKGROUND: Guidelines recommend Helicobacter pylori (HP) testing and treatment for patients with a history of peptic ulcer disease (PUD), assuming that PUD has been documented and that successful HP eradication would eliminate the need for further therapy and medical utilization. METHODS: An open-label, randomized controlled trial in a managed care setting evaluated the clinical outcome and costs of an HP test-and-treat (T & T) strategy in 650 patients receiving long-term acid suppression therapy for physician-diagnosed PUD. Patients were randomized to T & T for HP (n = 321) or to usual care (n = 329). Outcome measures included presence and severity of PUD symptoms, use of acid-reducing medication, and acid-peptic-related health care costs during 12-month follow-up. RESULTS: Only 17% of study participants had PUD confirmed by radiography or endoscopy; only 38% of the T & T group tested positive for HP. At 12 months, patients in the T & T group were less likely to report ulcerlike dyspepsia or use of acid-reducing medication; however, 75% of the T & T group used acid-reducing medication during the second half of the 12-month follow-up. In the 12 months after randomization, the T & T group had higher total acid-peptic-related costs than the usual care group. CONCLUSIONS: Most patients receiving long-term acid suppression therapy for physician-diagnosed PUD in community practice settings are likely to have HP-negative, uninvestigated dyspepsia. Routine testing and treating for HP will not reduce acid-peptic-related costs and have only a modest (though statistically significant) effect in reducing clinical symptoms and use of acid-reducing medications.
Authors: Allison JE; Hurley LB; Hiatt RA; Levin TR; Ackerson LM; Lieu TA
Arch Intern Med. 2003 May 26;163(10):1165-71.
Measuring dietary change in a diet intervention trial: comparing food frequency questionnaire and dietary recalls
Measurement of dietary change was assessed in a systematic quota subsample (n = 397) of women recruited into the Women’s Healthy Eating and Living Study between 1996 and 1998, a multicenter, randomized dietary intervention trial among breast cancer survivors. Women from the intervention and comparison arms completed the Arizona Food Frequency Questionnaire (AFFQ) and 24-hour dietary recalls at baseline (prerandomization) and at year 1 (postrandomization). Both dietary measurement methods demonstrated significant changes in intake of key intervention-associated nutrients at year 1 in the intervention group subjects compared with minimal or no change in the comparison group subjects. The reliability of the AFFQ and recalls was measured in the comparison group and showed correlations of 0.63 and 0.43, respectively. Both instruments captured differences in dietary intake associated with the diet intervention. These results demonstrate the utility of using a multimode, multimethod approach (AFFQ and 24-hour dietary recalls) to measure differences in self-reported dietary intake over time as shown in this dietary intervention trial being conducted among breast cancer survivors.
Authors: Thomson CA; Caan B; Marshall JR; et al.
Am J Epidemiol. 2003 Apr 15;157(8):754-62.
Does family history still matter in the era of screening colonoscopy?
Authors: Levin TR
Clin Gastroenterol Hepatol. 2003 Mar;1(2):69-70.
Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence
We have updated guidelines for screening for colorectal cancer. The original guidelines were prepared by a panel convened by the U.S. Agency for Health Care Policy and Research and published in 1997 under the sponsorship of a consortium of gastroenterology societies. Since then, much has changed, both in the research rature and in the clinical context. The present report summarizes new developments in this field and suggests how they should change practice. As with the previous version, these guidelines offer screening options and encourage the physician and patient to decide together which is the best approach for them. The guidelines also take into account not only the effectiveness of screening but also the risks, inconvenience, and cost of the various approaches. These guidelines differ from those published in 1997 in several ways: we recommend against rehydrating fecal occult blood tests; the screening interval for double contrast barium enema has been shortened to 5 years; colonoscopy is the preferred test for the diagnostic investigation of patients with findings on screening and for screening patients with a family history of hereditary nonpolyposis colorectal cancer; recommendations for people with a family history of colorectal cancer make greater use of risk stratification; and guidelines for genetic testing are included. Guidelines for surveillance are also included. Follow-up of postpolypectomy patients relies now on colonoscopy, and the first follow-up examination has been lengthened from 3 to 5 years for low-risk patients. If this were adopted nationally, surveillance resources could be shifted to screening and diagnosis. Promising new screening tests (virtual colonoscopy and tests for altered DNA in stool) are in development but are not yet ready for use outside of research studies. Despite a consensus among expert groups on the effectiveness of screening for colorectal cancer, screening rates remain low. Improvement depends on changes in patients’ attitudes, physicians’ behaviors, insurance coverage, and the surveillance and reminder systems necessary to support screening programs.
Authors: Winawer S; Levin T; Gastrointestinal Consortium Panel; et al.
Gastroenterology. 2003 Feb;124(2):544-60.
Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States)
OBJECTIVE: The association between body mass index (BMI) and colon cancer has been reported to be different for men and women. No prior literature has examined if estrogen influences these differences. METHODS: Using data from an incident population-based case (n = 1,972) and control (n = 2386) study of colon cancer we evaluated if estrogen modifies the association between BMI and risk of colon cancer. RESULTS: Women who were estrogen-negative (postmenopausal women not taking hormone replacement therapy, HRT) were at increased risk of colon cancer regardless of indicator of estrogen status used (i.e. estrogen-negative compared to estrogen-positive women defined as either being premenopausal or postmenopausal women using HRT, OR 1.54, 95% CI 1.23-1.93; no recent exposure to estrogens compared to current or HRT use within the past 2 years, OR 1.58, 95% CI 1.24-2.00; postmenopausal women not currently using HRT compared to postmenopausal women taking HRT, OR 1.65, 95% CI 1.29-2.12). BMI (kg/m2) was not associated with an increased risk of colon cancer among women who were estrogen-negative. However, women who were estrogen-positive experienced a greater than two-fold increase in colon cancer risk if they had a BMI of > 30 relative to those who had a BMI of <23 (for estrogen-positive, OR, 2.50, 95% CI 1.51-4.13; premenopausal, OR 2.19, 95% CI 0.94-5.07; postmenopausal using HRT, OR 3.36, 95% CI 1.58-7.13). Among men the colon cancer risk associated with BMI decreased with advancing age. Physical activity modified the increased colon cancer risk associated with a large BMI. CONCLUSIONS: These data suggest the importance of estrogen in colon cancer etiology. Being estrogen-negative resulted in a significant increased risk of colon cancer. However, BMI significantly increased the risk of colon cancer among women who were estrogen-positive. We hypothesize that estrogen up-regulates IGF-I receptors and IRS-I levels in the colon, which in turn increases susceptibility to obesity-induced increased levels of insulin. We further hypothesize that androgens may have similar effects in men given the decline in colon cancer risk associated with BMI with advancing age.
Authors: Slattery ML; Ballard-Barbash R; Edwards S; Caan BJ; Potter JD
Cancer Causes Control. 2003 Feb;14(1):75-84.
Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis
BACKGROUND & AIMS: Esophageal carcinomas have high fatality rates, making chemoprevention agents desirable. We performed a systematic review with meta-analysis of observational studies evaluating the association of aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and esophageal cancer. METHODS: We evaluated the MEDLINE, BIOSIS, and Web of Science electronic databases (1980-2001); manually reviewed the literature; and consulted with experts. Studies were included if they: (1) evaluated exposure to NSAIDs, aspirin, or both; (2) evaluated esophageal cancer; and (3) reported relative risks or odds ratios or provided data for their calculation. Data were independently abstracted by 2 investigators. The primary and sensitivity analyses used both fixed and random-effects models. RESULTS: Nine studies (2 cohort, 7 case control) containing 1813 cancer cases were identified. All primary summary estimates were homogeneous. Statistical pooling showed a protective association between any use of aspirin/NSAID and esophageal cancer (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.47-0.71). Both intermittent (OR = 0.82; CI, 0.67-0.99) and frequent medication use were protective (OR = 0.54; CI, 0.43-0.67), with greater protection with more frequent use. Stratified by medication type, aspirin use was protective (OR = 0.5; CI, 0.38-0.66), and NSAIDs had a borderline protective association (OR = 0.75; CI, 0.54-1.0). Any use was protective against both esophageal adenocarcinoma (OR = 0.67; CI, 0.51-0.87) and squamous cell carcinoma (OR = 0.58; CI, 0.43-0.78). CONCLUSIONS: Pooled results support a protective association between aspirin and NSAIDs and esophageal cancer (of both histological types) and provide evidence for a dose effect. These findings support evaluating these agents in clinical trials of high-risk patients.
Authors: Corley DA; Kerlikowske K; Verma R; Buffler P
Gastroenterology. 2003 Jan;124(1):47-56.
Dietary fat and cancer
Based on current epidemiologic knowledge, public health recommendations to decrease total fat intake for the prevention of cancer appear largely unwarranted. Recommendations to decrease red meat intake, particularly processed meat or beef intake, may, on the other hand, decrease the risk of colorectal cancer and prostate cancer; it may have a beneficial effect on breast cancer as well, although the evidence is much less compelling in this regard. There appears to be no particular benefit regarding cancer prevention that would accrue from reducing fat intake from vegetable sources, and in the case of breast cancer, there is some suggestive but preliminary evidence that olive oil or other sources of monounsaturated fatty acids may modestly decrease risk. Overall, recommendations focused on controlling weight by regular physical activity and avoidance of excessive energy intake from all sources; increasing plant food intake; consuming a variety of whole grains, vegetables, and fruits; and decreasing red meat intake are likely to be more effective in decreasing risk of breast, colorectal, and prostate cancer than decreasing total fat intake. This conclusion is consistent with current recommendations for cancer prevention as promulgated by the American Cancer Society.
Authors: Kushi L; Giovannucci E
Am J Med. 2002 Dec 30;113 Suppl 9B:63S-70S.
Initial treatment for prostate carcinoma in relation to comorbidity and symptoms
BACKGROUND: Evidence suggests the type of treatment received for prostate carcinoma is associated with comorbidity, but little information is available on associations with specific comorbid disease or symptoms. The authors examined the relations between treatment and comorbidity, specific comorbid disease, and symptoms. METHODS: Medical records were abstracted for 1054 male members of the Kaiser Permanente medical care program diagnosed with prostate carcinoma from 1975 to 1987. Information was obtained on demographic characteristics, comorbid conditions, symptoms, tumor stage and grade, and treatment. Logistic regression was used to determine the significant predictors of treatment (radiation vs. nonaggressive treatment and surgery vs. nonaggressive treatment). RESULTS: Compared to nonaggressive treatment, radiation treatment was less likely among men who had prior cancer (adjusted odds ratio [OR] 0.29, 95% confidence interval [CI] 0.09-0.90) or cerebrovascular disease (OR 0.33, 95% CI 0.13-0.83). There was a significant interaction between race and myocardial infarction (P = 0.02). Surgery, compared to nonaggressive treatment, was less common among men with a prior cancer (OR 0.21, 95% CI 0.07-0.63) or congestive heart failure (OR 0.29, 95% CI 0.09-0.90). Significant interactions were observed between race and myocardial infarction (P = 0.01), diabetes and dysuria or hematuria (P = 0.02), and para- or hemiplegia and urinary frequency or nocturia (P = 0.01). CONCLUSIONS: Specific symptoms and comorbidity appear to influence treatment for prostate carcinoma. More research is needed on treatment differences by race.
Authors: Hall HI; Satariano WA; Thompson T; Ragland KE; Van Den Eeden SK; Selvin S
Cancer. 2002 Dec 1;95(11):2308-15.
Flexible sigmoidoscopy for colorectal cancer screening: valid approach or short-sighted?
Flexible sigmoidoscopy is a safe, effective test that may be delivered feasibly on a large scale for mass colorectal cancer screening. Flexible sigmoidoscopy is 67% to 80% as sensitive as colonoscopy in a screening population, but is probably 10 to 20 times safer than colonoscopy in terms of complications. Several national guidelines recommend combining flexible sigmoidoscopy with fecal occult blood tests. There is limited evidence to support this practice, and the added benefit to an existing flexible sigmoidoscopy screening program although real, may be marginal. In the future, it is likely that flexible sigmoidoscopy screening among patients aged 50 to 65 will be supplemented with total colonic screening, using molecular-based fecal tests or virtual colonoscopy, after age 65.
Authors: Levin TR
Gastroenterol Clin North Am. 2002 Dec;31(4):1015-29, vii.
A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women’s Healthy Eating and Living (WHEL) Study
The Women’s Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.
Authors: Pierce JP; Caan BJ; Women's Healthy Eating and Living (WHEL) study group; et al.
Control Clin Trials. 2002 Dec;23(6):728-56.
Complications of screening flexible sigmoidoscopy
BACKGROUND & AIMS: Flexible sigmoidoscopy (FS) is recommended for mass screening for colorectal cancer (CRC), yet little is known about the risk of adverse events when FS is used in general clinical practice. We aimed to determine the incidence of gastrointestinal complications and acute myocardial infarction (MI) after screening FS. METHODS: Northern California Kaiser Permanente Medical Care Program members of average risk for CRC (n = 107,704) who underwent screening FS during 1994 to 1996 (109,534 FS), as part of the Colorectal Cancer Prevention (CoCaP) program. The main outcome measure was hospitalization for gastrointestinal complications or acute MI within 4 weeks of FS. RESULTS: The mean age of subjects was 61 years, and 48.8% were female. Nongastroenterologist physicians, nurses, or physician assistants performed 72% of FS. Overall, 24 persons were hospitalized for a gastrointestinal complication. Of these, 7 were serious (2 perforations, 2 episodes of diverticulitis requiring surgery, 2 cases of bleeding requiring transfusion, and 1 episode of unexplained colitis). In multivariate models, complications were significantly more common in men than in women (odds ratio, 3.34; 95% confidence interval [CI], 1.34-10.13). MI occurred in 33 persons within 4 weeks of FS, but the incidence for this period was similar to that in the subsequent 48 weeks (rate ratio, 0.8; 95% CI, 0.6-1.2). CONCLUSIONS: The risk of serious complications after screening FS in this setting appears to be modest. Although MI occurs after FS, the risk during the 4 weeks after the procedure appears to be similar to expectations for persons of screening age.
Authors: Levin TR; Conell C; Shapiro JA; Chazan SG; Nadel MR; Selby JV
Gastroenterology. 2002 Dec;123(6):1786-92.
Marked regional variation in adenocarcinomas of the esophagus and the gastric cardia in the United States
BACKGROUND: Adenocarcinomas of the esophagus and the gastric cardia recently have experienced rapidly increasing incidence rates. Although these sites frequently are combined, they may have different risk factors. METHODS: The authors compared regional incidence rates of esophageal adenocarcinoma, gastric cardia adenocarcinoma, and esophageal squamous cell carcinoma within the U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registry for the years 1973-1998. RESULTS: Regional incidence rates varied considerably. The Seattle-Puget Sound registry’s recent average esophageal adenocarcinoma rates were over twice as high as those of the Utah registry (5.3 vs. 2.4 per 100,000 persons per year; P < 0.01); gastric cardia rates also differed (4.0 vs. 2.8 per 100,000 persons per year; P < 0.01). The incidence rate increase also varied markedly between regions. Since 1974, white male esophageal adenocarcinoma rates increased by 800% in Seattle compared with an increase of only 300% in Utah. In contrast, white male cardia adenocarcinoma rates increased by only 16% in Seattle (from 3.1 per 100,000 persons per year in 1974 to 3.6 per 100,000 persons per year in 1998) compared with 300% in Utah (from 0.7 to 2.2 per 100,000 persons per year). Both types of adenocarcinoma were more common in males and in the white population in all regions, but recent esophageal adenocarcinoma rates for black males in Connecticut were significantly higher than the U.S. black male average (3.1 vs. 0.8 per 100,000 persons per year; P < 0.01) and equaled the rates for the white population in some areas. Esophageal adenocarcinoma rates continued rising for white males through 1998, whereas cardia adenocarcinoma rates stabilized after 1988. CONCLUSIONS: There are substantial regional, temporal, and ethnic differences between esophageal adenocarcinoma incidence rates and gastric cardia adenocarcinoma incidence rates within a single cancer registry system. Thus, these malignancies may differ in important ways and should not be combined routinely in research studies. Individual-level studies are needed to explain these substantial regional and ethnic differences.
Authors: Kubo A; Corley DA
Cancer. 2002 Nov 15;95(10):2096-102.
Interaction of dietary folate intake, alcohol, and risk of hormone receptor-defined breast cancer in a prospective study of postmenopausal women
Alcohol intake is an established risk factor for breast cancer, but the underlying mechanism remains unknown. Four recent studies have described interactions of alcohol and low folate intake. We examined this interaction on the risk of postmenopausal breast cancer stratified by tumor receptor status for estrogen (ER) and progesterone (PR). The Iowa Women’s Health Study is a prospective cohort study of 34,393 at-risk women. Alcohol use and folate intake from diet and supplements were estimated at baseline in 1986 through a semiquantitative food frequency questionnaire. Through 1999, 1,875 cases of breast cancer were identified through linkage to the Iowa Surveillance, Epidemiology, and End Results registry. Compared with nondrinkers with folate intakes above the 50(th) percentile, women with low folate and high alcohol were at 1.43-fold greater risk (1.02-2.02). When stratified by tumor receptor status for ER or PR, the risks for low folate/high alcohol were 2.1 (1.18-3.85), 1.0 (0.76-1.42), 1.2 (0.88-1.70), and 1.2 (0.69-2.02) for ER-, ER+, PR+, and PR- tumors, respectively. Because the results were limited primarily to ER- tumors, one plausible interpretation of these data is that alcohol influences breast cancer through its metabolite, acetaldehyde, rather than through effects on ER levels and receptor-mediated pathways.
Authors: Sellers TA; Vierkant RA; Cerhan JR; Gapstur SM; Vachon CM; Olson JE; Pankratz VS; Kushi LH; Folsom AR
Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):1104-7.
Risk of subsequent cancer following invasive or in situ squamous cell skin cancer
PURPOSE: Determine the risk of subsequent cancer following squamous cell skin cancer. METHODS: Using computerized surgical pathology records and membership data from a health maintenance organization, we retrospectively identified 822 individuals with primary squamous cell skin cancer (SCSC) and 3662 comparison subjects matched for age, sex, race, residence area, and length of membership. Patients were included in the study if they had no prior history of cancer, and received at least one multiphasic health checkup and questionnaire (MHC). Patients were followed for subsequent invasive cancer up to 24 years, with a mean follow-up time of 7.8 years. RESULTS: SCSC patients had a significantly greater risk [adjusted for body mass index (BMI) and education] for subsequent cancer overall (excluding non-melanoma skin cancer) [risk ratio (RR) = 1.4, 95% confidence interval (CI) = 1.2-1.6], and for basal cell skin cancer (RR = 13.8, 95% CI = 8.8-21.9), digestive (RR = 1.6, 95% CI = 1.1-2.4), and genitourinary cancers (RR = 1.5, 95% CI = 1.0-2.0). An increased, but not statistically significant, adjusted risk (RR > or = 1.4) was also observed for lip, oral cavity, and pharynx cancer (RR = 3.9, 95% CI = 0.6-25.0); non-cutaneous squamous cell cancer (RR = 1.9, 95% CI = 0.9-4.4); and respiratory and intrathoracic cancer (RR = 1.4, 95% CI = 0.8-2.6). The addition of alcohol consumption, combined occupational exposure, marital status, and smoking history to the multivariate model did not materially change any significant positive associations with SCSC. CONCLUSIONS: Our results suggest that patients diagnosed with SCSC may be at an increased risk of subsequent cancer at many sites, although several estimated risk estimates were within the limits of chance given no true association.
Authors: Efird JT; Friedman GD; Habel L; Tekawa IS; Nelson LM
Ann Epidemiol. 2002 Oct;12(7):469-75.
Dietary fat and risk of lung cancer in a pooled analysis of prospective studies
Lung cancer rates are highest in countries with the greatest fat intakes. In several case-control studies, positive associations have been observed between lung cancer and intakes of total and saturated fat, particularly among nonsmokers. We analyzed the association between fat and cholesterol intakes and lung cancer risk in eight prospective cohort studies that met predefined criteria. Among the 280,419 female and 149,862 male participants who were followed for up to 6-16 years, 3,188 lung cancer cases were documented. Using the Cox proportional hazards model, we calculated study-specific relative risks that were adjusted for smoking history and other potential risk factors. Pooled relative risks were computed using a random effects model. Fat intake was not associated with lung cancer risk. For an increment of 5% of energy from fat, the pooled multivariate relative risks were 1.01 [95% confidence interval (CI), 0.98-1.05] for total, 1.03 (95% CI, 0.96-1.11) for saturated, 1.01 (95% CI, 0.93-1.10) for monounsaturated, and 0.99 (95% CI, 0.90-1.10) for polyunsaturated fat. No associations were observed between intakes of total or specific types of fat and lung cancer risk among never, past, or current smokers. Dietary cholesterol was not associated with lung cancer incidence [for a 100-mg/day increment, the pooled multivariate relative risk was 1.01 (95% CI, 0.97-1.05)]. There was no statistically significant heterogeneity among studies or by sex. These data do not support an important relation between fat or cholesterol intakes and lung cancer risk. The means to prevent this important disease remains avoidance of smoking.
Authors: Smith-Warner SA; Kushi LH; Willett WC; et al.
Cancer Epidemiol Biomarkers Prev. 2002 Oct;11(10 Pt 1):987-92.
Factors associated with oxidative stress in human populations
Oxidation of biomolecules may play a role in susceptibility to a number of diseases. However, there are few large-scale survey data describing oxidative damage that occurs in humans and the demographic, physical, or nutritional factors that may be associated with it. Such information is essential for the design and analysis of studies investigating the role of oxidative stress in health and disease. This paper presents data on levels of two biomarkers of lipid peroxidation, malondialdehyde and F(2)-isoprostanes, in 298 healthy adults aged 19-78 years. The study was conducted in Berkeley and Oakland, California, in 1998-1999. Sex was the strongest predictor of lipid peroxidation as measured by both biomarkers (p < 0.0001); it was stronger than smoking. C-reactive protein was positively associated with lipid peroxidation (p = 0.004), as was plasma cholesterol. Plasma ascorbic acid had a strong inverse relation (p < 0.001) with both biomarkers. Plasma beta-carotene was also associated with F(2)-isoprostanes. Other plasma antioxidants were not associated with lipid peroxidation biomarkers, once ascorbic acid was included in the multivariate model. Future surveys and epidemiologic studies should measure at least one marker of oxidative damage, as well as plasma ascorbic acid. These data would permit a better understanding of the role that oxidants and antioxidants play in the health of human populations.
Authors: Block G; Dietrich M; Norkus EP; Morrow JD; Hudes M; Caan B; Packer L
Am J Epidemiol. 2002 Aug 1;156(3):274-85.
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial
CONTEXT: Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE: To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN: Estrogen plus progestin component of the Women’s Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Authors: Rossouw JE; Ockene J; Writing Group for the Women's Health Initiative Investigators; et al.
JAMA. 2002 Jul 17;288(3):321-33.
Daily aspirin use and prostate cancer risk in a large, multiracial cohort in the US
OBJECTIVE: To examine the relationship between daily aspirin use and risk of prostate cancer in a large, racially diverse cohort of men followed for up to 32 years. METHODS: The study population included 90,100 male subscribers to the Kaiser Permanente Medical Care Program who had received one or more multiphasic health checkups between 1964 and 1973. This general health checkup included a self-completed questionnaire that requested men to record if they took more than six aspirin almost every day during the previous year. Subjects were followed for the development of prostate cancer using the local tumor registry. Cox regression was used to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS: A total of 2,574 men developed prostate cancer. Of these, 1617 had local stage disease and 719 had either regional or distant disease at diagnosis. A total of 2466 men (2.7%) reported taking more than six aspirin almost every day during the past year at one or more health checkups. After adjusting for birth year, education, race, and the number of health checkups. the relative risk of prostate cancer associated with this amount of aspirin use was 0.76 (95% CI 0.60-0.98). Relative risks did not differ by race and were similar for both local stage and regional or distant stage prostate cancer. CONCLUSION: Results from our large, multiracial cohort study support a modest inverse relationship between daily consumption of more than six aspirin and prostate cancer risk.
Authors: Habel LA; Zhao W; Stanford JL
Cancer Causes Control. 2002 Jun;13(5):427-34.
Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer
Authors: Rex DK; Levin TR; U.S.Multi-Society Task Force on Colorectal Cancer; et al.
Am J Gastroenterol. 2002 Jun;97(6):1296-308.
Adenomatous polyp recurrence and physical activity in the Polyp Prevention Trial (United States)
OBJECTIVE: To examine prospectively the association between physical activity and adenomatous polyp recurrence. METHODS: Information on past year total physical activity was collected annually through an interview-administered questionnaire from the 1905 men and women enrolled in a randomized dietary intervention study, the Polyp Prevention Trial. Multiple logistic regression analysis was used to examine the association between physical activity and polyp recurrence in up to three years of follow-up from baseline colonoscopy. RESULTS: There were no significant associations between moderate, vigorous, or total physical activity at the start of the trial and overall polyp recurrence in either men or women. Participants who reported consistent vigorous activity throughout the trial period had no significantly reduced risk of polyp recurrence compared to those who reported consistent sedentary activity (OR = 0.8, CI = 0.5-1.1). Consistent vigorous activity was also not significantly associated with either advanced or multiple polyps, nor with polyp recurrence at any specific anatomical location in the large bowel. CONCLUSIONS: These prospective data suggest that recent physical activity is not associated with polyp recurrence in a three-year period.
Authors: Colbert LH; Caan B; Polyp Prevention Trial Study Group; et al.
Cancer Causes Control. 2002 Jun;13(5):445-53.
Gastric and duodenal safety of daily alendronate
BACKGROUND: Isolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use. PARTICIPANTS AND METHODS: Study subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization-matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review. RESULTS: Based on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations-restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2). CONCLUSIONS: Osteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.
Authors: Donahue JG; Levin TR; Platt R; et al.
Arch Intern Med. 2002 Apr 22;162(8):936-42.
Different slopes for different folks: socioeconomic and racial/ethnic disparities in asthma and hay fever among 173,859 U.S. men and women
Although allergic diseases such as asthma and hay fever are a major cause of morbidity in industrialized countries, most studies have focused on patterns of prevalence among children and adolescents, with relatively few studies on variations in prevalence by race/ethnicity and socioeconomic position among adults. Our study examined racial/ethnic and socioeconomic patterns in the prevalence of asthma overall, asthma with hay fever, asthma without hay fever, and hay fever overall, in a population of 173,859 women and men in a large prepaid health plan in northern California. Using education as a measure of socioeconomic position, we found evidence of a positive gradient for asthma with hay fever with increasing level of education but an inverse gradient for asthma without hay fever. Hay fever was also strongly associated with education. Compared with their White counterparts, Black women and men were more likely to report asthma without hay fever, and Black women were less likely to have asthma with hay fever. Asian men were also more likely to report asthma with hay fever, and Asian women and men were much more likely to have hay fever. Racial/ethnic disparities in prevalence of allergic diseases were largely independent of education. We discuss implications for understanding these social inequalities in allergic disease risk in relation to possible differences in exposure to allergens and determinants of immunologic susceptibility and suggest directions for future research.
Authors: Chen JT; Krieger N; Van Den Eeden SK; Quesenberry CP
Environ Health Perspect. 2002 Apr;110 Suppl 2:211-6.
Hereditary nonpolyposis colorectal cancer in young colorectal cancer patients: high-risk clinic versus population-based registry
BACKGROUND & AIMS: Early onset colorectal cancer (CRC) is an important feature of hereditary nonpolyposis colorectal cancer (HNPCC). We sought to compare rates of genetically defined HNPCC among individuals with early onset CRC drawn from a high-risk clinic and a population-based cancer registry. METHODS: Probands with CRC diagnosed before 36 years of age were enrolled from a high-risk CRC clinic at the University of California, San Francisco (UCSF), and a population-based Kaiser Permanente (KP) Health Plan cancer registry. Probands provided cancer family histories and tumors for microsatellite instability (MSI) testing and MSH2/MLH1 protein immunostaining. Germline MSH2 and MLH1 mutational analysis was performed. RESULTS: Forty-three probands were enrolled from UCSF and 23 from KP. The UCSF and KP probands had similar median age of onset of CRC (30 vs. 31 years) and the percentage with any personal or family history of another HNPCC-related cancer (70% vs. 74%). However, 28 of 40 (70%) of the UCSF tumors were MSI-H compared with 6 of 18 (33%) of KP tumors (P = 0.01), and 13 germline MSH2 or MLH1 mutations were found in the UCSF group compared with 0 in the KP group (P = 0.0001). In a multivariate analysis, institution (P = 0.002) and the total number of colorectal cancers in the family (P = 0.0001) were independent predictors of MSH2 or MLH1 mutation. CONCLUSIONS: Family history of cancer is an important feature of HNPCC, even among individuals with early onset CRC. Caution must be undertaken when extrapolating data regarding HNPCC from high-risk clinic populations to the general population.
Authors: Terdiman JP; Levin TR; Allen BA; Gum JR Jr; Fishbach A; Conrad PG; Miller GA; Weinberg V; Bachman R; Bergoffen J; Stembridge A; Toribara NW; Sleisenger MH; Kim YS
Gastroenterology. 2002 Apr;122(4):940-7.
Surveillance and survival in Barrett’s adenocarcinomas: a population-based study
BACKGROUND & AIMS: Guidelines recommend periodic endoscopic surveillance of Barrett’s esophagus (BE) patients to detect and treat early esophageal adenocarcinomas; however, no trials or population-based studies exist. We evaluated the association between endoscopic surveillance of BE and survival among esophageal/gastric cardia adenocarcinoma patients. METHODS: We studied a cohort of 23 BE patients, among 589 esophageal or gastric cardia adenocarcinoma patients diagnosed between 1990-1998 at Northern California Kaiser Permanente (a large health maintenance organization). We measured the presence of BE, detection of cancer by endoscopic surveillance, cancer stage, mortality, and potential confounders. RESULTS: BE was diagnosed in 135 of 589 adenocarcinoma patients, with 23 BE patients diagnosed greater than 6 months before cancer was diagnosed. Among these 23 patients, 73% of the surveillance-detected cancer patients (n = 15) were alive at the end of follow-up, compared with none of the patients without surveillance-detected cancers (n = 8; P = 0.001). All surveillance-detected cancer patients had low-stage disease and none died directly from cancer. The surveillance/survival association was not substantially altered by stratification for age at BE diagnosis or other potential confounders. CONCLUSIONS: Surveillance-detected BE-associated adenocarcinomas were associated with low-stage disease and improved survival. Additional studies are needed to evaluate potential biases and whether screening/surveillance programs decrease mortality among all patients in surveillance. Few patients (3.9%) had a BE diagnosed before their cancer. Thus, even if current surveillance techniques are effective, they are unlikely to substantially impact the population’s mortality from esophageal cancer; better methods are needed to identify at risk patients.
Authors: Corley DA; Levin TR; Habel LA; Weiss NS; Buffler PA
Gastroenterology. 2002 Mar;122(3):633-40.
CagA status of Helicobacter pylori infection and p53 gene mutations in gastric adenocarcinoma
Infection with Helicobacter pylori (H. pylori) increases stomach cancer risk. Helicobacter pylori strains with the cag pathogenicity island (PAI) induce more severe inflammation in the gastric epithelium and are more strongly associated with stomach cancer risk than strains lacking the PAI. We examined whether the prevalence of somatic p53 mutation in gastric adenocarcinoma differed between subjects with and without infection with CagA(+) (a marker for the PAI) H. pylori strains. DNA from 105 microdissected tumor specimens was analyzed for mutation in exons 5-8 of the p53 gene by polymerase chain reaction-based single-strand conformation polymorphism followed by direct DNA sequencing. Enzyme-linked immunosorbent assays for IgG antibodies against H. pylori and CagA were performed on sera collected 2-31 years prior to cancer diagnosis. Tumors from CagA(+) subjects were significantly more likely to have p53 mutations than tumors from CagA(-) subjects (including H. pylori- and H. pylori(+)/CagA(-)): odds ratio = 3.72; 95% confidence interval, 1.06-13.07 after adjustment for histologic type and anatomic subsite of tumor and age at diagnosis and sex of subjects. Mutations were predominantly insertions and deletions (43%) as well as transition mutations at CpG dinucleotides (33%). The data suggest that CagA(+) H. pylori infection, when compared with CagA(-) infection or the absence of H. pylori infection, is associated with a higher prevalence of p53 mutation in gastric adenocarcinoma.
Authors: Shibata A; Parsonnet J; Longacre TA; Garcia MI; Puligandla B; Davis RE; Vogelman JH; Orentreich N; Habel LA
Carcinogenesis. 2002 Mar;23(3):419-24.
Validation of diagnoses of peptic ulcers and bleeding from administrative databases: a multi-health maintenance organization study
The automated health plan data and data from medical chart abstractions from eight large health maintenance organizations were used to evaluate the positive predictive values (PPVs) of the International Classification of Diseases, 9th revision (ICD-9) codes for cases of peptic ulcers and upper gastrointestinal bleeding. Overall, 207 of 884 cases of peptic ulcers and upper gastrointestinal bleeding (23%) were confirmed by surgery, endoscopy, X-ray, or autopsy. The PPVs were 66% for hospitalizations with codes for duodenal ulcer (ICD-9-CM 532), 61% for gastric/gastrojejunal ulcer (ICD-9-CM 531, 534), 1% for peptic ulcer (ICD-9-CM 533), and 9% for gastrointestinal hemorrhage (ICD-9-CM578). The overall and diagnostic category-specific PPVs were generally similar for the various HMOs. This study, using data from a large number of health plans located in different geographical regions, underscores the importance of evaluating the accuracy of the diagnoses from automated health plan databases.
Authors: Andrade SE; Gurwitz JH; Chan KA; Donahue JG; Beck A; Boles M; Buist DS; Goodman M; LaCroix AZ; Levin TR; Platt R
J Clin Epidemiol. 2002 Mar;55(3):310-3.
Flexible sigmoidoscopy: an important screening option for average-risk individuals
Colorectal cancer screening techniques should be effective, acceptable to patients, affordable, widely available, and safe. For average-risk adults aged more than 50 years who do not have significant colorectal symptoms, significant family history, or significant predisposing conditions, flexible sigmoidoscopy is an important option for reducing the risk for colorectal cancer, meeting all criteria for an effective and feasible screening modality. This article discusses evidence supporting flexible sigmoidoscopy, practical issues in implementation, and current controversies.
Authors: Levin TR; Palitz AM
Gastrointest Endosc Clin N Am. 2002 Jan;12(1):23-40, vi.
Eating frequency and the risk of colon cancer
Eating frequency has been found in most previous studies to have a positive association or no association with colon cancer. We report data from a large case-control study to determine the effect of eating frequency on colon cancer risk. Data were analyzed from interviews of 1,966 cases of colon cancer and 2,380 controls from selected areas in Northern California, Utah, and Minnesota. Respondents were asked whether they usually ate or drank something besides water at eight different occasions during the day. We controlled for age, family history of colorectal cancer, body mass index, physical activity, intake of non-steroidal anti-inflammatory medication, and dietary intake of energy, fiber, and calcium. In fully adjusted models, we found no significant associations between number of daily eating occasions and colon cancer in women. In men, risk of overall colon cancer was lower for one to two times per day (odds ratio = 0.54, 95% confidence interval = 0.36-0.83) than for three times per day, but risk was not increased for more than three times per day. Compared with three times per day, we found no evidence for an association between colon cancer risk and eating frequencies more than three times per day. The increased risk of colon cancer limited to men eating less than three times per day may be due to uncontrolled confounding.
Authors: Coates AO; Potter JD; Caan BJ; Edwards SL; Slattery ML
Nutr Cancer. 2002;43(2):121-6.
The development of a questionnaire to assess past year physical activity in a multi-ethnic/racial urban population
OBJECTIVES: Describe the development of a questionnaire to assess past year physical activity, including activities of daily living, in a multi-ethnic/racial cohort. Describe energy expenditure (EE) patterns in the sample used for questionnaire development. METHODS: 24-hour activity recalls were collected from a convenience sample (N = 367) at four New York City health agencies (October 1999-February 2000). EE was determined at the population, subgroup, and individual level. EE distributions were compared. RESULTS: Activities identified were similar to those on established questionnaires. Subgroup and individual EE differences were noted. Median EE at the Chinese and Puerto Rican sites were lower than those at the Caribbean or Dominican sites. No clear age pattern was apparent. Overall, a greater percentage of daily EE was spent in low intensity activities. The resultant 30-minute interviewer-administered questionnaire ascertains patterns (frequency and duration) of domain-specific (recreational, household, occupational, and transportation) activity. This information combined with published intensity levels provides summary EE measures. CONCLUSION: Variation in EE levels requires information on activity type and amount. Summary activity measures can be used to rank individuals analogous to nutrient food frequency measures.
Authors: Britton JA; Kushi LH; Morabia A; Bernstein J; Shore R; Geringer W; Rohan T
Soz Praventivmed. 2002;47(3):178-94.
Low-energy reporters: evaluation of potential differential reporting in case-control studies
Errors in measuring dietary intake can threaten validity of data. Low-energy reporters (LER) are individuals who report lower levels of energy intake than deemed feasible given their basal metabolic rate and physical activity level (PAL). The purpose of this study was to determine whether LER differ by case/control status or by extent of disease of cases. Data from a large population-based case-control study of colon cancer were used to identify LER. Dietary data were collected using a diet history questionnaire. Age- and gender-specific basal metabolic rate was estimated, and Goldberg cut points were used to estimate plausible energy intake and adjusted for PAL. On the basis of standard methods that do not take PAL into account, 16.7% of male cases, 19.8% of male controls, 20.9% of female cases, and 22.2% of female controls were considered LER. There were no case-control differences in the proportion of LER in men or women when PAL-adjusted cut points were used, although more individuals were considered LER. Likewise, there were no differences in LER by colon cancer disease stage. Excluding LER from the population and assessing associations between energy intake and colon cancer yielded results similar to those observed for the total population. In this population, LER were significantly more likely to be older, never to have smoked cigarettes, to be more physically active, and to be overweight or obese. LER reported fewer total food items than non-LER. There does not appear to be differential reporting of low energy intake by cases and controls or by disease stage among cases. However, LER appear to differ depending on exposure characteristics that may be importantly associated with cancer.
Authors: Slattery ML; Edwards SL; Caan B
Nutr Cancer. 2002;42(2):173-9.
Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation using the Cancer Incidence in Five Continents database
BACKGROUND: Adenocarcinomas of the oesophagus and proximal stomach are the most rapidly increasing malignancies in some countries; however, there are no comparative studies on global disease incidence, and the relationships between these two malignancies are undefined. METHODS: We evaluated the cumulative rates and age-specific incidence rates per 100 000 population for adenocarcinomas of the oesophagus and proximal stomach for all countries in the Cancer Incidence in Five Continents database, and compared them with rates for oesophageal squamous cell carcinoma. RESULTS: Substantial variations in cumulative cancer rates were found between genders, between countries, between different ethnicities within the same country, and within the same ethnicity residing in different countries. Cumulative rates (ages 0-74 years) for oesophageal adenocarcinoma varied from 0 (e.g. Thailand) to 0.6 (Scotland, males, 95% CI : 0.56, 0.64); for proximal stomach cancer from 0 (Singapore, Malay females, 95% CI : -0.01, 0.11) to 0.52 (The Netherlands, males, 95% CI : 0.49, 0.55); and for oesophageal squamous cell carcinomas from 0 (non-Jews in Israel, females) to 1.84 (Brazil, Porto Alegre, males, 95% CI : 1.42, 2.26). There was a continuous increase in age-specific incidence rates with advancing age for oesophageal/proximal stomach adenocarcinomas, but a decrease in age-specific incidence rates for oesophageal squamous cell carcinoma after age 75 years. The cumulative rate trends for adenocarcinomas of the oesophagus and proximal stomach were often dissimilar, and varied by country, gender, and ethnicity. CONCLUSIONS: These results suggest that different risk factors may be associated with adenocarcinomas of the oesophagus versus the proximal stomach; the marked rate variation implies a substantial environmental component to the recent incidence changes.
Authors: Corley DA; Buffler PA
Int J Epidemiol. 2001 Dec;30(6):1415-25.
Quality of life measurement clarifies the cost-effectiveness of Helicobacter pylori eradication in peptic ulcer disease and uninvestigated dyspepsia
OBJECTIVES: Previous economic studies of Helicobacter pylori eradication in dyspepsia and peptic ulcer disease have not measured quality of life using utilities (preference probabilities), which are needed to compare the cost-effectiveness of such treatment to other health care interventions. The goals of this study were to measure quality of life in patients with dyspepsia or peptic ulcer and apply these measurements to published models of disease management to determine cost-effectiveness in dollars per quality-adjusted life year (QALY) gained. METHODS: Utilities for dyspepsia and peptic ulcer disease were measured in adult patients (n = 73) on chronic acid suppression for peptic ulcer or ulcer-like dyspepsia. Median utility values were applied to the results of published cost-effectiveness analyses and a previously validated dyspepsia model. Cost-utility ratios for early H. pylori eradication in uninvestigated dyspepsia and peptic ulcer disease were then computed. RESULTS: The total disutility, or lost quality of life, for an ulcer was 0.11 QALY, of which 0.09 QALY was attributed to dyspeptic symptoms. After these results were incorporated into published studies, cost-utility ratios for ulcer treatment varied from $3,100 to $12,500 per QALY gained, whereas estimates for uninvestigated dyspepsia management ranged from $26,800 to $59,400 per QALY. Sensitivity analyses indicated a range of $1,300 to $27,300 per QALY for management of duodenal ulcer and $15,000 to $129,700 per QALY for dyspepsia. CONCLUSIONS: Strategies that emphasize early H. pylori eradication were cost-effective for patients with peptic ulcer and possibly cost-effective for patients with uninvestigated dyspepsia, relative to other medical interventions. Dyspeptic symptoms cause significant disutility that should be incorporated in future cost-effectiveness analyses of treatment strategies.
Authors: Groeneveld PW; Lieu TA; Fendrick AM; Hurley LB; Ackerson LM; Levin TR; Allison JE
Am J Gastroenterol. 2001 Feb;96(2):338-47.
Reduction in fat intake is not associated with weight loss in most women after breast cancer diagnosis: evidence from a randomized controlled trial
BACKGROUND: A reduction in dietary fat intake has been suggested as a method to promote weight loss in women at risk for breast cancer recurrence. METHODS: Weight change in response to diet intervention was examined in 1010 women who had completed treatment for Stage I, Stage II, or Stage IIIA (American Joint Committee on Cancer staging system) primary operable breast cancer during their first year of participation in a randomized, controlled, diet intervention trial to reduce risk of recurrence. Diet intervention was performed by telephone counseling and promoted a low fat diet that also was high in fiber, vegetables, and fruit. The comparison group was provided with general dietary guidelines to reduce disease risk. Multiple linear regression models were used to examine the relations among demographic and personal characteristics, changes in diet composition and exercise level, and change in body weight or body mass index. RESULTS: The average weight change in the 1-year period was 0.04 kg for the intervention group and 0.46 kg for the comparison group. For the total group, body weight was stable (+/- 5% baseline weight) for 743 women (74%), whereas 114 (11%) lost weight, and 153 (15%) gained weight. These distributions were similar in the two study groups inclusive of all study participants and for only those women with a baseline body mass index of > or = 25 kg/m2. Initial body mass index and changes in fiber and vegetable intakes, but not change in percent of energy obtained from fat, were associated independently with change in weight or body mass index. CONCLUSIONS: For most women at risk for breast cancer recurrence, diet intervention to promote a reduction in fat intake was not associated with significant weight loss. Testing the effect of a substantial change in diet composition on risk for breast cancer recurrence is unlikely to be confounded by weight loss in subjects who were the recipients of intensive intervention efforts.
Authors: Rock CL; Thomson C; Caan BJ; Flatt SW; Newman V; Ritenbaugh C; Marshall JR; Hollenbach KA; Stefanick ML; Pierce JP
Cancer. 2001 Jan 1;91(1):25-34.
Histological classification of gastric adenocarcinoma for epidemiological research: concordance between pathologists
Epidemiology of gastric adenocarcinoma suggests that intestinal-type and diffuse-type cancers develop through distinct causal pathways. To examine the differences in risk factors and molecular changes between the histological types, reliable data on histological typing are essential. We evaluated the concordance between two pathologists in assessment of 95 gastric adenocarcinomas for Lauren classification and tumor grade. Two pathologists, each blinded to the other’s assessment, reviewed H&E-stained slides of gastric tumor. The responses of the two pathologists for histological type were considered as concordant if they fell on one of the three categories (intestinal type, diffuse type, or other). Tumor grade was classified into three categories (well, moderately, or poorly differentiated). The pathologists agreed on the classification of histological type for 71 of 92 (77%) tumors. Kappa coefficient was 0.59 (95% confidence interval, 0.44-0.73). Concordance for tumor grade was 87%, with a kappa coefficient of 0.72 (95% confidence interval, 0.57-0.87). Both observed concordance and kappa coefficient for histological type and tumor grade were similar across three calendar periods of study. Interobserver agreement was virtually identical between tumors with biopsy specimens only and those with surgical specimens. Although the level of disagreement for histological type observed in this study is comparable with that in other studies, the resulting misclassification would lead to the reduction in observed differences in prevalence and odds ratio estimates between two histological types.
Authors: Shibata A; Longacre TA; Puligandla B; Parsonnet J; Habel LA
Cancer Epidemiol Biomarkers Prev. 2001 Jan;10(1):75-8.
Risk factors for cervical stenosis after loop electrocautery excision procedure.
OBJECTIVE: To assess frequency of and identify risk factors for the development of cervical stenosis after loop electrosurgical excision procedure. METHODS: We reviewed outpatient charts of women treated by loop excision for cervical dysplasia between August 1996 and January 1998 in the colposcopy clinic at Massachusetts General Hospital. One hundred sixty-four women were evaluated for cervical stenosis during follow-up. Stenosis was considered present if manual dilation was required to allow endocervical sampling with an endocervical currette 3 mm wide. Multivariable analysis with stepwise logistic regression was used to evaluate age, parity, tobacco use, hormonal status, use of oral contraceptives, pathology, previous loop excision, performance of additional endocervical excision, and dimensions of excision specimens as predictors of cervical stenosis. RESULTS: The average age was 32 years. Cervical stenosis occurred in ten of 164 women (6%, 95% CI 3%, 11%). Among factors analyzed, previous loop excision and volume of excision specimen were the only independent predictors of stenosis. CONCLUSION: Cervical stenosis correlated with history of loop excision and volume of tissue removed, suggesting that women who have second excisions or large excisions should be counseled that their risk of stenosis might be higher.
Authors: Suh-Burgmann EJ; Whall-Strojwas D; Chang Y; Hundley D; Goodman A
Obstet Gynecol. 2000 Nov;96(5 Pt 1):657-60.
Low-energy reporting in women at risk for breast cancer recurrence. Women’s Healthy Eating and Living Group
This study examined the extent of low-energy reporting and its relationship with demographic and lifestyle factors in women previously treated for breast cancer. This study used data from a large multisite clinical trial testing the efficacy of a dietary intervention to reduce risk for breast cancer recurrence (Women’s Healthy Eating and Living Study). Using the Schofield equation to estimate energy needs and four 24-h dietary recalls to estimate energy intakes, we identified women who reported lower than expected energy intakes using criteria developed by G. R. Goldberg et al. (Eur. J. Clin. Nutr., 45: 569-581, 1991). We examined data from 1137 women diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer. Women were 18-70 years of age at diagnosis and were enrolled in the Women’s Healthy Eating and Living Study between August 19, 1995, and April 1, 1998, within 4 years after diagnosis. The Goldberg criteria classified about one-quarter (25.6%) as low-energy reporters (LERs) and 10.8% as very LERs. Women who had a body mass index >30 were almost twice (odds ratio, 1.95) as likely to be LERs. Women with a history of weight gain or weight fluctuations were one and a half times as likely (odds ratio, 1.55) to be LERs as those who were weight stable or weight losers. Age, ethnicity, alcohol intake, supplement use, and exercise level were also related to LER. Characteristics (such as body mass index, age, ethnicity, and weight history) that are associated with low-energy reporting in this group of cancer survivors are similar to those observed in other populations and might affect observed diet and breast cancer associations in epidemiological studies.
Authors: Caan BJ; Flatt SW; Rock CL; Ritenbaugh C; Newman V; Pierce JP
Cancer Epidemiol Biomarkers Prev. 2000 Oct;9(10):1091-7.
RESPONSE: patient costs on clinical trials
Authors: Fireman B; Fehrenbacher L; Ray GT
J Natl Cancer Inst. 2000 Sep 06;92(17):1442-3.
Interplay between dietary inducers of GST and the GSTM-1 genotype in colon cancer
The purpose of this study is to determine if cruciferous vegetables and coffee, two dietary inducers of glutatione-S-transferases, interact with GSTM-1 genotype to alter risk of colon cancer. Data were available on 1579 incident cases of adenocarcinoma of the colon and 1898 population-based controls. Intake of cruciferous vegetables, specific types of cruciferous vegetable, and coffee were not associated with colon cancer; GSTM-1 genotype did not modify these associations. However, age at diagnosis and cigarette smoking appeared to be important effect modifiers of the associations between GSTM-1, cruciferous vegetables and colon cancer. Among GSTM-1 null individuals, <55 years at diagnosis, we observed an inverse association between colon cancer and high levels of cruciferous vegetable intake relative to people who did not eat cruciferous vegetables (ORs 0.23 95% CI 0.10-0.54); broccoli was the cruciferous vegetable associated with the strongest inverse association (OR 0.30 95% CI 0.13-0.70). Among younger individuals who were GSTM-1 present (relative to those with GSTM-1 null), we observed an inverse association with colon cancer regardless of level of cruciferous vegetable intake (OR 0.74 95% CI 0.30-1.79 for no intake; OR 0.44 95% CI 0.21-0.92 for <4 servings/week; and OR 0. 44 95% CI 0.19-0.99 for >/=4 servings/week). These associations were further modified by cigarette smoking. People <65 years of age who smoked had a greater reduction in risk of colon cancer from consumption of cruciferous vegetables than non-smokers at the same age. In summary, although cruciferous vegetables do not appear to modify colon cancer risk in the total population, there are subgroups of the population for whom these vegetables may be important. These subgroups are defined mostly by age and smoking status.
Authors: Slattery ML; Kampman E; Samowitz W; Caan BJ; Potter JD
Int J Cancer. 2000 Sep 1;87(5):728-33.
Body size, age at shaving initiation, and prostate cancer in a large, multiracial cohort
BACKGROUND: The purpose of this study was to examine the potential relationship between body size, self-reported age at initiation of shaving, and subsequent risk of prostate cancer in a large, racially diverse cohort of men followed for up to 32 years. METHODS: The study population included 70,712 male subscribers to the Kaiser Permanente Medical Care Program who had received a multiphasic health checkup between 1964-1973. This general health checkup consisted of a number of laboratory tests and physical measurements, as well as a self-completed health questionnaire that included a request for men to record the age when they began shaving. Subjects were followed for the development of prostate cancer, using the local tumor registry. Cox regression was used to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS: Altogether, 2, 079 men in the study cohort were diagnosed with prostate cancer. There was a very strong positive association between prostate cancer risk and birth cohort. After adjusting for race, age, and birth year, there was no association between height, weight, body mass index, or several other anthropometric measures and prostate cancer risk in the full cohort. There was a suggestion of a very weak positive association between height and prostate cancer risk among white men. There also was no overall association between age at shaving initiation and prostate cancer risk, although nonwhite men who started shaving at a young age (
Authors: Habel LA; Van Den Eeden SK; Friedman GD
Prostate. 2000 May 1;43(2):136-43.
Calcium, vitamin D, sunshine exposure, dairy products and colon cancer risk (United States)
OBJECTIVE: Epidemiologic studies on calcium, vitamin D and colon cancer are inconsistent, whereas experimental studies more regularly show a protective effect. To evaluate potential sources of inconsistencies, data from a large case-control study were analyzed, stratifying on potential effect modifiers. METHODS: Data were collected by certified interviewers in Northern California, Utah and Minnesota. Analyses included 1993 incident colon cancer cases and 2410 population-based controls. Multivariate logistic regression models included age, sex, BMI, family history, physical activity, intake of energy, dietary fiber, aspirin and NSAIDs. RESULTS: Dietary calcium was inversely associated with colon cancer risk in men (OR highest vs lowest quintile = 0.6, 95% CI = 0.5-0.9) and women (OR = 0.6, 95% CI = 0.4-0.9). No statistically significant associations were observed for dietary vitamin D or sunshine exposure. Consumption of total low-fat dairy products was associated with a statistically significantly decreased risk in men and women (ORs highest vs lowest category of intake = 0.8 and 0.7 respectively). Calcium supplement use was inversely associated with risk in both sexes (ORs use vs non-use = 0.8). Vitamin D supplements were inversely associated with risk in men (OR = 0.5) and women (OR = 0.6) but confidence limits included 1.0. CONCLUSIONS: These data provide additional support of an inverse association between high levels of calcium intake and colon cancer risk.
Authors: Kampman E; Slattery ML; Caan B; Potter JD
Cancer Causes Control. 2000 May;11(5):459-66.
Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group
BACKGROUND: We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers. METHODS: We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization. RESULTS: A total of 1905 of the randomized subjects (91.6 percent) completed the study. Of the 958 subjects in the intervention group and the 947 in the control group who completed the study, 39.7 percent and 39.5 percent, respectively, had at least one recurrent adenoma; the unadjusted risk ratio was 1.00 (95 percent confidence interval, 0.90 to 1.12). Among subjects with recurrent adenomas, the mean (+/-SE) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group. The rate of recurrence of large adenomas (with a maximal diameter of at least 1 cm) and advanced adenomas (defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high-grade dysplasia, including carcinoma) did not differ significantly between the two groups. CONCLUSIONS: Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas.
Authors: Schatzkin A; Caan B; Cahill J; et al.
N Engl J Med. 2000 Apr 20;342(16):1149-55.
Cimetidine use and risk of breast, prostate, and other cancers
Purpose – The study was conducted to examine whether use of cimetidine is associated with the risk of cancer, with special attention to cancers of the breast and prostate because cimetidine increases estradiol levels and interferes with androgen binding. Methods – Individuals who received a prescription of cimetidine were identified from two computerized pharmacy databases of medications dispensed at Northern California Kaiser Permanente between 1982 and 1987. Users of ranitidine, a histamine-2 receptor antagonist that does not appear to influence estrogen levels or androgen binding, and non-users of either cimetidine or ranitidine, were also identified from these databases. Study subjects were followed through December 1995 for new diagnoses of cancer. Cox regression was used to estimate relative risks of cancer associated with use of cimetidine and ranitidine. Non-users of cimetidine and ranitidine were the referent group for all analyses. Result – While there were very modest increases and decreases in risk for some cancer sites among cimetidine users, most were within the limits of chance given no true association. Furthermore, similar risks of these cancers were also observed among ranitidine users. Conclusions – Although our results do not support an association between cancer risk and cimetidine use, it is one of the most widely prescribed drugs in the US and may now be purchased over-the-counter. The potential effect of cimetidine on risk of cancer, especially those that are hormone-related, should continue to be monitored, preferably in larger study populations. Copyright (c) 2000 John Wiley & Sons, Ltd.
Authors: Habel LA; Levin TR; Friedman GD
Pharmacoepidemiol Drug Saf. 2000 Mar;9(2):149-55.
The cost of health conditions in a health maintenance organization
In this retrospective cohort analysis of all adults who were members of Kaiser Permanente, Northern California, between July 1995 and June 1996 (N = 2,076,303), the authors estimated the prevalence, average annual costs per person, and percentage of total direct medical expenditures attributable to each of 25 chronic and acute conditions. Ordinary least squares regression was used to adjust for age, gender, and comorbidities. The costs attributable to the 25 conditions accounted for 78 percent of the health maintenance organization’s total direct medical expense for this age-group. Injury accounted for a higher proportion (11.5 percent) of expenditures than any other single condition. Three cardiovascular conditions–ischemic heart disease, hypertension, and congestive heart failure–together accounted for 17 percent of direct medical expense and separately accounted for 6.8 percent, 5.7 percent, and 4.0 percent, respectively. Renal failure ($22,636), colorectal cancer ($10,506), pneumonia ($9,499), and lung cancer ($8,612) were the most expensive conditions per person per year.
Authors: Ray GT; Collin F; Lieu T; Fireman B; Colby CJ; Quesenberry CP; Van Den Eeden SK; Selby JV
Med Care Res Rev. 2000 Mar;57(1):92-109.
Work loss costs due to peptic ulcer disease and gastroesophageal reflux disease in a health maintenance organization
OBJECTIVE: The aim of this study was to estimate the value of work time and productivity loss because of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). METHODS: A total of 300 adult members of Northern California Kaiser Permanente Medical Care Program with outpatient diagnoses of PUD or GERD were randomly selected for a record review to confirm diagnosis. A telephone survey was conducted soliciting information about work loss because of their disease. Reported work losses were valued at self-reported hourly wage to derive work loss costs. A total of 117 PUD and 102 GERD patients participated. RESULTS: About 75% of each sample was employed full-time or part-time. In all, 42% of potentially working PUD patients and 41% of GERD patients reported some lost work productivity because of their disease. The average loss (per person working) was $606 for PUD and $237 for GERD over a 3-month period. Reduced productivity while at work and part-time work because of the disease were the most costly productivity losses for PUD, whereas time off for physician visits and reduced productivity while at work were the most costly losses for GERD. CONCLUSIONS: Work loss costs for patients with PUD and GERD may be nearly as large as direct medical care costs, and are consistent with the more acute nature of PUD and the chronic pattern of GERD. The work losses resulting from these diseases are large enough to warrant consideration in guideline development and policy decisions for patients with PUD and GERD.
Authors: Henke CJ; Levin TR; Henning JM; Potter LP
Am J Gastroenterol. 2000 Mar;95(3):788-92.
Epidemiology of ductal carcinoma in situ
Authors: Habel LA
Semin Breast Dis. 2000;3:187-99.
Western diet, family history of colorectal cancer, NAT2, GSTM-1 and risk of colon cancer
OBJECTIVE: In this study we examine the combined effects of Western diet, age at diagnosis, and genetic susceptibility. METHODS: We use data collected as part of an incident case-control study of colon cancer. Family history of colorectal cancer, N-acetyltransferase (NAT2), and glutathione-S-transferase (GSTM-1) are studied with Western diet and age at diagnosis. RESULTS: A significant interaction between age at time of diagnosis, Western dietary pattern, and family history of colorectal cancer (p for interaction = 0.03) was detected. Those with a family history of colorectal cancer who ate a predominantly Western diet were at increased risk of colon cancer (OR 14.0, 95% CI 3.9-50.1 for < or = 55 years; OR 7.7, 95% CI 2.0-29.1 for 56-66 years; OR 1.6, 95% CI 0.8-3.2 for > or = 67 years) compared to those without a family history of colorectal cancer and low levels of a Western diet. Associations with the Western diet were stronger than individual components of the dietary pattern. Neither NAT2 nor GSTM-1 showed significant interaction with Western diet. CONCLUSION: The extent to which diet comprising a Western dietary pattern influences risk of colon cancer is dependent on age. This dietary pattern also appears to modulate the colon cancer risk associated with a family history of colon cancer.
Authors: Slattery ML; Potter JD; Ma KN; Caan BJ; Leppert M; Samowitz W
Cancer Causes Control. 2000 Jan;11(1):1-8.
Does nutritionist review of a self-administered food frequency questionnaire improve data quality?
OBJECTIVE: This study sought to evaluate the benefit of utilizing a nutritionist review of a self-administered food frequency questionnaire (FFQ), to determine whether accuracy could be improved beyond that produced by the self-administered questionnaire alone. DESIGN: Participants randomized into a dietary intervention trial completed both a FFQ and a 4-day food record (FR) at baseline before entry into the intervention. The FFQ was self-administered, photocopied and then reviewed by a nutritionist who used additional probes to help complete the questionnaire. Both the versions before nutritionist review and after nutritionist review – were individually compared on specific nutrients to the FR by means, correlations and per cent agreement into quintiles. SETTINGS AND SUBJECTS: Three hundred and twenty-four people, a subset of participants from the Polyp Prevention Trial – a randomized controlled trial examining the effect of a low-fat, high-fibre, high fruit and vegetable dietary pattern on the recurrence of adenomatous polyps – were recruited from clinical centres at the University of Utah, University of Buffalo, Memorial Sloan Kettering Cancer Center in New York and Kaiser Permanente Medical Program in Oakland. RESULTS: Reviewing the FFQ increased correlations with the FR for every nutrient, and per cent agreement into quintiles for all nutrients except calcium. Energy was underestimated in both versions of the FFQ but to a lesser degree in the version with review. CONCLUSIONS: One must further evaluate whether the increases seen with nutritionist review of the FFQ will enhance our ability to predict diet-disease relationships and whether it is cost-effective when participant burden and money spent utilizing trained personnel are considered.
Authors: Caan BJ; Lanza E; Schatzkin A; Coates AO; Brewer BK; Slattery ML; Marshall JR; Bloch A
Public Health Nutr. 1999 Dec;2(4):565-9.
Lifestyle and colon cancer: an assessment of factors associated with risk
Studies of the etiology of colon cancer indicate that it is strongly associated with diet and lifestyle factors. The authors use data from a population-based study conducted in northern California, Utah, and Minnesota in 1991-1995 to determine lifestyle patterns and their association with colon cancer. Data obtained from 1,993 cases and 2,410 controls were grouped by using factor analyses to describe various aspects of lifestyle patterns. The first five lifestyle patterns for both men and women loaded heavily on dietary variables and were labeled: ‘Western,’ ‘moderation,’ ‘calcium/low-fat dairy;’ ‘meat and mutagens,’ and ‘nibblers, smoking, and coffee.’ Other important lifestyle patterns that emerged were labeled ‘body size,’ ‘medication and supplementation,’ ‘alcohol,’ and ‘physical activity.’ Among both men and women, the lifestyle characterized by high levels of physical activity was the most marked lifestyle associated with colon cancer (odds ratios = 0.42, 95% confidence interval: 0.32, 0.55 and odds ratio = 0.52, 95% confidence interval: 0.39, 0.69, for men and women, respectively) followed by medication and supplementation (odds ratio = 1.68, 95% confidence interval: 1.29, 2.18 and odds ratio = 1.63, 95% CI 1.23, 2.16, respectively). Other lifestyles that were associated with colon cancer were the Western lifestyle, the lifestyle characterized by large body size, and the one characterized by calcium and low-fat dairy. Different lifestyle patterns appear to have age- and tumor site-specific associations.
Authors: Slattery ML; Edwards SL; Boucher KM; Anderson K; Caan BJ
Am J Epidemiol. 1999 Oct 15;150(8):869-77.
Colorectal cancer screening: new opportunities
Colorectal cancer is the third most common cancer among men and women in the United States, and the third leading cause of cancer death. Strategies currently available to screen for colorectal cancer include fecal occult blood tests, sigmoidoscopy, or both tests used in combination. Colonoscopy and double contrast barium enema are potentially preferable options because they offer improved sensitivity over currently available tests, but the feasibility of these tests for population screening remains in doubt. Future opportunities for screening include focusing special efforts to deliver screening to higher risk individuals based on family history or age and the use of molecular or computer-aided radiographic techniques as alternatives to colonoscopy.
Authors: Levin TR
Surg Oncol Clin N Am. 1999 Oct;8(4):673-91, vi-vii.
Hormone replacement therapy and improved survival among postmenopausal women diagnosed with colon cancer (USA)
OBJECTIVES: Hormone replacement therapy (HRT) has been inversely associated with colon cancer incidence in several epidemiologic studies. In this study we used data from a population-based incident case-control study of colon cancer to evaluate the role of HRT use in survival after diagnosis with colon cancer. METHODS: Data from 815 postmenopausal women living in Utah, California, and Minnesota diagnosed between 1 September 1991 and 30 September 1994 were used to examine associations between HRT and survival. RESULTS: After adjusting for age at time of diagnosis, stage of disease at time of diagnosis, study center, and body mass index (BMI), we observed that women who had ever used HRT had a 30% lesser probability of dying of any cause and a 40% lower probability of dying from colon cancer specifically during the follow-up period. Further evaluation by years of HRT use showed that those who had used HRT for 4 or more years had the lowest risk of dying of colon cancer (hazard rate ratio 0.5, 95% confidence interval 0.3-0.9). Evaluation of other lifestyle variables with HRT use did not show significant confounding or effect modification. CONCLUSIONS: These findings suggest that HRT use may improve short-term survival after diagnosis with colon cancer; there is no suggestion that HRT use is detrimental to survival.
Authors: Slattery ML; Anderson K; Samowitz W; Edwards SL; Curtin K; Caan B; Potter JD
Cancer Causes Control. 1999 Oct;10(5):467-73.
Factors associated with weight gain in women after diagnosis of breast cancer. Women’s Healthy Eating and Living Study Group
OBJECTIVE: To identify the factors associated with weight gain after diagnosis of breast cancer in a heterogeneous population of women. DESIGN: Descriptive cross-sectional study. SUBJECTS: 1,116 patients who had been diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer within the previous 4 years. Patients were recruited during enrollment into a diet intervention trial to reduce risk for breast cancer recurrence. Analysis Demographic data, weight history, and physical activity information obtained by questionnaire and medical information obtained by chart review; dietary assessment based on four 24-hour dietary recalls collected by telephone. Associations between weight change after the diagnosis of breast cancer and prediction variables were examined using univariate and multiple linear regression analyses. RESULTS: Overall, 60% of the subjects reported weight gain, 26% reported weight loss, and 14% reported no change in weight after the diagnosis of breast cancer. The overall mean weight change was a gain of 2.7 kg (6 lb). Factors positively and independently associated with weight gain were time since diagnosis of breast cancer, adjuvant chemotherapy, African-American ethnicity, current energy intake, and postmenopausal status at time of study entry. Factors inversely and independently associated with weight gain were prediagnosis body mass index, age at diagnosis, education level, and exercise index score. APPLICATIONS: Higher energy intake and lower level of physical activity are independently associated with increased risk for weight gain after the diagnosis of breast cancer. Strategies to modify these behaviors are likely to influence the long-term pattern of weight change.
Authors: Rock CL; Flatt SW; Newman V; Caan BJ; Haan MN; Stefanick ML; Faerber S; Pierce JP
J Am Diet Assoc. 1999 Oct;99(10):1212-21.
Surveillance for endometrial cancer in women receiving tamoxifen.
Recent studies showing a protective effect of tamoxifen in women at high risk for breast cancer have expanded the indications of the drug. While acting as an estrogen antagonist in the breast, tamoxifen can have estrogenic effects on the endometrium; consensus opinion is that tamoxifen increases the risk for endometrial cancer. Because an increasing number of women are taking tamoxifen, a strategy for gynecologic surveillance is needed. Studies examining the relation between risk for endometrial cancer and tamoxifen use have conflicting results. However, because of an overall interpretation that tamoxifen use slightly increases risk for endometrial cancer, some researchers advocate routine ultrasonography and endometrial biopsy for screening asymptomatic women receiving tamoxifen. This paper reviews the literature on endometrial cancer in women taking tamoxifen and the usefulness of various screening methods in this setting. Risk factors and screening criteria for endometrial cancer in the general population are discussed, and a strategy for surveillance of women taking tamoxifen is proposed. Patients should be screened for signs or symptoms of endometrial abnormality before taking tamoxifen. This evaluation, which should include a careful history, pelvic examination, and Papanicolaou smear, should be repeated annually while the patient is receiving tamoxifen. Although transvaginal ultrasonography is not recommended for routine screening, it is indicated if an adequate pelvic examination cannot be performed or if additional risk factors are present. The likelihood of abnormality is greater for patients who have abnormal bleeding, discharge, abnormal glandular cells on Papanicolaou smear, or an endometrial measurement on ultrasonography of more than 8 mm; these findings should prompt an aggressive evaluation of the endometrium.
Authors: Suh-Burgmann EJ; Goodman A
Ann Intern Med. 1999 Jul 20;131(2):127-35. doi: 10.7326/0003-4819-131-2-199907200-00009.
Expression of the HPV E7 oncoprotein mimics but does not evoke a p53-dependent cellular DNA damage response pathway.
Acute expression of the human papillomavirus E7 oncoprotein in preimmortal human fibroblasts induces changes in the abundances of multiple cellular regulatory proteins. These alterations include a destabilization of the retinoblastoma tumor suppressor protein pRB, stabilization of the tumor suppressor protein p53, and increases in the level of the cyclin-dependent kinase inhibitor p21(cip1). Since the HPV E7 oncoproteins can interfere with several cell cycle checkpoints and similar alterations in the levels of pRB, p53, and p21(cip1) are also observed in a p53-dependent response to DNA damage, we investigated whether E7 expression triggers this signal transduction pathway. The results demonstrate that E7-mediated destabilization of pRB does not require p53 activity and is independent of the ability of E7 to induce apoptosis. Moreover, E7-mediated increases in p21(cip1) levels are largely p53-independent and involve stabilization of the p21(cip1) protein. In contrast the decreases in pRB expression in response to DNA damage involve transcriptional downregulation of RB gene expression.
Authors: Jones DL; Thompson DA; Suh-Burgmann E; Grace M; Munger K
Virology. 1999 Jun 5;258(2):406-14. doi: 10.1006/viro.1999.9733.
Barbiturates and lung cancer: a re-evaluation
BACKGROUND: Barbiturates, particularly phenobarbital, have been shown to be a tumour promoter in animal experiments and were found to be associated with increased risk of lung cancer in our cohort follow-up study to screen pharmaceuticals for possible carcinogenic effects. Sixteen more years of follow-up have accumulated permitting a more detailed evaluation of this association. METHODS: In all, 10,213 subscribers of the Kaiser Permanente Medical Care Program who received barbiturates between 1969 and 1973 from its San Francisco pharmacy were followed up through 1992 and their incidence of lung cancer at biennial intervals was compared with what was expected based on the experience of the entire pharmacy cohort (143,594). Smoking-habit data were available on about half of the barbiturate users and were used to adjust for cigarette smoking in both the observed/expected analysis and in Cox proportional hazards analysis. RESULTS: The initially elevated standard morbidity ratio of 1.55 (95% CI: 1.25-1.91) with 3-7 years of follow-up gradually decreased and stabilized at about 1.3 after 11-15 years of follow-up. This trend for diminishing relative risk over time was more pronounced among the never smokers but their initial excess risk was not statistically significant due to small numbers. A dose-response trend was observed, based on the number of prescriptions dispensed. Analytical control for cigarette smoking reduced but did not eliminate either the association or the dose-response trend. Most of the barbiturate-associated cases in never smokers were women and the predominant histological type was adenocarcinoma. CONCLUSIONS: These findings from up to 23 years of follow-up are not conclusive because of the continuing small number of never smokers who developed lung cancer. However, they strengthen and refine previous observations of a barbiturate-lung cancer association, which is probably not fully explained by confounding by cigarette smoking. The diminution of excess risk over time is consistent with a tumour promoter effect. Findings among the never smokers suggest that this possible effect may be greatest on adenocarcinomas in women.
Authors: Friedman GD; Habel LA
Int J Epidemiol. 1999 Jun;28(3):375-9.
Survival and treatment for colorectal cancer Medicare patients in two group/staff health maintenance organizations and the fee-for-service setting
The current study compares treatment use and long-term survival in colorectal cancer patients between Medicare beneficiaries enrolled in two large prepaid group/staff health maintenance organizations (HMOs) and the fee-for-service (FFS) setting. The study is based on 15,352 colorectal cancer cases diagnosed between 1985 and 1992 and followed through 1995. Survival differences between the HMO and FFS cases were assessed using Cox regression. Treatment differences were evaluated using logistic regression. HMO cases had a lower overall mortality than did FFS cases but not a significantly lower colorectal cancer-specific mortality. Use of surgical resection was similar between HMO and FFS cases. However, rectal cancer cases in the HMOs were more likely to receive postsurgical radiation therapy than FFS cases. Superior overall survival in the HMOs may be the result of increased colorectal cancer screening, greater use of adjuvant therapies, and selection of healthier individuals.
Authors: Merrill RM; Brown ML; Potosky AL; Riley G; Taplin SH; Barlow W; Fireman BH
Med Care Res Rev. 1999 Jun;56(2):177-96.
Prostate cancer treatment and ten-year survival among group/staff HMO and fee-for-service Medicare patients
OBJECTIVE: To compare treatment patterns and the ten-year survival of prostate cancer patients in two large, nonprofit, group/staff HMOs to those of patients receiving care in the fee-for-service health setting. DATA SOURCES/STUDY DESIGN: A cohort of men age 65 and over diagnosed with prostate cancer between 1985 and the end of 1992 and followed through 1994. Subjects (n = 21,741) were ascertained by two population-based tumor registries covering the greater San Francisco-Oakland and Seattle-Puget Sound areas. Linkage of registry data with Medicare claims data and with HMO inpatient utilization data allowed the determination of health plan enrollment and the measurement of comorbid conditions. Multivariate regression models were used to examine HMO versus FFS treatment and survival differences adjusting for sociodemographic and clinical characteristics. PRINCIPAL FINDINGS: Among cases with non-metastatic prostate cancer, HMO patients were more likely than FFS patients to receive aggressive therapy (either prostatectomy or radiation) in San Francisco-Oakland (odds ratio [OR] = 1.69, 95% CI = 1.46-1.96) but not in Seattle (OR = 1.15, 0.93-1.43). Among men receiving aggressive therapy, HMO cases were three to five times more likely to receive radiation therapy than prostatectomy. Overall mortality was equivalent over ten years (HMO versus FFS mortality risk ratio [RR] = 1.01, 0.94-1.08), but prostate cancer mortality was higher for HMO cases than for FFS cases (RR = 1.25, 1.13-1.39). CONCLUSION: Despite marked treatment differences for clinically localized prostate cancer, overall ten-year survival for patients enrolled in two nonprofit group/staff HMOs was equivalent to survival among patients receiving care in the FFS setting, even after adjustment for sociodemographic and clinical characteristics. Similar overall but better prostate cancer-specific survival among FFS patients is most plausibly explained by differences between the HMO and FFS patients in both tumor characteristics and unmeasured patient selection factors.
Authors: Potosky AL; Merrill RM; Riley GF; Taplin SH; Barlow W; Fireman BH; Lubitz JD
Health Serv Res. 1999 Jun;34(2):525-46.
Predicting advanced proximal colonic neoplasia with screening sigmoidoscopy
CONTEXT: Indications are not well defined for follow-up colonoscopy for all patients with distal colonic tubular adenomas (TAs) found at screening sigmoidoscopy. OBJECTIVE: To determine whether distal adenoma size, number, and villous histology, along with family history and age, are predictors of advanced proximal colonic neoplasia. DESIGN: Cross-sectional analysis conducted between January 1, 1994, and December 31, 1995. SETTING: Large group-model health maintenance organization in northern California. PATIENTS: A total of 2972 asymptomatic subjects aged 50 years or older undergoing colonoscopy as follow-up to a screening sigmoidoscopy. MAIN OUTCOME MEASURE: Based on sigmoidoscopy, colonoscopy, and pathology reports, occurrence of advanced proximal neoplasia, defined as adenocarcinoma or TAs 1 cm or larger or with villous features or severe dysplasia located beyond sigmoidoscopic view. RESULTS: The prevalence of advanced proximal neoplasia was similar among patients with no TAs at sigmoidoscopy, those with TAs less than 1 cm in diameter, and those with TAs 1 cm in diameter or larger (prevalence, 5.3%, 5.5%, and 5.6%, respectively). Of patients with a distal tubulovillous or villous adenoma, 12.1% had advanced proximal neoplasia. In multivariate analyses, having a distal tubulovillous adenoma or villous adenoma was the strongest predictor of advanced proximal neoplasia (odds ratio, 2.30; 95% confidence interval, 1.69-3.14). Age of 65 years or older, having more than 1 adenoma, and a positive family history of colorectal cancer were also significant predictors. Distal adenoma size was not a significant predictor in any multivariate analyses. CONCLUSIONS: Advanced proximal neoplasia is not uncommon in subjects with or without distal TAs, but subjects with advanced distal histology and those older than 65 years are at increased risk. Age-specific screening using sigmoidoscopy starting at ages 50 to 55 years and colonoscopy after age 65 years may be justified.
Authors: Levin TR; Palitz A; Grossman S; Conell C; Finkler L; Ackerson L; Rumore G; Selby JV
JAMA. 1999 May 5;281(17):1611-7.
Comparison of the Block and the Willett self-administered semiquantitative food frequency questionnaires with an interviewer-administered dietary history
The performances of two commonly used diet instruments, the Block and the Willett food frequency questionnaires, were compared with a longer, interviewer-administered diet history. Participants in a case-control study on diet and colon cancer were interviewed between 1990 and 1994 in northern California, Utah, and Minnesota by trained nutritionists using a validated diet history. Two separate subsamples of participants were asked to complete either the Block or the Willett questionnaire exactly 5 days after they completed the original diet history. Data were analyzed separately by subsample comparing either the Block or the Willett questionnaire with the original diet history by using means, correlations, quintile agreement, and odds ratios for the relation between several nutrients and colon cancer. The Block and the Willett questionnaires generally provided lower absolute intake estimates than did the original diet history; however, the Block questionnaire underestimated more than did that by Willett. Both correlations and quintile agreement were slightly better for the Willett questionnaire than for that by Block when compared with the original diet history. In general, point estimates obtained from either the Block or the Willett questionnaire fell within the confidence intervals of the estimates of the odds ratios obtained from the original diet history, and no real difference in significance levels appeared. Although the Block and Willett questionnaires differed slightly from each other and from our original diet history in estimating absolute nutrients and ranking or classifying individuals, they were very similar in their ability to predict disease outcome.
Authors: Caan BJ; Slattery ML; Potter J; Quesenberry CP Jr; Coates AO; Schaffer DM
Am J Epidemiol. 1998 Dec 15;148(12):1137-47.
Proton vs. Photon Radiation Therapy for Primary Gliomas: An Analysis of the National Cancer Data Base.
Background: To investigate the impact of proton radiotherapy (PBT) on overall survival (OS) and evaluate PBT usage trends for patients with gliomas in the National Cancer Data Base (NCDB). Methods: Patients with a diagnosis of World Health Organization (WHO) Grade I-IV glioma treated with definitive radiation therapy (RT) between the years of 2004-13 were identified. Patients were stratified based on WHO Grade and photon radiotherapy (XRT) vs. PBT. Univariate (UVA) and multivariable analysis (MVA) with OS were performed by Cox proportional hazards model and log-rank tests. Propensity score (PS) weighting was utilized to account for differences in patient characteristics and to minimize selection bias. Results: There were a total of 49,405 patients treated with XRT and 170 patients treated with PBT. Median follow-up time was 62.1 months. On MVA, the following factors were associated with receipt of PBT (all p < 0.05): WHO Grade I-II gliomas, treatment at an academic/research program, west geographic facility location, and surgical resection. After PS weighting, all patients treated with PBT were found to have superior median and 5 year survival than patients treated with XRT: 45.9 vs. 29.7 months (p = 0.009) and 46.1 vs. 35.5% (p = 0.0160), respectively. Conclusions: PBT is associated with improved OS compared to XRT for patients with gliomas. This finding warrants verification in the randomized trial setting in order to account for potential patient imbalances not adequately captured by the NCDB, such as tumor molecular characteristics and patient performance status. Importance of the Study: This is the first study that compares the outcomes of patients treated with photon based radiotherapy vs. proton based radiotherapy for patients with gliomas. In this retrospective analysis, the results demonstrate that proton therapy is associated with improved outcomes which support ongoing prospective, randomized clinical trials comparing the two modalities in patients with gliomas.
Authors: Jhaveri J; Cheng E; Tian S; Buchwald Z; Chowdhary M; Liu Y; Gillespie TW; Olson JJ; Diaz AZ; Voloschin A; Eaton BR; Crocker IR; McDonald MW; Curran WJ; Patel KR
Front Oncol. 2018 Nov 28;8:440. doi: 10.3389/fonc.2018.00440. eCollection 2018.
Barbiturates, smoking, and bladder cancer risk
Phenobarbital treatment has been observed to be negatively associated with bladder cancer risk in a few studies. It has been suggested that phenobarbital may induce drug-metabolizing enzymes that detoxify the bladder carcinogens found in cigarette smoke. We examined the relationship of barbiturate use to bladder cancer risk and the potential modifying effect of cigarette smoking in a large cohort of Kaiser Permanente Medical Care Program members with computerized pharmacy prescriptions and smoking information. Newly diagnosed bladder cancers were identified among individuals in the study cohort by linkage with data from cancer registries. The overall standardized incidence ratio associated with barbiturate use was 0.71 [95% confidence interval (CI), 0.51-0.99]. Among current smokers, former smokers, and never smokers, the standardized incidence ratios were 0.56 (95% CI, 0.23-1.16), 0.68 (95% CI, 0.27-1.40), and 1.04 (95% CI, 0.48-1.98), respectively. Although our estimates were imprecise, the finding of an inverse association between barbiturate treatment and bladder cancer risk only among current and former cigarette smokers is consistent with the hypothesis that treatment with these medications induces drug-metabolizing enzymes that deactivate bladder carcinogens found in cigarette smoke.
Authors: Habel LA; Bull SA; Friedman GD
Cancer Epidemiol Biomarkers Prev. 1998 Nov;7(11):1049-50.
Cause of death in men diagnosed with prostate carcinoma
BACKGROUND: Prostate carcinoma is one of the leading causes of death in men. Although the mortality rate is high, it still may underestimate the number of deaths associated with the disease. This study was conducted to compare causes of death among men previously diagnosed with prostate carcinoma and to examine the extent to which differences in cause of death (death from prostate carcinoma vs. death from other causes) varied by age, race, clinical factors, and comorbid conditions. METHODS: A review was conducted of the medical records of decedent members of the Kaiser Permanente Medical Care program who previously were diagnosed with prostate carcinoma between January 1980 and December 1984 (n=584). The review focused on demographic factors, symptoms, diagnostic tests, stage of disease, and treatment. Data on comorbidity were obtained from a computerized discharge summary. Logistic regression analysis was used to estimate odds ratios. RESULTS: Approximately 54% of the decedent prostate carcinoma patients died of their prostate carcinoma. Decedents who were black, age < or = 65 years, diagnosed with more advanced disease stage, recipients of hormonal therapy, and whose death occurred > 6 months after diagnosis were more likely than others to die of prostate carcinoma. In contrast, the likelihood of dying of some other cause was associated with concurrent cardiovascular disease, after adjustment for the effects of race, age, and disease stage. There also were significant two-way age-race and age-time-to-death interactions. CONCLUSIONS: The prognostic significance of cardiovascular disease in prostate carcinoma patients should be investigated in subsequent survival studies. A number of questions need to be addressed delineating the complex relations between coexisting diseases and their treatment.
Authors: Satariano WA; Ragland KE; Van Den Eeden SK
Cancer. 1998 Sep 15;83(6):1180-8.
Race, prostate cancer survival, and membership in a large health maintenance organization
BACKGROUND: Population-based cancer registry data have shown that black men with prostate cancer have poorer stage-specific survival than white men, while studies in equal-access health care systems have not found racial differences in stage-specific survival. This study was designed to test the hypothesis that black men and white men with prostate cancer have equal stage-specific survival in equal-access health care systems. METHODS: We conducted a cohort study using cancer registry data from all incident cases of prostate cancer occurring in a five-county San Francisco Bay Area region. Incident cases occurred among members (5263 cases, from January 1973 through June 1995) and nonmembers (16,019 cases, from January 1973 through December 1992) of the Kaiser Permanente Medical Care Program, a large health maintenance organization. Death rate ratios (DRRs, black men versus white men) for Kaiser members and nonmembers were computed for all stages combined (adjusting for age and stage) and for each stage (adjusting for age). RESULTS: Among Kaiser members, adjusted DRRs comparing black men with white men were as follows: all stages combined, 1.28 (95% confidence interval [CI] = 1.14-1.44); local stage, 1.23 (95% CI = 1.01-1.51); regional stage, 1.30 (95% CI = 0.97-1.75); and distant stage, 1.27 (95% CI = 1.07-1.50). Corresponding DRRs for nonmembers were as follows: all stages combined, 1.22 (95% CI = 1.14-1.30); local stage, 1.24 (95% CI = 1.09-1.41); regional stage, 1.48 (95% CI = 1.29-1.68); and distant stage, 1.01 (95% CI = 0.91-1.12). CONCLUSIONS: These results show poorer prostate cancer survival for black men compared with white men in an equal-access medical care setting. The findings are most consistent with the hypothesis of increased tumor virulence in blacks.
Authors: Robbins AS; Whittemore AS; Van Den Eeden SK
J Natl Cancer Inst. 1998 Jul 1;90(13):986-90.
Atypical squamous cells of undetermined significance: management patterns at an academic medical center.
OBJECTIVE: Our intent was to compare the management of patients with atypical squamous cells of undetermined significance on cytologic screening at an academic center to published guidelines. STUDY DESIGN: We reviewed the management of 223 atypical squamous cells of undetermined significance cervical smears. Patients with a history of dysplasia were excluded. The time interval to and nature of follow-up testing was determined, and the influence of atypical squamous cells of undetermined significance qualifiers and provider specialty analyzed. RESULTS: Initial follow-up consisted of repeat cytologic examination alone in 94% of cases. Of patients with follow-up, 29% were retested within 2 months and 68% within 4 months. No conclusive differences in management were found by qualifier type or by provider specialty. Subsequent high-grade dysplasia was found in 2.6% of patients. CONCLUSIONS: A discrepancy exists between published guidelines and actual management of patients with atypical squamous cells of undetermined significance smears at this medical center. Patients often undergo follow-up testing at shorter intervals than those suggested despite a low likelihood of finding high-grade disease.
Authors: Suh-Burgmann E; Darragh T; Smith-McCune K
Am J Obstet Gynecol. 1998 May;178(5):991-5. doi: 10.1016/s0002-9378(98)70537-x.
Obesity, health services use, and health care costs among members of a health maintenance organization
BACKGROUND: Obesity is an independent risk factor for a variety of chronic diseases and is therefore a potential source of avoidable excess health care expenditures. Previous studies of obesity and health care costs have used group level data, applying estimates of population-attributable risks to estimates of US total costs of care for each obesity-related disease. OBJECTIVE: To quantify the association between body mass index (BMI) and health services use and costs stratified by age and use source at the patient level, a level of detail not previously reported. METHODS: In 17,118 respondents to a 1993 health survey of members of a large health maintenance organization, we ascertained through computerized databases all hospitalizations, laboratory services, outpatient visits, outpatient pharmacy and radiology services, and the direct costs of providing these services during 1993. RESULTS: There was an association between BMI and annual rates of inpatient days, number and costs of outpatient visits, costs of outpatient pharmacy and laboratory services, and total costs (P < or = .003). Relative to BMI of 20 to 24.9, mean annual total costs were 25% greater among those with BMI of 30 to 34.9 (rate ratio, 1.25; 95% confidence interval, 1.10-1.41), and 44% greater among those with BMI of 35 or greater (rate ratio, 1.44; 95% confidence interval, 1.22-1.71). The association between BMI and coronary heart disease, hypertension, and diabetes largely explained these elevated costs. CONCLUSION: Given the high prevalence of obesity and the associated elevated rates of health services use and costs, there is a significant potential for a reduction in health care expenditures through obesity prevention efforts.
Authors: Quesenberry CP Jr; Caan B; Jacobson A
Arch Intern Med. 1998 Mar 9;158(5):466-72.
Mentholated cigarettes and non-lung smoking related cancers in California, USA
Authors: Friedman GD; Sadler M; Tekawa IS; Sidney S
J Epidemiol Community Health. 1998 Mar;52(3):202.
Body size and the risk of colon cancer in a large case-control study
OBJECTIVE: To investigate the risks of height, weight and body fat distribution associated with colon cancer in subcategories of gender, age and site in the colon. Interaction with family history of colorectal cancer is also examined. DESIGN: Case-control study of diet, anthropometry and colon cancer risk. SUBJECTS: Nineteen hundred and eighty-three colon cancer cases (age 30-79 y) and 2400 age and gender matched population controls. MEASUREMENTS: Height, weight and waist and hip circumferences were obtained by trained interviewers. Body Mass Index (BMI) and Waist-Hip Ratio (WHR) were calculated. RESULTS: Of all anthropometric measurements examined, only BMI was consistently associated with an increased risk of colon cancer. The test for trend for BMI was significant for men and women overall and for the majority of subgroups examined. In younger persons those with a family history of colorectal cancer had a greater risk of colon cancer associated with BMI (Men odds ratio (OR) = 7.76, 95% confidence interval (CI) 2.60, 23.1; Women OR = 4.85, 95% CI 2.33, 10.12) comparing the third tertile to the first, than those with no family history (Men OR = 1.70, 95% CI 1.25, 2.32; Women OR = 1.53, 95% CI 1.22, 1.92). WHR, after controlling for BMI was not associated with colon cancer in men, and was associated with a slight increase in women (primarily in those with distal tumors). CONCLUSION: This study contributes to mounting evidence that excess weight is associated with an increased risk of colon cancer.
Authors: Caan BJ; Coates AO; Slattery ML; Potter JD; Quesenberry CP Jr; Edwards SM
Int J Obes Relat Metab Disord. 1998 Feb;22(2):178-84.
A comparison of fecal occult-blood tests for colorectal-cancer screening.
BACKGROUND: Hemoccult II, a widely used guaiac test for fecal occult blood, has a low sensitivity for detecting colorectal neoplasms in asymptomatic patients at average risk. In such patients, the performance characteristics of screening tests developed to improve on Hemoccult II are not known.METHODS: A set of three fecal occult-blood tests–Hemoccult II; Hemoccult II Sensa, a more sensitive guaiac test; and HemeSelect, an immunochemical test for human hemoglobin–was mailed to all patients 50 years of age or older who were scheduled for personal health appraisals at the Kaiser Permanente Medical Center in Oakland, California. The performance of each test and of a combination test (HemeSelect to confirm positive Hemoccult II Sensa results) was evaluated by identifying screened patients who had colorectal neoplasma (carcinoma or a polyp > or = 1 cm in diameter) in the two years after screening. RESULTS: Of the 10,702 eligible patients, 8104 (75.7 percent) had at least one interpretable sample and were screened on the basis of at least one test; 96 percent of these patients had complete two-year follow-up. The sensitivity of the tests for detecting carcinoma was lowest with Hemoccult II (37.1 percent; 95 percent confidence interval, 19.7 to 54.6 percent), intermediate with the combination test (65.6 percent; 95 percent confidence interval, 47.6 to 83.6 percent) and with HemeSelect (68.8 percent; 95 percent confidence interval, 51.1 to 86.4 percent), and highest with Hemoccult II Sensa (79.4 percent; 95 percent confidence interval, 64.3 to 94.5 percent). The specificity for detecting carcinoma was 86.7 percent with Hemoccult II Sensa, 94.4 percent with HemeSelect, 97.3 percent with the combination test, and 97.7 percent with Hemoccult II. HemeSelect and the combination test detected more colorectal carcinomas and polyps than Hemoccult II, with only slight increases in the number of colonoscopies needed. CONCLUSIONS: HemeSelect and a combination test in which HemeSelect is used to confirm positive Hemoccult II Sensa results improve on Hemoccult II in screening patients for colorectal carcinoma.
Authors: Allison, JE; Tekawa, IS; Ransom, LJ; Adrain, AL
The New England journal of medicine. 1996 Jan 18;334(3):155-9. Epub --.
