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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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

Cachexia: A systemic consequence of progressive, unresolved disease

Cachexia, a systemic wasting condition, is considered a late consequence of diseases, including cancer, organ failure, or infections, and contributes to significant morbidity and mortality. The induction process and mechanistic progression of cachexia are incompletely understood. Refocusing academic efforts away from advanced cachexia to the etiology of cachexia may enable discoveries of new therapeutic approaches. Here, we review drivers, mechanisms, organismal predispositions, evidence for multi-organ interaction, model systems, clinical research, trials, and care provision from early onset to late cachexia. Evidence is emerging that distinct inflammatory, metabolic, and neuro-modulatory drivers can initiate processes that ultimately converge on advanced cachexia.

Authors: Ferrer, Miriam; Caan, Bette J; Cespedes Feliciano, Elizabeth M; Janowitz, Tobias; et al.

Cell. 2023 Apr 27;186(9):1824-1845.

PubMed abstract

Current tobacco smoking and risk of SARS-CoV-2 infection and hospitalization: Evaluating the role of socio-demographic factors and comorbidities

Our recently published study of >2.4 million adults in Northern California indicated that current versus never-tobacco smoking was associated with lower risk of SARS-CoV-2 infection and less severe coronavirus disease 2019 (COVID-19). We extended this research by evaluating whether these associations were moderated by socio-demographic factors and medical comorbidities. This retrospective cohort study of 1,885,826 adults with current or never-smoking status in Kaiser Permanente Northern California from 3/5/2020 (baseline) to 12/31/2020 (pre-vaccine) included electronic health record-based socio-demographics (sex, age, race/ethnicity, neighborhood deprivation index (NDI)) and medical comorbidities (obesity, cardiovascular conditions, diabetes, renal disease, respiratory conditions). We estimated the adjusted risk of SARS-CoV-2 infection and hospitalization (≤30 days of infection) associated with smoking status using Cox proportional hazard regression models. We estimated associations within subgroups of socio-demographics and comorbidities, and tested for effect modification using interaction terms. During the study, 35,627 patients had SARS-CoV-2 infection. Current versus never-smoking status was associated with lower adjusted rates of SARS-CoV-2 infection (aHR ranging from 0.51 to 0.89) and hospitalization (aHR ranging from 0.32 to 0.70) within nearly every socio-demographic and comorbidity subgroup. Statistically significant interactions showed that the magnitude of protection for SARS-CoV-2 infection varied by sex, age, race/ethnicity, NDI, cardiovascular conditions and diabetes, and for SARS-CoV-2 hospitalization by age and renal disease. Taken together, results indicated that while some socio-demographics and comorbidities moderated the associations, the lower risk of SARS-CoV-2 infection and hospitalization associated with current versus never-smoking status persisted among patients regardless of socio-demographics or comorbidities.

Authors: Young-Wolff, Kelly C; Slama, Natalie; Sakoda, Lori C; Prochaska, Judith J; Fogelberg, Renee; Alexeeff, Stacey E

Prev Med. 2023 Apr 26;172:107523. Epub 2023-04-26.

PubMed abstract

Disparities in ovarian cancer survival: does place matter?

Social inequities in cancer survival are persistent. Ovarian cancer is the fifth leading cause of cancer-associated mortality among women, with persistent survival disparities seen across race and ethnicity, and by socioeconomic status, even after accounting for histology, stage, treatment differences, and other clinical factors. Neighborhood and environmental context can play an important role in ovarian cancer survival, and, to the extent that minority racial and ethnic groups, and populations of lower socioeconomic status are more likely to be segregated into neighborhoods with lower quality social, built, and physical environment neighborhoods, contextual factors may be a critical component to ovarian cancer survival disparities. However, research on the impact of different domains of structural, environmental, and neighborhood context in ovarian cancer survival, and in disparities in ovarian cancer survival is limited. This review focuses on the following contextual domains: structural and institutional factors, healthcare access and geographic medical accessibility, environmental exposures within the physical environment, social environment, built environment, and rurality and the research to date and offers recommendations for future research studies in disparities in ovarian cancer survival. Recommendations for future research studies to address disparities in ovarian cancer survival are proposed.

Authors: Gomez, Scarlett L; Kushi, Lawrence; Lawson, Andrew; et al.

Am J Obstet Gynecol. 2023 Apr 26.

PubMed abstract

Neighborhood attributes and cardiovascular disease risk in breast cancer survivors: The Pathways Study

Breast cancer survivors are at a higher risk of cardiovascular disease (CVD) morbidity and mortality compared with the general population. The impact of objective social and built neighborhood attributes on CVD risk in a cohort of female breast cancer survivors was examined. The 3975 participants came from the Pathways Study, a prospective cohort of women with invasive breast cancer from an integrated health care system in northern California. Women diagnosed with breast cancer from 2006 through 2013 were enrolled on average approximately 2 months after diagnosis. Their baseline addresses were geocoded and appended to neighborhood attributes for racial/ethnic composition, socioeconomic status (SES), population density, urbanization, crime, traffic density, street connectivity, parks, recreational facilities, and retail food environment. Incident CVD events included ischemic heart disease, heart failure, cardiomyopathy, or stroke. Cox proportional hazards models estimated associations of neighborhood attributes with CVD risk, which accounted for clustering by block groups. Fully adjusted models included sociodemographic, clinical, and behavioral factors. During follow-up through December 31, 2018, 340 participants (8.6%) had CVD events. A neighborhood racial/ethnic composition measure, percent of Asian American/Pacific Islander residents (lowest quintile hazard ratio [HR], 1.85; 95% CI, 1.03-3.33), and crime index (highest quartile HR, 1.48; 95% CI, 1.08-2.03) were associated with the risk of CVD events independent of individual SES, hormone receptor status, treatment, cardiometabolic comorbidities, body mass index, and physical activity. With the application of a socio-ecological framework, how residential environments shape health outcomes in women with breast cancer and affect CVD risk in this growing population can be understood.

Authors: Conroy, Shannon M; Kwan, Marilyn L; Kushi, Lawrence H; Iribarren, Carlos; Shariff-Marco, Salma; et al.

Cancer. 2023 Apr 25.

PubMed abstract

Impact of a scalable training program on the quality of colonoscopy performance and risk of post-colonoscopy colorectal cancer

Endoscopist adenoma detection rates (ADR) vary widely and are associated with patients’ risk of post-colonoscopy colorectal cancers (PCCRC). However, few scalable physician-directed interventions demonstrably both improve ADR and reduce PCCRC risk. Among patients undergoing colonoscopy, we evaluated a scalable online training’s influence 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 adenoma detection. Analyses included interrupted time series analyses for pre- vs. post-training 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 following training compared with 0.58%/quarter (95%CI: 0.40-0.77) and 0.33%/quarter (95%CI: 0.16-0.49) in the 3-year pre- and post-training periods, respectively. Post-training ADR increases were higher among endoscopists with pre-training ADRs below the median. Among 146,786 post-training colonoscopies (all indications), each 1% absolute increase in screening ADR post-training was associated with a 4% decrease in their patients’ PCCRC risk (hazard ratio [HR]: 0.96, 95%CI: 0.93-0.99). An ADR increase of ≥10% vs. <1% was associated with a 55% reduced risk of PCCRC (HR: 0.45, 95%CI: 0.24-0.82). A scalable online behavior-change training 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; Lee, Jeffrey K; Levin, Theodore R; Fireman, Bruce H; Quesenberry, Charles P; et al.

Gastrointest Endosc. 2023 Apr 22.

PubMed abstract

Associations of post-diagnosis lifestyle with prognosis in women with invasive breast cancer

Lifestyle habits can impact breast cancer (BC) development, but its impact on BC prognosis remains unclear. We investigated associations of post-diagnosis lifestyle with mortality and recurrence in 1,964 women with invasive BC enrolled in the Kaiser Permanente Northern California Pathways Study shortly after diagnosis with lifestyle information at baseline (2005-2013) and the 2-year follow-up. We calculated a post-diagnosis lifestyle score (range: 0-18) based on 9 diet, physical activity (PA), and body weight recommendations from the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO) using follow-up data (body weight also included baseline data); higher scores indicate greater guideline concordance. Similarly, we calculated a pre-diagnosis lifestyle score using baseline data to investigate pre- to post-diagnosis changes. We estimated hazard ratios (HR) and 95% CIs using Cox proportional hazard models, with follow-up through December 2018 (observing 290 deaths and 176 recurrences). The 2-year post-diagnosis lifestyle score was inversely associated with all-cause mortality (ACM) (HR per 2-point increase=0.90, 95%CI: 0.82, 0.98), and BC-mortality (HR=0.79, 95%CI: 0.67, 0.95), but not recurrence. Relative to women who maintained low concordance with recommendations at both time points, women who maintained high concordance had a lower risk of ACM (HR=0.61, 95%CI: 0.37, 1.03). Improved concordance with some specific recommendations (particularly PA) may be associated with a lower hazard of ACM (HRPA=0.52, 95%CI: 0.35, 0.78). Results suggest that women with BC may benefit from a post-diagnosis lifestyle aligned with ACS/ASCO guidelines. This information may potentially guide lifestyle recommendations for BC survivors to reduce mortality risk.

Authors: Troeschel, Alyssa N; Ergas, Isaac J; Kwan, Marilyn L; Cespedes Feliciano, Elizabeth M; Kushi, Lawrence H; et al.

Cancer Epidemiol Biomarkers Prev. 2023 Apr 20.

PubMed abstract

Distinct Serum Immune Profiles Define the Spectrum of Acute and Chronic Pancreatitis From the Multicenter Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) Study

Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis. Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57). A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status. Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression.

Authors: Lee, Bomi; Van Den Eeden, Stephen K; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC),; et al.

Gastroenterology. 2023 Apr 14.

PubMed abstract

Breast Cancer Recurrence by Subtype in a Diverse, Contemporary Cohort of Young Women

Young breast cancer (YBC) patients are a unique subpopulation that are often underrepresented in randomized clinical trials. Furthermore, large national cancer databases lack detailed information on recurrence, a meaningful oncologic outcome for young patients. Retrospective review of YBC patients (age ≤40) with Stage I-III breast cancer diagnosed from 2008 to 2018 was performed. Information on clinicopathologic characteristics, demographics, and outcomes were obtained from the electronic health record and chart review. Chi-square and Fisher exact tests were used for comparisons of categorical variables and parametric and nonparametric tests for continuous variables. The cohort included 1,431 women with a median follow-up of 4.8 years (range: 0.3-12.9 years). The median age was 37 (IQR: 34-39). The study population included 598 (41.8%) White, 112 (7.8%) Black, 420 (29.4%) Asian/Pacific Islander, 281 (19.6%) Hispanic, and 20 (1.4%) “other” race/ethnicity patients. Tumor subtype was as follows: [1] Hormone Receptor (HR)+/HER2-, Grade (G) 1-2 =541 (37.8%); [2] HR+/HER2-, G3 =268 (18.7%); [3] HR+/HER2+ =262 (18.3%); [4] HR-/HER2+ =101 (7.1%); [5] HR-/HER2- =259 (18.1%). The majority (64.2%) presented with Stage II/III disease. There were 230 (16.1%) recurrences during follow-up; 74.8% were distant. Locoregional only recurrence was seen in 17/463 (3.7%) patients who underwent breast conservation versus 41/968 (4.2%) of patients undergoing mastectomy (p<0.001). Recurrence varied by tumor subtype: [1] HR+/HER2-, G1-2 (14.0%); [2] HR+/HER2-, G3 (20.9%); [3] HR+/HER2+ (11.1%); [4] HR-/HER2+ (22.8%); [5] HR-/HER2- (17.8%) (p=0.005). In this large, diverse YBC cohort, recurrences were most frequent among HR+/HER2-, G3 or HR-/HER2+ invasive tumors; most were distant. There were numerically similar locoregional-only recurrences after breast conservation versus mastectomy. Additional research is needed to identify predictors of recurrence.

Authors: Vuong, Brooke; Darbinian, Jeanne; Savitz, Alison; Odele, Patience; Perry, Lauren M; Sandhu, Lakhbir; Habel, Laurel; Kuehner, Gillian

J Am Coll Surg. 2023 Apr 13.

PubMed abstract

Brief Communication: The Contemporary Probability of Occult Colorectal Cancer in Patients with Colitis-Related Dysplasia undergoing Colectomy

Occult colorectal cancer (CRC) has historically driven recommendations for colectomy in inflammatory bowel disease (IBD) patients with dysplasia. We defined the contemporary risk of occult CRC at colectomy among 93 IBD patients with dysplasia based on endoscopic appearance, resection, and concordance between site of cancer at colectomy and dysplasia at colonoscopy. Contrary to our hypothesis, we found that occult CRC at colectomy remains elevated in high-grade polypoid and invisible dysplasia. It was infrequent in other visible lesions. When present, occult cancer occurred in the same segment as dysplasia, suggesting the historic concern of missing a remote cancer is low.

Authors: Boparai, Eshandeep S; Lee, Jeffrey K; Zhu, Shiyun; Shirazi, Aida; Velayos, Fernando S

Am J Gastroenterol. 2023 Apr 11.

PubMed abstract

Interpersonal Stressors and Resources for Support: Associations with Lower Urinary Tract Symptoms and Impact Among Women

Introduction: This study utilizes Coronary Artery Risk Development in Young Adults (CARDIA) data to examine whether women’s perceived emotional support and interpersonal stressors are associated with lower urinary tract symptoms (LUTS) and their impact on quality of life. Methods: Emotional support was assessed at baseline/year 0 (1985-86), year 2 (1987-88), year 15 (2000-01), and year 20 (2005-06); interpersonal stressors were assessed at years 15 and 20. In 2012-13, LUTS and impact were assessed. LUTS/impact category (a composite variable ranging from bladder health to mild, moderate, and severe LUTS/impact) was regressed on trajectory groups of emotional support from years 0 to 20. Separately, LUTS/impact was regressed on mean emotional support and interpersonal stressors across years 15-20. Analyses were adjusted for age, race, education, and parity (n = 1104). Results: In comparison to women whose support trajectory from years 0 to 20 was consistently high, women whose support decreased from high to low had over twice the odds (odds ratio [OR] = 2.72; 95% confidence interval [CI] = 1.76-4.20) of being classified into a more burdensome LUTS/impact category. Mean support and interpersonal stressors across years 15-20 were independently associated with lower odds (OR = 0.59; 95% CI = 0.44-0.77) and greater odds (OR = 1.52; 95% CI = 1.19-1.94), respectively, of being classified into a more burdensome LUTS/impact category. Conclusions: In the CARDIA cohort, quality of women’s interpersonal relationships, assessed between 1985-86 and 2005-06, was associated with LUTS/impact assessed in 2012-13. Additional research collecting LUTS/impact data at multiple time points is needed to test potential bidirectional associations of emotional support and interpersonal stressors with LUTS/impact, as well as potential mechanisms of association.

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 Womens Health (Larchmt). 2023 Apr 11.

PubMed abstract

Associations of dietary isothiocyanate exposure from cruciferous vegetable consumption with recurrence and progression of non-muscle-invasive bladder cancer: findings from the Be-Well Study

High recurrence and progression rates are major clinical challenges for non-muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown. This study aimed to investigate the associations of dietary ITC exposure at diagnosis with NMIBC recurrence and progression. The study analyzed 1143 participants from the Be-Well study, a prospective cohort of newly diagnosed NMIBC cases in 2015-2019 with no prior history of BC. Dietary ITC exposure was indicated by self-reported CV intake, estimated ITC intake, urinary metabolites, and plasma ITC-albumin adducts. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression, and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for delayed and multiple recurrence. Over a mean follow-up of 25 mo, 347 (30%) developed recurrence and 77 (6.7%) had disease progression. Despite no significant associations with the overall risk of recurrence, urinary ITC metabolites (OR: 1.96; 95% CI: 1.01, 4.43) and dietary ITC intake (OR: 2.13; 95% CI: 1.03, 4.50) were associated with late recurrence after 12-mo postdiagnosis compared with before 12-mo postdiagnosis. Raw CV intake was associated with reduced odds of having ≥2 recurrences compared with having one (OR: 0.34; 95% CI: 0.16, 0.68). Higher plasma concentrations of ITC-albumin adducts were associated with a reduced risk of progression, including progression to muscle-invasive disease (for benzyl ITC, HR: 0.40; 95% CI: 0.17, 0.93; for phenethyl ITC, HR: 0.40; 95% CI: 0.19, 0.86). Our findings indicate the possible beneficial role of dietary ITCs in NMIBC prognosis. Given the compelling preclinical evidence, increasing dietary ITC exposure with CV intake could be a promising strategy to attenuate recurrence and progression risks in patients with NMIBC.

Authors: Wang, Zinian; Kwan, Marilyn L; Ergas, Isaac J; Quesenberry, Charles P; Kushi, Lawrence H; Tang, Li; et al.

Am J Clin Nutr. 2023 Apr 11.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract


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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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).

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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. 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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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).

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

“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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

Physician Adenoma Detection Rates and Colorectal Cancer-Reply

Authors: Corley, Douglas A; Schottinger, Joanne; Jensen, Christopher

JAMA. 2022 10 11;328(14):1462-1463.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract


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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

“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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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. 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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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).

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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:; 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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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 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.

PubMed abstract

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.

PubMed abstract


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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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 ( 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.

PubMed abstract

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.

PubMed abstract

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. (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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

Editors in Chief, Gastroenterology

Authors: Stange, Eduard F; von Bünau, Rudolf; Erhardt, Andreas

Gastroenterology. 2021 06;160(7):2632. Epub 2020-12-30.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

“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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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. Identifier: NCT03528863.

Authors: Dragomanovich, Hannah M; Kubo, Ai; Atreya, Chloe E; et al.

Glob Adv Health Med. 2021;10:21649561211044693. Epub 2021-11-03.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract


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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

COVID-19: What Should Clinicians and Scientists Do and When?

Authors: Corley DA; Peek RM

Gastroenterology. 2020 Mar 19.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

Surveillance of Gastric Intestinal Metaplasia

Authors: Shah SC; Gawron AJ; Li D

Am J Gastroenterol. 2020 05;115(5):641-644.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

Reservations Regarding O-RADS Recommendations

Authors: Suh-Burgmann E; Flanagan T; Brasic N

Radiology. 2020 04;295(1):248-249. Epub 2020-02-25.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract


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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

Immunotherapy-Associated Pseudomembranous Colitis

Authors: Kidambi TD; Chu P; Lee JK; Lin JL

Am J Gastroenterol. 2019 11;114(11):1708.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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 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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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.

PubMed abstract

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 stu