Promoting Equity of Cancer Screening and Follow-up for Lung Cancer
This research will elucidate factors that contribute to lung cancer disparities between rural and urban areas and provide contextual information for future interventions and policies. Our specific aims are to: characterize the delivery of evidence-based interventions for lung cancer prevention…
Investigating racial disparities in cancer treatment response
Genome-wide interaction analysis of folate for colorectal cancer risk
Epidemiological and experimental evidence suggests that higher folate intake is associated with a decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate…
A genetic locus within the FMN1/GREM1 gene region interacts with body mass index in colorectal cancer risk
Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G…
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…
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…
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…
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…
TRENDS IN SMOKING-SPECIFIC LUNG CANCER INCIDENCE RATES WITHIN A U.S. INTEGRATED HEALTH SYSTEM, 2007-2018
At least 10% of lung cancers arise in adults who have never smoked. Data remain inconclusive on whether lung cancer incidence has been increasing among never-smoking adults. How have age-adjusted incidence rates of lung cancer changed temporally, especially among never-smoking…
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…
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…
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…
Patterns, determinants, and outcomes of guideline-recommended imaging surveillance after surgical resection of early-stage lung cancer
High-quality evidence is limited on the utilization and outcomes of imaging surveillance after definitive surgery for early-stage lung cancer. This study examines patterns and factors associated with guideline-recommended imaging surveillance of lung cancer survivors, in addition to rates of new…
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…
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…
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…
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…
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…
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.…
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…
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…
Podcast: Improving lung cancer survival
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…
Identifying Barriers to Lung Cancer Screening among Asian Americans
This study will identify key barriers to lung cancer screening as well as develop tailored strategies and materials to increase the uptake of lung cancer screening and smoking cessation services among Asian Americans.
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…
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…
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…
What Factors Affect Time to Surgery for Lung Cancer and Moderate its Associations with Patient Outcomes
This study will determine factors that influence time to surgery and its associations with outcomes in patients with early-stage non-small cell lung cancer.
Utilization and Impact of Extended-Interval Dosing of Immunotherapy on Outcomes in Patients with Locally Advanced NSCLC
This study will evaluate the utilization and dosing of durvalumab and associations with treatment outcomes among patients with unresectable stage III non-small cell lung cancer in an integrated health care system.
Multilevel Determinants of Racial/Ethnic Disparities in Lung Cancer Screening Utilization
Lung cancer screening has been underutilized nationally to date, with growing evidence suggesting that screening rates differ by race. This research aims to identify multilevel factors that influence disparities in utilization of lung cancer screening from eligibility determination to screening…
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…
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…
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…
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…
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…
Comparative Effectiveness of Pretreatment Lung Cancer Nodal Staging
The proposed project will determine whether a guideline-recommended nodal staging strategy is superior to a guideline-discordant nodal staging strategy, and whether a validated risk-based nodal staging strategy that reduces unnecessary biopsies is an equivalent alternative to a guideline-recommended nodal staging…
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…
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…
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…
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…
Leveraging Diversity in Cancer Epidemiology Cohorts and Novel Methods to Improve Polygenic Risk Scores
Inadequate representation of diverse racial/ethnic populations in genetic studies is hindering the translational potential of polygenic risk scores (PRS) in cancer risk prediction. To address this shortcoming, we aim to construct and evaluate PRS for cancer and estimate the absolute…
Disparities in REsults of Immune Checkpoint Inhibitor Treatment (DiRECT): A Prospective Cohort Study of Cancer Survivors Treated with anti-PD-1/anti-PD-L1 in a Community Oncology Setting
This project will establish a prospective cohort of white and Black cancer patients treated with immune checkpoint inhibitors, leveraging the NCI Community Oncology Research Program network infrastructure, to investigate racial differences in immune-related adverse events and their predictors, treatment delay…
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…
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…
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…
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…
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…
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…
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…
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…
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…
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,…
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…
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…
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…
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…
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…
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-…
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…
Standardized reporting of chest CT scans improves odds of early lung cancer diagnosis
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…
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…
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…
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
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…
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…
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…
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…
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…
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…
Understanding Racial/Ethnic Disparities in Lung Cancer Screening Utilization
This study proposes to understand patterns and multilevel determinants of racial/ethnic disparities in Lung Cancer Screening utilization from 2017 onward at KPNC.
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…
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…
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…
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.…
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…
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…
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…
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…
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)…
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…
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…
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…
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…
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…
Discovery of common and rare genetic risk variants for colorectal cancer
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in…
Examining the role of access to care: Racial/ethnic differences in receipt of resection for early-stage non-small cell lung cancer among integrated system members and non-members
To examine the role of uniform access to care in reducing racial/ethnic disparities in receipt of resection for early stage non-small cell lung cancer (NSCLC) by comparing integrated health system member patients to demographically similar non-member patients. Using data from…
The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs
The TGFβ-signaling pathway plays an important role in the pathogenesis of colorectal cancer (CRC). Loss of function of several genes within this pathway, such as bone morphogenetic proteins (BMPs) have been seen as key events in CRC progression. In this…
Mutation analysis of adenomas and carcinomas of the colon: early and late drivers
Colorectal cancer (CRC) accounts for about 8% of all new cancer cases diagnosed in the US. We used whole exome sequence data from triplet samples (colon carcinoma, colon adenoma, and normal tissue) from 18 individuals to assess gene mutation rates.…
The p53-signaling pathway and colorectal cancer: Interactions between downstream p53 target genes and miRNAs
We examined expression of genes in the p53-signaling pathway. We determine if genes that have significantly different expression in carcinoma tissue compared to normal mucosa also have significantly differentially expressed miRNAs. We utilize a sample of 217 CRC cases. We…
MicroRNA-messenger RNA interactions involving JAK-STAT signaling genes in colorectal cancer
JAK-STAT signaling influences many downstream processes that, unchecked, contribute to carcinogenesis and metastasis. MicroRNAs (miRNAs) are hypothesized as a mechanism to prevent uncontrolled growth from continuous JAK-STAT activation. We investigated differential expression between paired carcinoma and normal colorectal mucosa of…
Dysregulated genes and miRNAs in the apoptosis pathway in colorectal cancer patients
Apoptosis is genetically regulated and involves intrinsic and extrinsic pathways. We examined 133 genes within these pathways to identify whether they are expressed differently in colorectal carcinoma (CRC) and normal tissue (N = 217) and if they are associated with similar differential…
Assessing Adherence to Follow-Up Care After Low-Dose Computed Tomography Screening for Lung Cancer
With the recent implementation of lung cancer screening in community-based practice, little is currently known about utilization patterns and outcomes in patients following the initial low-dose computed tomography (CT) screening exam. The primary goals of this study are to 1)…
The NF-κB signalling pathway in colorectal cancer: associations between dysregulated gene and miRNA expression
The nuclear factor-kappa B (NF-κB) signalling pathway is a regulator of immune response and inflammation that has been implicated in the carcinogenic process. We examined differentially expressed genes in this pathway and miRNAs to determine associations with colorectal cancer (CRC).…
Expression of Wnt-signaling pathway genes and their associations with miRNAs in colorectal cancer
The Wnt-signaling pathway functions in regulating cell growth and thus is involved in the carcinogenic process of several cancers, including colorectal cancer. We tested the hypothesis that multiple genes in this signaling pathway are dysregulated and that miRNAs are associated…
miRNA involvement in cell cycle regulation in colorectal cancer cases
Uncontrolled cell replication is a key component of carcinogenesis. MicroRNAs (miRNAs) regulate genes involved in checkpoints, DNA repair, and genes encoding for key proteins regulating the cell cycle. We investigated how miRNAs and mRNAs in colorectal cancer subjects interact to…
The MAPK-Signaling Pathway in Colorectal Cancer: Dysregulated Genes and Their Association With MicroRNAs
Mitogen-activated protein kinase (MAPK) pathways regulate many cellular functions including cell proliferation and apoptosis. We examined associations of differential gene and microRNA (miRNA) expression between carcinoma and paired normal mucosa for 241 genes in the KEGG-identified MAPK-signaling pathway among 217…
Common TDP1 polymorphisms in relation to survival among small cell lung cancer patients: a multicenter study from the International Lung Cancer Consortium
Purpose: DNA topoisomerase inhibitors are commonly used for treating small-cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single-nucleotide…
Applying Risk Prediction Models to Optimize Lung Cancer Screening: Current Knowledge, Challenges, and Future Directions
Risk prediction models may be useful for facilitating effective and high-quality decision-making at critical steps in the lung cancer screening process. This review provides a current overview of published lung cancer risk prediction models and their applications to lung cancer…
Monitoring Lung Cancer Screening Utilization and Outcomes in Four Cancer Research Network Sites
Lung cancer screening registries can monitor screening outcomes and improve quality of care. To describe nascent lung cancer screening programs and share efficient data collection approaches for mandatory registry reporting in four integrated health care systems of the National Cancer…
The co-regulatory networks of tumor suppressor genes, oncogenes, and miRNAs in colorectal cancer
Tumor suppressor genes (TSGs) and oncogenes (OG) are involved in carcinogenesis. MiRNAs also contribute to cellular pathways leading to cancer. We use data from 217 colorectal cancer (CRC) cases to evaluate differences in TSGs and OGs expression between paired CRC…
The PI3K/AKT Signaling Pathway: associations of miRNAs with dysregulated gene expression in colorectal cancer
The PI3K/AKT-signaling pathway is one of the most frequently activated signal-transduction pathways in cancer. We examined how dysregulated gene expression is associated with miRNA expression in this pathway in colorectal cancer (CRC). We used data from 217 CRC cases to…
Genetic contributors to variation in alcohol consumption vary by race/ethnicity in a large multi-ethnic genome-wide association study
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have been reported to be associated with variation in alcohol…
Effect of Angiotensin System Inhibitors on Survival in Patients Receiving Chemotherapy for Advanced Non-Small-Cell Lung Cancer
Preclinical studies suggest that angiotensin system inhibitors (ASI) and bevacizumab improve tumor perfusion and chemotherapy efficacy. We performed a retrospective study to examine whether concomitant ASI use during carboplatin and paclitaxel (CP) without or with bevacizumab (CPB) was associated with…
Evaluating a Risk Prediction Model for Lung Cancer
Screening with low-dose computed tomography (LDCT) presents an opportunity to improve early detection and reduce mortality from lung cancer. However, the potential harms of LDCT screening, including frequent false-positive findings that lead to unnecessary procedures and repeated radiation exposure, have…
Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer
Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa-such as genetics-can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente…
Shared Genetics of Chronic Obstructive Pulmonary Disease and Lung Cancer
Although COPD strongly predisposes to lung cancer, and both share tobacco smoke exposure as an etiologic risk factor, few studies have examined whether genetic constitution can also explain the overlap between these diseases. Among ever smokers in the Genetic Epidemiology…
Common coding variants in the HLA-DQB1 region confer susceptibility to age-related macular degeneration
Age-related macular degeneration (AMD) risk variants in the complement system point to the important role of immune response and inflammation in the pathogenesis of AMD. Although the human leukocyte antigen (HLA) region has a central role in regulating immune response,…
Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort
Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality…
Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort
The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement…
Genotyping Informatics and Quality Control for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort
The Kaiser Permanente (KP) Research Program on Genes, Environment and Health (RPGEH), in collaboration with the University of California-San Francisco, undertook genome-wide genotyping of >100,000 subjects that constitute the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. The…
A large multi-ethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences
A genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified…
Differences in the Genetic Susceptibility to Age-Related Macular Degeneration Clinical Subtypes
We compared across age-related macular degeneration (AMD) subtypes the effect of AMD risk variants, their predictive power, and heritability. The prevalence of AMD was estimated among active non-Hispanic white Kaiser Permanente Northern California members who were at least 65 years…
Metformin use and lung cancer risk in patients with diabetes
Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages…
Imputation of the Rare HOXB13 G84E Mutation and Cancer Risk in a Large Population-Based Cohort
An efficient approach to characterizing the disease burden of rare genetic variants is to impute them into large well-phenotyped cohorts with existing genome-wide genotype data using large sequenced referenced panels. The success of this approach hinges on the accuracy of…
Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia
Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated…
Turning of COGS moves forward findings for hormonally mediated cancers
The large-scale Collaborative Oncological Gene-environment Study (COGS) presents new findings that further characterize the genetic bases of breast, ovarian and prostate cancers. We summarize and provide insights into this collection of papers from COGS and discuss the implications of the…
DNA repair genotype and lung cancer risk in the beta-carotene and retinol efficacy trial
Many carcinogens in tobacco smoke cause DNA damage, and some of that damage can be mitigated by the actions of DNA repair enzymes. In a case-control study nested within the Beta-Carotene and Retinol Efficacy Trial, a randomized chemoprevention trial in…
HOXB13:IL17BR and molecular grade index and risk of breast cancer death among patients with lymph node-negative invasive disease
Studies have shown that a two-gene ratio (HOXB13:IL17BR) and a five-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) are predictive of clinical outcomes among early-stage breast cancer patients. In an independent population of lymph node-negative breast cancer patients…
Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics
BACKGROUND: One type of fecal occult blood test (FOBT), the unrehydrated guaiac fecal occult blood test (GT), is recommended by the United States Preventive Services Task Force and the Institute of Medicine for use in screening programs, but it has…