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Purpose: Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan).Methods: The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer.Results: Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52).Conclusions: These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation. [ABSTRACT FROM AUTHOR]

This report provides a summary of the identified evidence gaps and a general discussion of the next steps to advance cancer epidemiology research in Hispanic/Latino (H/L) populations based partly on the workshop, "Cancer Epidemiology in Hispanic Populations," convened by the NCI in September 2021. The cancer burden among H/L populations varies greatly by nativity and country of origin, yet this variation is not often captured due to systemic challenges in how racial/ethnic data have been collected and often reported in aggregate for this heterogeneous population. Developing culturally relevant assessment tools, increasing the representation of H/L participants, and adopting appropriate methodologic approaches are critical to enhancing cancer research. There is a variety of current funding mechanisms that may be used to address these evidence gaps and priorities, including investigator-initiated mechanisms. Cancer epidemiologic research in H/L populations should leverage existing resources where possible. New and ongoing studies should collect information on nativity status, country of origin, and related measures, use culturally specific assessment tools, engage in collaborative science, and maintain strong community engagement to build studies that will meaningfully address the cancer burden experienced by the growing H/L population., (©2024 American Association for Cancer Research.)

Background: More than 62 million people self-identified as Hispanic/Latino (H/L) in the 2020 United States census. The U.S. H/L population has higher burden of certain cancers compared with their non-Hispanic White counterparts., Methods: Key term search using the NIH Query/View/Report (QVR) system, along with Research, Condition, and Disease Categorization codes identified cancer epidemiology research grants in H/L populations funded by the NCI as a primary or secondary funder from fiscal years 2016 through 2021. Three reviewers identified eligible grants based on specified inclusion/exclusion criteria and a codebook for consistency extracting key characteristics., Results: A total of 450 grants were identified through the QVR system using key words related to H/Ls; 41 cancer epidemiology grants remained after applying exclusion criteria. These grants contained specific aims focused on H/Ls (32%) or included H/Ls as part of a racial/ethnic comparison (68%). NCI was the primary funder of the majority of the grants (85%), and most of the research grants focused on cancer etiology (44%) and/or survivorship (49%). Few grants (10%) investigated environmental exposures., Conclusions: This article provides an overview of NCI-funded cancer epidemiology research in H/L populations from 2016 to 2021. Future cancer epidemiology research should reflect the changing dynamics of the U.S. demography with diverse, representative populations and well-characterized ethnicity., Impact: Research that carefully measures the relevant biological, environmental, behavioral, psychologic, sociocultural, and clinical risk factors will be critical to better understanding the nuanced patterns influencing cancer-related outcomes in the heterogenous H/L population., (©2023 American Association for Cancer Research.)

Background: Gathering information directly from cancer survivors has advanced our understanding of the cancer survivorship experience. However, it is unknown whether surveys can distinguish important subgroups of cancer survivors. This study aimed to describe the current landscape of survey questions used to identify and describe cancer survivors in national cross-sectional studies., Methods: Using publicly available databases, the authors identified national cross-sectional surveys used in the United States within the past 15 years that included a question on self-reported history of cancer. After abstracting questions and response items used to identify cancer survivors, they conducted a descriptive analysis., Results: The authors identified 14 national cross-sectional surveys, with half administered to the general population and the other half administered to cancer survivors. The most common question used to identify cancer survivors was "Have you ever been told by a doctor or other health professional that you had cancer?" Most surveys had questions asking participants to identify a single cancer type (n = 11), multiple prior cancer diagnoses or types (n = 11), and the time from diagnosis (n = 12). Treatment questions varied from active treatment status to specific treatments received. Questions addressing cancer stage (n = 2), subtypes (n = 1), metastatic status (n = 3), and recurrence (n = 4) were less frequently included., Conclusions: There is no standard method for assessing self-reported cancer history, and this limits the ability to distinguish among potentially important subgroups of survivors. Future cross-sectional surveys that capture nuanced data elements, such as cancer types, stages/subtypes, metastatic/recurrent status, and treatments received, can help to fill important gaps in cancer survivorship research and clinical care., (© 2021 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Strategic planning is conducted by many organizations to systematically evaluate and assess their current state, establish or update their mission and/or goals, and identify strategies and activities to achieve the goals. The National Cancer Institute (NCI) Cohort Consortium is a collaborative network of 62 prospective cohort studies and their affiliated investigators that focus on cancer etiology and outcome research. The organization's membership grew markedly from 10 cohort studies at its inception in 2001 to 59 cohort studies at the time of the launch of the Consortium's strategic planning in 2017. This paper describes the strategic planning process that was conducted to establish organizational goals and to develop strategies and activities consistent with the Consortium's mission. The process involved a 2-year iterative approach combining surveys and in-person meetings. The resulting goals focus on communication, career development, research facilitation, scientific gaps, and common scientific challenges. The NCI Cohort Consortium's strategic plan and evaluation of its progress will advance new initiatives in cancer etiology and survivorship research., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: While the primary role of central cancer registries in the United States is to provide vital information needed for cancer surveillance and control, these registries can also be leveraged for population-based epidemiologic studies of cancer survivors. This study was undertaken to assess the feasibility of using the NCI's Surveillance, Epidemiology, and End Results (SEER) Program registries to rapidly identify, recruit, and enroll individuals for survivor research studies and to assess their willingness to engage in a variety of research activities., Methods: In 2016 and 2017, six SEER registries recruited both recently diagnosed and longer-term survivors with early age-onset multiple myeloma or colorectal, breast, prostate, or ovarian cancer. Potential participants were asked to complete a survey, providing data on demographics, health, and their willingness to participate in various aspects of research studies., Results: Response rates across the registries ranged from 24.9% to 46.9%, with sample sizes of 115 to 239 enrolled by each registry over a 12- to 18-month period. Among the 992 total respondents, 90% answered that they would be willing to fill out a survey for a future research study, 91% reported that they would donate a biospecimen of some type, and approximately 82% reported that they would consent to have their medical records accessed for research., Conclusions: This study demonstrated the feasibility of leveraging SEER registries to recruit a geographically and racially diverse group of cancer survivors., Impact: Central cancer registries are a source of high-quality data that can be utilized to conduct population-based cancer survivor studies., (©2020 American Association for Cancer Research.)

Skeletal muscle fat infiltration (known as myosteatosis) is an ectopic fat depot that increases with aging and is recognized to negatively correlate with muscle mass, strength, and mobility and disrupt metabolism (insulin resistance, diabetes). An interdisciplinary workshop convened by the National Institute on Aging Division of Geriatrics and Clinical Gerontology on September 2018, discussed myosteatosis in the context of skeletal muscle function deficit (SMFD). Its purpose was to gain a better understanding of the roles of myosteatosis in aging muscles and metabolic disease, particularly its potential determinants and clinical consequences, and ways of properly assessing it. Special attention was given to functional status and standardization of measures of body composition (including the value of D 3 -creatine dilution method) and imaging approaches [including ways to better use dual-energy X-ray absorptiometry (DXA) through the shape and appearance modeling] to assess lean mass, sarcopenia, and myosteatosis. The workshop convened innovative new areas of scientific relevance to light such as the effect of circadian rhythms and clock disruption in skeletal muscle structure, function, metabolism, and potential contribution to increased myosteatosis. A muscle-bone interaction perspective compared mechanisms associated with myosteatosis and bone marrow adiposity. Potential preventive and therapeutic approaches highlighted ongoing work on physical activity, myostatin treatment, and calorie restriction. Myosteatosis' impact on cancer survivors raised new possibilities to identify its role and to engage in cross-disciplinary collaboration. A wide range of research opportunities and challenges in planning for the most appropriate study design, interpretation, and translation of findings into clinical practice were discussed and are presented here., (Copyright © 2020 Correa-de-Araujo, Addison, Miljkovic, Goodpaster, Bergman, Clark, Elena, Esser, Ferrucci, Harris-Love, Kritchevsky, Lorbergs, Shepherd, Shulman and Rosen.)

Background: Central cancer registries are often used to survey population-based samples of cancer survivors. These surveys are typically administered via paper or telephone. In most populations, web surveys obtain much lower response rates than paper surveys. This study assessed the feasibility of web surveys for collecting patient-reported outcomes via a central cancer registry., Methods: Potential participants were sampled from Utah Cancer Registry records. Sample members were randomly assigned to receive a web or paper survey, and then randomized to either receive or not receive an informative brochure describing the cancer registry. We calculated adjusted risk ratios with 95% confidence intervals to compare response likelihood and the demographic profile of respondents across study arms., Results: The web survey response rate (43.2%) was lower than the paper survey (50.4%), but this difference was not statistically significant (adjusted risk ratio = 0.88, 95% confidence interval = 0.72, 1.07). The brochure also did not significantly influence the proportion responding (adjusted risk ratio = 1.03, 95% confidence interval = 0.85, 1.25). There were few differences in the demographic profiles of respondents across the survey modes. Older age increased likelihood of response to a paper questionnaire but not a web questionnaire., Conclusions: Web surveys of cancer survivors are feasible without significantly influencing response rates, but providing a paper response option may be advisable particularly when surveying older individuals. Further examination of the varying effects of brochure enclosures across different survey modes is warranted.

Background: An inventory of cancer survivorship cohorts is necessary to identify important gaps in what is being studied among cancer survivors., Methods: 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., Results: 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)., Conclusions: 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., Impact: 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., (©2019 American Association for Cancer Research.)

Background: We report on the establishment of a web-based Cancer Epidemiology Descriptive Cohort Database (CEDCD). The CEDCD's goals are to enhance awareness of resources, facilitate interdisciplinary research collaborations, and support existing cohorts for the study of cancer-related outcomes., Methods: Comprehensive descriptive data were collected from large cohorts established to study cancer as primary outcome using a newly developed questionnaire. These included an inventory of baseline and follow-up data, biospecimens, genomics, policies, and protocols. Additional descriptive data extracted from publicly available sources were also collected. This information was entered in a searchable and publicly accessible database. We summarized the descriptive data across cohorts and reported the characteristics of this resource., Results: As of December 2015, the CEDCD includes data from 46 cohorts representing more than 6.5 million individuals (29% ethnic/racial minorities). Overall, 78% of the cohorts have collected blood at least once, 57% at multiple time points, and 46% collected tissue samples. Genotyping has been performed by 67% of the cohorts, while 46% have performed whole-genome or exome sequencing in subsets of enrolled individuals. Information on medical conditions other than cancer has been collected in more than 50% of the cohorts. More than 600,000 incident cancer cases and more than 40,000 prevalent cases are reported, with 24 cancer sites represented., Conclusions: The CEDCD assembles detailed descriptive information on a large number of cancer cohorts in a searchable database., Impact: Information from the CEDCD may assist the interdisciplinary research community by facilitating identification of well-established population resources and large-scale collaborative and integrative research. Cancer Epidemiol Biomarkers Prev; 25(10); 1392-401. ©2016 AACR., (©2016 American Association for Cancer Research.)

There is considerable evidence that a healthy lifestyle consisting of physical activity, healthy diet, and weight control is associated with reduced risk of morbidity and mortality after cancer. However, these behavioral interventions are not widely adopted in practice or community settings. Integrating heath behavior change interventions into standard survivorship care for the growing number of cancer survivors requires an understanding of the current state of the science and a coordinated scientific agenda for the future with focused attention in several priority areas. To facilitate this goal, this paper presents trends over the past decade of the National Cancer Institute (NCI) research portfolio, fiscal year 2004 to 2014, by funding mechanism, research focus, research design and methodology, primary study exposures and outcomes, and study team expertise and composition. These data inform a prioritized research agenda for the next decade focused on demonstrating value and feasibility and creating desire for health behavior change interventions at multiple levels including the survivor, clinician, and healthcare payer to facilitate the development and implementation of appropriately targeted, adaptive, effective, and sustainable programs for all survivors., (Published by Oxford University Press (2015). This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk., Design: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models., Results: Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m(2), HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m(2), HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m(2), HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m(2))., Conclusions: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci., (Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Few studies have examined the relationship of lifestyle factors with mortality among patients with colorectal cancer., Methods: Among NIH-AARP Diet and Health study participants, 4213 colon and 1514 rectal cancer cases were identified through linkage to state cancer registries and determined date and cause of death using the National Death Index. Lifestyle factors were assessed at baseline and included: healthy diet (measured by Healthy Eating Index 2005 [HEI-2005]), body mass index (BMI), physical activity, alcohol consumption and smoking. The association of factors was examined individually and combined into a lifestyle score with 5-year mortality from all-causes, colorectal cancer, and cardiovascular disease (CVD). Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models., Results: Among colon cancer survivors, smokers had increased risk of total mortality (RR = 1.74; 95% CI = 1.45-2.08) and colorectal cancer mortality (RR = 1.46; 95% CI = 1.17-1.82), compared to never smokers. Obese (BMI, ≥ 30) individuals had increased risk of all death (RR = 1.19; 95% CI = 1.02-1.39) and CVD death (RR = 1.84; 95% CI = 1.05-3.23), compared to normal weight (BMI, 18.5 to < 25) individuals. Compared to those with the lowest lifestyle score, those with the highest score had a 34% lower risk of all-cause mortality (RR = 0.66; 95% CI = 0.50-0.87). Among rectal cancer survivors, individuals in the highest quintile of HEI-2005 scores had reduced all-cause mortality (RR = 0.60; 95% CI = 0.42-0.86) compared to those in the lowest. Higher combined lifestyle scores were associated with a 46% lower risk of total mortality (0.54; 0.32-0.91)., Conclusions: Healthier lifestyle before cancer diagnosis was associated with improved overall survival after diagnosis with colorectal cancer., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

Background and Objective: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma., Methods: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC)., Results: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis., Conclusions: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

Purpose: The evidence of a relation between folate intake and one-carbon metabolism (OCM) with pancreatic cancer (PanCa) is inconsistent. In this study, the association between genes and single-nucleotide polymorphisms (SNPs) related to OCM and PanCa was assessed., Methods: Using biochemical knowledge of the OCM pathway, we identified thirty-seven genes and 834 SNPs to examine in association with PanCa. Our study included 1,408 cases and 1,463 controls nested within twelve cohorts (PanScan). The ten SNPs and five genes with lowest p values (<0.02) were followed up in 2,323 cases and 2,340 controls from eight case-control studies (PanC4) that participated in PanScan2. The correlation of SNPs with metabolite levels was assessed for 649 controls from the European Prospective Investigation into Cancer and Nutrition., Results: When both stages were combined, we observed suggestive associations with PanCa for rs10887710 (MAT1A) (OR 1.13, 95 %CI 1.04-1.23), rs1552462 (SYT9) (OR 1.27, 95 %CI 1.02-1.59), and rs7074891 (CUBN) (OR 1.91, 95 %CI 1.12-3.26). After correcting for multiple comparisons, no significant associations were observed in either the first or second stage. The three suggested SNPs showed no correlations with one-carbon biomarkers., Conclusions: This is the largest genetic study to date to examine the relation between germline variations in OCM-related genes polymorphisms and the risk of PanCa. Suggestive evidence for an association between polymorphisms and PanCa was observed among the cohort-nested studies, but this did not replicate in the case-control studies. Our results do not strongly support the hypothesis that genes related to OCM play a role in pancreatic carcinogenesis.

As the number of cancer survivors continues to grow, research investigating the factors that affect cancer outcomes, such as disease recurrence, risk of second malignant neoplasms, and the late effects of cancer treatments, becomes ever more important. Numerous epidemiologic studies have investigated factors that affect cancer risk, but far fewer have addressed the extent to which demographic, lifestyle, genomic, clinical, and psychosocial factors influence cancer outcomes. To identify research priorities as well as resources and infrastructure needed to advance the field of cancer outcomes and survivorship research, the National Cancer Institute sponsored a workshop titled "Utilizing Data from Cancer Survivor Cohorts: Understanding the Current State of Knowledge and Developing Future Research Priorities" on November 3, 2011, in Washington, DC. This commentary highlights recent findings presented at the workshop, opportunities to leverage existing data, and recommendations for future research, data, and infrastructure needed to address high priority clinical and research questions. Multidisciplinary teams that include epidemiologists, clinicians, biostatisticians, and bioinformaticists will be essential to facilitate future cancer outcome studies focused on improving clinical care of cancer patients, identifying those at high risk of poor outcomes, and implementing effective interventions to ultimately improve the quality and duration of survival.

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.