Cohort Consortium Projects

Background: The African American BMI and Mortality Pooling Project, established in 2011, examines the relation between BMI and disease mortality, including cancer and cardiovascular disease, in African American men and women. The project draws data from seven cohorts that contain at least 10,000 African American participants.

Background: The Biliary Tract Cancers Pooling Project, begun in 2012, is a prospective study to evaluate risk factors for individual types of biliary tract cancers, including smoking, diabetes, anti-inflammatory drug use, and family history of cancer. Gallbladder cancer accounts for more than 50 percent of biliary tract cancers and occurs more often in women than in men.

In addition, other cancers of the biliary tract display distinct demographic and molecular profiles indicating that they are separate disease entities. Little is known about the etiology of these rare cancers beyond a positive association with history of cholesterol gallstones.

Background: The secondary analysis project, begun in 2011, uses BMI and Mortality Pooling Project data to examine the relationship between BMI and all-cause mortality among subgroups defined by smoking status, health status, gender, and age. NHANES data and other samples will be used to examine corrections for the self-reporting of body weight and height.

Background: This project began in 2011 to assess the association of waist circumference with total and selected cause-specific (e.g., cardiovascular, cancer) mortality. A secondary analysis will assess hip circumference and waist-to-hip ratio. The project is using data on more than 650,000 participants from 11 cohorts in the BMI and Mortality and Physical Activity Pooling Projects.

Background: This new BPC3 study will expand the first phase of BPC3 to serve as a rapid verification test set for SNPs identified in the scans other than the CGEMS scan, and to examine gene-environment interactions in the SNPs identified in CGEMS and other studies as being associated with breast and prostate cancer.

With the completion of GWAS for breast cancer and prostate cancers in aggregate, important questions remain that the BPC3 is uniquely positioned to answer. Estrogen receptor negative (ER-) breast cancers have specific epidemiologic characteristics and greater lethality, but the current generation of scans is underpowered to discover gene variants associated with these tumors. Aggressive forms of prostate cancer, characterized by extraprostatic extension (Stage C/D) or high histologic grade (Gleason score 8+), differ epidemiologically from the vastly more common indolent forms of prostate cancer and are of the greatest clinical importance, but again the current scans are underpowered to discover associated genetic determinants. No single study is likely to have enough cases of these cancer subtypes to perform a GWAS. By pooling cases across the BPC3 studies, the investigators can achieve adequate power to discover genetic variation that gives rise to these important clinical subtypes.

Background: GliomaScan, begun in 2008, investigates the etiology, prevention, and treatment of brain tumors by conducting a GWAS study of glioma with a large number of cohort-derived samples. Follow-up analyses are examining genetic pathways, gene-gene, and gene-environment interactions. The study has found evidence of strong replication for three previously reported associations; larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

Background: This project began in 2010 and aims to (1) study associations of risk factors for invasive ovarian cancer, including how these factors differ by histologic subtype, tumor dominance, and tumor aggressiveness; and (2) develop ovarian cancer risk prediction models accounting for differential associations by cancer phenotype. The project will create an infrastructure with a core dataset of variables for studying ovarian cancer epidemiology including projects that will use prospectively collected biological specimens.

Background: The Diet/Activity Assessment Methods Project, initiated in 2008, evaluates the measurement error structure of several self-reported, Internet-based, diet and physical activity assessment tools and questionnaires (e.g., food frequency and physical activity) and compares them against reference biomarkers and activity monitors among participants in the NIH-AARP Diet and Health Study, Harvard's Nurses' Health Study, and Health Professionals Follow-up Study.

Background: The E3C3 was established in 2009 to evaluate the association between lifestyle habits and esophageal cancer risk, overall and by histologic subtype. The risk factors being studied include alcohol and tobacco use, excess body weight, sedentary lifestyle, history of adult-onset diabetes mellitus, chemopreventive agents, as well as occupation and ethnicity.

The study will also assess risk for developing esophageal cancer if individuals have certain medical conditions including Helicobacter pylori infection, celiac disease, hemochromotosis, and pernicious anemia.

Background: This study began in 2012 to conduct a prospective, pooled analysis of circulating levels of folate, other B vitamins, and metabolites involved in one-carbon metabolism in relation to breast cancer risk, overall and by tumor subtype, folic acid fortification use, genetic variation in folate metabolism, and other risk factors. This study should shed light on the influence of folic acid fortification and/or supplement use on breast cancer risk and the role of one-carbon metabolism in breast cancer etiology.

Background: This study, initiated in 2008, is conducting a GWAS in two anatomically different upper gastrointestinal cancer sites in two populations with distinctly different disease rates and genetic profiles. One population has very high rates of both esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC) and consists of participants from East Asian countries. The other population has low rates of ESCC and GC and includes participants from the Americas, Europe, Australia, the Middle East, and others.

Background: Begun in 2008, this project is identifying the genes involved in endometrial cancer to help identify novel targets for endometrial cancer risk prediction, prevention, and treatment. The researchers are genotyping more than 2,600 Type I endometrial cancer cases of European descent and an equal number of controls. The effect of the SNPs that indicate genome-wide significance will be characterized in terms of body mass index, exogenous hormone use, and other established endometrial cancer risk factors.

Background: This project, begun in 2008, is conducting a GWAS of NHL and selected NHL subtypes in cases from the InterLymph Consortium. Genome scanning is completed and data analysis is in progress. The analysis will focus on individual NHL histologic subtypes, where appropriate, and compare across subtypes to evaluate heterogeneity in genetic susceptibility to NHL. Secondary analyses of genotype data and gene-environment studies are planned.

Background: Within the framework of the NCI-sponsored Cohort Consortium, investigators from 12 prospective epidemiologic cohorts formed the Pancreatic Cancer Cohort Consortium in 2006. The group's first study, also known as "PanScan I," involved a genome-wide association study (GWAS) of common genetic variants to identify markers of susceptibility to pancreatic cancer. In 2007, the study was expanded to include 8 case-control studies (PanScan II). PanScan I and II led to the discovery of four novel regions in the genome associated with risk for pancreatic adenocarcinoma.

The third phase of PanScan (PanScan III), will study recently identified incident pancreatic cancer cases and controls drawn from 14 cohorts from the Cohort Consortium, including the 10 prospective cohorts who participated in PanScan I and II, and four newly joined cohorts. Therefore, PanScan III will include approximately 2,400 additional cases for genome-wide scanning. In a replication study, PanScan III investigators will genotype the top 20-50 loci from the GWAS. A joint analysis of the newly scanned cases will be conducted with cases from PanScan I and II to identify novel regions of the genome associated with pancreatic cancer susceptibility. With the larger sample size (about 6,200 cases and 13,900 controls), it is anticipated that the PanScan III study will identify new genetic risk variants for etiology.

Background: This project, begun in 2009, will expand the existing GWAS of Renal Cell Carcinoma by scanning an additional 5,000 cases and controls, identifying novel RCC susceptibility loci, and obtaining survival data to enable GWAS of RCC survival. It also will search for evidence of interaction between genetic variants and established risk factors for RCC.

Background: This project, established in 2012, will estimate risk ratios and attributable fractions for established and suspected head and neck cancer (HNC) risk factors. The project will validate the International Head and Neck Cancer Epidemiology (INHANCE) HNC risk prediction model with data from the Cohort Consortium and establish the Cohort's own risk prediction model both overall and for subsites (e.g., oral cavity, oropharynx, hypopharynx, larynx) as well as exploring other HNC risk factors such as coffee/tea intake, sexual behaviors, reproductive factors for women, and physical activity.

Background: The Liver Cancer Pooling Project was formed in 2008 to study known and novel risk factors for the increasing incidence of liver cancer in the United States. Possible factors include BMI, diabetes, physical activity, reproductive history, hormone levels, hypertension, occupational and pesticide exposure, and inflammatory markers. The project has compiled data and serum samples from 14 participating U.S. cohorts encompassing more than 2,000 individuals with liver cancer.

Background: This project began in 2009 to evaluate etiological factors of lung cancer and to develop extensive risk prediction models, with particular focus on biomarkers of one-carbon metabolism, as well as vitamin D and inflammation. Biochemical and genetic analyses will be conducted on more than 5,000 lung cancer cases from 24 individual cohorts.

Background: The Male Breast Cancer Pooling Project, begun in 2008, is evaluating data from case-control studies to better understand causes of this rare cancer. Hormonal factors and multiple exposures considered include BMI, physical activity, diet, and family history of breast cancer. Other exposures studied include alcohol consumption, liver and thyroid diseases, infertility history, and occupational exposures. Future studies may involve genetic assays and more detailed pathologic and molecular characterization of the tumors.

Background: This project, begun in 2009, is evaluating the association between HPV and HNCs, including cancers of the oral cavity, oropharynx, and larynx, by testing incident cancer cases and matched controls using new serologic assays that allow measurement of anti-HPV antibodies. Results are expected in autumn 2012.

Background: The goal of this project, begun in 2012, is to perform detailed evaluations of the relationship between BMI and Waist-Hip Ratio and lethal prostate cancer. This will be the largest prospective analysis of obesity yet and could provide critical information toward establishing whether obesity is related to lethal prostate cancer, as well as the dose-response relationship, the timing of exposure, and the role of central adiposity. The study also will assess whether the association is confounded/modified by smoking, physical activity, diabetes, and race.

Background: This project began in 2011 to evaluate the association between BMI and risks of thyroid, gallbladder, and HNCs, drawing on data from existing cancer cohorts. This would be the largest prospective analysis yet for these cancer sites and could provide critical information toward establishing whether they are related to obesity.

Background: This project began in 2011 to characterize folate, particularly unmetabolized folic acid, and its association with colorectal cancer. The study will explore folate status in different populations, the dose-response relationship between plasma folate and colorectal cancer and assess the effects by demographic, lifestyle, and genetic factors. By pooling data from several NCI cohorts, the project expects to improve comparability among the blood measurements in different cohorts and provide scientific evidence to inform policies on folic acid fortification.

Background: This study, begun in 2007, assesses the association between concentrations of one-carbon metabolites in pre-diagnostic blood and the risk of developing hepatocellular carcinoma. The study also is evaluating the modifying effect of genetic polymorphisms in the genes that are involved in one-carbon metabolites and risk of hepatocellular carcinoma. Laboratory measurements of serum one-carbon metabolism biomarkers, with statistical analyses, have been completed on all hepatocellular carcinoma cases and controls of the Shanghai Cohort Study.

Background: This study began in 2011 and will assess the association between physical activity and individual cancer sites and overall cancer burden. In addition, the project will include hazard ratios for each cancer site studied to estimate the dose-response relation between physical activity and cancers of the breast, endometrium, and colon and rare cancers that have not been adequately examined in prior physical activity studies.

Background: The Pooled Analysis of Active Smoking and Breast Cancer Risk began in 2012 to address remaining inconsistencies in key methodological issues in individual studies of the relationship between active cigarette smoking and breast cancer, by analyzing pooled data from prospective cohort studies. The factors studied will include smoking duration, alcohol consumption, mammographic screening, age at menopause, BMI, socioeconomic status, reproductive patterns, and use of postmenopausal hormones, and family history of breast cancer.

Background: This study, begun in 2012, examines non-treatment risk factors for second cancers. The etiology of most second cancers is unknown, and the risk factors for these cancers likely account for the majority of multiple primary malignancies. Pooling data from five cohorts, three projects have been launched to study: (1) second cancer incidence and methodological challenges of studying second cancer risk factors in epidemiologic cohorts; (2) obesity and second cancer risk among colorectal cancer survivors; and (3) tobacco, alcohol, and risk of multiple primary cancers.

Background: This project, which began in 2007, is exploring the association between the risk for MM and markers of dysregulation in insulin-like growth factor (IGF), insulin, and interleukin (IL)-6 signaling pathways. The analyses of plasma studies are complete, and an expanded series of studies on genetic markers was developed to permit replication of newly published genetic susceptibility findings in pathways related to signaling by IGF, IL-6, insulin or other mediators of inflammation or innate immunity. The genotyping of DNA samples also is finished, and data analysis is in progress.

Background: This project, initiated in 2011, is the first prospective assessment of risk factors for inflammatory breast cancer. Exposures to be considered include reproductive factors, smoking history, alcohol intake, BMI, and family history. Although inflammatory breast cancer comprises 1 to 2 percent of total breast cancer cases, it is an aggressive form of breast cancer that has been studied only by a small number of case-control studies.

Background: Begun in 2008, this project includes 20 cohort studies and is investigating the association between circulating 25-hydroxyvitamin D levels and the risk of breast and colorectal cancers. Analyses will be conducted by tumor subtype, population subgroups, lifestyle factors, polymorphisms in vitamin D receptor and metabolism genes, and other biomarkers.

Background: This project began in 2007 as a collaborative effort among more than 20 prospective epidemiologic studies to examine and quantify the relationship between BMI and all-cause mortality; and determine the extent to which the relationship between BMI and all-cause mortality varies by factors such as age, sex, smoking status, preexisting heart disease or cancer, physical activity, alcohol intake, education, and marital status.

The project analyzed pooled data from prospective studies encompassing 1.46 million adults to estimate hazard ratios for the association between BMI and all-cause mortality. The results were published in 2010.

Background: The BPC3 began in 2003 to study hormone-related gene variants and environmental factors involved in the development of breast and prostate cancers. The goal was to characterize variations in about 55 candidate genes that mediate the steroid hormone metabolism and insulin-like growth factor (IGF) signaling pathways, and associate these variations with cancer risk.

In 2007, the BPC3 expanded the study population and used a genome-wide association approach to identify genetic variants that may be associated with estrogen receptor negative breast cancer, as well as aggressive forms of prostate cancer.

Background: Not available.

Background: Begun in 2011, the goal of this study is to identify risk of death and years of life lost or gained according to physical activity and BMI levels. This study has been completed and a manuscript has been accepted for publication.

Background: Not available.

Background: This project, initiated in 2007, is a nested case-control study that analyzed the association between 25(OH)D (serum vitamin D concentrations) and the development of seven rarer cancers: endometrial, esophageal, stomach, ovarian, pancreatic, and kidney cancers, and non-Hodgkin lymphoma (NHL). The study involved 10 cohorts, and participants' vitamin D levels were measured in serum collected before the development of cancer. Study findings do not support the hypothesis that circulating 25(OH) D concentrations are associated with a reduced risk of developing any of these seven rarer cancers. The results were published in 2010.