The WHS began in 1992 as a randomized controlled trial testing aspirin, beta-carotene, and vitamin E for preventing cancer and cardiovascular disease (CVD) in 39,876 healthy women, aged >45, The trial ended in 2004, and women have been followed observationally since that time. At study entry and annually, women report via questionnaires on a wide range of exposures and endpoints, including cancer and CVD. We confirm these self-reported endpoints with medical records, and cause of death in decedents is ascertained using medical records and death certificates. At baseline, 28,345 women also provided a blood sample, from which plasma, buffy coat, and red blood cells were obtained and stored at -170 ?C. GWAS data on common variation are available for all women with blood, measurement of rare variants in exomes have just been completed for >23,000 women; and all samples have been assayed for several biomarkers. Objectively assessed 7-day physical activity by accelerometer is being collected on ~18,000 women. The WHS cohort is unique in having GWAS and objectively-assessed physical activity in such a large cohort. Follow-up is excellent; after almost 20 years, morbidity follow-up is 94 percent; and mortality follow-up is virtually 100 percent. At the end of current funding, 6,086 confirmed cancers (2,440 breast, 583 colorectal, 537 lung, 1,517 cancer deaths) will have occurred. During the proposed funding period, cancer and CVD endpoints will increase by 30 percent and 51 percent. The WHS has actively provided data to internal and external researchers, with 444 papers published, 89 ancillary studies funded, and participation in 19 NCI Cohort Consortium collaborative projects. In the proposed funding period, we intend to: (1) continue to update exposure and endpoint information, and maintain the repository of biospecimens, to further facilitate data sharing and collaboration, and (2) use the WHS infrastructure to address specific aims related to physical activity; evaluate the translational potential of gene-based risk and explore gene-by-environment interactions; and examine long-term chemo-protection of low-dose aspirin on cancer. None of the ancillary studies provides funding for ascertainment and validation of cancer (and CVD) endpoints. Continued infrastructure support and follow-up is crucial for maximizing the cost-effective use of this valuable large-scale cohort of women with a rich bank of already collected phenotypic and genetic data.

Public Health Relevance

This application seeks support over the next 5 years for the infrastructure of the Women's Health Study, a large-scale cancer epidemiology cohort of 39,876 women followed since 1992, Data are available on a wide range of characteristics, chronic disease development, blood biomarkers, genetic information, and objectively measured physical activity. Continued follow-up is crucial for building on the enormous amount of data already collected in order to answer critical questions related to cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1CA182913-04
Application #
9338194
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Elena, Joanne W
Project Start
2014-09-17
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Ahmad, Shafqat; Mora, Samia; Franks, Paul W et al. (2018) Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study. Clin Chem 64:231-241
Yu, Y H; Doucette-Stamm, L; Rogus, J et al. (2018) Family History of MI, Smoking, and Risk of Periodontal Disease. J Dent Res 97:1106-1113
Emdin, Connor A; Khera, Amit V; Chaffin, Mark et al. (2018) Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease. Nat Commun 9:1613
Tobias, Deirdre K; Akinkuolie, Akintunde O; Chandler, Paulette D et al. (2018) Markers of Inflammation and Incident Breast Cancer Risk in the Women's Health Study. Am J Epidemiol 187:705-716
Lee, I-Min; Shiroma, Eric J; Evenson, Kelly R et al. (2018) Accelerometer-Measured Physical Activity and Sedentary Behavior in Relation to All-Cause Mortality: The Women's Health Study. Circulation 137:203-205
Tobias, Deirdre K; Lawler, Patrick R; Harada, Paulo H et al. (2018) Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women. Circ Genom Precis Med 11:e002157
Chandler, Paulette D; Tobias, Deirdre K; Wang, Lu et al. (2018) Association between Vitamin D Genetic Risk Score and Cancer Risk in a Large Cohort of U.S. Women. Nutrients 10:
Rist, Pamela M; Winter, Anke C; Buring, Julie E et al. (2018) Migraine and the risk of incident hypertension among women. Cephalalgia 38:1817-1824
Samieri, Cécilia; Morris, Martha-Clare; Bennett, David A et al. (2018) Fish Intake, Genetic Predisposition to Alzheimer Disease, and Decline in Global Cognition and Memory in 5 Cohorts of Older Persons. Am J Epidemiol 187:933-940
Rice, Megan S; Rist, Pamela M; Winter, Anke C et al. (2018) Migraine and invasive epithelial ovarian cancer risk in the Nurses' Health Study II and the Women's Health Study. Int J Cancer 142:534-539

Showing the most recent 10 out of 137 publications