This proposal seeks funding to continue observational follow-up of the 39,876 Women's Health Study (WHS) participants for an additional 5 years, with the overarching aim of accruing and validating a substantially increased number of both cancer and cardiovascular disease (CVD) endpoints to evaluate clinically important questions related to lifestyle, biochemical markers, genetic markers, and gene-environment interactions. At a very low incremental cost per participant, an added 5 years of observational follow-up will increase total cancer and CVD endpoints by 57% to 86% over the numbers occurring in the first 15 years of the study. The WHS began in 1992 as a randomized trial of aspirin and vitamin E in the primary prevention of cancer and CVD among 39,876 female health professionals aged e45 years, ending in 2004 after a mean of 10 years. Pre-randomization blood samples provided by >28,000 participants were processed, frozen, and stored, and federal and non-federal funding has allowed the conduct of extensive plasma biomarker analyses and a whole genome association scan (GWAS). Women are now followed observationally with yearly endpoint and risk factor questionnaires. After 15 years, morbidity follow-up is well over 90% and mortality follow-up is virtually 100%. Endpoint validation is up to date, with review of 89-95% of medical records completed for self-reported cancer and CVD endpoints. Thus, this study represents an extremely rich resource of high-quality data for studying important health concerns in women. In addition to the overarching aim, the proposal specifically seeks to evaluate questions that have not had adequate sample sizes to date. For cancer, we will investigate aspects of energy balance, vitamin D metabolism, and colorectal cancer risk by examining: (1) the interaction between obesity and physical activity on colon cancer risk;(2) obesity-associated gene variants and colorectal cancer risk;(3) the associations of adiponectin, related gene variants, and colorectal cancer risk;and (4) gene variants related to vitamin D metabolism and colorectal cancer. For CVD, the application seeks to evaluate clinical, biochemical, and genetic risk factors for subtypes of stroke and functional outcomes from stroke in women, an understudied group. With an additional 5 years of endpoints, power will now be adequate to address these questions. Finally, augmenting the existing WHS biorepository with additional cancer and CVD endpoints will allow continued fruitful collaborations with cancer, CVD, and genomic consortia to answer questions regarding genetic and environmental risk factors and gene-environment interactions (the WHS has 44 completed and 36 currently funded ancillary studies). Failure to secure an additional 5 years of endpoints will jeopardize not only the parent study, but also all ancillary studies as well as the ability to capitalize on this enormously valuable data resource and GWAS already available. 1

Public Health Relevance

The Women's Health Study (WHS) is an ongoing observational follow-up of the 39,876 initially healthy women who were enrolled in the WHS trial, begun in 1992, to evaluate the roles of low-dose aspirin and vitamin E in the primary prevention of cancer and cardiovascular disease (CVD). The participants have now been followed for an average of 15 years, and extensive clinical and risk factor data have been collected over that time. Biochemical and genome-wide scan data are also available for the more than 28,000 participants who provided a baseline blood sample. This proposal requests funding for 5 more years of ascertainment and validation of cancer and CVD endpoints, to allow the evaluation of clinically important questions related to the influence of lifestyle, biochemical markers, genetic markers, and gene-environment interactions on cancer and CVD risk. 1

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA047988-23
Application #
8598073
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Perloff, Marjorie
Project Start
1991-02-01
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
23
Fiscal Year
2014
Total Cost
$1,651,870
Indirect Cost
$351,185
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Wong, Jorge A; Rexrode, Kathryn M; Sandhu, Roopinder K et al. (2017) Number of Pregnancies and Atrial Fibrillation Risk: The Women's Health Study. Circulation 135:622-624
Sapkota, Yadav; Vivo, Immaculata De; Steinthorsdottir, Valgerdur et al. (2017) Analysis of potential protein-modifying variants in 9000 endometriosis patients and 150000 controls of European ancestry. Sci Rep 7:11380
Albert, Michelle A; Durazo, Eva M; Slopen, Natalie et al. (2017) Cumulative psychological stress and cardiovascular disease risk in middle aged and older women: Rationale, design, and baseline characteristics. Am Heart J 192:1-12
Lindström, Sara; Germain, Marine; Crous-Bou, Marta et al. (2017) Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study. Hum Genet 136:897-902
Campbell, Peter T; Newton, Christina C; Kitahara, Cari M et al. (2017) Body Size Indicators and Risk of Gallbladder Cancer: Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies. Cancer Epidemiol Biomarkers Prev 26:597-606
Harada, Paulo H N; Buring, Julie E; Cook, Nancy R et al. (2017) Impact of Subclinical Hypothyroidism on Cardiometabolic Biomarkers in Women. J Endocr Soc 1:113-123
Harada, Paulo H N; Demler, Olga V; Dugani, Sagar B et al. (2017) Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study. J Clin Lipidol 11:1257-1267.e2
Rhee, Jinnie J; Kim, Eunjung; Buring, Julie E et al. (2017) Fish Consumption, Omega-3 Fatty Acids, and Risk of Cardiovascular Disease. Am J Prev Med 52:10-19
Shiroma, Eric J; Cook, Nancy R; Manson, Joann E et al. (2017) Strength Training and the Risk of Type 2 Diabetes and Cardiovascular Disease. Med Sci Sports Exerc 49:40-46
Pettee Gabriel, Kelley; Sternfeld, Barbara; Shiroma, Eric J et al. (2017) Bidirectional associations of accelerometer-determined sedentary behavior and physical activity with reported time in bed: Women's Health Study. Sleep Health 3:49-55

Showing the most recent 10 out of 351 publications