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

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Perloff, Marjorie
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Brigham and Women's Hospital
United States
Zip Code
Rist, Pamela M; Buring, Julie E; Kurth, Tobias (2015) Dietary patterns according to headache and migraine status: a cross-sectional study. Cephalalgia 35:767-75
Yu, Yau-Hua; Chasman, Daniel I; Buring, Julie E et al. (2015) Cardiovascular risks associated with incident and prevalent periodontal disease. J Clin Periodontol 42:21-8
Mora, Samia; Akinkuolie, Akintunde O; Sandhu, Roopinder K et al. (2014) Paradoxical association of lipoprotein measures with incident atrial fibrillation. Circ Arrhythm Electrophysiol 7:612-9
Sandhu, Roopinder K; Conen, David; Tedrow, Usha B et al. (2014) Predisposing factors associated with development of persistent compared with paroxysmal atrial fibrillation. J Am Heart Assoc 3:e000916
Kraja, Aldi T; Chasman, Daniel I; North, Kari E et al. (2014) Pleiotropic genes for metabolic syndrome and inflammation. Mol Genet Metab 112:317-38
Chasman, Daniel I; Anttila, Verneri; Buring, Julie E et al. (2014) Selectivity in genetic association with sub-classified migraine in women. PLoS Genet 10:e1004366
Akinkuolie, Akintunde O; Paynter, Nina P; Padmanabhan, Latha et al. (2014) High-density lipoprotein particle subclass heterogeneity and incident coronary heart disease. Circ Cardiovasc Qual Outcomes 7:55-63
Qi, Qibin; Chu, Audrey Y; Kang, Jae H et al. (2014) Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies. BMJ 348:g1610
Rist, Pamela M; Glymour, M Maria; Orav, E John et al. (2014) Non-steroidal anti-inflammatory drug use and functional outcome from ischemic cerebral events among women. Eur J Intern Med 25:255-8
Hall, Kathryn T; Nelson, Christopher P; Davis, Roger B et al. (2014) Polymorphisms in catechol-O-methyltransferase modify treatment effects of aspirin on risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 34:2160-7

Showing the most recent 10 out of 242 publications