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Grant Abstract: The Womens Health Study: Infrastructure Support for Continued Cohort Follow-up

Grant Number: 5UM1CA182913-03
PI Name: Buring
Project Title: The Womens Health Study: Infrastructure Support for Continued Cohort Follow-up

Abstract: Abstract: DESCRIPTION (provided by applicant): Despite compelling postulated mechanisms of action and observed benefits in observational studies, trials of dietary supplements in chronic disease prevention have not found consistent benefit, and in some instances, shown harm. This so-called “efficacy paradox” has been attributed to variability in patient demographics, disease state, or supplement dose and duration, but although individual responses to supplements vary widely, the contribution of genetics to this variability is not well understood. This knowledge gap is partly due to the lack of clinical trials with a large sample size, long term follow-up and genome-wide association study (GWAS) data required to identify genetic effects. Consequently the promise of pharmacogenomics to guide development of precision prevention with supplements remains unrealized. Given the popularity and wide-availability of supplements and outstanding questions of efficacy and harm, rigorous research designed to answer these questions and guide the development of precision prevention supplements is warranted.

The Women’s Health Study (WHS), with its extensive phenotype and genotype information from an ongoing large, long-term, and aging cohort of women, has the potential to be a rich resource for the study of dietary supplements and their pharmacogenetic effects. The specific aims of this administrative supplement are to: extend the evaluation of the effects of randomized supplementation with vitamin E; evaluate the effects of candidate gene (COMT) interaction with vitamin E on cancer in the WHS; use a GWIS to identify additional genes that modify vitamin E treatment effects; and develop a survey to more fully characterize supplement use in the WHS cohort.

This supplement will allow the use of the WHS cohort to evaluate the potential importance of considering genetic composition in evaluating clinical efficacy and use pharmacogenomics to guide the development of more individualized strategies for supplement use. This has the crucial potential to yield important insights into differences in the ways that dietary supplements could prevent chronic disease. Finally, building this resource in the WHS will allow this study to contribute in the future to consortium activities on the effect of dietary supplements.

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