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    Awarded Grants
    A Prospective Study of Alcohol Intake, Genetic Susceptibility and Breast Cancer Overall Health Risk

    Scientific Abstract:
    Alcohol intake, at low to moderate levels, has both beneficial and adverse effects on health outcomes. It is one of the few known modifiable risk factors for breast cancer. An increased risk of breast cancer is observed at levels of intake that are associated with lower risks of cardiovascular disease and diabetes. Given the high prevalence of the exposure, this means that as much as 40% of breast cancer could be attributed to alcohol intake. Because of the mixed effects of alcohol intake, it is critical to gain the “big picture” of the effects of alcohol use in combination with genetic susceptibility factors. The proposed study will take a “holistic approach” to determining overall risks and benefits of low levels of alcohol intake. We hypothesize that an individual’s net benefit or net risk is due to genetic influences as well as environmental factors such as diet and supplement use. We propose a population-based cohort study to examine the association between alcohol intake and its impact on the development of breast cancer and global health, and the variation in outcomes according to genotypes of specific candidate genes. This aim will be accomplished efficiently by analyzing data from on ongoing community-based cohort study. Specifically, we will examine the association between alcohol intake and breast cancer incidence and survival according to polymorphisms in genes within relevant biological pathways such as alcohol metabolizing, hormone and inflammatory pathway genes. We will also assess if the progression from proliferative forms of benign breast disease to invasive breast cancer is associated or modified by alcohol intake. To examine the overall impact of alcohol on health outcomes, we will assess the association between alcohol intake and a global assessment of health as well as specific health outcomes of cancer, cardiovascular disease, diabetes, and sleep disturbance. The results of this study will be broadly applicable in counseling individuals regarding the overall risks and benefits of low to moderate levels of alcohol. The study also will examine if subgroups of individuals, defined by their genetic profile, have different risk/benefit profiles. These results will help guide clinical practice, and have policy implications if common genotypes are associated with variation in alcohol’s effects. This is particularly relevant, as companies have begun to directly market DNA tests examining common polymorphisms in the proposed candidate genes, despite the paucity of information regarding their impact on health outcomes.

    Lay Abstract:
    Women often find themselves in a quandary when it comes to weighing risks and benefits of low levels of alcohol intake. Levels of alcohol intake that have been associated with lower risk of heart disease are also associated with a higher risk of breast cancer. The overall impact on health is seldom assessed in these studies. It is critical to understand the “big picture” of the potential benefits and risk of low levels of alcohol intake. We propose to take a holistic approach to determine the overall health risks and benefits and to help women make educated choices about factors that can change their risk of heart disease and cancer. Factors that may change risks for in individual include the amount of alcohol consumed, how it is metabolized and processed in the body, other existing health problems and medication and vitamin use. Genes influence how we metabolize and process chemicals such as alcohol and other nutrients that may influence the effects of alcohol. We will look at how the effects of alcohol intake differ by genetic factors as well as other factors such as medication use, diet and vitamin use. We will examine if an individual’s net benefit or net risk is due to genetic influences as well as other factors we can control such as diet or supplement use. To answer these questions we will use information gathered from individuals who have taken part in an ongoing study based in a rural/suburban community. Men and women joined the study in 1989 and answered questions about their diet habits, alcohol intake, medicine and vitamin use. They also gave a blood sample to be used for medical research purposes. We have asked individuals about their health and other risk factors about every 2 years since 1996. We also have information on common genetic changes in genes that affect how alcohol is processed by the body. We will look to see if these genetic changes as well as other factors such as diet, medication and vitamin supplements can help us determine how alcohol intake effects overall global health. In others words, we aim to examine whether alcohol intake has a net positive or negative impact on the development and survival from breast cancer, as well as the occurrence of other common medical conditions such as heart disease, diabetes, and sleep disturbance. The results of this study will be helpful to women in deciding whether they will be helped or hurt by drinking low to moderate amounts of alcohol. We may be able to determine who will reap the benefits of low alcohol intake for their heart without causing overall harm.