This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sex hormone mediated cancers, such as breast, present a significant problem in the United States. It is important to develop safe and effective preventative strategies for these diseases. Epidemiological evidence and animal studies show that dietary fat is associated with risk of development of sex hormone mediated cancer. Specifically, that a high intake of omega-6 fatty acids increases risk while omega-3 fatty acids are associated with risk reduction. Although the associations between dietary fat and sex hormone mediated cancers is unclear, it is likely due to mechanisms of endocrine balance, eicosanoid production, or immune function. This proposal addresses important questions about the effects of dietary total fat and fatty acids on sex hormone concentrations in postmenopausal women. The specific objectives are: 1) to evaluate the effects of total fat and omega-3 fatty acid intake on plasma and urinary sex hormone levels in postmenopausal women, 2) to evaluate the relationship between plasma concentrations of fatty acids and of plasma and urinary sex hormones, and 3) to evaluate the effects of total fat and omega-3 fatty acids on the association between sex hormone concentrations and urinary prostaglandin E2 and thromboxane B2 concentrations. In order to evaluate these relationships we wil conduct a well-controlled feeding study to evaluate dietary fat and fatty acid effects. The diets to be tested in 8 week feeding periods include a 'high risk' American diet (40% fat), a low fat diet (20% fat) and a low fat diet with supplemental omega-3 fatty acids (23% fat). Endpoint measures of urinary and plasma sex hormones, plasma fatty acids, and the urinary eicosanoids, prostaglandin E2 and thromboxane B2, will be made at baseline, and at 4 and 8 week of each dietary treatment.
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