DIETARY FATTY ACIDS--ROLE IN HORMONALLY MEDIATED CANCER

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DESCRIPTION: (Applicant's Description) Etiologic factors responsible for the development of sex steroid hormone-dependent cancer, such as breast cancer, are not fully understood, but level and type of dietary fat consumed have been hypothesized to contribute to the development of this cancer. Plant food intake has been consistently associated with lower risk for breast cancer. Specific non-nutrient phytochemicals, such as soy isoflavonoids, are similar in structure to sex steroid hormones and may therefore act in vivo to alter hormone metabolism and subsequent cancer risk. Because the majority of breast cancer cases appear to involve a strong hormonal component, it is probable that dietary fats and phytochemicals may influence this risk. The overall objective of this application is to explore the effects of varying types of dietary fat (thus, varying specific fatty acid content in the diet), but not the amount of total fat, on circulating steroid hormone (especially endogenous estrogen) in premenopausal women. Thus, in Feeding Study 1 (Year), two diets, both of which will provide 36 percent energy as fat and 15g dietary fiber (similar to American diet), will be used. The high saturated fat diet will pro-vide 23 percent of energy as saturated fat. The specific aim of this application is to determine whether serum concentrations and urinary excretion of sex hormones and binding proteins are influenced by type of fat, when fat intake is high and dietary fiber is moderate. Another objective of this project is to examine whether dietary soy may moderate the effect of dietary saturated fatty acids on hormones metabolism. Thus, in Feeding Study 2 (Year 2), the high saturated fat diet with and without added soy will be used. Both feeding studies will be implemented as randomized, crossover, controlling feeding trials. Twenty-four premenopausal women will be recruited for each study. After a baseline period (1 menstrual cycle), where data on usual diet, exercise habits, menstrual cycle, and serum and urinary hormones will be collected, the women will be randomized onto one of the two study diets. Each woman will consume that diet for two menstrual cycles; after a washout period of 1 menstrual cycle, a woman will cross over to the other experimental diet for another two cycles. Women will recorded basal body temperature daily for all six cycles, as well as perform serial urinary luteinizing hormone (LH) surge testing for several days mid-cycle; in addition, serial blood will be drawn and 24-h urine collected twice each cycle for midfollicular and midluteal serum and urinary hormone and sex hormone binding globulin analysis to determine the effects of varying types of dietary fat on hormone profiles. In addition, in Feeding Study 2, urinary isoflavonoids will be measured to determine metabolism and excretion patterns. This randomized clinical trial expands our knowledge of women's health and provides more precise information to understand: 1) the epidemiologic associations between dietary fat intake and breast cancer; 2) the use of diet exposure markers; and 3) potential indicators of breast risk which may be monitored for the primary prevention of cancer.