Dietary Fat, Eicosanoids and Breast Cancer Risk
The guiding concept of our proposal is that both the total fat and the fatty acid
composition of the diet contribute to a milieu associated with the risk for sex-hormone
mediated cancers. Specifically, we hypothesize that an increased concentration of
circulating n3 fatty acids will reduce the biochemical markers associated with increased
risk for developing certain sex hormone mediated cancers such as breast cancer. When
compared with the high fat diet, we expect n3 concentrations to increase and sex hormone
levels to decrease after both low fat and low fat/n3 rich diets, with the greatest response
in the low fat-n3 supplemented group. The aims of this project are: 1) to evaluate the
effects of total fat and n3 fatty acid consumption on plasma and urine sex hormone
concentrations in postmenopausal women, 2) to evaluate the relationship between plasma
concentrations of fatty acids and plasma and urinary sex hormone concentrations, and 3) to
evaluate the effects of total fat and n3 fatty acid consumption on the associations between
sex hormone concentrations and urinary prostaglandin E2 and thromboxane B2 concentrations.
The primary objective of this investigation is to determine whether diets designed to
increase plasma n3 concentrations (a low fat diet, with or without n3 fatty acid
enrichment), will favorably affect sex hormone distribution in women in a direction
associated with reduced risk of sex hormone-mediated cancer development. The primary
endpoints to be evaluated include plasma and urinary sex hormone concentrations as follows:
Endpoints associates with increased risk factors for breast cancer risk: plasma estradiol
(E2), estrone (E1), estrone sulfate (E1 sulfate), testosterone, androstenedione, sex
hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), dehydroepiandrosterone
sulfate (DHEAS), Measures of estrogen action: plasma follicle stimulating hormone (FSH),
urinary estrogen metabolites.
Measures of systemic arachidonic acid-derived eicosanoids: urinary bicyclo-prostaglandin E2
(PGEa), 2,3-dinor thromboxane B2 (TXB2).
Measures reflecting influence of dietary fat and fatty acid intake: plasma phospholipid,
cholesterol ester, triglyceride and free fatty acid composition.
Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Prevention
plasma sex hormone levels
United States: Federal Government
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