DETERMINANTS OF STEROID HORMONES IN BLACK AND WHITE MEN

点击翻译按钮获取中文摘要

A diverse body of evidence suggests that long-term exposure to elevated levels of endogenous androgenic hormones increases the risk of prostate cancer. Moreover, African-American ancestry, a high- fat diet, obesity, physical inactivity and polymorphisms in the gene encoding the androgen receptor also have been linked to prostate cancer risk. The effect of these lifestyle and genetic factors on prostate cancer etiology could be mediated, at least partly, through alterations in steroid hormone levels or metabolism. However, reasons for the substantial inter- individual variation in hormone levels observed among men have not been adequately studied. The primary objective of the proposed project is to evaluate, in longitudinal analyses, lifestyle and genetic determinants of serum steroid hormone and binding protein levels in 631 black and 873 white male participants of the Coronary Artery Risk Development in (Young) Adults (CARDIA) Study. Baseline data were collected from the CARDIA cohort in 1985-86, and subsequent Follow-up examinations occurred at Years 2, 5, 7, and 10. For the proposed project, previously collected and stored serum samples obtained at the Years 2, 7 and 10 follow-up exams, and DNA samples from the Year 5 exams will be utilized. Specifically, eight-year longitudinal changes in serum concentrations of steroid hormones will be compared between African- American and white men. Independent effects of changes in potentially modifiable factors such as obesity, diet and physical activity on longitudinal changes in steroid hormone levels will be examined. In addition, we will evaluate associations between serum androgen levels and CAG repeat length in the androgen receptor gene, and conduct exploratory analyses of the relation between polymorphisms in the gene for 5-alpha- reductase and serum levels of 3a-androstanediol glucuronide, a potential phenotypic marker of 5-alpha-reductase activity. Results of this study will provide the first longitudinal analyses of steroid hormone changes and their correlated in a bi-racial population.