The evidence from epidemiologic studies that hormone replacement therapy is associated with a decreased risk of colorectal cancer (CRC) has been considerably strengthened by the recent observation of a statistically significant reduction in risk of CRC in the Women's Health Initiative, a large, randomized, placebo-controlled, clinical trial. Despite the evidence on the protective role of exogenous estrogens in CRC development, there are no epidemiologic studies to date on the association of endogenous estrogens with CRC risk. We propose to test the hypothesis that postmenopausal serum levels of estrogens and androgens are negatively associated with subsequent risk of CRC in a case-control study nested within the New York University Women's Health Study (NYUWHS) cohort. Between 1985 and 1991, the NYUWHS enrolled 14,275 healthy women who have been actively followed up ever since. Serum samples collected at time of enrollment were frozen for future biochemical analyses. A total of 227 cases of colorectal adenocarcinoma are expected to be diagnosed by March 2005 in participants who were postmenopausal at entry, and these cases will be included in the proposed study. For each case, two controls will be selected who match the case on age at, and date of, enrollment, and menopausal status at enrollment. Frozen serum samples from cases and matched controls will be retrieved and assayed for estradiol, estrone, estrone sulfate, androstenedione, testosterone, and SHBG. Data on potential confounders were collected previously. This study will be the first study on the association of postmenopausal circulating estrogen and androgen levels with CRC risk. The NYUWHS is particularly well suited to study the proposed hypothesis because of its prospective design which minimizes the risk for bias and allows to examine pre-diagnostic hormone levels, and because the role of endogenous sex hormones in the development of diseases has always been its primary focus. [unreadable] [unreadable]