Endogenous Estrogens and Colorectal Cancer Risk in Women

描述(申请人提供)：流行病学研究的证据表明，激素替代疗法与降低结直肠癌(CRC)的风险有关，最近在妇女健康倡议中观察到在统计上显著降低了CRC的风险，这一证据得到了相当大的加强，这是一项大型、随机、安慰剂对照的临床试验。尽管有证据表明外源性雌激素在结直肠癌的发展中具有保护作用，但到目前为止，还没有关于内源性雌激素与结直肠癌风险之间关系的流行病学研究。我们建议在纽约大学妇女健康研究(NYUWHS)队列中嵌套的一项病例对照研究中，检验绝经后血清雌激素和雄激素水平与随后的CRC风险负相关的假设。1985至1991年间，NYUWHS招募了14,275名健康女性，从那以后一直积极跟踪调查。在登记时收集的血清样本被冻结，用于未来的生化分析。预计到2005年3月，在进入研究时处于绝经后的参与者中，总共有227例结直肠腺癌被诊断出来，这些病例将包括在拟议的研究中。对于每个病例，将选择两个在登记时的年龄、登记日期和登记时的更年期状态与病例匹配的对照。将从病例和匹配的对照中提取冷冻血清样本，并对其进行雌二醇、雌酮、雌酮硫酸酯、雄烯二酮、睾酮和SHBG的检测。关于潜在混杂因素的数据之前已经收集过。这项研究将首次研究绝经后循环雌激素和雄激素水平与结直肠癌风险的关系。NYUWHS特别适合于研究拟议的假设，因为它的前瞻性设计将偏见的风险降至最低，并允许检查诊断前的激素水平，而且内源性性激素在疾病发展中的作用一直是其主要关注点。

DESCRIPTION (provided by applicant): 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.