Endogenous Estrogens and Colorectal Cancer Risk in Women

描述（由申请人提供）：来自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）风险相关，最近在妇女健康倡议（一项大型随机、安慰剂对照的临床试验）中观察到的结直肠癌风险的统计学显着降低已大大加强。尽管有证据表明外源性雌激素在结直肠癌发展中的保护作用，但迄今为止还没有关于内源性雌激素与结直肠癌风险关联的流行病学研究。我们建议在纽约大学妇女健康研究（NYUWHS）队列中进行一项病例对照研究，验证绝经后血清雌激素和雄激素水平与随后的结直肠癌风险负相关的假设。从1985年到1991年，纽约大学健康研究中心招募了14275名健康女性，这些女性一直在积极随访。在入组时收集的血清样本被冷冻以备将来的生化分析。到2005年3月，预计将在绝经后的参与者中诊断出227例结直肠腺癌，这些病例将纳入拟议的研究。对于每个病例，将选择两名对照，他们在年龄、入组日期和入组时的绝经状态方面与病例相匹配。从病例和匹配对照中提取冷冻血清样本，检测雌二醇、雌酮、硫酸雌酮、雄烯二酮、睾酮和SHBG。先前收集了潜在混杂因素的数据。本研究将是第一个关于绝经后循环雌激素和雄激素水平与结直肠癌风险相关性的研究。NYUWHS特别适合研究提出的假设，因为它的前瞻性设计使偏倚风险最小化，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它的主要焦点。

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.