ANDROGENS AND CANCER OF THE ENDOMETRIUM

实验和流行病学数据都支持雌激素促进子宫内膜细胞增殖，从而增加子宫内膜癌风险的假说。由于雄激素是绝经后妇女循环雌激素的主要来源，因此循环中的雄激素与子宫内膜癌风险之间也存在正相关关系。这项研究将首次评估绝经后妇女诊断前循环雌激素和雄激素水平与子宫内膜癌风险的关系。该项目的具体目标是：(1)在纽约大学妇女健康研究(NYUWHS)、意大利米兰的Ordet研究和瑞典Umea的瑞典北部健康和疾病研究三个前瞻性队列中嵌套的病例对照研究中，评估绝经后内源性雌激素与子宫内膜癌风险的关系；(2)在同一病例对照研究中评估绝经后内源性雄激素与子宫内膜癌风险的关系。对于所有三个队列，在注册时收集并存储在80oC的血清样本可用于生化分析。一项关于子宫内膜癌和绝经后内源性雌激素的病例对照研究已经在进行中，该研究嵌套在NYUWHS内，由NCI(R29 CA66189，PI：A.Zeleniuch-Jacquotte)资助。这项研究的设计将在另外两个队列中实施。所有在研究中诊断的事故案例都将包括在内。将从同一队列中的所有受试者中选择具有以下特征的单独匹配的对照：绝经后进入，活着，无癌症，确诊时子宫完整，登记时年龄(+6个月)和登记日期(3个月)与病例匹配。就像目前对NYUWHS参与者所做的那样，将通过电话采访UMEA和Ordet参与者来收集关于潜在混杂因素的数据。所有病例和配对对照的血清样本将在同一实验室进行雌二醇、游离雌二醇、ESTRIGN、睾酮、雄烯二酮、DHEA和SHBG的检测。将三个队列的病例合并在一起将导致总共140个病例，这一数字远远超过每个单独队列的预期数字。

The hypothesis that estrogens unopposed by progesterone promote endometrial cell proliferation, and therefore increase risk of endometrial cancer, is supported by experimental as well as epidemiologic data. Because androgens are the main source of circulating estrogens in postmenopausal women, a positive association of circulating androgens with endometrial cancer risk is also expected. This study will be the first to assess the association of prediagnostic levels of circulating estrogens and androgens with endometrial cancer risk in postmenopausal women. The specific objectives of this project are to: (1) Assess the relation of postmenopausal endogenous estrogens with endometrial cancer risk in a case-control study nested within three prospective cohorts: the New York University Women's Health Study (NYUWHS), the ORDET Study in Milan, Italy, and the Northern Sweden Health and Disease Study in Umea, Sweden; (2) Assess the relation of postmenopausal endogenous androgens with endometrial cancer risk in the same case-control study. For all three cohorts, serum samples collected at enrollment and stored at 80oC are available for biochemical analyses. A case-control study of endometrial cancer and postmenopausal endogenous estrogens nested within the NYUWHS and funded by the NCI (R29 CA66189, PI: A. Zeleniuch- Jacquotte) is already ongoing. The design of this study will be implemented in the two other cohorts. All incident cases diagnosed within the studies will be included. Individually-matched controls will be selected among all subjects from the same cohort with the following characteristics: postmenopausal at entry, alive, free of cancer and with an intact uterus at the time of diagnosis of the case, and matching the case on age at enrollment (+6 months), and date of enrollment (3 months). As is currently done for the NYUWHS participants, data on potential confounders will be collected through telephone interviews for Umea and ORDET participants. Serum samples of all cases and matched controls will be assayed in the same laboratory for estradiol, free-estradiol, estrange, testosterone, androstenedione, DHEA, and SHBG. Combining cases from the three cohorts will result in a total of 140 cases, a much larger number than would be expected in each individual cohort.