Prospective Study of Serum MIS and Gynecologic Cancer Risk

描述(申请人提供)：有几条证据表明苗勒氏抑制物质对卵巢癌和子宫内膜癌有保护作用。目的/假设：我们假设绝经前妇女血液中的MIS浓度与她们随后发生上皮性卵巢癌和子宫内膜癌的风险呈负相关。具体目标：1)前瞻性地确定绝经前的循环管理信息系统水平与随后的上皮性卵巢癌风险之间的关系；以及2)与子宫内膜癌风险之间的关系。研究设计：前瞻性病例对照研究将嵌套在9个已建立的队列中，包括哥伦比亚大学、MO血清库、马里兰州华盛顿县的线索I和线索II、纽约大学(NYU)妇女健康研究、护士健康研究、格恩西岛、英国队列、瑞典北部健康和疾病研究、欧洲营养与癌症前瞻性调查(EPIC)、乳腺癌病因中的激素和饮食(ORDET)和上海妇女健康研究。这9个队列包括在绝经前45岁提供血样并随后发展为浸润性卵巢癌(n=305)或子宫内膜癌(n=373)的妇女。对于每个病例，将选择两个与队列、年龄和采血日期相匹配的对照。MI将使用商业上可用的和经过验证的MI酶联免疫吸附试验(ELISA)进行测量。分析将使用条件Logistic回归进行。意义：这项拟议的研究将前瞻性地评估一种新的生物标记物--管理信息系统与发生卵巢癌和子宫内膜癌的风险之间的关系。拟议的研究结果将增加我们对这些癌症的病因的理解。这项拟议的研究还可能确定卵巢癌和子宫内膜癌风险评估和筛查研究的新途径。 与公共卫生相关：子宫内膜癌和卵巢癌是美国最常见的妇科癌症。这些癌症的病因尚不清楚，但苗勒氏抑制物质(MIS)是一种很有前途的风险生物标志物。拟议的研究结果将增加我们对卵巢癌和子宫内膜癌病因的理解，并可能为风险评估和筛查方法的研究找到新的途径。

DESCRIPTION (provided by applicant): Several lines of evidence indicate a protective effect of Mullerian inhibiting substance (MIS) for ovarian and endometrial cancers. Objectives/Hypothesis: We hypothesize that premenopuasal women's circulating MIS concentrations are inversely associated with their risk of subsequently developing epithelial ovarian and endometrial cancer. Specific Aims: 1) Prospectively determine the association of premenopausal circulating MIS levels with risk of subsequent epithelial ovarian cancer; and 2) with risk of endometrial cancer. Study Design: A prospective case-control study will be conducted nested in 9 established cohorts including the Columbia, MO Serum Bank, CLUE I and CLUE II in Washington County Maryland, New York University (NYU) Women's Health Study, Nurses' Health Study, Guernsey, UK Cohort, Northern Sweden Health and Disease Study, European Prospective Investigation into Nutrition and Cancer (EPIC), Hormones and Diet in the Etiology of Breast Cancer (ORDET), and Shanghai Women's Health Study. The 9 cohorts include women who provided a blood sample at d 45 years old while premenopausal and subsequently developed invasive ovarian cancer (n=305) or endometrial cancer (n=373). For each of these cases, two controls will be selected matched on cohort, age and date of blood collection. MIS will be measured using a commercially available and validated MIS enzyme-linked immunosorbent assay (ELISA). Analysis will be conducted using conditional logistic regression. Significance: The proposed study will prospectively evaluate the association of a novel biomarker, MIS, with risk of developing ovarian and endometrial cancers. Results of the proposed study will increase our understanding of the etiologies of these cancers. The proposed study also could potentially identify new avenues for research on ovarian and endometrial cancer risk assessment and screening. PUBLIC HEALTH RELEVANCE: Endometrial and ovarian cancers are the most common gynecological cancers in the US. The etiologies of these cancers are not well understood, but Mullerian Inhibiting Substance (MIS) is a promising biomarker of risk. Results of the proposed study will increase our understanding of the etiologies of ovarian and endometrial cancer and could potentially identify new avenues for research on approaches to risk assessment and screening.