Prospective Study of Serum MIS and Gynecologic Cancer Risk

描述（由申请人提供）：多项证据表明苗勒管抑制物质（MIS）对卵巢癌和子宫内膜癌具有保护作用。目的/假设：我们推测，绝经前妇女的循环MIS浓度与其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）Prostaglandin确定绝经前循环MIS水平与随后的上皮性卵巢癌风险的关联;和2）与子宫内膜癌风险的关联。研究设计：前瞻性病例对照研究将在9个已建立的队列中进行，包括哥伦比亚、MO血清库、华盛顿县马里兰州的CLUE I和CLUE II、纽约大学（NYU）妇女健康研究、护士健康研究、根西岛、英国队列、北方瑞典健康与疾病研究、欧洲营养与癌症前瞻性研究（EPIC）、激素和饮食在乳腺癌病因学（ORDET），和上海妇女的健康研究。9个队列包括在绝经前45岁时提供血液样本，随后发生浸润性卵巢癌（n=305）或子宫内膜癌（n=373）的女性。对于这些病例中的每一个，将选择在队列、年龄和采血日期上匹配的两个对照。将使用市售和经验证的MIS酶联免疫吸附试验（ELISA）测量MIS。将使用条件logistic回归进行分析。重要性：这项研究将前瞻性地评估一种新的生物标志物MIS与卵巢癌和子宫内膜癌发生风险的关系。这项研究的结果将增加我们对这些癌症病因的了解。这项拟议的研究还可能为卵巢癌和子宫内膜癌风险评估和筛查的研究确定新的途径。

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.