Development of an endometrial cancer risk model

描述（由申请人提供）：I型子宫内膜癌是美国妇女中最常见的妇科癌症，被认为是受可改变的生活方式因素强烈影响的激素致癌模型。虽然子宫内膜癌与乳腺癌和卵巢癌有着共同的生殖和月经风险因素，但这些暴露与癌症风险之间的时间关系因部位而异。不同的协会表明存在重要的，但不明确的生物学机制，是组织类型特异性。因此，这些病因差异已成为化学预防措施的挑战。致癌过程如突变、增殖和凋亡影响“组织老化”的速率，癌前细胞的数量随时间成倍增加。历史事件和暴露对特定癌症的增加率有不同的影响。将流行病学危险因素与子宫内膜癌联系起来的生物数学模型可以提供一个观察癌变过程的结构。这种见解可以提供额外的途径，实验和/或流行病学研究，治疗或预防子宫内膜癌的健康妇女以及乳腺癌患者接受激素治疗。获得准确的风险估计和确定病因因素如何共同影响风险是癌症建模的重要方面。因此，我们将通过在护士健康研究中建立子宫内膜癌风险预测对数发病率模型，量化已建立的生殖和生活方式风险因素对I型子宫内膜癌累积发病率的联合和时间效应，该模型将在前列腺、肺、结直肠和卵巢癌筛查试验的女性参与者中得到验证。

DESCRIPTION (provided by applicant): Type I endometrial cancer, the most common gynecological cancer among U.S. women, is considered a model of hormonal carcinogenesis that is strongly influenced by modifiable lifestyle factors. While endometrial cancer shares common reproductive and menstrual risk factors with the hormonally-regulated cancers of the breast and ovary, the temporal relationships between these exposures and cancer risk differs for each site. The diverse associations suggest the existence of important, but undefined biologic mechanisms that are tissue type-specific. Consequently, these etiologic differences have emerged as challenges for chemopreventive measures. Carcinogenic processes such as mutation, proliferation, and apoptosis affect the rate of 'tissue aging' with the number of precancerous cells increasing multiplicatively over time. Historical events and exposures differentially affect the rate of increase for a specific cancer. Biomathematical models relating epidemiologic risk factors to endometrial cancer can provide a structure with which to view the process of carcinogenesis. Such insight could provide additional avenues of experimental and/or epidemiologic research for treatment or prevention of endometrial cancer among healthy women as well as breast cancer patients undergoing hormonal therapies. Obtaining accurate risk estimates and determining how etiologic factors jointly affect risk are important aspects in cancer modeling. Thus, we will quantify the joint and temporal effects of established reproductive and lifestyle risk factors on cumulative incidence of Type I endometrial cancer by developing an endometrial cancer risk prediction log-incidence model in the Nurses' Health Study that will be validated among female participants of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.