Development of an endometrial cancer risk model

描述(申请人提供)：I型子宫内膜癌是美国女性中最常见的妇科癌症，被认为是荷尔蒙致癌的一种模式，受到可改变的生活方式因素的强烈影响。虽然子宫内膜癌与荷尔蒙调节的乳腺癌和卵巢癌具有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在每个部位都不同。这种不同的关联表明存在重要的、但未明确的生物机制，这些机制是组织类型特有的。因此，这些病因学上的差异成为化学预防措施的挑战。突变、增殖和凋亡等致癌过程会影响“组织老化”的速度，癌前细胞的数量会随着时间的推移而成倍增加。历史事件和暴露对特定癌症的增长速度有不同的影响。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种观察癌变过程的结构。这种洞察力可以为治疗或预防健康女性以及接受激素治疗的乳腺癌患者的子宫内膜癌提供额外的实验和/或流行病学研究途径。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中的重要方面。因此，我们将通过在护士健康研究中开发子宫内膜癌风险预测对数发病率模型来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影响，该模型将在前列腺癌、肺癌、结直肠癌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.