GENETIC SUSCEPTIBILITY TO ENDOMETRIAL CANCER

描述：(改编自《调查者摘要》)：过量雌激素 与黄体酮无关的暴露会增加患 子宫内膜癌。雌激素代谢相关基因的多态性 影响这些荷尔蒙的水平，并可能与改变 患子宫内膜癌的风险。到目前为止，还没有关于这些多态的研究 与子宫内膜癌有关的报道很少，可用信息很少 这些基因多态性与循环激素水平的关系。 子宫内膜癌特别值得研究，因为它是最值得研究的 雌激素反应性肿瘤和激素代谢基因的适度影响 可能更容易被检测到。我们建议利用 特征良好的队列，护士的健康研究，以确定共同的 关键激素相关基因的多态，并评估这些 基因分型可以预测未来子宫内膜癌的风险，以及 评估这些基因变异等位基因的功能意义 将这些变异与血浆激素水平相关联。我们将确定和 研究细胞色素P19和孕激素受体的多态 作为量化已知的CYP17-A2、COMT-MET、 UGT-A(TA)7AA与子宫内膜癌的关系 经已确定的子宫内膜癌危险因素修正。这些研究将是 嵌套在来自护士健康研究的32,826名女性的子队列中 1989年至1990年的血液样本，因此将是为数不多的能够 使用Complete在已定义的队列中前瞻性地检查这些问题 查明事故案例和全面的预期信息 其他子宫内膜癌危险因素。将两个控件与每个案例匹配，我们 将拥有98%的检测相对风险2.0的能力和80%的检测能力 具有8%纯合子突变基因的多态的相对风险为1.75 流行率。

DESCRIPTION: (Adapted from the Investigator's Abstract): Excess estrogen exposure unopposed by progesterone is associated with increased risk of endometrial cancer. Polymorphisms in genes involved in estrogen metabolism influence the levels of these hormones and may be associated with an altered risk of endometrial cancer. To date no studies of these polymorphisms have been reported in relation to endometrial cancer and little information is available on the relation between these polymorphisms and circulating hormone levels. Endometrial cancer is particularly worth studying because it is the most estrogen responsive tumor and thus modest effects of hormone-metabolizing genes may be more easily detectable. We propose to use the resources of the well-characterized cohort, the Nurses' Health Study, to ascertain the common polymorphisms in key hormone-related genes and to assess whether these genotypes are predictive of future endometrial cancer risk, as well as assessing the functional significance of the variant alleles of these genes by correlating these variants with plasma hormone levels. We will identify and characterize polymorphisms within CYP19 and the progesterone receptor, as well as quantify the association of the known polymorphisms CYP17-A2, COMT-MET, UGT-A(TA)7AA with endometrial cancer and test whether these associations are modified by established endometrial cancer risk factors. These studies will be nested in the subcohort of 32,826 women from Nurses' Health Study who gave blood samples in 1989-1990, and thus will be among the few studies able to prospectively examine these issues in a defined cohort with complete ascertainment of incident cases and comprehensive prospective information on other endometrial cancer risk factors. Matching two controls to each case we will have 98% power to detect a relative risk of 2.0 and 80% power to detect a relative risk of 1.75 for a polymorphism with an 8% homozygous mutant genotype prevalence.