GENETIC SUSCEPTIBILITY TO ENDOMETRIAL CANCER

子宫内膜癌的遗传易感性

• 批准号: 2898831
• 负责人: Immaculata De Vivo
• 金额: $ 25.29万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-16 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2898831
• 关键词: aromatase; cancer risk; clinical research; estrogens; female; gene environment interaction; genetic polymorphism; genetic susceptibility; genotype; hormone related neoplasm /cancer; hormone therapy; human data; human genetic material tag; human subject; human tissue; neoplasm /cancer epidemiology; neoplasm /cancer genetics; postmenopause; progesterone receptors; steroid hormone metabolism; uterus neoplasms; women's health

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.

描述：（改编自研究者摘要）：过量雌激素 孕酮未对抗的暴露与以下风险增加有关： 子宫内膜癌雌激素代谢相关基因的多态性 影响这些激素的水平，并可能与改变 子宫内膜癌的风险。到目前为止，还没有关于这些多态性的研究。 据报道，与子宫内膜癌有关的信息很少 这些多态性与循环激素水平之间的关系。 子宫内膜癌特别值得研究，因为它是最 雌激素反应性肿瘤，因此代谢酶基因的作用不大 可能更容易被检测到。我们建议利用 一个特征良好的队列，护士健康研究，以确定共同的 在关键的乳腺癌相关基因的多态性，并评估这些是否 基因型预测未来子宫内膜癌的风险，以及 评估这些基因的变体等位基因的功能意义， 将这些变异与血浆激素水平相关联。我们将查明和 表征CYP 19和孕酮受体内的多态性，以及 作为量化已知多态性CYP 17-A2，COMT-MET， UGT-A（TA）7AA与子宫内膜癌的关系，并测试这些相关性是否是 由确定的子宫内膜癌风险因素修改。这些研究报告将 嵌套在来自护士健康研究的32，826名女性的子队列中， 血液样本在1989-1990年，因此将是少数几个研究能够 前瞻性地检查这些问题，在一个定义的队列中， 查明事件案例和全面的前瞻性信息， 其他子宫内膜癌危险因素。将两个对照组与每个病例匹配， 将有98%的把握度检测相对风险2.0，80%的把握度检测相对风险2.0， 8%纯合突变基因型多态性的相对风险为1.75 普遍性。