ESTROGEN, DIET, GENETICS AND ENDOMETRIAL CANCER

雌激素、饮食、遗传学和子宫内膜癌

• 批准号: 6771028
• 负责人: SARA H. OLSON
• 金额: $ 44.69万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-02 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6771028
• 关键词: aromatase; cancer risk; catechol methyltransferase; clinical research; cytochrome P450; diet; enzyme activity; estrogens; female; genetic susceptibility; hormone regulation /control mechanism; hormone related neoplasm /cancer; human subject; neoplasm /cancer epidemiology; neoplasm /cancer genetics; nutrition related neoplasm /cancer; nutrition related tag; steroid 17alpha monooxygenase; uterus neoplasms; women' s health

Risk factors for endometrial cancer, including weight and a high-fat diet, operate through estrogen-related mechanisms. Estrogen promotes growth of transformed cells and there is evidence that some metabolites may have carcinogenic properties. Some of the genes that are important in estrogen metabolism have been found to be polymorphic (CYP17, CYP1 Al, catechol 0-methyltransferase, CYP1 Bi, and CYP19), raising the question of whether genotypes are related to risk. The primary aim of this study is to compare endometrial cancer cases to controls to determine the associations of weight, diet, and genetic susceptibility, independently and jointly, with endometrial cancer. Most endometrial tumors are of endometrioid histology. The rarer serous and clear cell tumors are more aggressive and lethal. Aside from their higher prevalence in older women and in blacks, little is known about risk factors for these tumors, although they appear not to be related to estrogen. The secondary aim is to compare cases with these tumor types to controls to assess risk factors for these poorly-understood tumors. We will conduct a population-based case-control study in six counties in New Jersey. Cases will be women with newly-diagnosed endometrial cancer. Controls will be matched by 5-year age groups and selected by random digit dialing (for those under 65) or from HCFA files (for those aged 65 and over). There will be 600 cases with endometrioid tumors, 200 with serous or clear cell tumors, and 600 controls. Endometrial cancer, already a serious cause of morbidity in the US, is likely to become more common in future years as the population ages and obesity increases. Risk factors such as obesity and poor diets are potentially modifiable. This study will provide data on genetic susceptibility in endometrial cancer in conjunction with established risk factors, as well as the first epidemiologic data on the more lethal serous and clear cell tumors.

子宫内膜癌的危险因素，包括体重和年龄 高脂肪饮食，通过雌激素相关机制发挥作用。雌激素促进 转化细胞的生长，有证据表明一些代谢物可能 具有致癌特性。一些对雌激素很重要的基因 已发现代谢是多态的(CYP17，CYP1A1，儿茶酚 0-甲基转移酶、细胞色素P1B1和细胞色素P19)，提出了基因型别是否与风险相关的问题。这项研究的主要目的是比较 确定子宫内膜癌病例与对照组体重的相关性， 饮食和遗传易感性，独立和联合与子宫内膜 癌症。 子宫内膜肿瘤多为子宫内膜样癌。越是稀有的严肃和 透明细胞瘤更具侵袭性和致命性。除了他们的更高 老年妇女和黑人的患病率，对其危险因素知之甚少 这些肿瘤，尽管它们似乎与雌激素无关。第二个 目的是将这些肿瘤类型的病例与对照组进行比较，以评估风险 这些鲜为人知的肿瘤的致病因素。 我们将在纽约6个县进行以人群为基础的病例对照研究 泽西岛。病例将是新诊断为子宫内膜癌的妇女。控制 将由5岁年龄组匹配，并通过随机数字拨号选择(用于 65岁以下的人)或来自HCFA档案的(65岁及以上的人)。会有 子宫内膜样瘤600例，浆液性或透明细胞瘤200例。 600个控制点。 子宫内膜癌在美国已经是一个严重的发病率原因，很可能 随着人口老龄化和肥胖在未来几年变得更加常见 增加。肥胖和不良饮食等风险因素是潜在的 可修改的。这项研究将提供关于人类遗传易感性的数据 子宫内膜癌与已确定的危险因素，以及 第一份关于致命性更强的浆液性和透明细胞肿瘤的流行病学数据。