Reproductive and Hormonal Risk Factors for Adenomyosis

子宫腺肌症的生殖和激素危险因素

• 批准号: 6706936
• 负责人: Victoria L Holt
• 金额: $ 61.9万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6706936
• 关键词: catechol methyltransferase; clinical research; contraceptives; cytochrome P450; disease /disorder proneness /risk; endometriosis; epidemiology; estrogens; female; female reproductive system surgery; gene environment interaction; genetic polymorphism; genetic screening; genetic susceptibility; human subject; induced abortion; interview; lifestyle; obesity; progesterone; prolactin; racial /ethnic difference; reproduction; smoking; steroid hormone; steroid hormone biosynthesis; steroid hormone metabolism; tobacco abuse; women' s health

Adenomyosis, also known as internal endometriosis, is the progressive invasion of endometrial glands and stroma from the uterine endometrial lining down into the myometrium, the inner muscle wall of the uterus. This condition is diagnosed in over 150,000 women in the U.S. annually, can be associated with severe pelvic and menstrual pain and excessive bleeding, and almost always requires hysterectomy for definitive treatment. Clinical observations have raised the hypothesis that multiparity and excessive estrogen may increase disease risk; however, there is little epidemiologic data to confirm or deny this hypothesis. Consequently, we propose to conduct a case-control study to investigate the relationships between adenomyosis and reproductive and hormonally-related exposures, including polymorphisms in genes involved in steroid hormone synthesis and metabolism. The study will be conducted at Group Health Cooperative of Puget Sound (GHC), a health maintenance organization serving approximately 500,000 people in western Washington State. Cases will be 500 female GHC enrollees 18-59 years of age diagnosed with adenomyosis between March 1, 2001 and Feb. 28, 2006. Two control groups will be used: 1) 500 women undergoing hysterectomy during the study period who are found to have a condition other than adenomyosis, endometriosis, or leiomyoma, frequency matched to cases on age, and 2) 500 women randomly selected from computerized enrollment files, also frequency matched to cases on age. Data will be obtained from cases and controls by in-person interview, anthropometric measurement and collection of a blood sample for DNA analysis; and these data will be linked with the GHC computerized pharmacy database. Subjects will be interviewed regarding factors known or suspected to be associated with uterine trauma or steroid hormone levels (including reproductive, contraceptive, and menstrual histories; obesity; exercise; diet; cigarette smoking) as well as other potential risk factors for adenomyosis. Blood samples will be analyzed for two polymorphic genes coding enzymes active in estrogen metabolism (CYP17, COMT). Analyses comparing cases and controls with respect to reproductive and hormonal risk factors and their interactions with genetic polymorphisms will be conducted to address the specific aims.

子宫腺肌病，也称为内部子宫内膜异位症，是子宫内膜腺体和间质从子宫内膜衬里向下侵入子宫肌层（子宫的内部肌肉壁）的进行性侵入。 在美国，每年有超过150，000名女性被诊断出患有这种疾病，可能与严重的盆腔和月经疼痛以及过度出血有关，并且几乎总是需要子宫切除术进行明确治疗。临床观察提出了一个假设，即多产和过量的雌激素可能会增加疾病的风险，但是，很少有流行病学数据来证实或否认这一假设。因此，我们建议进行一项病例对照研究，以调查子宫腺肌病和生殖和生殖相关的暴露，包括参与类固醇激素合成和代谢的基因多态性之间的关系。 本研究将在普吉特海湾团体健康合作社（GHC）进行，GHC是一家为华盛顿州西部约50万人提供服务的健康维护组织。 病例将是500名年龄18-59岁的女性GHC入组者，在2001年3月1日至2006年2月28日期间诊断为子宫腺肌病。将使用两个对照组：1）500名在研究期间接受子宫切除术的女性，发现她们患有子宫腺肌病、子宫内膜异位症或平滑肌瘤以外的疾病，频率与年龄上的病例相匹配，以及2）500名从计算机化入组文件中随机选择的女性，频率也与年龄上的病例相匹配。 将通过面对面访谈、人体测量和采集血样进行DNA分析从病例和对照组中获得数据;这些数据将与GHC计算机化药房数据库相关联。将对受试者进行访谈，了解已知或疑似与子宫创伤或类固醇激素水平相关的因素（包括生殖、避孕和月经史;肥胖;运动;饮食;吸烟）以及子宫腺肌病的其他潜在风险因素。 将分析血样中编码雌激素代谢活性酶（CYP 17、COMT）的两种多态性基因。 将进行比较病例和对照组生殖和激素风险因素及其与遗传多态性的相互作用的分析，以解决具体目标。