Hormone Therapy and Risk of Ovarian Cancer

项目A：荷尔蒙疗法与卵巢癌风险。自2001年以来，有三个 观察性研究报告了卵巢上皮细胞侵袭性风险显著增加。 与激素治疗(HT)相关的癌症(IEOC)。2003年《妇女杂志》的一份报告 健康倡议组织支持这一发现。我们对10项观察性研究的综合分析提供了 强有力的证据表明，使用非反对的雌激素治疗(ET)会增加IEOC的风险，但 风险的程度尚不确定。虽然我们的分析也表明IEOC的风险可能是 随着雌激素-孕激素疗法(EPT)的使用而增加，这一结论是基于 数据更少。需要更多的数据来准确地估计持续时间-反应关系 ET和EPT。还需要通过剂量和时间因素来表征风险模式，通过 其他风险因素(例如，身体大小)，以及IEOC的组织学。如果高血压增加了IEOC的风险， 行动机制还没有被很好地理解。 我们建议在洛杉矶县进行一项基于人群的IEOC病例对照研究 (Lac)由大约952起事件和相同数量的控制对象组成 年龄在45岁到79岁之间。拟议研究的数据将与另一项 来自IEOC WE的另外三项基于人群的病例对照研究的986例IEOC和1,121例对照 在过去十年里在拉丁美洲和加勒比地区进行了多项活动。除了获得关于HT的完整信息之外 使用，DNA样本将从这项拟议研究的受试者中获得(DNA样本为 在我们之前的研究中，已经从653个病例和862个对照中获得)。DNA的可获得性 大约1,510例IEOC病例和1,719名对照受试者的样本将允许我们进行 单核苷酸测定的基因变异的综合研究 多态和单倍型，参与羟色胺的代谢、运输或作用。我们会调查的 遗传变异是否对IEOC的风险产生独立的影响和/或改变HT-IEOC 协会。

Project A: Hormone Therapy and Risk of Ovarian Cancer. Since 2001, three observational studies have reported a significantly increased risk of invasive epithelial ovarian cancer (IEOC) in association with use of hormone therapy (HT). A 2003 report from the Women's Health Initiative supports this finding. Our combined analysis of 10 observational studies provides strong evidence that risk of IEOC is increased with the use of unopposed estrogen therapy (ET) but the extent of the risk is uncertain. While our analysis also suggests that risk of IEOC may be increased in association with use of estrogen-progestin therapy (EPT), this conclusion is based on fewer data. Additional data are needed to estimate precisely the duration-response relationship for ET and EPT. There is also a need to characterize risk patterns by dose and temporal factors, by other risk factors (e.g., body size), and by histology of IEOC. If HT increases the risk of IEOC, the mechanisms of action are not well-understood. We propose a large population-based case-control study of IEOC in Los Angeles County (LAC) consisting of approximately 952 incident cases and an equal number of control subjects between 45 and 79 years of age. Data from the proposed study will be combined with an additional 986 IEOC and 1,121 controls from three other population-based case-control studies of IEOC we have conducted in LAC during the last decade. In addition to obtaining complete information on HT use, DNA specimens will be obtained from subjects in this proposed study (DNAsamples are already available from 653 cases and 862 controls in our previous studies). The availability of DNA samples on approximately 1,510 IEOC cases and 1,719 control subjects will allow us to conduct a comprehensive investigation of variations in genes, as measured by single nucleotide polymorphisms and haplotypes, involved in HT metabolism, transport or action. We will investigate whether the genetic variants exert independent effects on risk of IEOC and/or modify the HT-IEOC association.