DNA POLYMORPHISMS IN OVARIAN CANCER--CASE CONTROL STUDY

据估计，1997年美国有超过2.6万例新的卵巢癌病例，约有1.4万名妇女死于卵巢癌，使其成为最致命的妇科恶性肿瘤。近2%的女性在她们的一生中受到影响。卵巢癌很难治疗，因为患者经常出现在病程较晚的时候，直到晚期才可能没有症状。少数已确定的危险因素似乎并不是疾病发病率的一大部分，这些因素影响卵巢癌发生风险的可能机制仍未被很好地了解。基于大量的病理学、内分泌学和流行病学证据，我们最近提出了一种关于卵巢癌病因的新的激素假说。为了验证这一假设，我们正在康涅狄格州进行一项基于人群的病例对照访谈研究，该研究将检查与生殖年中和之后的荷尔蒙表达有关的一系列因素。通过我们的快速病例确定系统，该州总共有大约580例年龄在35-79岁之间的卵巢癌病例被前瞻性地识别出来，1000名随机选择的人群对照正在与三个年龄组的病例进行频率匹配。我们现在建议分析从所有研究对象收集的口腔涂片细胞样本，以检查所研究的激素和激素机制中某些已知的、常见的、生殖系遗传多态变异是否与卵巢癌风险改变有关。将使用聚合酶链式反应方法进行遗传分析。总的来说，在卵巢癌方面，激素因素只得到了很少的关注，我们正在进行的项目是第一个在严格的、大规模的研究中对它们进行系统评估的项目，该研究将把所有因素整合在一个连贯的病因框架内。本文提出的新研究将通过遗传学的考虑，证实我们现有研究中所考虑的激素气候表现的风险关联，并可能为卵巢癌可能的病因机制提供进一步的洞察。

In the United States in 1997, it has been estimated that there were more than 26,000 new cases of cancer of the ovary, and that approximately 14,000 women died from it, making it the most lethal of the gynecological malignancies. Close to 2 percent of women are affected during their lifetimes. Ovarian cancer is difficult to treat because patients frequently present late in the disease course, which may be asymptomatic until advanced stages. The few established risk factors do not appear to account for a large fraction of disease incidence, and the possible mechanisms by which these factors affect risk of developing ovarian cancer are still not well understood. Based upon a substantial body of pathologic, endocrinology and epidemiologic evidence, we have recently suggested a new hormonal hypothesis regarding the etiology of ovarian cancer. To examine this hypothesis, we are conducting, in the state of Connecticut, a population-based case-control interview study which will examine a collection of factors related to hormonal expression during and after the reproductive years. In total, about 580 ovarian-cancer cases aged 35-79 years are being identified prospectively in the state through our Rapid Case Ascertainment system, and 1,000 randomly selected population controls are being frequency matched to the cases in three age groups. We now propose to analyze buccal-smear cell samples collected from all of the study subjects, in order to examine whether certain known, common, germline genetic polymorphism variants in the hormones and hormonal mechanisms under study are associated with altered risk of ovarian cancer. PCR methods will be used for the genetic analyses. In general, the hormonal factors being examined have received only a little attention with respect to ovarian cancer, and our ongoing project is the first to evaluate them systematically in a rigorous, large-scale study which will integrate all of the factors within a coherent etiologic framework. The new study proposed here will substantiate, through genetic considerations, the risk associations seen for the hormonal climate manifestations considered in our existing study, and may provide further insight into possible etiologic mechanisms of ovarian cancer.