DNA POLYMORPHISMS IN OVARIAN CANCER--CASE CONTROL STUDY

据估计，1997年美国有26，000多例卵巢癌新发病例，约14，000名妇女死于卵巢癌，使其成为最致命的妇科恶性肿瘤。 近2%的妇女在其一生中受到影响。卵巢癌很难治疗，因为患者经常出现在病程的晚期，可能直到晚期才出现症状。少数已确定的风险因素似乎并不占疾病发病率的很大一部分，这些因素影响卵巢癌风险的可能机制仍然没有得到很好的理解。基于大量的病理学、内分泌学和流行病学证据，我们最近提出了一个关于卵巢癌病因的新的激素假说。 为了检验这一假设，我们正在康涅狄格州进行一项以人口为基础的病例对照访谈研究，该研究将研究生殖期间和之后与激素表达相关的一系列因素。总的来说，通过我们的快速病例确定系统，在该州前瞻性地确定了大约580例年龄在35 - 79岁之间的卵巢癌病例，并将1,000名随机选择的人群对照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中收集的颊涂片细胞样本，以检查研究中的激素和激素机制中某些已知的、常见的生殖系遗传多态性变异是否与卵巢癌风险改变相关。 将使用PCR方法进行遗传分析。总的来说，激素因素在卵巢癌中只受到很少的关注，我们正在进行的项目是第一个在一个严格的大规模研究中系统地评估它们的项目，该研究将在一个连贯的病因学框架内整合所有因素。本文提出的新研究将通过遗传因素证实我们现有研究中考虑的激素气候表现的风险相关性，并可能进一步深入了解卵巢癌的可能病因机制。

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.