DNA POLYMORPHISMS IN OVARIAN CANCER--CASE CONTROL STUDY

在1997年的美国，据估计有超过26000例新的卵巢癌病例，大约14000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晚期，可能直到晚期才无症状。少数确定的风险因素似乎不能解释大部分疾病发病率，这些因素影响卵巢癌发病风险的可能机制仍未得到很好的理解。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，我们在康涅狄格州进行了一项以人群为基础的病例对照访谈研究，该研究将检查生育期间和生育后与激素表达相关的一系列因素。通过我们的快速病例确定系统，在该州总共发现了大约580例年龄在35-79岁之间的卵巢癌病例，并在三个年龄组中随机选择1000例人口对照进行频率匹配。我们现在建议分析从所有研究对象中收集的口腔涂片细胞样本，以检查在所研究的激素和激素机制中是否存在某些已知的、常见的种系遗传多态性变异与卵巢癌的风险改变有关。基因分析将采用PCR方法。一般来说，在卵巢癌方面，正在检查的激素因素只受到很少的关注，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学方面的考虑，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.