PCBs, CYP1A1 Polymorphism and Breast Cancer Risk in CT

（修订摘要）描述：多氯联苯（PCBs）是一种强有力的环境内分泌干扰物。它们也是参与类固醇的关键基因的强诱导剂 代谢和异生物质代谢，如人细胞色素CYP1A1。最近的流行病学研究表明，妇女患乳腺癌的风险增加， 他们体内多氯联苯的含量较高，且具有CYP1A1 m2基因型。毒理学研究 通过显示PCBs诱导CYP1A1代谢来支持这些发现， 环境致癌物转化为高活性中间体， 损害并最终致癌。由于多氯联苯的广泛接触 以及CYP1A1在致癌物活化和类固醇激素中的重要作用 代谢，迫切需要研究多氯联苯之间的关系， CYP1A1基因型与乳腺癌风险 在此背景下，病例对照 康涅狄格州是美国乳腺癌发病率最高的地区之一，因此建议对多氯联苯、CYP1A1基因多态性和乳腺癌风险的身体负担进行研究。这项研究的主要目的是检验这一假设，即 多氯联苯的体内负荷升高，并具有特定的CYP1A1基因型， 增加乳腺癌的风险。用于测定CYP1A1的血样 病例对照研究的基因型将来自最近完成的乳腺癌 在康涅狄格州进行的一项癌症病例对照研究中， 乳腺癌病例和502例对照。关于环境暴露的信息 已经收集了潜在的混杂因素， 通过上述母体乳房分析样品中的PCB和DDE 癌症病例对照研究。使用现有血液样本和环境 母乳腺癌研究收集的暴露数据提供了成本 学习的效率。

(Revised Abstract) DESCRIPTION: Polychlorinated biphenyls (PCBs) are potent environmental endocrine disruptors. They are also strong inducers of key genes involved in steroid metabolism and xenobiotic metabolism, such as human cytochrome CYP1A1. Recent epidemiological studies suggest that women are at increased risk of breast cancer if they have an elevated body burden of PCBs and a CYP1A1 m2 genotype. Toxicological studies support these findings by showing that PCBs induce CYP1A1 to metabolize environmental carcinogens into highly reactive intermediates resulting in DNA damage and ultimately carcinogenesis. Due to the widespread exposure to PCBs and the important role of CYP1A1 in carcinogen activation and steroid hormone metabolism, there exists an urgent need to study the relationship between PCBs, the CYP1A1 genotype and breast cancer risk. Against this background, a case-control study of body burden of PCBs, CYP1A1 genetic polymorphisms and breast cancer risk is proposed in Connecticut, one of the areas with the highest incidence rates of breast cancer in the United States. The primary aim of this study is to test the hypothesis that women with an elevated body burden of PCBs and with specific CYP1A1 genotypes have an increased risk of breast cancer. The blood samples used to determine CYP1A1 genotypes for the case-control study will come from a recently completed breast cancer case-control study in Connecticut, which has recruited 475 incident breast cancer cases and 502 controls. Information on environmental exposures and potential confounding factors has already been collected and blood serum samples were analyzed for PCBs and DDE through the aforementioned parent breast cancer case-control study. Use of existing blood samples and environmental exposure data collected by the parent breast cancer study provide cost efficiency to the study.