PCBs, CYP1A1 Polymorphism and Breast Cancer Risk in CT

描述：多氯联苯(PCB)是一种强有力的环境内分泌干扰物。它们也是涉及类固醇的关键基因的强烈诱导者。 代谢和异体代谢，如人细胞色素CYP1A1。最近的流行病学研究表明，女性患乳腺癌的风险如果 他们体内的多氯联苯负荷较高，且存在CYP1A1m2基因。毒理学研究 通过显示多氯联苯诱导细胞色素P1A1代谢来支持这些发现 将环境致癌物转化为高活性的中间体，产生DNA 损害并最终致癌。由于广泛接触多氯联苯 以及CYP1A1在致癌物活化和类固醇激素中的重要作用 新陈代谢方面，迫切需要研究多氯联苯 CYP1A1基因与乳腺癌风险。在此背景下，病例对照 在美国乳腺癌发病率最高的地区之一康涅狄格州，提出了一项关于多氯联苯的身体负担、CYP1A1基因多态和乳腺癌风险的研究。这项研究的主要目的是检验这样一种假设，即患有癌症的女性 体内多氯联苯负荷增加，且具有特定的CYP1A1基因型者 增加患乳腺癌的风险。用于检测细胞色素P1A1的血液样本 病例对照研究的基因类型将来自最近完成的一个乳房 康涅狄格州癌症病例对照研究，招募了475起事件 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和血清 通过上述亲本乳房对样品进行多氯联苯和DDE分析 癌症病例对照研究。利用现有的血液样本和环境 母体乳腺癌研究收集的暴露数据提供了成本 提高学习效率。

(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.