Persistent Organochlorines and Testicular Cancer Risk

产品说明： 睾丸生殖细胞癌（TGCC）的发病率最高， 自20世纪50年代以来，年轻男性中发生的恶性肿瘤增加了几倍。 动物系统的实验和观察研究引起了人们的关注 增长率的部分原因是人口范围内的，持续的 暴露于工业和农业排放的内分泌干扰化合物 应用.人类接触此类化学品是否与TGCC有关 风险尚未直接研究。我们建议确定， TGCC与持久性有机氯的血清水平有关，重点是 p，p '-DDE、多氯联苯（PCB）和其他化合物（例如， 狄氏剂、六氯环己烷、六氯苯）。我们还将研究 与这些化合物相关的TGCC风险是否通过遗传修饰 对这些化合物可能改变TGCC风险的机制的敏感性。 例如，我们将确定TGCC风险是否与相互作用有关 1）血清p，p '-DDE和多聚谷氨酰胺重复序列多态性升高 雄激素受体（AR）基因，和2）血清PCB水平升高， 氧化应激防御酶基因多态性。 为了实现这些目标，我们将对马累进行辅助调查。 雄激素研究（MARS），一个最近发起的，由国家癌症研究所资助， TGCC分子遗传危险因素的人群病例对照研究 MARS资助包括标准的基于人群的病例和控制确定 和招聘，详细的面对面面试，抽血，和分子 雄激素合成、代谢和 信号基因（包括AR）。辅助研究将包括大约 作为MARS的一部分，招募了250例TGCC病例和750例对照。资金 辅助研究将提供1）快速病例确定和招募 最小化化疗对血清有机氯测定影响的系统 TGCC患者中的有机氯农药残留; 2）通过 高分辨气相色谱/同位素稀释高分辨质谱 基因多态性的测定;和3）参与的基因中常见多态性的测定。 氧化应激防御系统（锰超氧化物歧化酶、谷胱甘肽 S-转移酶M1、M3、T1和P1）。将有足够的统计能力， 检测相对较弱的整体关联，以及小于3倍 交互作用这些结果将为我们的研究提供重要的新信息。 了解环境污染物在发病机制中的作用 TGCC。

DESCRIPTION: The incidence of testicular germ cell carcinoma (TGCC), the most common malignancy developing in young men, has increased several-fold since the 1950s. Experimental and observational studies in animal systems have raised concern that the increasing rates are due in part to population-wide, persistent exposure to endocrine disrupting compounds from industrial and agricultural applications. Whether human exposure to such chemicals is associated with TGCC risk has not been directly studied. We propose to determine whether the risk of TGCC is related to serum levels of persistent organochlorines, focusing on p,p'-DDE, polychlorinated biphenyls (PCBs), and other compounds (e.g., dieldrin, hexachlorocyclohexanes, hexachlorobenzene). We also will examine whether the risk of TGCC associated with these compounds is modified by genetic susceptibility to mechanisms through which these compounds may alter TGCC risk. For example, we will determine whether TGCC risk is related to interactions between 1) elevated serum p,p'-DDE and polyglutamine repeat tract polymorphisms in the androgen receptor (AR) gene, and 2) elevated serum PCB levels and polymorphisms in oxidative stress defense enzyme genes. To address these aims, we will conduct an ancillary investigation to the Male Androgen Research Study (MARS), a recently-initiated, NCI-funded, population-based case-control study of molecular genetic risk factors for TGCC. MARS funding includes standard population-based case and control ascertainment and recruitment, a detailed in-person interview, blood draw, and molecular genetic analyses of polymorphisms in androgen synthesis, metabolism, and signaling genes (including AR). The ancillary study will include approximately 250 cases of TGCC and 750 controls recruited as part of MARS. Funding for the ancillary study will provide for 1) a rapid case ascertainment and recruitment system to minimize effects of chemotherapy on serum measures of organochlorine residues among TGCC patients; 2) assay of organochlorine pesticides and PCBs by high resolution gas chromatography/isotope dilution high resolution mass spectometry; and 3) assays for common polymorphisms in genes involved in oxidative stress defense systems (manganese superoxide dismutase, glutathione S-transferases M1, M3, T1, and P1). There will be adequate statistical power to detect relatively weak overall associations, as well as less than 3-fold interaction effects. The results should add significant new information to our understanding of the role of environmental contaminants to the pathogenesis of TGCC.