Environment, Gene and Testicular Cancer Risk

在过去的几十年里，睾丸癌在美国和其他国家的发病率一直在迅速上升。睾丸癌现在已经成为年轻人最常见的恶性肿瘤。人们对观察到的睾丸癌发病率增加的病因知之甚少。最近的几项研究表明，环境中暴露于有机氯物质，如多氯联苯和氯化杀虫剂，可能会增加睾丸癌的风险。这种关系在生物学上是可信的，因为许多有机氯具有荷尔蒙活性，并被怀疑或可能是人类致癌物。康涅狄格州和马萨诸塞州拟议的睾丸癌病例对照研究将调查以下假设：1)暴露于有机氯化合物会增加睾丸癌风险；2)与有机氯暴露相关的睾丸癌风险由主要基因改变，这些基因与内源和外源激素的调节、代谢或功能活动有关。病例将包括800例(300例来自康涅狄格州，500例来自马萨诸塞州)，通过每个州的快速病例确定系统在4年内诊断出组织学确诊的睾丸癌患者。同样数量的基于人群的控制措施(300人来自康涅狄格州，500人来自马萨诸塞州)将按年龄(-5岁)和性别与病例频率匹配，并将通过随机数字拨号进行选择。病例和对照将由训练有素的面试者面谈，以获得有关主要潜在风险因素和混杂因素的详细信息，如出生史、生活方式因素和病史。将采集血液样本进行化学分析和基因测试。由陈博士和阿尔特舒尔博士领导的研究实验室目前正在分别为睾丸癌和其他男性生殖障碍的研究进行基因分型和有机氯分析，这代表了该提案的独特优势。另一个优势是通过在两个州进行研究而实现的大样本量。这将为这项研究提供足够的统计力量来检验假设。

Over the last several decades, testicular cancer rates have been rapidly increasing in the United States, as well as in other countries. Testicular cancer has now become the most common malignancy in young men. Little is known about the etiology of the observed increases in testicular cancer incidence. Several recent studies suggest that environmental exposure to organochlorines, such as polychlorinated biphenyls (PCBs) and chlorinated pesticides, may increase testicular cancer risk. This relationship is biologically plausible since many organochlorines possess hormonal activities and are suspected or probable human carcinogens. The proposed case-control study of testicular cancer in Connecticut and Massachusetts will investigate the hypotheses that: 1) exposure to organochlorine compounds increases testicular cancer risk; and 2) risk of testicular cancer associated with organochlorine exposure is modified by major genes which have been associated with either the regulation, metabolism, or functional activities of endogenous and exogenous hormones. Cases will consist of 800 (300 from Connecticut and 500 from Massachusetts) histologically confirmed incident testicular cancer patients diagnosed over a 4 year period through the rapid case ascertainment system in each state. An equal number of population-based controls (300 from Connecticut and 500 from Massachusetts) will be frequency matched to the cases by age (-5 years) and sex and will be selected by random digit dialing. Cases and controls will be interviewed by trained interviewers to obtain detailed information on major potential risk factors and confounders, such as birth history, lifestyle factors, and medical history. A blood sample will be collected for chemical analyses and for genetic testing. The study laboratories led by Drs. Chen and Altshul, who are currently conducting the genotyping and organochlorine analyses for studies of testicular cancer and other male reproductive disorders, respectively, represent a unique strength of the proposal. Another strength is the large sample size, achieved by conducting the study in two states. This will provide the study with sufficient statistical power to test the hypotheses.