Environment, Gene and Testicular Cancer Risk

环境、基因和睾丸癌风险

• 批准号: 7032766
• 负责人: Tongzhang Zheng
• 金额: $ 93.36万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-11 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032766
• 关键词: cancer risk; case history; clinical research; cycloalkene; cytochromes; dichlorodiphenyltrichloroethane; disease /disorder etiology; endocrine disrupting compound; environment related neoplasm /cancer; gene environment interaction; genetic polymorphism; glutathione transferase; halobiphenyl /halotriphenyl compound; hexachlorobenzene; human population genetics; human subject; interview; lifestyle; male; mirex /kepone; neoplasm /cancer genetics; patient oriented research; superoxide dismutase; telecommunications; testis neoplasms; transforming growth factors

DESCRIPTION (provided by applicant): 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 pplychlorinated 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.

描述（由申请人提供）：在过去的几十年里，睾丸癌的发病率在美国和其他国家迅速增加。睾丸癌现已成为青年男性最常见的恶性肿瘤。 关于睾丸癌发病率增加的病因学知之甚少。最近的几项研究表明，环境中暴露于有机氯，如多氯联苯和氯化农药，可能会增加睾丸癌的风险。这种关系在生物学上是合理的，因为许多有机氯具有激素活性，被怀疑或可能是人类致癌物。拟在康涅狄格州和马萨诸塞州开展的睾丸癌病例对照研究将调查以下假设：1）接触有机氯化合物会增加睾丸癌风险; 2）与有机氯接触相关的睾丸癌风险受到与内源性和外源性激素的调节、代谢或功能活动相关的主要基因的影响。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）经组织学确认的偶发睾丸癌患者，这些患者通过各州的快速病例确定系统在4年内诊断。将相同数量的基于人群的对照（300例来自康涅狄格州，500例来自马萨诸塞州）与病例按年龄（~ 5岁）和性别进行频率匹配，并通过随机数字拨号进行选择。病例和对照将由经过培训的访谈者进行访谈，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检测。由Chen博士和Altshul博士领导的研究实验室目前分别为睾丸癌和其他男性生殖疾病的研究进行基因分型和有机氯分析，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实现的大样本量。这将为研究提供足够的统计功效来检验假设。