INFECTIOUS ETIOLOGY TESTICULAR CANCER

传染性病因睾丸癌

• 批准号: 2853540
• 负责人: LOREN LIPWORTH
• 金额: $ 7.6万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-02 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2853540
• 关键词: Chlamydia trachomatis; Scandinavian country; age difference; antibody titering; cancer registry /resource; cancer risk; clinical research; disease /disorder etiology; enzyme linked immunosorbent assay; herpes simplex virus 2; human data; human herpesvirus 8; human papillomavirus; human tissue; immunofluorescence technique; infection related neoplasm /cancer; male; mathematical model; neoplasm /cancer diagnosis; neoplasm /cancer epidemiology; serum; sexually transmitted diseases; testis neoplasms

The trend of increasing testicular cancer incidence is unlikely to be explained by known risk factors such as cryptorchidism. An infectious etiology of testicular cancer has been proposed, based on similarities between the age-specific incidence pattern of testicular cancer and that of other virus-associated malignancies. Only a small number of epidemiologic studies have evaluated this hypothesis, but collective results suggest that exposure to EBV and CMV may relate to testicular cancer risk. Further indirect evidence comes from studies showing increased risk among immunocompromised men, as well as from studies indicating a relation between testicular cancer and history of sexually transmitted diseases. Direct epidemiologic evidence regarding the role of sexually transmitted infectious agents in testicular cancer etiology is limited although suggestive. Using serum collected prospectively, we propose to evaluate the association between antibody response to HSV-2, HPV-16 and 15, HHV-8 and Chlamydia trachomatis on the one hand and the occurrence of testicular cancer on the other. As a secondary aim, we will examine whether the associations between infection with any of these agents and testicular cancer are modified by age. The proposed study is a case-control study nested in a well-defined cohort of men who donated blood samples as part of the JANUS project in Norway. The JANUS project, sponsored by the Norwegian Cancer Society, was established in 1973 for the purpose of prospectively collecting serum to be used in epidemiologic studies of cancer development and cardiovascular disease. As of October 1993, the JANUS serum bank contained 424,938 serum samples from 293,692 individuals, none of whom had cancer at the time of blood sampling. All blood donors to the JANUS serum bank are annually linked, through a unique, individual identification number, with the Cancer Registry of Norway. Eligible cases for the present analysis are male blood donors listed in the Cancer Registry through 1993 with a diagnosis of invasive testicular cancer. For each case, three blood donors, individually matched by age and year at sample collection, have been randomly selected from the JANUS serum bank as controls. A total of 88 case patients and 262 matched controls have been identified and will be included in the proposed analysis. Serum antibody titers against HSV-2, HPV, HHV-8 and C. trachomatis will be determined using enzyme-linked immunosorbent and immunofluorescence assays. Individual antibody titer values will be distributed into quartiles based on the distribution of the entire study population. The data will be modeled through conditional logistic regression, taking into account the individual matching. The JANUS cohort provides a unique opportunity to study infectious agents in relation to testicular cancer risk. To our knowledge, this is the first study to evaluate the viral origin of testicular cancer using serum collected prior to diagnosis.

睾丸癌发病率增加的趋势不太可能用隐睾等已知的危险因素来解释。基于睾丸癌的年龄特异性发病模式与其他病毒相关恶性肿瘤之间的相似性，提出了睾丸癌的感染性病因。只有少数流行病学研究评估了这一假设，但集体结果表明，接触 EBV 和 CMV 可能与睾丸癌风险相关。进一步的间接证据来自显示免疫功能低下男性风险增加的研究，以及表明睾丸癌与性传播疾病史之间关系的研究。关于性传播感染因子在睾丸癌病因学中的作用的直接流行病学证据虽然具有提示性，但仍然有限。利用前瞻性收集的血清，我们建议一方面评估对 HSV-2、HPV-16 和 15、HHV-8 和沙眼衣原体的抗体反应与睾丸癌发生之间的关联。作为次要目标，我们将检查这些药物的感染与睾丸癌之间的关联是否会因年龄而改变。拟议的研究是一项病例对照研究，对象是一组明确的男性，他们作为挪威 JANUS 项目的一部分捐献了血液样本。 JANUS 项目由挪威癌症协会赞助，成立于 1973 年，旨在前瞻性地收集血清，用于癌症发展和心血管疾病的流行病学研究。截至 1993 年 10 月，JANUS 血清库包含来自 293,692 人的 424,938 份血清样本，在采血时没有一人患有癌症。 JANUS 血清库的所有献血者每年都会通过唯一的个人识别号与挪威癌症登记处建立联系。目前分析的合格病例是 1993 年癌症登记处列出的诊断为浸润性睾丸癌的男性献血者。对于每个病例，从 JANUS 血清库中随机选择三名按样本采集时年龄和年份进行匹配的献血者作为对照。总共 88 名病例患者和 262 名匹配对照已被确定，并将纳入拟议的分析中。针对 HSV-2、HPV、HHV-8 和沙眼衣原体的血清抗体滴度将使用酶联免疫吸附和免疫荧光测定法测定。个体抗体滴度值将根据整个研究人群的分布分布到四分位数中。数据将通过条件逻辑回归建模，同时考虑个体匹配。 JANUS 队列提供了一个独特的机会来研究与睾丸癌风险相关的感染因子。据我们所知，这是第一项利用诊断前收集的血清评估睾丸癌病毒起源的研究。