INFECTIOUS ETIOLOGY TESTICULAR CANCER

睾丸癌发病率上升的趋势不太可能用隐睾症等已知风险因素来解释。基于睾丸癌与其他病毒相关恶性肿瘤的年龄相关发病模式之间的相似性，提出了睾丸癌的感染性病因学。只有一小部分流行病学研究评估了这一假说，但集体结果表明，暴露于EBV和CMV可能与睾丸癌风险有关。进一步的间接证据来自于表明免疫受损男性风险增加的研究，以及表明睾丸癌与性传播疾病病史之间的关系的研究。关于性传播传染病病原体在睾丸癌病因中的作用的直接流行病学证据是有限的，尽管具有提示性。利用前瞻性收集的血清，我们建议一方面评估HSV-2、HPV-16和15、HHV-8和沙眼衣原体抗体应答与睾丸癌发生的关系。作为第二个目标，我们将检查感染这些病原体和睾丸癌之间的关联是否会随着年龄的变化而改变。这项拟议的研究是一项病例对照研究，嵌套在挪威Janus项目中捐献血样的男性队列中。由挪威癌症协会赞助的Janus项目成立于1973年，目的是前瞻性地收集血清，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血清库有293,692人的424,938份血清样本，在采血时没有人患有癌症。JANUS血清库的所有献血者每年都通过一个唯一的个人识别号码与挪威癌症登记处联系在一起。符合本分析条件的病例是1993年癌症登记处登记的被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献血者作为对照，他们在样本采集时分别与年龄和年份匹配。总共确定了88例患者和262名匹配的对照，并将包括在拟议的分析中。血清中针对HSV-2、HPV、HHV-8和沙眼衣原体的抗体效价将用酶联免疫吸附和免疫荧光法测定。个体抗体滴定值将根据整个研究人群的分布被分配到四分位数。数据将通过条件Logistic回归进行建模，并考虑个体匹配。Janus队列为研究与睾丸癌风险有关的感染性病原体提供了一个独特的机会。据我们所知，这是第一次使用诊断前收集的血清来评估睾丸癌的病毒来源的研究。

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.