ANOGENITAL CANCER--EPIDEMIOLOGY/BIOCHEMISTRY/IMMUNOLOGY

我们建议研究多种原发性肛门生殖器癌的危险因素，并继续进行宫颈癌和外阴癌的病例对照研究。这两项研究的目标都是阐明HPV以外的因素，这些因素有助于肛门生殖器癌的病因学。新的，主要的焦点，这一建议将是危险因素的发展多发性原发性器官肿瘤。我们会将这些女性中的每一位与患有一种生殖器官肿瘤的女性进行配对，并且她们不会再长出第二种肿瘤。我们将采访多个原发性肛门生殖器癌病例和匹配的单一原发性对照，了解可能与他们患第二原发性肿瘤的风险相关的特征，并收集档案肿瘤组织以检测HPV DNA类型和非原型变体。将采集血液进行血清学和基因检测。我们计划确定多发原发性肛门生殖器癌的风险是否与以下因素有关：1)吸烟，特别是在初次发病后继续吸烟；2) HLA II类等位基因；3)有生殖道肿瘤家族史；4)原发性癌的HPV型和非原型变异。本研究的数据可能有助于第二原发癌高风险的肛门生殖器癌患者的临床监测设计，并可能为减少多发性肛门生殖器肿瘤的发生率提供行为改变的靶点。在继续我们的病例对照研究中，我们将举例说明与宫颈癌和外阴癌风险相关的HPV辅助因素。这项研究将在华盛顿西部的三个县进行。所有在2000年1月至2004年12月期间被诊断患有子宫颈癌或外阴癌的18至74岁的妇女都将通过以人口为基础的癌症监测系统得到确认。将对病例和以人口为基础的对照进行访谈，了解性传播疾病的病史、吸烟状况、肛门生殖和其他癌症的家族史以及每种肿瘤的已知危险因素。将从所有病例中获得组织标本，并检测HPV DNA。将收集血液并检测HPV抗体和HLA等位基因。这些数据将为检测HLA等位基因之间以及HLA等位基因与生活方式风险因素之间的重要相互作用提供足够的力量。

We propose to study risk factors for multiple primary anogenital cancers and to continue our case-control studiers of cervical and vulvar cancer. Both studies have as their goal the elucidation of factors, beyond HPV, that contribute to the etiology of anogenital cancer. The new, major focus of this proposal will be risk factors for the development of multiple primary anogenital tumors. We will match each of these women to a women with one anogenital tumor who does not go on to develop a second tumor. We will interview multiple primary anogenital cancer cases and matched single primary controls about characteristics that may be related to their risk of a second primary tumor, and collect archival tumor tissue to test for HPV DNA types and non- prototype variants. Blood will be collected for serologic and genetic testing. We plan to determine whether the risk of multiple primary anogenital cancers is related to: 1) cigarette smoking, particularly continued smoking following the initial primary; 2) HLA class II alleles; 3) family history of anogenital cancers; 4) HPV type and non-prototype variant in the initial primary cancer. The data from this study may contribute to the design of clinical monitoring for anogenital cancer patients at high risk of second primary cancer, and may provide targets for behavior modification that could reduce the incidence of multiple anogenital tumors. In continuing our case-control study, we will example HPV co-factors in relation to risk cervical and vulvar carcinoma. The study will be conducted in three counties of western Washington. All women engaged 18-74 who are diagnosed from January 2000 through December 2004 with cervical or vulvar cancer will be identified through the population- based Cancer Surveillance System. Cases and population-based controls will be interviewed regarding history of sexually transmitted diseases, smoking status, family history of anogenital and other cancers, as well as known risk factors for each tumor. Tissue specimens will be obtained from all cases and will be assayed for HPV DNA. Blood will be collected and tested for antibodies to HPV and for HLA alleles. The data will provide sufficient power for testing important interactions among HLA alleles, and between HLA alleles and lifestyle risk factors.