ANOGENITAL CANCER--EPIDEMIOLOGY/BIOCHEMISTRY/IMMUNOLOGY

我们建议研究多原发肛门生殖道癌的危险因素，并继续我们的宫颈癌和外阴癌病例对照研究。这两项研究都以阐明HPV以外的因素为目标，这些因素对肛门癌的病因有贡献。这项提案的新的主要焦点将是多原发肛门生殖系统肿瘤的危险因素。我们将把这些女性中的每一位都与一位患有一种肛门生殖系统肿瘤的女性进行配对，该女性不会继续发展为第二种肿瘤。我们将采访多个原发肛门癌病例和匹配的单个原发对照病例，了解可能与他们患第二原发癌风险有关的特征，并收集档案肿瘤组织以检测HPV DNA类型和非原型变异。将采集血液进行血清学和基因检测。我们计划确定多原发肛门生殖器癌的风险是否与：1)吸烟，特别是在最初的原发癌后继续吸烟；2)人类白细胞抗原II类等位基因；3)肛门癌的家族史；4)最初的原发癌中的HPV型和非原型变异。这项研究的数据可能有助于设计第二原发癌高危肛门癌患者的临床监测，并可能为降低多发性肛门肿瘤发生率的行为矫正提供靶点。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。从2000年1月到2004年12月，所有18-74岁被诊断患有宫颈癌或外阴癌的妇女都将通过基于人口的癌症监测系统进行识别。将就性传播疾病病史、吸烟状况、肛门和其他癌症的家族病史以及每种肿瘤的已知危险因素对病例和以人群为基础的对照人员进行访谈。组织标本将从所有病例中获得，并将进行HPV DNA检测。将采集血液并进行HPV抗体和HLA等位基因检测。这些数据将为检验HLA等位基因之间的重要交互作用以及HLA等位基因与生活方式危险因素之间的相互作用提供足够的动力。

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.