Molecular epidemiology of cervical adenocarcinoma

宫颈腺癌的分子流行病学

• 批准号: 6855636
• 负责人: HANS-OLOV ADAMI
• 金额: $ 42.38万
• 依托单位: KAROLINSKA INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6855636
• 关键词: MHC class II antigen; Scandinavian; Scandinavian country; adenocarcinoma; cancer risk; cervical /vaginal smear; cervix neoplasms; clinical research; disease /disorder etiology; female; genetic registry /resource /referral center; genetic susceptibility; histopathology; human papillomavirus; human subject; human tissue; longitudinal human study; neoplasm /cancer epidemiology; technology /technique development; virus DNA; virus load; virus related neoplasm /cancer

DESCRIPTION (provided by applicant): The overall objective of this project is to improve the biologic understanding of adenocarcinoma and adenosquamous cancer of the cervix uteri (in the following referred to as adenocarcinoma) through investigation of its viral etiology, and genes encoding certain human leukocyte antigen (HLA) haplotypes. The long-term objective is to propose rational prevention strategies for this disease. Our main specific aims are to: 1) estimate the relative risks for adenocarcinoma both as a function of HPV presence overall and as a function of time since first detected infection with human papillomavirus (HPV); 2) to assess whether persistence and/or a high initial HPV 16/18/45 viral load is a determinant of adenocarcinoma; 3) to assess whether certain HLA haplotypes are associated with risk for adenocarcinoma, and if the association is mediated via a higher viral load and/or persistence of HPV 16/18/45. This project will build on experience from two previous studies examining squamous cell cervical cancer and HPV (both funded by NIH). Our capacity to conduct these studies is derived from the utilization of unique prerequisites in Sweden, namely the extensive documentation present in computerized registers for population-based PAP-smear screening, potential ascertainment of all incident cases of adenocarcinoma, and access to archival smears and tissue specimens. Using a nested case-control design in this large study base, with up to 32 years of complete follow-up, 511 women with adenocarcinoma and 511 individually matched control women will be identified. Using validated and sensitive PCR-assays, the presence of HPV DNA will be analyzed in all available smears from each participant (on an average four smears per individual, giving totally about 4,088 smears).HPV persistence, HPV16/18/45 viral load and HLA (types DQ6 and DR15) will be analyzed for all included women. Relative risks of cervical adenocarcinoma for oncogenic HPV infections, HPV persistence,HPV16/18/45 high viral load, HLA haplotype and interactions between these factors will be estimated with conditional logistic regression. The likelihood ratio test will be used to discriminate between nested models. Statistical power calculations produced for the specific aims show that our study is adequately sized.

描述（由申请人提供）：该项目的总体目标是通过研究其病毒病因和编码某些人类白细胞的基因，提高对子宫颈腺癌和腺鳞癌（以下简称腺癌）的生物学认识抗原（HLA）单倍型。长期目标是针对该疾病提出合理的预防策略。我们的主要具体目标是：1) 评估腺癌的相对风险，既作为 HPV 总体存在的函数，又作为自首次检测到人乳头瘤病毒 (HPV) 感染以来时间的函数； 2) 评估持续性和/或高初始 HPV 16/18/45 病毒载量是否是腺癌的决定因素； 3) 评估某些 HLA 单倍型是否与腺癌风险相关，以及这种关联是否是通过较高的病毒载量和/或 HPV 16/18/45 的持续存在介导的。该项目将借鉴之前两项检查鳞状细胞宫颈癌和 HPV 的研究（均由 NIH 资助）的经验。我们进行这些研究的能力源于利用瑞典独特的先决条件，即计算机化登记册中存在用于基于人群的子宫颈涂片筛查的大量文件、所有腺癌病例的潜在确定以及档案涂片和组织的获取标本。在这个大型研究基地中使用巢式病例对照设计，经过长达 32 年的完整随访，将确定 511 名腺癌女性和 511 名单独匹配的对照女性。 使用经过验证且灵敏的 PCR 检测，将对每位参与者的所有可用涂片中 HPV DNA 的存在进行分析（平均每个人四份涂片，总共约 4,088 份涂片）。HPV 持久性、HPV16/18/45 病毒载量和将对所有纳入的女性进行 HLA（DQ6 和 DR15 型）分析。致癌性 HPV 感染、HPV 持续性、HPV16/18/45 高病毒载量、HLA 单倍型以及这些因素之间的相互作用将通过条件逻辑回归来估计宫颈腺癌的相对风险。似然比检验将用于区分嵌套模型。针对特定目标进行的统计功效计算表明，我们的研究规模足够。