Molecular epidemiology of cervical adenocarcinoma

宫颈腺癌的分子流行病学

基本信息

批准号：
7227781
负责人：
HANS-OLOV ADAMI
金额：
$ 39.51万
依托单位：
KAROLINSKA INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-05-01 至 2010-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7227781
关键词：
Adenocarcinoma Biological Assay Build-it Carcinoma in Situ Cervical Adenocarcinoma Cervix Uteri Cohort Studies Condition DNA Databases Detection Developed Countries Developing Countries Development Diagnosis Disease Documentation Epidemiologic Studies Etiology Exposure to Funding Future Genes HLA Antigens Haplotypes Human Human Papillomavirus Human papilloma virus infection Human papillomavirus 16 Incidence Individual Infection Invasive Investigation Logistic Regressions Malignant Neoplasms Malignant neoplasm of cervix uteri Mediating Modeling Molecular Epidemiology Nested Case-Control Study Oncogenic Pap smear Papillomavirus Participant Polymerase Chain Reaction Population Population Registers Prevention strategy Process Relative Risks Risk Role Sampling Screening for cancer Screening procedure Specimen Squamous Cell Sweden Testing Text Time Tissues United States National Institutes of Health Viral Viral Load result Woman Work base cancer risk case control cohort computerized design experience follow-up improved insight leukocyte antigen typing prevent prospective repository size viral DNA

项目摘要

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）：该项目的总体目的是通过研究其病毒病因和编码某些人类白细胞抗原（HLA）Haplotys的基因来改善子宫颈子宫颈腺瘤和腺形癌的生物学理解（以下称为腺癌）。长期目标是提出针对该疾病的理性预防策略。我们的主要特定目的是：1）估计腺癌的相对风险既是HPV存在的函数，并且自从首次检测到人类乳头瘤病毒（HPV）感染以来的时间和时间的函数； 2）评估持久性和/或高初始HPV 16/18/45病毒负荷是腺癌的决定因素； 3）评估某些HLA单倍型是否与腺癌的风险有关，以及该关联是否是通过较高的病毒载量和/或HPV 16/18/45的持久性介导的。该项目将基于先前的两项研究的经验，研究了鳞状细胞宫颈癌和HPV（均由NIH资助）。我们进行这些研究的能力来自瑞典的独特先决条件的利用，即计算机寄存器中存在的广泛文档，用于基于人群的子宫颈抹片筛查，对所有腺癌的所有事件案例的潜在确定，以及对档案涂片的访问权限。在这个大型研究基础上使用嵌套的病例对照设计，将确定511名患有腺癌的女性和511名单独匹配的对照妇女，最多可完成32年的完整随访。使用经过验证且敏感的PCR测定，将在每个参与者的所有可用涂片中分析HPV DNA的存在（平均每人四张涂片，完全可提供约4,088个涂片）.hpv持久性，HPV16/18/18/45病毒载荷和HLA（型号dq6 and dr15）都将分析所有女性。宫颈腺癌对致癌性HPV感染，HPV持久性，HPV16/18/45高病毒载荷，HLA单倍型和这些因素之间相互作用的相对风险将通过条件逻辑回归进行估算。似然比测试将用于区分嵌套模型。针对特定目的产生的统计功率计算表明，我们的研究大小适当。