Genetic Epidemiology of HPV Infection Outcome in Men

男性 HPV 感染结果的遗传流行病学

• 批准号: 8719926
• 负责人: Sadeep Shrestha
• 金额: $ 7.66万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-12 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8719926
• 关键词: Accounting; Alabama; Anogenital cancer; Anogenital venereal warts; Archives; Autoimmune Diseases; Biological; Brazil; Cancer Center; Cancerous; Caring; Caucasians; Caucasoid Race; Cervical; Cohort Studies; Communicable Diseases; DNA; Data; Detection; Development; Disease; Doctor of Philosophy; Enrollment; Epidemiology; Equilibrium; Etiology; Female; Florida; Foundations; Genes; Genetic; Genetic Models; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genital system; Genomic DNA; Genomics; Genotype; HPV-High Risk; Human; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune; Immune response; Immunogenetics; Incidence; Individual; Infection; International; Intervention; Investigation; Lesion; Logistic Regressions; Malignant Neoplasms; Malignant Vaginal Neoplasm; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Malignant neoplasm of penis; Malignant neoplasm of vulva; Mediating; Mexico; Molecular Profiling; Natural History; Natural Immunity; Oncogenic; Outcome; Participant; Pathogenesis; Phenotype; Pilot Projects; Prevalence; Prospective Studies; Public Health; Reporting; Research; Research Institute; Research Personnel; Risk Factors; Sampling; Sex Behavior; Sexual Partners; Sexually Transmitted Diseases; Testing; Therapeutic; United States; Universities; Variant; Virus; Virus Diseases; Visit; Whole Blood; Woman; adaptive immunity; age group; chemokine; cost effective; cytokine; experience; genetic epidemiology; genetic variant; male; malignant oropharynx neoplasm; men; novel; prospective; public health relevance; sex; transmission process

DESCRIPTION (provided by investigator): Persistent infection with human papillomavirus (HPV) causes essentially pre-cancerous and cancer lesions in both men and women and also likely influences HPV transmission within sexual partners and thus is an important "intermediate phenotype." To date, most efforts in etiological research of HPV have focused in women. Given that men are important in transmitting HPV to their female sexual partners along with the public health burden of genital warts and several cancers, understanding the natural history of HPV in men would benefit both men and women. The purpose of this study is to test the hypothesis that differences in host genes influence HPV persistence in men. Although the mechanism for HPV persistence is unknown, several studies implicate immune evasion, involving genetically mediated determinants of the host immune response. Genetic influences of HPV in women have been reported and we propose test this hypothesis in the context of men. Our collaborative team with investigators from UAB and Moffitt Cancer Center and Research Institute has the experience and expertise that provides a unique opportunity to evaluate the genetic effects with well- documented HPV infection outcomes in men. For this new investigation, we will draw upon data from 500 Caucasian men nested within the HPV infection in Men (HIM), the only multi-national prospective study of men, which consists of 4299 participants, 18-70 years residing in southern Florida, USA, Sao Paulo, Brazil and Cuernavaca, Mexico. We will identify 250 individuals who cleared HPV16 within 6 months after acquisition and another set of 250 individuals in whom HPV16 has persisted for over 12 months and perform genotyping of variants in immune-related genes using the ImmunoChip ((~200,000 SNPs compiled from association studies of infectious and autoimmune diseases). We will perform a logistic regression type of genetic models to examine differential distribution of the genetic polymorphisms in the two groups, accounting for correlations of multiple co-infections with each HPV type as an individual outcome. Three specific aims of the study are: 1) Extract genomic DNA from archived whole blood collected at the enrollment visit among 250 men with persistent (e 12 months) genital HPV 16 infection and 250 with transient (1x detection only) genital HPV 16; 2) Genotype all 500 samples using the ImmunoChip array; and 3) Conduct statistical analyses to identify genetic variants associated with genital HPV 16 DNA clearance and persistence To our knowledge, this would be the first immunogenetic study of HPV infection outcome among men, to date. Any informative data from this study would fill in the gap of immunological effects with HPV pathogenesis in men and may help identify molecular signatures amenable to specific therapeutic approaches in men and their partners.

描述（由研究者提供）：人乳头瘤病毒（HPV）的持续感染会导致男性和女性的癌前病变和癌前病变，也可能影响HPV在性伴侣中的传播，因此是一种重要的“中间表型”。迄今为止，大多数HPV病因学研究都集中在女性身上。考虑到男性在将HPV传播给女性性伴侣以及生殖器疣和几种癌症的公共卫生负担方面起着重要作用，了解男性HPV的自然历史将对男性和女性都有好处。本研究的目的是检验宿主基因差异影响男性HPV持久性的假设。尽管HPV持续存在的机制尚不清楚，但一些研究暗示免疫逃避，涉及宿主免疫反应的遗传介导决定因素。HPV在女性中的遗传影响已被报道，我们建议在男性的背景下测试这一假设。我们与来自UAB和莫菲特癌症中心和研究所的研究人员合作的团队拥有丰富的经验和专业知识，为评估男性HPV感染结果的遗传影响提供了独特的机会。在这项新的调查中，我们将利用来自500名男性HPV感染（HIM）的数据，这是唯一一项针对男性的跨国前瞻性研究，其中包括4299名参与者，年龄在18-70岁，居住在美国佛罗里达州南部、巴西圣保罗和墨西哥库尔纳瓦卡。我们将鉴定250名在获得HPV16后6个月内清除HPV16的个体和另外250名HPV16持续超过12个月的个体，并使用免疫芯片对免疫相关基因的变异进行基因分型（从感染性和自身免疫性疾病的关联研究中编译的~200,000个snp）。我们将执行遗传模型的逻辑回归类型来检查两组中遗传多态性的差异分布，并将每种HPV类型作为个体结果的多重合并感染的相关性考虑在内。该研究的三个具体目的是：1)从250名持续（12个月）生殖器HPV 16感染的男性和250名短暂（仅1次检测）生殖器HPV 16感染的男性的入组时收集的存档全血中提取基因组DNA；2)使用ImmunoChip芯片对所有500份样本进行基因分型；3)进行统计分析，以确定与生殖器HPV 16 DNA清除和持久性相关的遗传变异。据我们所知，这将是迄今为止首次对男性HPV感染结果进行免疫遗传学研究。本研究的任何信息数据都将填补男性HPV发病机制免疫学效应的空白，并可能有助于确定适合男性及其伴侣的特定治疗方法的分子特征。