The Microbiome and Anal Cancer Pathogenesis in HIV-infected Men who have Sex with Men

男男性行为艾滋病毒感染男性的微生物组和肛门癌发病机制

基本信息

批准号：
9270852
负责人：
JOEL Michael PALEFSKY
金额：
$ 7.93万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-13 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9270852
关键词：
Adoption Affect Anaerobic Bacteria Anal canal Anti-Infective Agents Anti-Inflammatory Agents Anti-Retroviral Agents Anti-inflammatory Anus Bacteria Bacteroidaceae CD4 Lymphocyte Count Cell Proliferation Cervix Uteri Chronic Colorectal Cancer Communities Development Diagnosis Disease Disease Progression Enterobacteriaceae Environment Family Fusobacterium Gastrointestinal tract structure Genetic study Genome HIV HIV Infections HPV-High Risk Human Papillomavirus Human body Human papilloma virus infection Human papillomavirus 16 Incidence Individual Infection Inflammation Inflammatory Inflammatory Bowel Diseases Lead Lesion Life Expectancy Link Malignant - descriptor Malignant Neoplasms Malignant neoplasm of anus Measurement Mediator of activation protein Microbe Papillomavirus Infections Participant Pathogenesis Pathogenicity Pathway interactions Patients Persons Pilot Projects Premalignant Production Risk Sampling Squamous cell carcinoma Squamous intraepithelial lesion Sum Superoxides Technology Time Toxin Viral Load result carcinogenesis carcinogenicity commensal microbes gut microbiome high risk high risk men lifetime risk men men who have sex with men microbiome model development novel strategies pathogenic bacteria prevent tumor growth

项目摘要

PROJECT SUMMARY/ABSTRACT The risk of anal cancer in HIV-infected individuals has markedly increased following the advent of anti-retroviral therapy, especially in HIV-infected men who have sex with men (MSM). 90% percent of invasive anal squamous cell carcinomas are associated with human papillomavirus (HPV) infection, of which 80-90% are associated with HPV type 16. Although anal HPV-16 infection is common in HIV-infected MSM, only a small fraction of infected men ever develops anal cancer. Why this occurs in some but not others is unknown. Recent advances in technology have made it feasible to sequence and study the genetic composition, or “microbiome”, of the community of microbes that colonize different parts of the human body. The expansion of otherwise commensal bacteria within the gastrointestinal tract is postulated to contribute to inflammation and carcinogenesis via a variety of pathways including the production of superoxide radicals and toxins. These imbalances have been associated with disease states such as inflammatory bowel disease and colorectal cancer. This study will determine whether a similar association exists between the anal canal microbiome and high- grade squamous intraepithelial lesions (HSIL), the precursor to invasive anal cancer. We will determine whether enrichment of the anal canal with pro-inflammatory bacteria and depletion of anti-inflammatory bacteria is associated with anal HSIL, particularly because long-term chronic inflammation has been proposed as a key mediator in HPV cancer pathogenesis. Accordingly our specific aims are: 1) To characterize the differences in α and β-diversity of the anal microbiome in HIV-infected, anal HPV-16 infected, MSM on effective ART with and without anal HSIL; and 2) To identify specific differences in the composition of the anal microbiome between HIV-infected, anal HPV-16 infected, MSM on effective ART with and without anal HSIL. Our results will contribute to our understanding of HPV carcinogenesis and may potentially provide new approaches to diagnosis and treatment of anal HSIL.

项目摘要/摘要抗逆转录病毒出现后，艾滋病毒感染者患肛门癌的风险显着增加疗法，特别是与男性性行为的艾滋病毒感染者（MSM）。鳞状细胞癌与人乳头瘤病毒（HPV）感染有关，其中80-90％与HPV类型16相关。尽管肛门HPV-16在HIV感染的MSM中很常见，但只有一个小感染男性的一部分曾经患上肛门癌。技术的最新进展使得对遗传组成进行顺序和研究变得可行 “微生物组”的微生物社区殖民地的不同部分的扩张否则，假定胃静脉内的共生骨骼会导致炎症和通过多种途径发生的癌变，包括产生超氧化物自由基和毒素。失衡与疾病状态有关，例如炎性肠肠肠道疾病结直肠疾病癌症。这项研究将确定在肛管管道运河微生物组和高 - 高 - 之间是否存在类似的关联我们将确定。是否富集肛管，具有促炎性的双脚治疗和抗炎的耗竭细菌与肛门HSIL有关，特别是因为已经提出了长期慢性炎症作为HPV癌症发病机理的关键介体。 HIV感染，肛门HPV-16感染的肛门微生物组的α和β多样性的差异，MSM ON 有效的艺术和不带肛门HSIL和2）在有效的情况下，有效的，在有效的情况下感染了HIV感染的HIV感染，肛门HPV-16，MSM之间的微生物组。我们的结果将有助于我们对HPV癌变的理解，并有可能提供新的诊断和治疗肛门HSIL的方法。