Methylation and Related Anogenital HPV Cancers

甲基化和相关的肛门生殖器 HPV 癌症

基本信息

批准号：
7231117
负责人：
DOROTHY J. WILEY
金额：
$ 15.08万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-01 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7231117
关键词：
Algorithms Anal Intraepithelial Neoplasia Anus Biological Markers Biological Process Bisexual Caring Cell physiology Cells Cervix Uteri Cessation of life Characteristics Chronic Clinical Clinical Data Consensus Cytosine DNA Data Diagnostic Disease Disease Progression Dysplasia Enhancers Environmental Risk Factor Enzymes Epidemiologic Methods Epigenetic Process Event Gays Genetic Transcription Genome HIV HPV-High Risk Health Homosexuals Human Human Papillomavirus Human papilloma virus 31 Human papilloma virus infection Human papillomavirus 16 Individual Infection Invasive Investigation Lesion Malignant Neoplasms Malignant neoplasm of anus Malignant neoplasm of cervix uteri Medical Surveillance Methylation Molecular Biology Techniques Morbidity - disease rate Neoplasms Numbers Pattern Play Population Premalignant Prevalence Public Health Recording of previous events Risk Role Sampling Screening procedure Standards of Weights and Measures Testing Time Treatment outcome Viral Genome Viral load measurement Virus Diseases Visit burden of illness cohort disease natural history improved latent infection men men who have sex with men men&apos s group mortality prevent promoter tool transcription factor transgender

项目摘要

DESCRIPTION (provided by applicant): Anal cancer is an emerging health crisis for homosexual men, especially within the context of human immunodeficiency virus (HIV) infection. Like invasive cervical cancer, intra-anal cancers are largely attributable to chronic, high-risk human papillomavirus (HPV) infections. These infections and their associated low- and high-grade anal intraepithelial neoplasias (AIM) are common for men with a history of receptive anal intercourse. Though the prevalence of anal dysplasia is high, malignancy is a relatively rare occurrence. Domestically, there is no consensus for standards of care, and the outcome of treatment algorithms is largely unsatisfactory. There is an urgent need to identify key events in the underlying natural history of disease, which will enable clinicians to determine which individuals need immediate treatment or can remain under careful surveillance. More sensitive biomarkers that can discriminate between men likely to progress from those that do not will allow better clinical algorithms to be tested. In the long term, these strategies will reduce morbidity and mortality and diminish the population's burden of disease. Methylation is an adaptive cellular process that hinders transcription of foreign DNA by making viral genomes less accessible to host-cell transcription factors and enzymes. Our recent studies suggest methylation of HPV genomes may be an epigenetic determinant, responsible for promoting latent infection and clinical disease progression. This investigation focuses on two aims using epidemiological methods and molecular biology techniques. First, we will determine whether previously observed relationships between methylation of HPV16 genomes and disease state are observable in 91 HIV/HPV16 co-infected men that have been evaluated for AIM. Second, using longitudinally-collected clinical samples and controlling for the effect of time-dependent covariates, we will determine whether particular baseline patterns of methylation in HPV16 genomes predict methylation patterns overtime in three high-risk HPVs. PUBLIC HEALTH STATEMENT: The findings from this study will improve the public's health by improving anal cancer screening accuracy through the identification of reliable biomarkers, to ultimately prevent premature death.

描述（由申请人提供）：肛门癌是同性恋男性的新兴健康危机，尤其是在人类免疫缺陷病毒（HIV）感染的背景下。像浸润性宫颈癌一样，纳尔癌基本上归因于慢性，高风险的人乳头瘤病毒（HPV）感染。这些感染及其相关的低级和高级肛门上皮内肿瘤（AIM）对于患有接受性肛门性交病史的男性很常见。尽管肛门发育不良的患病率很高，但恶性肿瘤是相对罕见的发生。在国内，护理标准尚无共识，治疗算法的结果在很大程度上不令人满意。迫切需要确定疾病潜在自然史上的关键事件，这将使临床医生能够确定哪些人需要立即治疗或可以仔细监视。更敏感的生物标志物可以区分可能与不脱离的男性相比，将允许对更好的临床算法进行测试。从长远来看，这些策略将降低发病率和死亡率，并减轻人口的疾病负担。甲基化是一种适应性的细胞过程，它通过使病毒基因组较少访问宿主细胞转录因子和酶来阻止异物的转录。我们最近的研究表明，HPV基因组的甲基化可能是表观遗传的决定因素，负责促进潜在的感染和临床疾病进展。这项研究的重点是使用流行病学方法和分子生物学技术的两个目标。首先，我们将确定在91 HIV/HPV16共同感染的男性中，是否可以观察到以前观察到的HPV16基因组和疾病状态之间的甲基化关系。其次，使用纵向收集的临床样本并控制时间依赖性协变量的影响，我们将确定在HPV16基因组中的特定基线基线模式是否预测三种高风险HPV中的甲基化模式会加班。公共卫生声明：这项研究的发现将通过鉴定可靠的生物标志物来提高肛门癌筛查准确性，从而改善公众的健康状况，从而最终防止早亡。