Methylation and Related Anogenital HPV Cancers

甲基化和相关的肛门生殖器 HPV 癌症

• 批准号: 7348432
• 负责人: DOROTHY J. WILEY
• 金额: $ 18.54万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348432
• 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; 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 Characteristics; 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; Virus Diseases; Visit; burden of illness; cohort; disease natural history; improved; latent infection; men; men who have sex with men; men' s group; mortality; prevent; promoter; tool; transcription factor; transgender

Anal cancer is an emerging health crisis for homosexual men, especially within the context of human mmunodeficiency 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 biomarkersthat 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 DMA 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 coinfected 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.

肛门癌是同性恋男性的新兴健康危机，尤其是在人类的背景下 MMUNOSDICKITION病毒（HIV）感染。像浸润性宫颈癌一样，纳尔癌在很大程度上是 归因于慢性高危人乳头瘤病毒（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）对于有病史的男性很常见 接受肛门性交。尽管肛门发育不良的患病率很高，但恶性肿瘤是一个相对罕见的 发生。在国内，护理标准尚无共识和治疗结果 算法在很大程度上不令人满意。迫切需要确定基础自然中的关键事件 疾病史，这将使临床医生能够确定哪些人需要立即治疗或 可以保持仔细的监视。更敏感的生物标志物可以区分可能的男性 从那些不允许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，可通过使病毒来阻碍外国DMA的转录 基因组对宿主细胞转录因子和酶的访问较低。我们最近的研究表明 HPV基因组的甲基化可能是表观遗传决定因素，负责促进潜在感染 和临床疾病进展。这项调查的重点是使用流行病学方法和 分子生物学技术。首先，我们将确定是否在以前观察到 在91 HIV/HPV16共同感染的男性中，可以观察到HPV16基因组和疾病状态的甲基化 已经评估了目标。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，我们将确定特定的甲基化基线模式是否在 HPV16基因组预测三个高风险HPV中的甲基化模式加班。 公共卫生声明：这项研究的发现将改善公众的健康 通过鉴定可靠的生物标志物来提高肛门癌筛查精度，最终 防止过早死亡。