Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria

项目摘要 尼日利亚HIV相关癌症的表观基因组生物标记物是美国和尼日利亚的一项提议 科学家将在尼日利亚建立一个联盟，研究两种高度优先的艾滋病毒相关癌症： 肝细胞癌和宫颈癌。该财团还将支持加强 尼日利亚的研究能力，这是一个负担第二高的撒哈拉以南低收入国家 世界上最大的艾滋病毒感染。这项建议的主题是进行分子流行病学研究，以 了解这些致命癌症的表观遗传决定因素。我们提议的前提是癌症 表观遗传学和感染有着千丝万缕的联系，但在像尼日利亚这样的国家，表观遗传学和感染研究严重不足。 有很高的艾滋病毒、肝癌和宫颈癌负担。艾滋病毒及其对免疫系统的不良影响促进 乙型和丙型肝炎、人乳头状瘤等致癌病毒混合感染的传播和再激活 病毒(HPV)，大大增加了艾滋病毒感染者的致癌潜力。感染艾滋病毒的患者可能 还经历了艾滋病毒复制引起的免疫激活和暴露在传统风险因素下的增加。所有的 这些因素影响表观遗传生物标记物，如DNA甲基化，这被认为是癌症的标志， 血液和组织中DNA甲基化的异常与各种癌症的风险增加有关。 该财团将由来自美国西北大学和梅奥医学院的调查人员领导， 与尼日利亚的拉各斯大学和乔斯大学合作。该财团提议执行两项 将确定HIV相关肝细胞癌特异性DNA甲基化特征的研究项目(项目1) 和宫颈癌(项目2)。表观基因组生物标记物的研究将提高我们对其作用的理解。 HIV合并感染，为癌前和早期癌症的早期诊断提供了主要优势 这反过来可能导致有效的预防、诊断和治疗战略。我们财团的目标是 是：1)确定尼日利亚艾滋病毒相关肝癌和宫颈癌的表观遗传决定因素；2)检查 表观遗传生物标记物是否与HIV相关性肝癌和宫颈癌的临床特征相关 以及这些生物标志物是否可以预测这两种癌症的发生；3)提供培训和指导 尼日利亚研究人员在开展以表观遗传学为重点的分子流行病学研究方面的机会 生物标志物；以及4)建立两个共享的核心设施，用于i)生物医学信息学和统计学，以及ii)病理学 和基因组学。这项合作协议将提供一个特殊的机会，利用我们现有的 并在人口最多的国家尼日利亚的两所顶尖医科大学扩大这一努力 在艾滋病毒和致癌病毒如HPV、乙肝和丙型肝炎负担特别高的非洲，我们 研究结果将为艾滋病相关癌症的预防和治疗提供有用的新信息 与低收入和中等收入国家相关。

Project Summary Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria is a proposal from U.S. and Nigerian scientists to establish a consortium for research on two high priority HIV-associated cancers in Nigeria: hepatocellular carcinoma (HCC) and cervical cancer. The consortium will also support the enhancement of research capacity in Nigeria, a low strata middle-income sub-Saharan country with the second highest burden of HIV infection in the world. The theme of this proposal is to conduct molecular epidemiologic research to understand the epigenetic determinants of these deadly cancers. The premise for our proposal is that cancer epigenetics and infections are inextricably linked, yet significantly understudied in countries like Nigeria which have a high burden of HIV, HCC and cervical cancer. HIV and its adverse effects on the immune system promote transmission and reactivation of oncogenic viral co-infections such as hepatitis B and C, and human papilloma virus (HPV), greatly increasing the oncogenic potential in HIV-infected individuals. HIV-infected patients may also experience immune activation from HIV replication and increased exposure to traditional risk factors. All of these factors affect epigenetic biomarkers such as DNA methylation, which is considered a hallmark of cancer, and aberrations of DNA methylation in both blood and tissue have linked to increased risk of various cancers. The consortium will be led by investigators from Northwestern University and Mayo Medical School in the U.S., with partners University of Lagos and University of Jos in Nigeria. The consortium proposes to perform two Research Projects which will identify DNA methylation signatures specific to HIV-associated HCC (Project 1) and cervical cancer (Project 2). Study of epigenomic biomarkers will improve our understanding of the role of HIV co-infection and offers the main advantage of earlier diagnosis of premalignant and early stage cancers which may in turn lead to effective strategies for prevention, diagnosis and treatment. The aims of our consortium are: 1) identify epigenetic determinants of HIV-associated HCC and cervical caner in Nigeria; 2) examine whether epigenetic biomarkers are associated with clinical features of HIV-associated HCC and cervical cancer and whether such biomarkers predict development of for these two cancers; 3) provide training and mentoring opportunities for Nigerian investigators in conducting molecular epidemiology studies with a focus on epigenetic biomarkers; and 4) establish two shared core facilities for i) biomedical informatics and statistics, and ii) pathology and genomics. This cooperative agreement will provide an exceptional opportunity to leverage our existing expertise and expand that effort at two of the leading medical universities in Nigeria, the most populous country in Africa with an exceptionally high burden HIV and oncogenic viruses such as HPV and hepatitis B and C. Our results will provide useful and novel information for HIV-associated cancer prevention and treatment most relevant to low- and middle-income countries.