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志物是美国和尼日利亚的一项提案 科学家建立一个联盟，研究尼日利亚两种高度优先的艾滋病毒相关癌症： 肝细胞癌（HCC）和宫颈癌。该联盟还将支持加强 研究能力在尼日利亚，一个低阶层的中等收入撒哈拉以南国家的第二个最高负担 艾滋病病毒感染的最高峰本提案的主题是开展分子流行病学研究， 了解这些致命癌症的表观遗传决定因素。我们提案的前提是癌症 表观遗传学和感染是密不可分的，但在像尼日利亚这样的国家， 艾滋病毒、肝癌和宫颈癌的负担很高。艾滋病毒及其对免疫系统的不利影响促进了 致癌病毒合并感染（如B和C型肝炎以及人乳头状瘤）的传播和再激活 人乳头瘤病毒（HPV），大大增加了艾滋病毒感染者的致癌潜力。HIV感染者可能 艾滋病毒复制也会激活免疫系统，并增加对传统危险因素的暴露。所有 这些因素影响表观遗传生物标记，例如DNA甲基化，它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。 该联盟将由美国西北大学和马约医学院的研究人员领导， 与拉各斯大学和尼日利亚乔斯大学合作。联合体建议执行两项 研究项目，将确定特定于HIV相关HCC的DNA甲基化特征（项目1） 宫颈癌（项目2）。表观基因组生物标志物的研究将提高我们对 艾滋病毒合并感染，并提供了早期诊断癌前和早期癌症的主要优势 这反过来又可能导致有效的预防、诊断和治疗战略。我们联盟的目标是 是：1）确定尼日利亚HIV相关HCC和宫颈癌的表观遗传决定因素; 2）检查 表观遗传生物标志物是否与HIV相关HCC和宫颈癌的临床特征相关 以及这些生物标志物是否预测这两种癌症的发展; 3）提供培训和指导 尼日利亚研究人员进行分子流行病学研究的机会，重点是表观遗传学 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 并扩大人口最多国家尼日利亚两所主要医科大学的努力 在非洲，艾滋病毒和致癌病毒如人乳头瘤病毒、B型和C型肝炎负担特别高。我们 这些结果将为HIV相关癌症的预防和治疗提供有用和新颖的信息， 与低收入和中等收入国家有关。

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.