Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria

尼日利亚艾滋病毒相关癌症的表观基因组生物标志物

• 批准号: 10242887
• 负责人: Lifang Hou
• 金额: $ 78.7万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242887
• 关键词: AIDS related cancer; Address; Adverse effects; Affect; Africa; American; Area; Biological; Biological Markers; Blood; Cancer Patient; Canes; Cervical; Chronic; Clinic; Clinical; Core Facility; Country; DNA Methylation; Detection; Development; Diagnosis; Early Diagnosis; Educational Curriculum; Epigenetic Process; Exposure to; Funding; Genomics; HIV; HIV Infections; Hepatitis B; Hepatitis B Virus; Hepatitis C; Hepatitis C virus; Human Development; Human Papillomavirus; Immune system; Immunologic Deficiency Syndromes; Income; Individual; Infection; Inflammation; Infrastructure; Institution; K-Series Research Career Programs; Lead; Link; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Medical; Medical Informatics; Mentors; Methods; Molecular; Molecular Epidemiology; Mutation; Nigeria; Nigerian; Oncogenic; Oncogenic Viruses; Outcome; Pathologic; Pathology; Patients; Physicians; Pilot Projects; Play; Precancerous Conditions; Predisposition; Prevention approach; Prevention strategy; Primary carcinoma of the liver cells; Research; Research Personnel; Research Project Grants; Research Support; Risk; Risk Factors; Role; Scientist; Structure; System; Time; Tissues; Training; Training Programs; U-Series Cooperative Agreements; Universities; Ursidae Family; Viral; anticancer research; antiretroviral therapy; biomedical informatics; cancer prevention; cancer therapy; co-infection; cost; epidemiology study; epigenetic marker; epigenomics; experience; genome-wide; high risk; immune activation; improved; indexing; innovation; low and middle-income countries; medical schools; novel; predictive marker; premalignant; statistics; transmission process; tumor

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.

项目摘要 尼日利亚的艾滋病毒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建议 科学家建立一个研究尼日利亚两种高优先级HIV相关癌症的研究财团： 肝细胞癌（HCC）和宫颈癌。该财团还将支持增强 尼日利亚的研究能力，尼日利亚是一个低层收入萨哈拉州国家，负担第二高 世界上的艾滋病毒感染。该提案的主题是进行分子流行病学研究 了解这些致命癌症的表观遗传决定因素。我们建议的前提是癌症 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进行了显着研究 艾滋病毒，HCC和宫颈癌负担很高。艾滋病毒及其对免疫系统的不利影响促进 致癌病毒共同感染（例如丙型肝炎）的传播和重新激活，人类乳头状瘤 病毒（HPV），大大增加了感染HIV感染者的致癌潜力。感染HIV的患者可以 还会经历来自艾滋病毒复制的免疫激活，并增加了对传统危险因素的接触。所有人 这些因素会影响表观遗传生物标志物，例如DNA甲基化，被认为是癌症的标志， 血液和组织中DNA甲基化的畸变与各种癌症的风险增加有关。 该财团将由西北大学和美国梅奥医学院的调查人员领导 与拉各斯大学和尼日利亚乔斯大学合作伙伴。该财团提议执行两个 研究项目将确定与HIV相关HCC特异性的DNA甲基化特征（项目1） 和宫颈癌（项目2）。研究表观基因组生物标志物将提高我们对 HIV共同感染，并提供了早期诊断前癌症和早期癌症的主要优势 这反过来可能导致预防，诊断和治疗的有效策略。我们财团的目标 是：1）确定尼日利亚与HIV相关的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有关 以及这种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； 4）为i）生物医学信息学和统计数据建立两个共享核心设施，ii）病理 和基因组学。该合作协议将为我们提供极大的机会来利用我们现有的 专业知识并将这项工作扩展到尼日利亚的两所主要医学大学，这是人口最多的国家 在非洲，患有异常高的HIV和致癌病毒，例如HPV和乙型肝炎和C。 结果将为HIV相关的预防癌症和治疗提供有用的新信息 与低收入和中等收入国家有关。

项目成果

Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria.

• DOI: 10.1186/s12885-023-11187-5
• 发表时间: 2023-07-20
• 期刊: BMC CANCER
• 影响因子: 3.8
• 作者: Musa, Jonah;Maiga, Mamoudou;Green, Stefan J.;Magaji, Francis A.;Maryam, Ali J.;Okolo, Mark;Nyam, Chuwang J.;Cosmas, Nanma T.;Silas, Olugbenga A.;Imade, Godwin E.;Zheng, Yinan;Joyce, Brian T.;Diakite, Brehima;Morhason-Bello, Imran;Achenbach, Chad J.;Sagay, Atiene S.;Ujah, Innocent A. O.;Murphy, Robert L.;Hou, Lifang;Mehta, Supriya Dinesh
• 通讯作者: Mehta, Supriya Dinesh

Hepatocellular carcinoma presentation and prognosis among Nigerian adults with and without HIV.

• DOI: 10.1371/journal.pone.0282539
• 发表时间: 2023
• 期刊: PloS one
• 影响因子: 3.7