Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria

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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.