Genetic Susceptibility to HIV-1 in African Cancer Cohort Revealed by GWAS

Purpose: HIV is a recognised carcinogen, and its prevalence remains high in sub-Saharan Africa. Although there has been a decline in HIV-related deaths due to antiviral therapy, HIV-associated malignancies have not shown the same trend. Not all individuals exposed to HIV-1 acquire the virus and genetic variability has been found to account for some of this variability. Genome-wide association studies (GWAS) screen many genomes to identify common genetic variants associated with a trait or disease and offer the potential to identify novel common variants and genes associated with the trait of interest. Relatively few GWAS for HIV have been performed on sub-Saharan populations with inconclusive results, despite the region having the highest burden of HIV (∼20%) worldwide. This makes our cohort ideal for the investigation of HIV-1 infection. This study aims to identify host genetic factors associated with susceptibility to HIV-1 in an African cancer cohort. Methods: The study used data from 4,595 adult female participants who self-identified as black Africans from the Johannesburg Cancer Study. Participants were part of the breast, cervical, and oesophageal cancer cohorts, as well as a non-cancer cohort. Genetic data includes genotyped and imputed variants and serology data includes antibody response to HIV-1 measured by a multiplex serology assay. Data was used to calculate HIV-1 seroprevalence and conduct GWAS. Results: Of the 4, 595 individuals 185 were removed due to population substructure, retaining 4,410 individuals of African ancestry for downstream analysis. Overall HIV-1 seropositivity was 29.0% (1,279/4,410). The cervical cancer group had the highest HIV-1 prevalence (43.2%) followed by the breast cancer group (21.8%). The oesophageal cancer (17.5%) and non-cancer (17.3%) groups had the lowest HIV-1 prevalence. GWAS results show suggestive significant associations (P < 5×10^−7) with HIV-1 infection on chromosomes 2, 8 and 14. Further results and possible implications will be shared during the symposium. Conclusion: This data will contribute to the limited GWAS studies available that can provide insight into genetic susceptibility to HIV-1 infection, particularly in African populations. Citation Format: Isabel Fourie, Wenlong Carl Chen, Mazvita Muchengeti, Tim Waterboer, Christopher Mathew, Jean-Tristan Brandenburg. Genetic Susceptibility to Infection with HIV-1 in a Cancer Cohort of African Ancestry [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 25.