Genomic Basis of Ethnic Susceptibility Differences in Prostate Cancer Among Nigerian Men: A Multi-Ethnic Case-Control Genome-Wide Study

Prostate cancer exhibits marked ethnic disparities in incidence and mortality, with men of African ancestry experiencing the highest rates globally. Within Nigeria, inter-ethnic differences in prostate cancer risk have been clinically observed but not investigated at the genomic level. This dissertation investigates the genomic basis of ethnic susceptibility differences in prostate cancer among Nigerian men through a multi-ethnic case-control genome-wide association study. One thousand prostate cancer cases and 1,000 age-matched controls were recruited from urology and oncology units across tertiary hospitals representing the Yoruba (South West), Igbo (South East), Hausa-Fulani (North West), and Ijaw (South South) populations. Genome-wide SNP genotyping was conducted using the H3Africa array, followed by imputation against the African Genome Resources reference panel. Ancestry-stratified GWAS was performed, followed by multi-ethnic meta-analysis using METAL. Genetic risk score comparisons across ethnic groups were performed, with functional annotation of significant loci using GTEx and ENCODE chromatin accessibility data. Four genome-wide significant loci were identified in the multi-ethnic meta-analysis, including a novel locus not previously reported in prostate cancer GWAS. Ethnic differences in susceptibility locus allele frequencies partially accounted for observed clinical risk differences. This dissertation advances the molecular epidemiology of prostate cancer in Africa. Keywords: prostate cancer, GWAS, multi-ethnic, Nigerian men, genetic susceptibility