Targeted sequencing of common cancer susceptibility genes reveals germline variants in African prostate cancer patients

Background : Prostate cancer (PCa) is the leading cause of cancer-related deaths globally and disproportionately affects men of African ancestry. African men often present at younger ages and with more aggressive disease, and approximately half of the PCa risk has been attributed to genetic factors. Africa is the most genetically diverse region of the world, and even within the continent, populations show important differences in allele frequencies and patterns of pathogenic variation. Despite this diversity, African men remain underrepresented in genomic studies, creating significant gaps in knowledge that limit precision medicine efforts. Methods: A total of 182 prostate cancer patients were recruited from teaching hospitals in Benin, Côte d'Ivoire, Ghana, Kenya and Nigeria. 50 cancer susceptibility genes using the Aviseq ONCO50 panel and the Illumina MiSeq platform. Variant calling was performed using an in-house Snakemake workflow, followed by additional bioinformatic steps to distinguish true PMS2 variants from PMS2CL-related artifacts. Pathogenicity assessment relied on annotations from ClinVar and LOVD databases. Results: Pathogenic and likely pathogenic variants were detected in 31.3% of the study group identified in 26 genes. The five most frequently altered genes were RAD50, PTCH1, MSH6, MUTYH, and NF1. Nigerian patients accounted for 52.6 percent of all pathogenic variants, with recurrent alterations observed in MSH6, MUTYH, NF1, and PTCH1. In contrast, pathogenic BRCA1 and BRCA2 variants were observed primarily in patients from Kenya, Benin, and Côte d'Ivoire. Several frameshift, nonsense, and splice-site variants identified in this study have not been previously reported in African populations.[SR1] Conclusion: This study provides one of the most detailed assessments of inherited cancer susceptibility gene variants in African PCa patients. The findings reveal substantial regional variation in the spectrum of pathogenic variants and highlight population-specific genomic signatures that may contribute to the unequal burden of PCa in men of African ancestry. These data emphasize the importance of expanding genomic research efforts within Africa to strengthen precision oncology and reduce global PCa disparities.