Abstract:
African ancestry is a significant risk factor for prostate cancer and advanced
disease. Yet, genetic studies have largely been conducted outside the context
of Sub-Saharan Africa, identifying 278 common risk variants contributing to a
multiethnic polygenic risk score, with rare variants focused on a panel of
roughly 20 pathogenic genes. Based on this knowledge, we are unable to
determine polygenic risk or differentiate prostate cancer status interrogating
whole genome data for 113 Black South African men. To further assess for
potentially functional common and rare variant associations, here we interrogate
247,780 exomic variants for 798 Black South African men using a case
versus control or aggressive versus non-aggressive study design. Notable genes
of interest include HCP5, RFX6 and H3C1 for risk, and MKI67 and KLF5 for
aggressive disease. Our study highlights the need for further inclusion across
the African diaspora to establish African-relevant risk models aimed at reducing
prostate cancer health disparities.
