Prostate cancer genetic risk and associated aggressive disease in men of African ancestry.

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.

Nature communications. 2023 Dec 05*** epublish ***

Pamela X Y Soh, Naledi Mmekwa, Desiree C Petersen, Kazzem Gheybi, Smit van Zyl, Jue Jiang, Sean M Patrick, Raymond Campbell, Weerachai Jaratlerdseri, Shingai B A Mutambirwa, M S Riana Bornman, Vanessa M Hayes

Ancestry and Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, 2006, Australia., School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa., South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Faculty of Health Sciences, University of Limpopo, Turfloop Campus, South Africa., Phulukisa health Care, Pretoria, South Africa., Department of Urology, Sefako Makgatho Health Science University, Dr George Mukhari Academic Hospital, Medunsa, South Africa., Ancestry and Health Genomics Laboratory, Charles Perkins Centre, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, 2006, Australia. .