Refining Prostate Cancer Risk Prediction in Men of African Ancestry: Integrating Pathogenic Variants, Polygenic Scores, and Family History

Highlights

• Identification of five key pathogenic variants (ATM, BRCA2, CHEK2, HOXB13, PALB2) significantly associated with aggressive prostate cancer risk in men of African ancestry.
• Integration of rare germline variants, polygenic risk scores (PRS), and family history refines lifetime absolute risk estimates for prostate cancer, including aggressive and metastatic forms.
• Substantial risk variability supports moving beyond race-based screening guidelines toward personalized screening approaches based on genetic risk stratification.
• Early detection strategies focusing on high-risk individuals could improve outcomes and reduce overdiagnosis in African ancestry populations.

Introduction