Polygenic hazard score predicts aggressive and fatal prostate cancer in multi-ethnic populations

摘要: Abstract Objectives A polygenic hazard score (PHS1)—weighted sum of 54 single-nucleotide polymorphism genotypes—was previously associated with age at prostate cancer (PCa) diagnosis and improved PCa screening accuracy in Europeans. Performance more diverse populations is unknown. We evaluated PHS association multi-ethnic populations. Design PHS1 was adapted for compatibility genotype data from the OncoArray project (PHS2) tested diagnosis, aggressive death. Setting Multiple international institutions. Participants Men available PRACTICAL consortium who were not included development/validation. Main Outcomes Measures PHS2 via Cox proportional hazards models (any of: Gleason ≥7, stage T3-T4, PSA≥10 ng/mL, nodal/distant metastasis), PCa-specific Results 80,491 men various self-reported race/ethnicities (30,575 controls, 49,916 cases; genetic ancestry groups: 71,856 European, 6,253 African, 2,382 Asian). Median last follow-up 70 years (IQR 63-76); 3,983 deaths, 5,806 other 70,702 still alive. had 46 polymorphisms: 24 directly genotyped 22 acceptable proxies (r2 ≥0.94). dataset (z=54, p Conclusions strongly a dataset. stratifies Asian, African by risk any, aggressive, fatal PCa. Summary boxes What already known on this topic Genetic stratification can identify greater predisposition developing cancer, but these may worsen health disparities, as most have only been validated European Europeans unknown study adds In race/ethnicities, cancer.