Polygenic risk score for tumor aggressiveness and early-onset prostate cancer in Asians

Abstract

We attempted to assess the performance of an ethnic-specific polygenic risk score (PRS) designed from a Korean population to predict aggressive prostate cancer (PCa) and early-onset (age < 60). A PRS score comprised of 22 SNPs was computed in 3695 patients gathered from one of 4 tertiary centers in Korea. Males with biopsy or radical prostatectomy-proven PCa were included for analysis, collecting additional clinical parameters such as age, BMI, PSA, Gleason Group (GG), and staging. Patients were divided into 4 groups of PRS quartiles. Intergroup differences were assessed, as well as risk ratio and predictive performance based on GG using logistic regression analysis and AUC. No significant intergroup differences were observed for BMI, PSA, and rate of ≥ T3a tumors on pathology. Rate of GG ≥ 2, GG ≥ 3, and GG ≥ 4 showed a significant pattern of increase by PRS quartile (p < 0.001, < 0.001, and 0.039, respectively). With the lowest PRS quartile as reference, higher PRS groups showed sequentially escalating risk for GG ≥ 2 and GG ≥ 3 pathology, with a 4.6-fold rise in GG ≥ 2 (p < 0.001) and 2.0-fold rise in GG ≥ 3 (p < 0.001) for the highest PRS quartiles. Combining PRS with PSA improved prediction of early onset csPCa (AUC 0.759) compared to PRS (AUC 0.627) and PSA alone (AUC 0.736). To conclude, an ethnic-specific PRS was found to predict susceptibility of aggressive PCa in addition to improving detection of csPCa when combined with PSA in early onset populations. PRS may have a role as a risk-stratification model in actual practice. Large scale, multi-ethnic trials are required to validate our results.