Polygenic risk score predicting susceptibility and outcome of benign prostatic hyperplasia in the Han Chinese

Abstract

Abstract Importance: Polygenic risk score (PRS) is effective in predict benign prostatic hyperplasia (BPH) incidence, prognosis and risk of operation in Han Chinese. Objective: The aim of our study is to investigate the role of PRS for BPH incidence and treatment outcome through hospital-based genome-wide association study (GWAS). Design, setting, and participants: The Affymetrix Genome-Wide TWB 2.0 SNP Array genotyped 6,237 male participants with benign prostatic hyperplasia (BPH) and 17,170 non-BPH controls from the Taiwan Precision Medicine Initiative (TPMI). PRS was determined using PGS001865, which included 1,712 single nucleotide polymorphisms. PRS scores were categorized into quartiles (Q1-Q4) and their association with outcomes in BPH patients was analyzed using logistic regression models. Main outcomes and measures: We investigated the PRS association with BPH incidence, adjusting for age and PSA levels. We explored PSA's relationship with prostate volume and assessed 5ARI treatment response via percentage reduction in prostate volume per patient. Additionally, we studied the PRS association with TURP risk. Results: In a cohort of 23,407 men, 6,237 were diagnosed with BPH. Risk of BPH was higher in the fourth quartile (Q4) than the first quartile (Q1) (OR=1.34, 95% CI=1.24-1.46, p<0.0001), even after adjusting for age (OR=1.39, 95% CI=1.27-1.52, p<0.0001). The Q4 group had larger prostate volume (43.1 ± 25.0 ml) than Q1 (34.6 ± 19.0 ml) (p<0.001), and less volume reduction after 5ARI treatment (Q1: 29.9 ± 16.6 ml, Q4: 25.0 ± 18.6 ml, p=0.011). Q1 had lower cumulative TURP probability at 3, 5, and 10 years compared to Q4 (p=0.045, p=0.009, p<0.001, respectively). PRS Q4 was an independent TURP risk in multivariate COX hazard regression (HR=1.45, 95% CI=1.09-1.92, p=0.012). Conclusions and relevance: In this hospital-based cohort, a higher PRS was associated with the susceptibility to BPH in male Han Chinese. In patients with BPH, a higher PRS was associated higher PSA level, larger prostate volume, inferior response of 5ARI and higher risk of TURP. Age, PSA and prostate volume were also independent risk of TURP. Prospective large-scale study with longer follow-up would be needed to validate our result.