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

Hum Genomics. 2024 May 22;18(1):49. doi: 10.1186/s40246-024-00619-3.

Abstract

Background: Given the high prevalence of BPH among elderly men, pinpointing those at elevated risk can aid in early intervention and effective management. This study aimed to explore that polygenic risk score (PRS) is effective in predicting benign prostatic hyperplasia (BPH) incidence, prognosis and risk of operation in Han Chinese.

Methods: A retrospective cohort study included 12,474 male participants (6,237 with BPH and 6,237 non-BPH controls) from the Taiwan Precision Medicine Initiative (TPMI). Genotyping was performed using the Affymetrix Genome-Wide TWB 2.0 SNP Array. PRS was calculated using PGS001865, comprising 1,712 single nucleotide polymorphisms. Logistic regression models assessed the association between PRS and BPH incidence, adjusting for age and prostate-specific antigen (PSA) levels. The study also examined the relationship between PSA, prostate volume, and response to 5-α-reductase inhibitor (5ARI) treatment, as well as the association between PRS and the risk of TURP.

Results: Individuals in the highest PRS quartile (Q4) had a significantly higher risk of BPH compared to the lowest quartile (Q1) (OR = 1.51, 95% CI = 1.274-1.783, p < 0.0001), after adjusting for PSA level. The Q4 group exhibited larger prostate volumes and a smaller volume reduction after 5ARI treatment. The Q1 group had a lower cumulative TURP probability at 3, 5, and 10 years compared to the Q4 group. PRS Q4 was an independent risk factor for TURP.

Conclusions: In this Han Chinese cohort, higher PRS was associated with an increased susceptibility to BPH, larger prostate volumes, poorer response to 5ARI treatment, and a higher risk of TURP. Larger prospective studies with longer follow-up are warranted to further validate these findings.

Keywords: 5-α-reductase inhibitor; Benign prostatic hyperplasia; Incidence; Polygenic risk score; Prognosis; Prostate-specific antigen level.

MeSH terms

  • 5-alpha Reductase Inhibitors / therapeutic use
  • Aged
  • Asian People / genetics
  • East Asian People
  • Genetic Predisposition to Disease*
  • Genetic Risk Score
  • Humans
  • Male
  • Middle Aged
  • Multifactorial Inheritance* / genetics
  • Polymorphism, Single Nucleotide* / genetics
  • Prognosis
  • Prostate / pathology
  • Prostate-Specific Antigen / blood
  • Prostate-Specific Antigen / genetics
  • Prostatic Hyperplasia* / genetics
  • Prostatic Hyperplasia* / pathology
  • Retrospective Studies
  • Risk Factors
  • Taiwan / epidemiology

Substances

  • 5-alpha Reductase Inhibitors
  • Prostate-Specific Antigen

Supplementary concepts

  • Han Chinese people