Abstract
Abstract
Background
The genetic risk of aggressive prostate cancer (PCa) is hard to be assessed due to the lack of aggressiveness-related single-nucleotide polymorphisms (SNPs). Prostate volume (PV) is a potential well-established risk factor for aggressive PCa, we hypothesize that polygenic risk score (PRS) based on benign prostate hyperplasia (BPH) or PV-related SNPs may also predict the risk of aggressive PCa or PCa death.
Methods
We evaluated a PRS using 21 BPH/PV-associated SNPs, two established PCa risk-related PRS and 10 guideline-recommended hereditary cancer risk genes in the population-based UK Biobank cohort (N = 209,502).
Results
The BPH/PV PRS was significantly inversely associated with the incidence of lethal PCa as well as the natural progress in PCa patients (hazard ratio, HR = 0.92, 95% confidence interval [CI]: 0.87–0.98, P = 0.02; HR = 0.92, 95% CI 0.86–0.98, P = 0.01). Compared with men at the top 25th PRS, PCa patients with bottom 25th PRS would have a 1.41-fold (HR, 95% CI 1.16–1.69, P = 0.001) increased PCa fatal risk and shorter survival time at 0.37 yr (95% CI 0.14–0.61, P = 0.002). In addition, patients with BRCA2 or PALB2 pathogenic mutations would also have a high risk of PCa death (HR = 3.90, 95% CI 2.34–6.51, P = 1.79 × 10–7; HR = 4.29, 95% CI 1.36–13.50, P = 0.01, respectively). However, no interactive but independent effects were detected between this PRS and pathogenic mutations.
Conclusions
Our findings provide a new measurement of PCa patients’ natural disease outcomes via genetic risk ways.
Funder
National Natural Science Foundation of China
Innovative research team of high-level local universities in Shanghai
Shanghai Youth Talent Support Program
Intramural grant of The University of Hong Kong
Shanghai Sailing Program
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine