Investig Clin Urol.  2022 Jan;63(1):42-52. 10.4111/icu.20210305.

Prediction of clinically significant prostate cancer using polygenic risk models in Asians

• Song SH
• Kim E
• Woo E
• Kwon E
• Yoon S
• Kim JK
• Lee H
• Oh JJ
• Lee S
• Hong SK
• Byun SS

• KMID: 2524272
• DOI: http://doi.org/10.4111/icu.20210305

Abstract

Purpose
To develop and evaluate the performance of a polygenic risk score (PRS) constructed in a Korean male population to predict clinically significant prostate cancer (csPCa).
Materials and Methods
Total 2,702 PCa samples and 7,485 controls were used to discover csPCa susceptible single nucleotide polymorphisms (SNPs). Males with biopsy-proven or post-radical prostatectomy Gleason score 7 or higher were included for analysis. After genotype imputation for quality control, logistic regression models were applied to test association and calculate effect size. Extracted candidate SNPs were further tested to compare predictive performance according to number of SNPs included in the PRS. The best-fit model was validated in an independent cohort of 311 cases and 822 controls.
Results
Of the 83 candidate SNPs with significant PCa association reported in previous literature, rs72725879 located in PRNCR1 showed the highest significance for PCa risk (odds ratio, 0.597; 95% confidence interval [CI], 0.555–0.641; p=4.3×10 -45 ). Thirty-two SNPs within 26 distinct loci were further selected for PRS construction. Best performance was found with the top 29 SNPs, with AUC found to be 0.700 (95% CI, 0.667–0.734). Males with very-high PRS (above the 95th percentile) had a 4.92-fold increased risk for csPCa.
Conclusions
Ethnic-specific PRS was developed and validated in Korean males to predict csPCa susceptibility using the largest csPCa sample size in Asia. PRS can be a potential biomarker to predict individual risk. Future multi-ethnic trials are required to further validate our results.

Keyword

Genome-wide association study; Multifactorial inheritance; Polymorphism; single nucleotide; Prostatic neoplasms