Application of European-specific polygenic risk scores for predicting prostate cancer risk in different ancestry populations

Prostate. 2023 Jan;83(1):30-38. doi: 10.1002/pros.24431. Epub 2022 Aug 22.


Background: Polygenic risk score (PRS) has shown promise in predicting prostate cancer (PCa) risk. However, the application of PRS in non-European ancestry was poorly studied.

Methods: We constructed PRS using 68, 86, or 128 PCa-associated single-nucleotide polymorphisms (SNPs) identified through a large-scale Genome-wide association study (GWAS) in the European ancestry population. A calibration approach was performed to adjust the PRS exact value for each ancestry. The study was conducted in East Asian (ChinaPCa Consortium, n = 2379), European (UK Biobank, n = 209,172), and African American (African Ancestry Prostate Cancer Consortium, n = 6016).

Results: Individuals with the highest PRS (in >97.5th percentile) had over 2.5-fold increased risk of PCa than those with average PRS (in 40th-60th percentile) in both European (odds ratio [OR] = 3.79, 95% confidence interval [CI] = 3.46-4.16, p < 0.001) and Chinese (OR = 2.87, 95% CI = 1.29-6.40, p = 0.010), while slightly lower in African American (OR = 1.77, 95% CI = 1.22-2.58, p = 0.008). Compared with the lowest PRS (in <2.5th percentile), increased PRS was also associated with the earlier onset of PCa (All log-rank p < 0.05). The highest PRS contributed to having about 5- to 12-fold higher lifetime risk and 5-10 years earlier at disease onset than the lowest category across different ancestry populations.

Conclusion: We demonstrated that European-GWAS-based PRS could also significantly predict PCa risk in Asian ancestry and African ancestry populations.

Keywords: European; PRS; SNP; ancestry; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black or African American
  • East Asian People
  • European People
  • Genome-Wide Association Study*
  • Humans
  • Prostatic Neoplasms* / ethnology
  • Prostatic Neoplasms* / genetics
  • Risk Factors