Risk Allele Frequency Analysis and Risk Prediction of Single-Nucleotide Polymorphisms for Prostate Cancer.

Abstract

The incidence of prostate cancer (PCa) varies by ethnicity. This study aimed to provide insights into the genetic cause of PCa, which can result in differences in incidence among individuals of diverse ancestry. We collected data on PCa-associated single-nucleotide polymorphisms (SNPs) from a genome-wide association study catalog. Fisher's exact tests were used to analyze the significance of enrichment or depletion of the effect on the allele at a given SNP. A network analysis was performed based on PCa-related SNPs that showed significant differences among ethnicities. The SNP-based polygenic risk score (PRS) was calculated, and its correlation with PCa incidence was evaluated. European, African, and East Asian populations had different heatmap patterns. Calculated PRS from the allele frequencies of PCa was the highest among Africans, followed by Europeans, and was the lowest among East Asians. PRS was positively correlated with the incidence and mortality of PCa. Network analysis revealed that AR, CDKN1B, and MAD1L1 are genes related to ethnic differences in PCa. The incidence and mortality of PCa showed a strong correlation with PRS according to ethnicity, which may suggest the effect of genetic factors, such as the AR gene, on PCa pathogenesis.