Polygenic risk and germline genetics for prostate cancer in Asians: Where do we stand?

Prostate cancer exhibits marked ethnic differences in genetic architecture. Although polygenic risk scores (PRS) and germline genetic testing have shown clinical utility in European populations, their applicability to Asian populations remains limited. This review synthesizes evidence published between 2020 and 2025 on PRS and germline genetics in Asian prostate cancer cohorts, focusing on Chinese, Japanese, and Korean populations. Recent studies demonstrate that population-specific PRS models effectively stratify prostate cancer risk in Asian men, with individuals in the highest decile showing a 4- to 5-fold increased risk. The 2025 BARCODE1 trial reported a 40.0% cancer detection rate, with 55.1% clinically significant disease, among PRS-selected European men, highlighting the need for population-specific validation in Asians. Germline profiling indicates that 25.1%-29% of Chinese patients harbor deleterious variants, most frequently involving BRCA2. Ethnic-specific susceptibility variants have also been identified, including HOXB13 G132E in Asians, contrasting with the G84E variant predominant in Europeans. The 2022 Hong Kong Consensus provides the first comprehensive guideline tailored to germline testing in Asian populations. Despite these advances, current PRS models primarily predict disease incidence rather than aggressive phenotypes. Key challenges include smaller genome-wide association study sample sizes, limited prospective validation, and heterogeneous clinical and research infrastructure across Asia. In conclusion, while substantial progress has been made in characterizing genetic risk in Asian prostate cancer, European-derived models show reduced accuracy. Future priorities include large-scale multiethnic collaborations, prospective validation studies, and development of predictors for aggressive disease.