Germline DNA Repair Gene Mutation Landscape in Chinese Prostate Cancer Patients

Genetic testing for prostate cancer (PCa) patients is in constant development. Specific genetic alterations indicate personalized managing strategies, requiring clinicians to refer appropriate patients for genetic testing. However, our understanding of genetic epidemiology of PCa is mainly based on data from Caucasian populations. In addition, there is evidence that alterations in DNA repair genes (DRGs) may be ethnic specific in other cancers such as breast cancer. Thus, whether Caucasian-based genetic information can be used to guide clinical practice in Chinese population remains unknown. Aiming to clarify the landscape of germline DRG mutation in Chinese patients with PCa, we sequenced 316 patients for 18 DRGs. Among all cases, 9.8% (31/316, 95% confidence interval [CI]: 6.5–13%) carried pathogenic mutations in 18 PCa-related DRGs: 6.3% in BRCA2, 0.63% in BRCA1, 0.63% in ATM, and 2.5% in 15 other genes. Overall, we observed similar germline DRG mutation frequencies, although there is large disparity in the risk of PCa between China and the West. Our study called for a comprehensive analysis in detailed mutation spectra to refine management strategies further, given the ethnic diversity. We sequenced germline pathogenic mutations in 18 DNA repair genes in 316 patients and elucidated the mutation landscape of Chinese prostate cancer (PCa) patients. Our study confirmed the necessity of genetic testing in Chinese PCa and called for a comprehensive analysis in detailed mutation spectra to refine management strategies further, given the ethnic diversity. Germline DNA repair gene pathogenic mutation frequency is 12% in Chinese metastatic prostate cancer cases and 8.1% in high-risk localized patients. A similar prevalence was observed, although there is large disparity in the risk of prostate cancer between China and the West.