Abstract: Background and purpose: Pathogenic germline mutations in BRCA1/2 and ATM are significantly associated with risk and progression of prostate cancer. In addition, metastatic castration-resistant prostate cancer (mCRPC) patients, who possess germline pathogenic BRCA1/2 or ATM mutation, can be treated with PARP inhibitor olaparib and platinum-based chemotherapy. However, few such studies in the Chinese population have been reported by far. This study aimed to reveal the frequency of such mutations in Chinese patients, so as to guide genetic testing and clinical management. Methods: Germline DNA samples of 53 prostate cancer patients were sequenced for these three genes. Pathogenic and likely pathogenic mutations were screened out in accordance with the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines. Statistical methods were used to analyze the association between germline mutation status and clinical relevance. Results: A total of 4 germline mutations in BRCA1/2 and ATM that were presumed to be pathogenic were identified among 53 men (7.55%). The frequency of germline mutations in these genes among metastatic cases was 9.68% which was similar to the figure reported by the foreigners. And mutation frequency among early-onset cases significantly exceeded the others (P=0.011). However, there was no difference in mutation frequencies according to family history, Gleason score or PSA value (P>0.05). Conclusion: We initially established the criteria on genetic testing for the Chinese patients. Genetic testing and counseling should be encouraged for metastatic and early-onset cases in order to adopt a better treatment strategy.

Key words: Prostate cancer, Germline mutations, Chinese population, BRCA1/2 gene, ATM gene