Germline mutations in 5' to c.7914 of BRCA2 significantly increase risk of prostate cancer.

carriers. BRCA2 -mutant prostate tumors were associated with high-grade disease and progression to metastatic castration-resistant PCa, affecting treatment effectiveness. 4,5 Some recent studies suggested that pathogenic mutations in the PCCR of BRCA2 were related to a higher PCa risk than mutations elsewhere in the gene, by 1.78–2.34-fold hazard ratio (HR). 6,7 Both studies evaluated the hypothesis of the PCCR in BRCA2 carrier cohorts of Caucasians or nonrace-specific populations under either a prospective or retrospective design. However, whether PCCR mutations are associated with PCa risk at the population level is still unknown. In addition, the relationship between BRCA2 regions and PCa has been poorly studied in the Chinese population. We conducted the present study in two cohorts, the UK Biobank (UKB) prospective cohort and a Chinese PCa cohort. The study was approved by the North West Multi-centre Research Ethics Committee in Manchester, UK (IRAS project ID: 299116; approval No. 66813), and the Institutional Review Board of Shanghai Huashan Hospital in Shanghai, China (approval No. KY2011-009). Written informed consent was obtained from each participant. The UKB is a large-scale biomedical database containing genetic and phenotype information from a prospective cohort study. 8 We established a prospective cohort of 83 181 European who had not been diagnosed with PCa at recruitment and had not developed any other types of cancers during follow-up (last follow-up in January 2022). A PCa diagnosis was identified from national cancer registries and self-report records (International Classification of Diseases [ICD] 10: C61). PCa-related death ( i.e. , lethal PCa) information was identified from death registries. The Chinese PCa cohort was a retrospective case-only cohort of 235 PCa patients who had undergone whole-exome sequencing (WES) of