Identifying and characterizing the germinal genetic landscape of men with prostate cancer: A real-life, retrospective, multicenter study.

PURPOSE: Genetic factors play a role in prostate cancer (PCa) development. This real-life, retrospective, multicenter study aimed to identify and characterize the germline genetic testing landscape in men with PCa and to assess the added benefit of next-generation sequencing (NGS) testing compared with testing for founder disease-causing variants.

METHODS

This study included all men who were referred for genetic counseling because of PCa. All patients were offered germline genetic testing. Demographic, clinical, and pathological information was retrieved from their medical records. Variant classification was determined using the American College of Medical Genetics and Genomics guidelines.

RESULTS

Of the 293 men with PCa tested, in 39 (13.3%), a positive genetic finding (pathogenic variant, likely pathogenic, or risk variant) was reported: 18 (6.1%) men had a positive test result for high-penetrance genes (BRCA1, BRCA2, ATM, NF1, and MSH6), and 21 (7.2%) had risk allele variants. One-third (33%) of the disease-causing or likely disease-causing variants identified through NGS in our PCa cohort were unique rather than founder variants. The only significant correlation between positive results and demographic or clinical factors was observed between a positive test result and a family history of cancer.

CONCLUSION

Our findings underscore the importance of NGS genetic investigations in patients with PCa, regardless of ethnicity or disease stage.