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

Objective: Prostate cancer (PCa) is a significant global health concern, with genetic factors playing a crucial role in its development. Identifying pathogenic variants in high-penetrant genes significantly impacts the treatment of PCa patients and their families. This real-life retrospective multicenter study aimed to identify and characterize the germinal genetic landscape of men with PCa, focusing on the prevalence of disease-causing genetic alterations and their association with demographic and clinical factors. Material and Methods: The study included all men who were referred for genetic counseling due to prostate cancer in the genetic institutions of Beilinson Hospital and Assuta (Ashdod) Hospital. All patients were offered germline genetic testing. Demographic, clinical, and pathological information was retrieved from medical records. Pathogenic (P), likely pathogenic (LP), variants of unknown significance (VOUS), and risk allele variants (RV) were determined using the American College of Medical Genetics guidelines. Results: Two hundred ninety-three men affected by PCa were tested. In 14% of them, a positive A genetic finding (PV LP or RV) was reported: 20 (6.8%) had a positive result in high-penetrance genes (BRCA1, BRCA2, ATM, NF1, MSH6), and 21 (7.2%) had risk allele 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 genetic investigations in PCa patients, regardless of ethnicity or disease stage, and contribute to the growing body of knowledge on PCa genetics.