Targeted Cascade Genetic Testing in Korean Prostate Cancer Probands: High Detection Rate of Heritable Germline Variants in First-Degree Relatives From a Retrospective Cohort

Purpose: This study aimed to assess the rate of germline variant detection following targeted cascade genetic testing among family members of prostate cancer (PCa) probands.Materials and Methods: Records of PCa patients with confirmed germline mutations and their family members recommended for cascade testing were retrospectively reviewed. Cascade testing for germline mutations identified in PCa probands was conducted among first-degree relatives (FDRs) and second-degree relatives. The rate of counseled family members who proceeded to actual testing, the proportion of mutation carriers detected, and the reasons for test refusal were analyzed. Clinical variables, including family history of malignancy and variant type, were also collected.Results: A total of 15 PCa patients and 44 eligible relatives were included in the final analysis. Eleven probands (73.3%) had a positive family history of cancer across 22 family members (18 FDRs). Among FDRs, breast/ovarian cancer (27.8%) and gastric cancer (22.2%) were the most common, followed by lymphoma, prostate, esophageal, and lung cancer (each 11.1%). Among probands, <i>BRCA2</i> variants were predominant (80%, 12 of 15), followed by <i>BRCA1</i> (n=2) and MLH1 (n=1) mutations. Of 41 eligible FDRs, 21 (51.2%) underwent genetic testing, and 61.9% (13 of 21) were found to carry identical germline mutations. Approximately half of the counseled family members declined testing due to concerns regarding privacy and disclosure, travel distance to the clinic, or loss to follow-up.Conclusion: Over half of the FDRs who underwent cascade testing were confirmed to carry pathogenic germline variants. As the first study to evaluate cascade testing in family members of PCa probands in Korea, these findings underscore the strong heritable component of PCa and highlight the need to enhance participation in familial genetic screening.