Mp17-17 germline mutational carrier frequency analysis in korean metastatic prostate cancer : a large cohort study

You have accessJournal of UrologyCME1 Apr 2023MP17-17 GERMLINE MUTATIONAL CARRIER FREQUENCY ANALYSIS IN KOREAN METASTATIC PROSTATE CANCER : A LARGE COHORT STUDY Sang Hun Song, Jin Noh, Hae Sung Lee, Jun Hyun Nam, Byeongdo Song, Jung Kwon Kim, Hakmin Lee, Jong Jin Oh, Sangchul Lee, Seong Jin Jeong, Sung Kyu Hong, and Seok-Soo Byun Sang Hun SongSang Hun Song More articles by this author , Jin NohJin Noh More articles by this author , Hae Sung LeeHae Sung Lee More articles by this author , Jun Hyun NamJun Hyun Nam More articles by this author , Byeongdo SongByeongdo Song More articles by this author , Jung Kwon KimJung Kwon Kim More articles by this author , Hakmin LeeHakmin Lee More articles by this author , Jong Jin OhJong Jin Oh More articles by this author , Sangchul LeeSangchul Lee More articles by this author , Seong Jin JeongSeong Jin Jeong More articles by this author , Sung Kyu HongSung Kyu Hong More articles by this author , and Seok-Soo ByunSeok-Soo Byun More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003237.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Germline mutations in DNA-damage repair (DDR) genes such as BRCA2 have been associated with prostate cancer (PC) risk but has not been thoroughly evaluated for metastatic prostate cancer (mPC) in Asian men. This study attempts to evaluate frequency of DDR mutations in the largest cohort of Koreans. METHODS: We recruited 340 patients with mPC unselected for family history of cancer and compared to 495 controls. Whole genome sequencing was applied to assess germline pathogenic/likely pathogenic variants (PVs/LPVs) in 26 DDR genes and HOXB13, including 7 genes (ATM, BRCA1/2, CHEK2, BRIP1, PALB2, and NBN) associated with hereditary PC. Comparisons to published Caucasian and Japanese cohorts were performed. RESULTS: Total of 28 PVs/LPVs were identified in 30 (8.5%) patients; mutations were found in 13 genes, including BRCA2 (15 men [4.4%]), ATM (2 men [0.6%]), NBN (2 men [0.6%], and BRIP1 (2 men [0.6%]). Only one patient had HOXB13 mutation (0.3%). Compared with the germline variant frequency of previously reported mPC studies (8.5% and 11.8%), a slightly lower or similar rate was found in Korean mPC, but notably differed from Caucasian and geographically similar Japanese cohorts. PVs/LPVs in DDR genes tended to increase gradually with higher Gleason Scores (GS 7, 7.1%; GS 8, 7.5%; GS 9-10, 9.9%). CONCLUSIONS: We successfully identified 26 DDR and HOXB13-related deleterious variants in 30 Korean men with aggressive mPC. Germline PV/LPV profiles show comparable frequency of overall carriers (8.5%) but distinctly different distribution when contrasted to previous studies in European and even geographically nearby Japanese cohorts, with BRCA2 playing a dominant role. These results illustrate further evidence for population-based, ethnic-specific analyses for genetic testing as well as highlighting the potential differences that exist even in common East Asian ancestry. These findings may further emphasize the importance of genomic background in Korean PC. Future combinatory efforts must be made in larger, multiethnic trials to identify PVs of variable importance depending on ancestry. Source of Funding: This study was supported by the SNUBH Research foundation and KUOS © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e219 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sang Hun Song More articles by this author Jin Noh More articles by this author Hae Sung Lee More articles by this author Jun Hyun Nam More articles by this author Byeongdo Song More articles by this author Jung Kwon Kim More articles by this author Hakmin Lee More articles by this author Jong Jin Oh More articles by this author Sangchul Lee More articles by this author Seong Jin Jeong More articles by this author Sung Kyu Hong More articles by this author Seok-Soo Byun More articles by this author Expand All Advertisement PDF downloadLoading ...