PD47-07 THE ASSOCIATION BETWEEN GERMLINE MUTATIONS IN DNA DAMAGE RESPONSE AND REPAIR (DDR) GENES AND BLADDER CANCER: RESULTS FROM THE UK BIOBANK

Abstract

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II (PD47)1 Sep 2021PD47-07 THE ASSOCIATION BETWEEN GERMLINE MUTATIONS IN DNA DAMAGE RESPONSE AND REPAIR (DDR) GENES AND BLADDER CANCER: RESULTS FROM THE UK BIOBANK Norm Smith, Matthew Sloan, Jun Wei, Zhuqing Shi, Jianfeng Xu, and Brian Helfand Norm SmithNorm Smith More articles by this author , Matthew SloanMatthew Sloan More articles by this author , Jun WeiJun Wei More articles by this author , Zhuqing ShiZhuqing Shi More articles by this author , Jianfeng XuJianfeng Xu More articles by this author , and Brian HelfandBrian Helfand More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002069.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Muscle invasive bladder cancer (MIBC) is notable for a relatively high frequency of somatic DDR gene mutations and the potential for these mutations to impact selection of systemic therapies including cisplatin or immunotherapies. However, the association between germline mutations within these genes and bladder cancer (BCa) risk remains to be determined. METHODS: Caucasian men in the UK Biobank (UKB), average 9.3 years of follow-up were included. Men who were diagnosed with BCa were identified. Pathogenic or likely pathogenic mutations within a panel of 180 DDR mutations were analyzed from Whole Exon Sequencing. Comparisons of the frequency of these mutations within BCa patients and controls were analyzed. RESULTS: A total of 1,138 patients with BCa and 187,012 controls were included. Mutations within several DDR mutations were present at significantly higher frequencies among cases versus controls (Table). Men with these mutations tended to be diagnosed at younger ages compared to non-carriers (63.0 years vs 65.8 years, p=0.07). However, this was most exaggerated in men with MLH1 mutations (44.7yr vs. 65.7yr, p=0.03). CONCLUSIONS: Germline mutations within specific DDR genes increase BCa risk. Because of their association with younger age of diagnosis and previously described treatment responses; knowledge of these mutations may influence screening for BCa and/or therapy selection. Source of Funding: No funding source reported © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e835-e835 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Norm Smith More articles by this author Matthew Sloan More articles by this author Jun Wei More articles by this author Zhuqing Shi More articles by this author Jianfeng Xu More articles by this author Brian Helfand More articles by this author Expand All Advertisement PDF downloadLoading ...