PD65-11 INCLUSION OF KLK3 GERMLINE NONSYNONYMOUS MUTATION I179T AS PART OF MULTIGENE PANEL TESTING FOR PREDICTING PROSTATE CANCER PROGRESSION

Abstract

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII (PD65)1 Sep 2021PD65-11 INCLUSION OF KLK3 GERMLINE NONSYNONYMOUS MUTATION I179T AS PART OF MULTIGENE PANEL TESTING FOR PREDICTING PROSTATE CANCER PROGRESSION Jianfeng Xu, Zhuqing Shi, Jun Wei, Rong Na, W. Kyle Resurreccion, Chi-Hsiung Wang, Chris Sample, Misop Han, S. Lilly Zheng, Kathleen Cooney, Brian Helfand, and William Isaacs Jianfeng XuJianfeng Xu More articles by this author , Zhuqing ShiZhuqing Shi More articles by this author , Jun WeiJun Wei More articles by this author , Rong NaRong Na More articles by this author , W. Kyle ResurreccionW. Kyle Resurreccion More articles by this author , Chi-Hsiung WangChi-Hsiung Wang More articles by this author , Chris SampleChris Sample More articles by this author , Misop HanMisop Han More articles by this author , S. Lilly ZhengS. Lilly Zheng More articles by this author , Kathleen CooneyKathleen Cooney More articles by this author , Brian HelfandBrian Helfand More articles by this author , and William IsaacsWilliam Isaacs More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002109.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Clinical guidelines now include germline testing for prostate cancer (PCa). Currently, only 11 genes are routinely evaluated for rare pathogenic mutations (RPMs). Common variants in the KLK3 gene, despite being consistently associated with PCa progression, are not included in these recommendations. The objective of the current study is to assess the added value of a nonsynonymous mutation (I179T) in KLK3 to RPMs in 11 guideline-recommended genes for predicting PCa progression. METHODS: Retrospective analysis of two prospective cohorts: 1) PCa patients treated with radical surgery at the Johns Hopkins Hospital (JHH), average 7.9 years of follow-up, 2) PCa patients in the UK Biobank (UKB), average 9.3 years of follow-up. Subjects in the JHH cohort were selected from PCa patients who underwent radical prostatectomy, including all “progressors” (developed metastasis and/or died of PCa) and a subset of “non-progressors”. Subjects in the UKB cohort were all men diagnosed with PCa. Only Caucasian subjects were analyzed. RPMs of 11 genes from Whole Exon Sequencing and variants of KLK3 from SNP arrays. RESULTS: There were 1,943 (JHH) and 10,228 (UKB) PCa patients with mean ages of diagnosis at 59.01 years and 64.36 years, respectively. In the JHH cohort, 5.2% (95/1,843) of patients had RPMs in the 11 genes; hazard ratio (HR) (95% confidence interval [CI]) for progression was 2.69 (1.77-4.07), P<.001. In comparison, more patients [9.7% (189/1,943)] carried the KLK3 I179T mutation; HR was 1.55 (1.07-2.24), P=.02. Virtually the same results were found in the UKB cohort. Added value of KLK3 to 11 genes was demonstrated when RPMs of 11 genes and KLK3 I179T were analyzed jointly. In the combined cohort, compared to patients without any mutation (RPMs-/KLK3-), RPMs-/KLK3+ patients had modestly increased risk for progression [HR=1.43 (1.05-1.94), P=.02], and RPMs+/KLK3+ patients had greatly increased risk for progression; [HR 5.38 (2.95-9.81), P<.001]. CONCLUSIONS: These two vastly different cohorts consistently demonstrate the added value of KLK3 I179T to the 11 guideline-recommended genes for predicting PCa progression and provide a robust basis for its inclusion in germline testing for predicting PCa progression. Source of Funding: This study was partially supported by grants from Department of Defense (W81XWH-16-1-0764, W81XWH-16-1-0765, and W81XWH-16-1-0766). © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1157-e1157 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jianfeng Xu More articles by this author Zhuqing Shi More articles by this author Jun Wei More articles by this author Rong Na More articles by this author W. Kyle Resurreccion More articles by this author Chi-Hsiung Wang More articles by this author Chris Sample More articles by this author Misop Han More articles by this author S. Lilly Zheng More articles by this author Kathleen Cooney More articles by this author Brian Helfand More articles by this author William Isaacs More articles by this author Expand All Advertisement Loading ...