GERMLINE MUTATIONS IN DNA REPAIR GENES ARE INDEPENDENT PREDICTORS OF GRADE RECLASSIFICATION IN ACTIVE SURVEILLANCE FOR PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance III1 Apr 2018PD20-04 GERMLINE MUTATIONS IN DNA REPAIR GENES ARE INDEPENDENT PREDICTORS OF GRADE RECLASSIFICATION IN ACTIVE SURVEILLANCE FOR PROSTATE CANCER PATIENTS H. Ballentine Carter, Mufaddal Mamawala, Tricia Landis, Kathleen Wiley, Isaacs William B., Brian Helfand, Hongjie Yu, Yishuo Wu, Rong Na, Zhuqing Shi, Jacqueline Petkewicz, Sameep Shah, Richard J. Fantus, Kristian Novakovic, Michael McGuire, Charles B. Brendler, S. Lilly Zheng, and Jianfeng Xu H. Ballentine CarterH. Ballentine Carter More articles by this author , Mufaddal MamawalaMufaddal Mamawala More articles by this author , Tricia LandisTricia Landis More articles by this author , Kathleen WileyKathleen Wiley More articles by this author , Isaacs William B.Isaacs William B. More articles by this author , Brian HelfandBrian Helfand More articles by this author , Hongjie YuHongjie Yu More articles by this author , Yishuo WuYishuo Wu More articles by this author , Rong NaRong Na More articles by this author , Zhuqing ShiZhuqing Shi More articles by this author , Jacqueline PetkewiczJacqueline Petkewicz More articles by this author , Sameep ShahSameep Shah More articles by this author , Richard J. FantusRichard J. Fantus More articles by this author , Kristian NovakovicKristian Novakovic More articles by this author , Michael McGuireMichael McGuire More articles by this author , Charles B. BrendlerCharles B. Brendler More articles by this author , S. Lilly ZhengS. Lilly Zheng More articles by this author , and Jianfeng XuJianfeng Xu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1008AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Germline mutations in several DNA repair genes were recently found to be associated with metastatic and lethal prostate cancer (PCa). The objective of this study was to assess whether germline mutation carrier status is an independent predictor of grade reclassification in patients undergoing active surveillance. METHODS Two independent cohorts of PCa patients undergoing active surveillance and with available germline DNA samples were studied: 892 and 365 patients from Johns Hopkins School of Medicine (Hopkins) and NorthShore University Healthcare (NorthShore). Grade reclassification was defined by an increase in Gleason Grade Group between diagnostic and surveillance biopsies. Germline DNA from each patient was sequenced for 54 DNA repair genes, including BRCA1/2 and ATM, using a targeted next-generation sequencing panel. Pathogenicity of mutations was defined according to the American College of Medical Genetics guidelines. Association of mutation carrier status and grade reclassification was tested using both logistic and Cox regression models. RESULTS Overall, 291 of 1,257 patients (23.15%) experienced grade reclassification during the surveillance period. The carrier rate of pathogenic mutations in BRCA1/2 and ATM was significantly higher in those reclassified (3.78%) as compared to those not (1.57%), P=0.01. In a multivariable logistic regression analysis adjusting for age and PSA at diagnosis, carrying any pathogenic mutation of these three genes was significantly associated with 2.56-fold increased risk for grade progression (95% Confidence Interval: 1.15-5.71). There was, however no significant difference in the mutation carrier rate for the remaining 51 DNA repair genes between those reclassified vs not. When the above analyses were repeated separately for the Hopkins and NorthShore cohort, or in the European Americans only (93% of all patients), similar trends were found. CONCLUSIONS Germline pathogenic mutations in BRCA1/2 and ATM may independently identify men at risk of grade reclassification in active surveillance. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e402-e403 Advertisement Copyright & Permissions© 2018MetricsAuthor Information H. Ballentine Carter More articles by this author Mufaddal Mamawala More articles by this author Tricia Landis More articles by this author Kathleen Wiley More articles by this author Isaacs William B. More articles by this author Brian Helfand More articles by this author Hongjie Yu More articles by this author Yishuo Wu More articles by this author Rong Na More articles by this author Zhuqing Shi More articles by this author Jacqueline Petkewicz More articles by this author Sameep Shah More articles by this author Richard J. Fantus More articles by this author Kristian Novakovic More articles by this author Michael McGuire More articles by this author Charles B. Brendler More articles by this author S. Lilly Zheng More articles by this author Jianfeng Xu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...