MP39-18 HIGHER FREQUENCY OF GERMLINE BRCA1 AND BRCA2 MUTATIONS IN AFRICAN AMERICAN PROSTATE CANCER

Abstract

You have accessJournal of UrologyProstate Cancer: Detection & Screening V1 Apr 2016MP39-18 HIGHER FREQUENCY OF GERMLINE BRCA1 AND BRCA2 MUTATIONS IN AFRICAN AMERICAN PROSTATE CANCER Gyorgy Petrovics, Lakshmi Ravindranath, Yongmei Chen, Kai Ying, Amina Ali, Denise Young, David McLeod, Isabell Sesterhenn, Inger Rosner, William Dahut, Shiv Srivastava, and Michael Dean Gyorgy PetrovicsGyorgy Petrovics More articles by this author , Lakshmi RavindranathLakshmi Ravindranath More articles by this author , Yongmei ChenYongmei Chen More articles by this author , Kai YingKai Ying More articles by this author , Amina AliAmina Ali More articles by this author , Denise YoungDenise Young More articles by this author , David McLeodDavid McLeod More articles by this author , Isabell SesterhennIsabell Sesterhenn More articles by this author , Inger RosnerInger Rosner More articles by this author , William DahutWilliam Dahut More articles by this author , Shiv SrivastavaShiv Srivastava More articles by this author , and Michael DeanMichael Dean More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.143AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES BRCA1 and BRCA2 tumor suppressor proteins play a critical role in protecting genome integrity by participating in the repair of damaged DNA and have been implicated in breast, ovarian and other cancers. Mutations in BRCA2 have been linked to a higher risk of prostate cancer (CaP), and high frequency of BRCA2 and BRCA1 gene alterations were recently reported in metastatic castration resistant CaP specimens. Mutations in BRCA2 vary in racial and ethnic groups including African American (AA) and Caucasian American (CA) populations. The goal of this study was to assess the frequency and clinical correlation of BRCA1 and BRCA2 mutations in AA and CA CaP. METHODS BRCA1 and BRCA2 genes were sequenced (Ion AmpliSeq targeted sequencing) in archived blood DNA specimens (N=1139) collected from CaP patients undergoing radical prostatectomy treatment at WRNMMC. Evaluable sequences (N=1074) were analyzed for known and novel mutations in BRCA1 and BRCA2. Statistical analyses were performed (N=857 cases with complete associated data) to determine associations of the mutations with clinico-pathological parameters. RESULTS Mutations in the BRCA1 and BRCA2 genes were categorized as benign, likely benign, variant of unknown significance (VUS) and pathogenic. Pathogenic and VUS mutations in BRCA1 and BRCA2 (N=32) associated with African ancestry (7.3% in AA versus 2.2% in CA). A trend of increased metastasis frequency (9.4%) was noted in patients with pathogenic/VUS mutations compared to patients with no such mutations (2.4%). Time to metastasis was significantly shorter in patients with these mutations (Kaplan-Meier analysis, p=0.044). Analyses of BRCA2 mutations alone (N=30) showed similar association with African ancestry (7.4% in AA versus 2.1% in CA), but the shorter time to metastasis dropped to borderline significance (p=0.052). CONCLUSIONS Germline mutations in BRCA1 and BRCA2 were more frequent in AA than CA CaP patients. Patients carrying these mutations are more likely to progress to metastasis. Testing for BRCA1 and BRCA2 germline mutations, especially in AA patients, may provide useful information for treatment stratification and improving current nomograms. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e548 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Gyorgy Petrovics More articles by this author Lakshmi Ravindranath More articles by this author Yongmei Chen More articles by this author Kai Ying More articles by this author Amina Ali More articles by this author Denise Young More articles by this author David McLeod More articles by this author Isabell Sesterhenn More articles by this author Inger Rosner More articles by this author William Dahut More articles by this author Shiv Srivastava More articles by this author Michael Dean More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...