You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (MP51)1 Apr 2020MP51-19 ASSOCIATION BETWEEN BRCA 1/2 POLYMORPHISMS AND DISEASE AGGRESSIVENESS IN A PROSPECTIVE COHORT OF PROSTATE CANCER PATIENTS UNDERGOING RADICAL PROSTATECTOMY Vito Cucchiara*, Dejan Lazarevic, Davide Cittaro, Matteo Zoccolillo, Marco Bianchi, Nicola Longo, Simone Scuderi, Francesco Barletta, Nicola Fossati, Giorgio Gandaglia, Andrea Necchi, Vincenzo Mirone, Francesco Montorsi, Giovanni Tonon, and Alberto Briganti Vito Cucchiara*Vito Cucchiara* More articles by this author , Dejan LazarevicDejan Lazarevic More articles by this author , Davide CittaroDavide Cittaro More articles by this author , Matteo ZoccolilloMatteo Zoccolillo More articles by this author , Marco BianchiMarco Bianchi More articles by this author , Nicola LongoNicola Longo More articles by this author , Simone ScuderiSimone Scuderi More articles by this author , Francesco BarlettaFrancesco Barletta More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , Vincenzo MironeVincenzo Mirone More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Giovanni TononGiovanni Tonon More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000913.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Single-nucleotide polymorphisms (SNPs) are the most common genetic alterations and SNPs in DNA repair genes, such as BRCA1/2, have a relationship with a variety of cancers. The aim of this study was to test the association between BRCA gene variants and the risk of aggressive PCa in a prospective cohort of patients undergoing radical prostatectomy (RP). METHODS: After IRB approval, whole blood genomic DNA was extracted from 345 PCa patients with localized PCa treated with RP (cases) and from 267 healthy individuals with no family history of PCa (controls). Haloplex gene panels covering the exons of 78 genes and 128 SNPs (>2,000 polymorphisms evaluated) identified population-specific PCa risk polymorphisms in 98 cases and 91 controls. Variants rs1799952 BRCA2 and rs75129942 BRCA1 resulted significantly linked to PCa in a larger country-specific population. These two variants were further investigated in a validation cohort of 247 PCa patients. Gene enriched library was prepared by using Fluidigm System and loaded on Illumina MiSeq platform. Pathologic specimens were evaluated by a single high-volume uro-pathologist. Multivariable logistic regression analyses tested the association between SNPs and adverse RP features: pathological grade group 4-5 (pGG4-5), extra-capsular extension (ECE) and lymph node invasion (LNI). RESULTS: Overall, 54 (21.5%), 27 (10.9%) and 117 (47.4%) patients had pathologic grade group 4-5, LNI and ECE at RP. The genotype A of BRCA1-gene rs75129942 and the genotype A of BRCA2-gene rs1799952 were present in 4.5% (n=11) and 4% (n=10) of the entire population, respectively. At univariable analysis, BRCA1 gene rs75129942 was not significantly associated with any adverse feature after RP (all p>0.6). On the other hand, the genotype A of BRCA2 gene rs1799952 was associated with an increased risk of LNI (p=0.008), pathologic grade group 4-5 (p=0.039) and ECE (p=0.04). These results were confirmed at multivariable analysis, where genotype A of rs1799952 BRCA2 was associated with an increased risk of pGG4-5 (OR: 3.81 95%CI: 1.11-13.71), ECE (OR: 4.51 95%CI: 1.38-16,713) and LNI (OR: 6.06 95%CI: 1.59- 18.15) after adjusting for preoperative confounders. CONCLUSIONS: Using a comprehensive approach, we showed that rs1799952 BRCA2 is a significant predictor of adverse pathology at RP such as LNI, pGG4-5 and ECE. These data confirm the role of BRCA2 mutation/variants in PCa aggressiveness. Further data is needed to assess the role of this polymorphism in cancer control outcomes after surgery. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e771-e771 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Vito Cucchiara* More articles by this author Dejan Lazarevic More articles by this author Davide Cittaro More articles by this author Matteo Zoccolillo More articles by this author Marco Bianchi More articles by this author Nicola Longo More articles by this author Simone Scuderi More articles by this author Francesco Barletta More articles by this author Nicola Fossati More articles by this author Giorgio Gandaglia More articles by this author Andrea Necchi More articles by this author Vincenzo Mirone More articles by this author Francesco Montorsi More articles by this author Giovanni Tonon More articles by this author Alberto Briganti More articles by this author Expand All Advertisement PDF downloadLoading ...