MP82-14 SINGLE NUCLEOTIDE POLYMORPHISMS AND RISK OF PROSTATE CANCER: DEVELOPMENT AND VALIDATION OF A NOVEL GENETIC RISK SCORE FOR INDIVIDUALIZED SCREENING AND DIAGNOSTIC PROGRAMMES

Abstract

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII1 Apr 2018MP82-14 SINGLE NUCLEOTIDE POLYMORPHISMS AND RISK OF PROSTATE CANCER: DEVELOPMENT AND VALIDATION OF A NOVEL GENETIC RISK SCORE FOR INDIVIDUALIZED SCREENING AND DIAGNOSTIC PROGRAMMES Vito Cucchiara, Vincenzo Mirone, Dejan Lazarevic, Davide Cittaro, Giovanni Tonon, Matteo Zoccolillo, Marco Emilio Bianchi, Giorgio Gandaglia, Nicola Fossati, Shahrokh F Shariat, Francesco Montorsi, and Alberto Briganti Vito CucchiaraVito Cucchiara More articles by this author , Vincenzo MironeVincenzo Mirone More articles by this author , Dejan LazarevicDejan Lazarevic More articles by this author , Davide CittaroDavide Cittaro More articles by this author , Giovanni TononGiovanni Tonon More articles by this author , Matteo ZoccolilloMatteo Zoccolillo More articles by this author , Marco Emilio BianchiMarco Emilio Bianchi More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Shahrokh F ShariatShahrokh F Shariat More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2742AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Genome-wide association studies have characterized more than 100 common SNPs associated with prostate cancer (PCa) that can explain approximately one third of the genetic susceptibility. We aimed at discovering and validating a SNPs signature able to identify individuals at higher risk of PCa in an unscreened patient population METHODS After IRB approval, whole blood genomic DNA (gDNA) was extracted from 354 PCa patients with localized PCa treated with radical prostatectomy (cases) and from 267 healthy individuals with no family history of PCa (controls). Haloplex custom designed-gene panels covering the exons of 78 genes and 128 SNPs identified population-specific PCa risk polymorphisms in 98 cases and 91 controls. Of more than 2,000 variants evaluated, 26 SNPs (p<0.05) were investigated in a validation cohort of 256 PCa patients and 176 controls. In the validation study, gene enriched library was prepared by using Fluidigm Access Array System and loaded on Illumina MiSeq. Genotype frequencies were tested by using Cochran-Armitage test. Wilcoxon-Mann-Whitney test and logistic regressions analyzed the association of SNPs sets with PCa (p<0.05). Individual weighted genetic risk scores (wGRSs) were calculated based on the natural logarithm of the OR of the selected polymorphisms. The AUC was assessed whether the wGRS in addition to pre-diagnostic PSA improved PCa prediction RESULTS Of the 26 genotyped SNPs evaluated in the validation study, we identified 7 variants (rs7141529, rs117879878, rs34764062, rs1419133, rs2227983, rs5919432, and rs6152) more frequent in cases versus controls (all p<0.001) with ORs ranging from 1.51 to 3.08 per risk allele. The wGRS was higher in patients as compared to controls, even after age-matching (p<0.001). The addition of cumulative risk alleles to the model containing PSA levels improved (p=0.004) the predictive value in discriminating individuals with PCa and without cancer (AUC from 0.584 to 0.711; p<0.001). When considering disease characteristics, variant rs5919432 (locus Xq12, androgen receptor-gene) was associated with a higher preoperative PSA with a mean difference between patients and controls of 1.3±0.22 ng/mL (p=0.005) CONCLUSIONS Our study defines a population-specific set of SNPs associated with PCa. Genetic markers might provide an opportunity to identify men at highest risk of PCa. Incorporation of a genetic signature of PCa risk into clinical practice may offer improvements in patient selection for PCa screening and decision making. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1111-e1112 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Vito Cucchiara More articles by this author Vincenzo Mirone More articles by this author Dejan Lazarevic More articles by this author Davide Cittaro More articles by this author Giovanni Tonon More articles by this author Matteo Zoccolillo More articles by this author Marco Emilio Bianchi More articles by this author Giorgio Gandaglia More articles by this author Nicola Fossati More articles by this author Shahrokh F Shariat More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...