MP49-20 FINE-MAPPING OF THE KALLIKREIN REGION AND ITS ROLE IN PROSTATE CANCER AGGRESSIVENESS: RESULTS FROM A CANADIAN COHORT AND THE EUROPEAN RANDOMIZED STUDY FOR PROSTATE CANCER SCREENING

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2014MP49-20 FINE-MAPPING OF THE KALLIKREIN REGION AND ITS ROLE IN PROSTATE CANCER AGGRESSIVENESS: RESULTS FROM A CANADIAN COHORT AND THE EUROPEAN RANDOMIZED STUDY FOR PROSTATE CANCER SCREENING Laurent Briollais, Jingxiong Xu, Maciej Kwiatkowski, Matt Friedlander, Franz Recker, Cynthia Kuk, Sally Hanna, Neil E. Fleshner, Bharati Bapat, Tristan Juvet, Hong Li, Theodorus H. van der Kwast, Eleftherios P. Diamandis, Alexandre R. Zlotta, and Hilmi Ozcelik Laurent BriollaisLaurent Briollais More articles by this author , Jingxiong XuJingxiong Xu More articles by this author , Maciej KwiatkowskiMaciej Kwiatkowski More articles by this author , Matt FriedlanderMatt Friedlander More articles by this author , Franz ReckerFranz Recker More articles by this author , Cynthia KukCynthia Kuk More articles by this author , Sally HannaSally Hanna More articles by this author , Neil E. FleshnerNeil E. Fleshner More articles by this author , Bharati BapatBharati Bapat More articles by this author , Tristan JuvetTristan Juvet More articles by this author , Hong LiHong Li More articles by this author , Theodorus H. van der KwastTheodorus H. van der Kwast More articles by this author , Eleftherios P. DiamandisEleftherios P. Diamandis More articles by this author , Alexandre R. ZlottaAlexandre R. Zlotta More articles by this author , and Hilmi OzcelikHilmi Ozcelik More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1121AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Prostate specific antigen (PSA) or kallikrein 3 (KLK3) is used for early diagnosis of prostate cancer (PCa). Other KLKs, notably KLK2, 4, 5, 6, 10, 11, 13, 14 and 15, have also been associated with PCa. There is a growing need for novel PCa markers that can identify individuals at an increased risk of harbouring aggressive disease. Data from genome-wide association studies have pointed out several candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes associated with PCa. We aimed to study the role of SNPs in the entire KLK gene region in predicting PCa aggressiveness. Methods The discovery cohort consists of 540 PCa cases accrued from Toronto. The validation cohort included 380 PCa cases from the Swiss arm of the European Randomized Study of Screening for PCa. We genotyped a total of 143 SNPs within the entire kallikrein region (KLK 1-15) and analyzed their association with PCa aggressiveness, stratifying PCa according to Gleason score (GS) or analyzed as a continuous variable. Genotyping was carried out using an Illumina platform. We expanded the analysis by imputing additional SNPs in the region based on the 1,000 genomes reference dataset. The imputed data comprised of 987 SNPs, with approximately 200 that were in complete linkage disequilibrium (LD) with each other. Our statistical analyses included univariate analyses, multivariate analyses with the Group Lasso and Bayesian graphical modeling. Results In Toronto, 223 PCa’s were GS≤6, 275 GS7, 26 GS8, 15 GS9 and 1 was GS10. In the Swiss cohort, 278 PCa’s were GS≤6 whereas 77 were GS7, 18 GS8, 9 GS9 and 1 was GS10. Four SNPs in very strong LD in the KLK6 gene (rs113640578, rs79324425, rs11666929, rs28384475) were strongly associated with GS when used as GS≥7 vs. GS<7 in the Toronto cohort (p= 0.006529, 0.007501, 0.008589 and 0.008589, respectively, OR from 2.618 to 5.247) and in the Swiss validation cohort (all p= 0.0001, all OR= 5.861). Interestingly, the region encompassed by these four SNPs includes another SNP, rs147992404, which corresponds to a rare missense mutation. Another interesting region associated with GS is downstream KLK3 and include the SNPs rs1058205 (OR 1.8, p=0.001), rs2569735 (p=0.004), rs2735839 (p=0.004) and rs62113216 (p=0.004) in the Toronto cohort and the SNP rs55799315 (p=0.009) in the Swiss cohort. Conclusions Our analyses point out interesting variants in the KLK genes, in particular KLK6 and KLK3, associated with PCa aggressiveness and that could have potential clinical applications. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e509 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Laurent Briollais More articles by this author Jingxiong Xu More articles by this author Maciej Kwiatkowski More articles by this author Matt Friedlander More articles by this author Franz Recker More articles by this author Cynthia Kuk More articles by this author Sally Hanna More articles by this author Neil E. Fleshner More articles by this author Bharati Bapat More articles by this author Tristan Juvet More articles by this author Hong Li More articles by this author Theodorus H. van der Kwast More articles by this author Eleftherios P. Diamandis More articles by this author Alexandre R. Zlotta More articles by this author Hilmi Ozcelik More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.