2122 COPY NUMBER VARIATION OF SEX-STEROID METABOLIZING GENES AS BIOMARKERS OF PROSTATE CANCER RECURRENCE AFTER PROSTATECTOMY: LOOKING AT THE END OF THE ANDROGENIC SIGNAL

Abstract

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 20102122 COPY NUMBER VARIATION OF SEX-STEROID METABOLIZING GENES AS BIOMARKERS OF PROSTATE CANCER RECURRENCE AFTER PROSTATECTOMY: LOOKING AT THE END OF THE ANDROGENIC SIGNAL Genevieve Nadeau, Judith Bellemare, Pierre Douville, Francois Meyer, Yves Fradet, Chantal Guillemette, Louis Lacombe, and Eric Lévesque Genevieve NadeauGenevieve Nadeau More articles by this author , Judith BellemareJudith Bellemare More articles by this author , Pierre DouvillePierre Douville More articles by this author , Francois MeyerFrancois Meyer More articles by this author , Yves FradetYves Fradet More articles by this author , Chantal GuillemetteChantal Guillemette More articles by this author , Louis LacombeLouis Lacombe More articles by this author , and Eric LévesqueEric Lévesque More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2210AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Inherited variations in hormone-related genes have been investigated for a possible association with prostate cancer risk, but their prognostic value has not been well studied. The glucuronidation pathway catalyzed by UDP-glucuronosyltransferases (UGT) leads to inactivation of sex-steroids, thus influencing the intracellular levels of these hormones in target cells. Our aim was to determine if genomic variations in five candidate UGT genes are associated with an elevated risk of biochemical recurrence of prostate cancer after prostatectomy. METHODS The study included 526 French-Canadian men who underwent radical prostatectomy for clinically localized (cT2/T3) prostate cancer between 1999 and 2002. The genotypes for common variations in UGT2B7, UGT2B15, UGT2B17, UGT2B28, and UGT1A1 and their relationship with biochemical recurrence-free survival (bRFS) were assessed using Cox proportional hazard models. RESULTS At a median follow-up of 7.4 years, 130 patients (24.7%) experienced prostate-specific antigen (PSA) failure. Polymorphic deletions of UGT2B17 and UGT2B28 were both associated with an increased likelihood of PSA failure (hazard ratio (HR) 1.43, 95% CI [1.01; 2.01] and HR 1.57, 95% CI [1.10; 2.25], respectively). The deletion of two or more copies of these genes resulted in an HR of 2.12 (95% CI [1.34; 3.37]) for biochemical recurrence. No significant association was observed for other UGT variants. CONCLUSIONS Copy number variations of UGT2B17 and UGT2B28 are prognostic molecular biomarkers of early biochemical recurrence after prostatectomy. This study is the first to recognize copy number variation in genes at the end of the androgenic signal as independent predictors of prostate cancer recurrence. Quebec, Canada© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e824-e825 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Genevieve Nadeau More articles by this author Judith Bellemare More articles by this author Pierre Douville More articles by this author Francois Meyer More articles by this author Yves Fradet More articles by this author Chantal Guillemette More articles by this author Louis Lacombe More articles by this author Eric Lévesque More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...