518 EVALUATION OF THE MISSENSE VARIANT RS 2294008 IN THE PROSTATE STEM CELL ANTIGEN GENE IN PATIENTS WITH CONCOMITANT UROTHELIAL AND PROSTATE CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research1 Apr 2011518 EVALUATION OF THE MISSENSE VARIANT RS 2294008 IN THE PROSTATE STEM CELL ANTIGEN GENE IN PATIENTS WITH CONCOMITANT UROTHELIAL AND PROSTATE CANCER Markus Renninger, Sven Perner, Marita Munz, Arnulf Stenzl, and Georgios Gakis Markus RenningerMarkus Renninger Tuebingen, Germany More articles by this author , Sven PernerSven Perner Tuebingen, Germany More articles by this author , Marita MunzMarita Munz Tuebingen, Germany More articles by this author , Arnulf StenzlArnulf Stenzl Tuebingen, Germany More articles by this author , and Georgios GakisGeorgios Gakis Tuebingen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1214AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The prostate stem cell antigen (PSCA) gene is overexpressed in patients with advanced prostate cancer (PCa) (Gu et al, Oncogene, 2009). A missense genetic variant of the PSCA gene, rs2294008, has recently been identified as a new susceptibility locus for bladder cancer (Wu et al., Nat. Gen, 2009), and this allelic (T-) missense variant leads to a significant reduction of the promoter activity of the PSCA gene. Concomitant PCa is found in approximately 25% of the patients undergoing a radical cystoprostatectomy for urothelial carcinoma of the bladder (UCB) (Gakis et al, BJU Int, 2009). Therefore, we hypothesized that the T-allelic missense variant may also be present as a genetic disposition in non-malignant lymphatic cells confering susceptibility to both UCB and PCa. METHODS Cystoprostatectomy specimens of 36 patients (median age 71 years; range 51–86 years) with concomitant UCB and PCa were considered for analysis. For genotyping we used the corresponding tumor free lymphatic tissue and a specifically designed primer for a 116 base pair region around this single nucleotide polymorphism (SNP). A Sanger standard sequencing procedure with an ABI 3730 capillary sequencer was performed. Logistic regression was used for univariate and Cox regression analysis for multivariate analysis of risk factors for tumor recurrence. P<0.05 was considered as level of significant difference. RESULTS Of the 36 patients, 18 (50%) were heterozygous and 8 (22%) homozygous carriers of the T-allelic variant whereas 10 displayed no mutation in the PSCA gene. The presence of at least one T-allelic variant in non-malignant cells was significantly associated with the presence of concomitant UCB and PCa (p=0.0102). In multivariate analysis, adjusted for tumour stage, lymph node tumour involvement and soft-tissue surgical margins, the presence of the homozygous T-allelic variant was an independent risk factor for UCB recurrence (p=0.0264). CONCLUSIONS In patients with concomitant UCB and PCa, the missence variant rs2294008 of the PSCA gene is frequently present as a genetic disposition. This hints at the possibility that both tumor entities share a common pathway of carcinogenesis. Moreover, in homozygous carriers, the T-allelic variant was an independent risk faktor for urothelial cancer recurrence. Further studies are warranted to investigate the incidence of this missense variant in urothelial and prostate cancer cells in order to determine additional somatic mutations which might contribute to cancer development. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e210-e211 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Markus Renninger Tuebingen, Germany More articles by this author Sven Perner Tuebingen, Germany More articles by this author Marita Munz Tuebingen, Germany More articles by this author Arnulf Stenzl Tuebingen, Germany More articles by this author Georgios Gakis Tuebingen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...