Jochen Hess1,2, Patrick Stelmach3, Andreas Eisenhardt4, Herbert Rübben5, Henning Reis6, Kurt Werner Schmid6, Hagen Sjard Bachmann3. 1. Clinic of Urology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. jochen.hess@uk-essen.de. 2. Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. jochen.hess@uk-essen.de. 3. Institute of Pharmacogenetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 4. Praxisklinik Urologie Rhein/Ruhr, Mülheim, Germany. 5. Clinic of Urology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. 6. Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Abstract
PURPOSE: To evaluate the impact of three BCL2 single-nucleotide polymorphisms, i.e., c.-938C>A (rs2279115), c.21G>A (rs1801018), and c.*2203A>G (rs4987853) on survival in patients with transitional cell carcinoma of the bladder. METHODS: We analyzed 179 patients who underwent surgical treatment for bladder cancer at the Clinic of Urology, University Hospital Essen, Germany. Genomic DNA was extracted and genotyped for the polymorphisms. For all polymorphisms, linkage analysis was performed. Kaplan-Meier and Cox regression analyses were used to determine the putative impact of the three polymorphisms on outcome. RESULTS: c.-938C>A and c.21G>A, but not c.*2203A>G, are in strong linkage disequilibrium (D' 0.96). We found a significant association between c.-938C>A and relapse-free survival (p = 0.024) with an allele dose effect. In the same way, c.21G>A had a significant impact on both relapse-free survival (p = 0.009) and progression-free survival (p = 0.012), as well as a pronounced allele dose effect. Regression analysis proved c.21G>A and c.-938C>A, to be an independent risk factor in univariate and multivariable analyses. CONCLUSIONS: In our cohort, both c.-938C>A and c.21G>A showed a significant impact on outcome with TCC of the bladder. Due to the linkage disequilibrium of both SNPs, maybe, only one of them could mediate this effect. In multivariable analysis, however, both proved to be independently associated with overall survival. Contrary to other findings which found the c.-938C>A mainly influencing outcome, our data may suggest that the main effect on TCC could be due to the c.21G>A polymorphism.
PURPOSE: To evaluate the impact of three BCL2 single-nucleotide polymorphisms, i.e., c.-938C>A (rs2279115), c.21G>A (rs1801018), and c.*2203A>G (rs4987853) on survival in patients with transitional cell carcinoma of the bladder. METHODS: We analyzed 179 patients who underwent surgical treatment for bladder cancer at the Clinic of Urology, University Hospital Essen, Germany. Genomic DNA was extracted and genotyped for the polymorphisms. For all polymorphisms, linkage analysis was performed. Kaplan-Meier and Cox regression analyses were used to determine the putative impact of the three polymorphisms on outcome. RESULTS: c.-938C>A and c.21G>A, but not c.*2203A>G, are in strong linkage disequilibrium (D' 0.96). We found a significant association between c.-938C>A and relapse-free survival (p = 0.024) with an allele dose effect. In the same way, c.21G>A had a significant impact on both relapse-free survival (p = 0.009) and progression-free survival (p = 0.012), as well as a pronounced allele dose effect. Regression analysis proved c.21G>A and c.-938C>A, to be an independent risk factor in univariate and multivariable analyses. CONCLUSIONS: In our cohort, both c.-938C>A and c.21G>A showed a significant impact on outcome with TCC of the bladder. Due to the linkage disequilibrium of both SNPs, maybe, only one of them could mediate this effect. In multivariable analysis, however, both proved to be independently associated with overall survival. Contrary to other findings which found the c.-938C>A mainly influencing outcome, our data may suggest that the main effect on TCC could be due to the c.21G>A polymorphism.
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