title: Prognostic relevance of urinary bladder cancer susceptibility loci.
abstract: In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76-1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23-2.66), P for trend = 2.6 × 10(-3)). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools.
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Grotenhuis
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Dudek
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Verhaegh
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J Alfred
authors.initials: JA
authors.lastname: Witjes
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands ; Comprehensive Cancer Center The Netherlands, Utrecht, The Netherlands.
authors.forename: Katja K
authors.initials: KK
authors.lastname: Aben
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Saskia L
authors.initials: SL
authors.lastname: van der Marel
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands ; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Sita H
authors.initials: SH
authors.lastname: Vermeulen
authors.affiliation: Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands ; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology