title: Independent Replication of Published Germline Polymorphisms Associated with Urinary Bladder Cancer Prognosis and Treatment Response.
abstract: BACKGROUND
  Many studies investigated the prognostic or predictive relevance of single nucleotide polymorphisms (SNPs) in biologically plausible genes in urinary bladder cancer (UBC) patients. Most published SNP associations have never been replicated in independent patient series.
  
  
  OBJECTIVE
  To independently replicate all previously reported associations between germline SNPs and disease prognosis or treatment response in UBC.
  
  
  METHODS
  A Pubmed search was performed to identify studies published by July 1, 2014 reporting on germline SNP associations with UBC prognosis or treatment response. For the replication series, consisting of 1,284 non-muscle-invasive bladder cancer (NMIBC) and 275 muscle-invasive or metastatic bladder cancer (MIBC) patients recruited through the Netherlands Cancer Registry, detailed clinical data were retrieved from medical charts. Patients were genotyped using a genome-wide SNP array. SNP association with recurrence-free, progression-free, and overall survival (OS) within specific patient and treatment strata was tested using Cox regression analyses.
  
  
  RESULTS
  For only six of the 114 evaluated SNPs, the association with either UBC prognosis or treatment response was replicated at thep<  0.05 level: rs1799793 (ERCC2) and rs187238 (IL18) for BCG recurrence; rs6678136 (RGS4) and rs11585883 (RGS5) for NMIBC progression; rs12035879 (RGS5) and rs2075786 (TERT) for MIBC OS.
  
  
  CONCLUSIONS
  Non-replicated genetic associations in the literature require cautious interpretation. This single replication does not provide definitive proof of association for the six SNPs, and non-replication of other SNPs may result from population-specific effects or the retrospective patient enrollment.
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences , Nijmegen, The Netherlands.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Grotenhuis
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Dudek
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Verhaegh
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands; Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands.
authors.forename: Katja K
authors.initials: KK
authors.lastname: Aben
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences , Nijmegen, The Netherlands.
authors.forename: J Alfred
authors.initials: JA
authors.lastname: Witjes
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences , Nijmegen, The Netherlands.
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.affiliation: Radboud University Medical Center, Radboud Institute for Health Sciences , Nijmegen, The Netherlands.
authors.forename: Sita H
authors.initials: SH
authors.lastname: Vermeulen
keywords: Treatment outcome; genetic association studies; prognosis; reproducibility of results; single nucleotide polymorphisms; urinary bladder neoplasms