title: Comprehensive pathway-based interrogation of genetic variations in the nucleotide excision DNA repair pathway and risk of bladder cancer.
abstract: BACKGROUND
  Growing evidence suggests that single nucleotide polymorphisms (SNPs) in nucleotide excision repair (NER) pathway genes play an important role in bladder cancer etiology. However, only a limited number of genes and variations in this pathway have been evaluated to date.
  
  
  METHODS
  In this study, the authors applied a comprehensive pathway-based approach to assess the effects of 207 tagging and potentially functional SNPs in 26 NER genes on bladder cancer risk using a large case-control study that included 803 bladder cancer cases and 803 controls.
  
  
  RESULTS
  In total, 17 SNPs were associated significantly with altered bladder cancer risk (P < .05), of which, 7 SNPs retained noteworthiness after they were assessed with a Bayesian approach for the probability of false discovery. The most noteworthy SNP was reference SNP 11132186 (rs11132186) in the inhibitor of growth family, member 2 (ING2) gene. Compared with the major allele-containing genotypes, the odds ratio was 0.52 (95% confidence interval, 0.32-0.83; P = .005) for the homozygous variant genotype. Three additional ING2 variants also exhibited significant associations with bladder cancer risk. Significant gene-smoking interactions were observed for 3 of the top 17 SNPs. Furthermore, through an exploratory classification and regression tree (CART) analysis, potential gene-gene interactions were identified.
  
  
  CONCLUSIONS
  In this a large association study of the NER pathway and the risk of bladder cancer, several novel predisposition variants were identified along with potential gene-gene and gene-environment interactions in modulating bladder cancer risk. The results reinforce the importance of a comprehensive, pathway-focused, and tagging SNP-based candidate gene approach to identify low-penetrance cancer susceptibility loci.
authors.affiliation: State Key Laboratory of Cancer Biology, Cell Engineering Research Center and Department of Cell Biology, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
authors.forename: Maosheng
authors.initials: M
authors.lastname: Huang
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hildebrandt
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics*