title: Profiling of genetic variations in inflammation pathway genes in relation to bladder cancer predisposition.
abstract: OBJECTIVE
  Compelling evidence has indicated that inflammation plays an important role in cancer development. We sought to test the hypothesis that common sequence variants in the inflammation pathway modulate bladder cancer risk.
  
  
  METHODS
  We genotyped 59 potentially functional single nucleotide polymorphisms from 35 candidate inflammation genes in a case-control study including 635 Caucasian bladder cancer patients and 635 matched controls.
  
  
  RESULTS
  The most significant finding was in the 3'-untranslated region of PTGS2 (exon10+837T>C, rs5275), which was associated with a significantly reduced risk (odds ratio, 0.68; 95% confidence interval, 0.54-0.87; P=0.002) and remained significant after multiple comparison adjustment. Consistently, the most common PTGS2 haplotype containing the common allele of exon10+837T>C was associated with a significantly increased risk (odds ratio, 1.27; 95% confidence interval, 1.06-1.52; P=0.008). In contrast, the haplotypes containing at least one variant allele of exon10+837T>C were all associated with a decreased risk. In a combined analysis to assess the cumulative effects of inflammation single nucleotide polymorphisms on bladder cancer risk, we found that in the anti-inflammation pathway, but not in the proinflammation pathway, when compared with individuals with a few adverse alleles, individuals with more adverse alleles had a significantly increased risk in a dose-dependent manner (P(trend)=0.012). To further elucidate the functional mechanism of these associations, we redefined the adverse alleles based on literature-reported functional results and found that individuals with a higher number of inflammation-enhancing alleles in the anti-inflammation pathway exhibited a greater bladder cancer risk.
  
  
  CONCLUSIONS
  Our results strongly suggest that common variants in inflammation genes affect bladder cancer susceptibility individually and jointly.
authors.affiliation: Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human