Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk

Arch Toxicol. 2012 Sep;86(9):1369-78. doi: 10.1007/s00204-012-0854-y. Epub 2012 Apr 25.

Abstract

Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.

Publication types

  • Meta-Analysis

MeSH terms

  • Animals
  • Carcinogens, Environmental / administration & dosage
  • Carcinogens, Environmental / pharmacokinetics
  • Carcinogens, Environmental / toxicity*
  • Chromosomes, Human, Pair 2 / genetics*
  • Genetic Association Studies
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Glucuronosyltransferase / genetics*
  • Glucuronosyltransferase / metabolism
  • Humans
  • Inactivation, Metabolic
  • Introns
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Multigene Family
  • Occupational Exposure
  • Polymorphism, Single Nucleotide*
  • Risk
  • Smoking / adverse effects
  • Toxicogenetics / methods
  • Urinary Bladder Neoplasms / chemically induced*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism

Substances

  • Carcinogens, Environmental
  • Isoenzymes
  • Glucuronosyltransferase