title: Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk.
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.
authors.affiliation: Leibniz Research Centre for Working Environment and Human Factors, Ardeystrasse 67, 44139 Dortmund, Germany. selinski@ifado.de
authors.forename: Silvia
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authors.lastname: Selinski
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authors.lastname: Bánfi
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authors.forename: Katja
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mesh_terms: D000818:Animals; D002274:Carcinogens, Environmental / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D007438:Introns; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D016273:Occupational Exposure; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012907:Smoking / Q000009:adverse effects; D043922:Toxicogenetics / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism
chemical_list: D002274:Carcinogens, Environmental; D007527:Isoenzymes; D014453:Glucuronosyltransferase