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

Silvia Selinski, Marie Louise Lehmann, Meinolf Blaszkewicz, Daniel Ovsiannikov, Oliver Moormann, Christoph Guballa, Alexander Kress, Michael C. Truß, Holger Gerullis, Thomas Otto, Dimitri Barski, Günter Niegisch, Peter Albers, Sebastian Frees, Walburgis Brenner, Joachim W. Thüroff, Miriam Angeli-Greaves, Thilo Seidel, Gerhard Roth, Frank VolkertRainer Ebbinghaus, Hans M. Prager, Hermann M. Bolt, Michael Falkenstein, Anna Zimmermann, Torsten Klein, Thomas Reckwitz, Hermann C. Roemer, Mark Hartel, Wobbeke Weistenhöfer, Wolfgang Schöps, S. Adibul Hassan Rizvi, Muhammad Aslam, Gergely Bánfi, Imre Romics, Katja Ickstadt, Jan G. Hengstler, Klaus Golka

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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 IfADocase-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 diVerences 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.

Original languageEnglish
Pages (from-to)1369-1378
Number of pages10
JournalArchives of Toxicology
Volume86
Issue number9
DOIs
Publication statusPublished - Sep 1 2012

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Keywords

  • Aromatic amines
  • Benzidine
  • Polycyclic aromatic hydrocarbons (PAH)
  • Single nucleotide polymorphism (SNP)
  • UDP-glucuronosyltransferase 1A
  • rs17863783

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Selinski, S., Lehmann, M. L., Blaszkewicz, M., Ovsiannikov, D., Moormann, O., Guballa, C., Kress, A., Truß, M. C., Gerullis, H., Otto, T., Barski, D., Niegisch, G., Albers, P., Frees, S., Brenner, W., Thüroff, J. W., Angeli-Greaves, M., Seidel, T., Roth, G., ... Golka, K. (2012). Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk. Archives of Toxicology, 86(9), 1369-1378. https://doi.org/10.1007/s00204-012-0854-y