Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene

Silvia Selinski, Marie Louise Lehmann, Meinolf Blaszkewicz, Daniel Ovsiannikov, Oliver Moormann, Christoph Guballa, Alexander Kress, Michael C. Tru, 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 Martin Prager, Cordula Lukas, 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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

Original languageEnglish
Pages (from-to)195-203
Number of pages9
JournalArchives of Toxicology
Volume86
Issue number2
DOIs
Publication statusPublished - Feb 1 2012

Keywords

  • Ethnic differences
  • Genome-wide association study (GWAS)
  • Insulin growth factor 1 (IGF1)
  • Single nucleotide polymorphism (SNP)
  • Validation study

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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    Selinski, S., Lehmann, M. L., Blaszkewicz, M., Ovsiannikov, D., Moormann, O., Guballa, C., Kress, A., Tru, 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). Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene. Archives of Toxicology, 86(2), 195-203. https://doi.org/10.1007/s00204-011-0747-5