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

  • Toxicogenomics
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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.

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Acknowledgments

The authors thank Ms Kirsten Liesenhoff-Henze, Ms Marion Page and Ms Claudia Schulte-Dahmann for excellent technical support.

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Authors and Affiliations

  1. Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany

    Silvia Selinski, Marie-Louise Lehmann, Meinolf Blaszkewicz, Hermann M. Bolt, Michael Falkenstein, Anna Zimmermann, Hermann C. Roemer, Wobbeke Weistenhöfer, Jan G. Hengstler & Klaus Golka

  2. Department of Urology, St.-Josefs-Hospital, Dortmund, Germany

    Daniel Ovsiannikov & Oliver Moormann

  3. Department of Urology, Klinikum Dortmund gGmbH, Dortmund, Germany

    Christoph Guballa, Alexander Kress, Michael C. Truß & Thomas Reckwitz

  4. Department of Urology, Lukasklinik Neuss, Neuss, Germany

    Holger Gerullis & Thomas Otto

  5. Department of Urology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany

    Dimitri Barski, Günter Niegisch & Peter Albers

  6. Department of Urology, Johannes Gutenberg University Mainz, Mainz, Germany

    Sebastian Frees, Walburgis Brenner & Joachim W. Thüroff

  7. Department of Pharmacology and Toxicology, Medical School, Universidad Central de Venezuela, Caracas, Venezuela

    Miriam Angeli-Greaves

  8. Department of Urology, Paul Gerhardt Foundation, Lutherstadt Wittenberg, Germany

    Thilo Seidel, Gerhard Roth & Frank Volkert

  9. Institute for Occupational, Social and Environmental Medicine, Castrop-Rauxel, Germany

    Rainer Ebbinghaus, Hans-Martin Prager & Cordula Lukas

  10. Department of Anaesthesia and Critical Care, St. Vincenz Hospital, Menden, Germany

    Torsten Klein

  11. Institute for General Medicine, University Hospital of Essen, Essen, Germany

    Hermann C. Roemer

  12. Department of Surgery, Klinikum Dortmund gGmbH, Dortmund, Germany

    Mark Hartel

  13. Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine (IPASUM), University of Erlangen-Nuremberg, Erlangen, Germany

    Wobbeke Weistenhöfer

  14. Practice for Urology, St. Augustin, Germany

    Wolfgang Schöps

  15. Sindh Institute of Urology and Transplantation, Karachi, Pakistan

    S. Adibul Hassan Rizvi

  16. Department of Pharmaceutics, Faculty of Pharmacy, University Karachi, Karachi, Pakistan

    Muhammad Aslam

  17. Department of Urology, Semmelweis University Budapest, Budapest, Hungary

    Gergely Bánfi & Imre Romics

  18. Faculty of Statistics, TU Dortmund University, Dortmund, Germany

    Katja Ickstadt

Authors
  1. Silvia Selinski
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  2. Marie-Louise Lehmann
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  3. Meinolf Blaszkewicz
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  14. Sebastian Frees
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  15. Walburgis Brenner
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  17. Miriam Angeli-Greaves
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  19. Gerhard Roth
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  20. Frank Volkert
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  26. Anna Zimmermann
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  27. Torsten Klein
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  28. Thomas Reckwitz
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  29. Hermann C. Roemer
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  30. Mark Hartel
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  31. Wobbeke Weistenhöfer
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  32. Wolfgang Schöps
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  33. S. Adibul Hassan Rizvi
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  34. Muhammad Aslam
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  35. Gergely Bánfi
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  36. Imre Romics
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  37. Katja Ickstadt
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  38. Jan G. Hengstler
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  39. Klaus Golka
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Corresponding author

Correspondence to Silvia Selinski.

Additional information

Jan G. Hengstler and Klaus Golka shared senior authorship.

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Selinski, S., Lehmann, ML., Blaszkewicz, M. et al. Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene. Arch Toxicol 86, 195–203 (2012). https://doi.org/10.1007/s00204-011-0747-5

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