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

• Published in: Archives of toxicology 2012-02, Vol.86 (2), p.195-203
• Main Authors: Selinski, Silvia, Lehmann, Marie-Louise, Blaszkewicz, Meinolf, Ovsiannikov, Daniel, Moormann, Oliver, Guballa, Christoph, Kress, Alexander, Truß, Michael C., Gerullis, Holger, Otto, Thomas, Barski, Dimitri, Niegisch, Günter, Albers, Peter, Frees, Sebastian, Brenner, Walburgis, Thüroff, Joachim W., Angeli-Greaves, Miriam, Seidel, Thilo, Roth, Gerhard, Volkert, Frank, Ebbinghaus, Rainer, Prager, Hans-Martin, Lukas, Cordula, Bolt, Hermann M., Falkenstein, Michael, Zimmermann, Anna, Klein, Torsten, Reckwitz, Thomas, Roemer, Hermann C., Hartel, Mark, Weistenhöfer, Wobbeke, Schöps, Wolfgang, Rizvi, S. Adibul Hassan, Aslam, Muhammad, Bánfi, Gergely, Romics, Imre, Ickstadt, Katja, Hengstler, Jan G., Golka, Klaus
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Binding sites; Biomedical and Life Sciences; Biomedicine; Bladder; Bladder cancer; Cancer; Case-Control Studies; Environmental Health; Female; Genes; Genetic Predisposition to Disease - ethnology; Germany; Humans; Hungary; Insulin-Like Growth Factor Binding Protein 3 - genetics; Male; Middle Aged; Occupational Medicine/Industrial Medicine; Pakistan; Pharmacology/Toxicology; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Toxicogenomics; Urinary Bladder Neoplasms - ethnology; Urinary Bladder Neoplasms - genetics; Urinary tract diseases; Venezuela
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-011-0747-5

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.