title: Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.
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.
authors: Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany. selinski@ifado.de
authors: Silvia
authors: S
authors: Selinski
authors: Marie-Louise
authors: ML
authors: Lehmann
authors: Meinolf
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authors: Blaszkewicz
authors: Daniel
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authors: Ovsiannikov
authors: Oliver
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authors: Moormann
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authors: Guballa
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authors: Gerullis
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authors: Barski
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authors: Niegisch
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authors: Albers
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authors: Frees
authors: Walburgis
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authors: Brenner
authors: Joachim W
authors: JW
authors: Thüroff
authors: Miriam
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authors: Angeli-Greaves
authors: Thilo
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authors: Seidel
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authors: Roth
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authors: Volkert
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authors: Ebbinghaus
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authors: Falkenstein
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authors: Zimmermann
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authors: Klein
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authors: Reckwitz
authors: Hermann C
authors: HC
authors: Roemer
authors: Mark
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authors: Hartel
authors: Wobbeke
authors: W
authors: Weistenhöfer
authors: Wolfgang
authors: W
authors: Schöps
authors: S Adibul Hassan
authors: SA
authors: Rizvi
authors: Muhammad
authors: M
authors: Aslam
authors: Gergely
authors: G
authors: Bánfi
authors: Imre
authors: I
authors: Romics
authors: Katja
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authors: Ickstadt
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authors: JG
authors: Hengstler
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authors: Golka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005858:Germany; D006801:Humans; D006814:Hungary; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics*; D014687:Venezuela
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3