title: Transcription factor 7-like 2 polymorphism and colon cancer.
abstract: Polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been associated with insulin sensitivity and diabetes, and the TCF7L2 gene is involved in the Wnt/beta-catenin signaling pathway, all factors thought to be important in the etiology of colon cancer. In this confirmatory study, we evaluated the rs7903146 TCF7L2 polymorphism with colon cancer using previously collected data on 1,578 cases and 1,966 controls. We did not observe a statistically significant association between the rs7903146 polymorphisms and risk of colon cancer [odds ratio (OR), 1.12; 95% confidence interval (95% CI), 0.98-1.28] when evaluating the total population. We did, however, observe a statistically significant interaction between the rs7903146 TCF7L2 polymorphism and recent use of aspirin/nonsteroidal anti-inflammatory drugs (NSAID; P = 0.001). Increased colon cancer risk associated with the T allele was restricted to those without recent use of aspirin/NSAIDs (OR, 1.65; 95% CI, 1.35-2.02, relative to recent aspirin users, i.e., use of aspirin/NSAIDS within the 2 years before diagnosis, with the CC genotype). Among individuals who reported recent use of aspirin/NSAIDs, the T allele reduced risk of colon cancer (OR, 0.78; 95% CI, 0.62-0.98) in a dose-response fashion (P for linear trend across genotypes = 0.03). These data suggest that colon cancer risk associated with the rs7903146 TCF7L2 polymorphism is modified by use of aspirin/NSAIDs.
authors.affiliation: Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT 84108, USA. mslattery@hrc.utah.edu
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: Roger
authors.initials: R
authors.lastname: Wolff
authors.forename: Jenifer
authors.initials: J
authors.lastname: Herrick
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011110:Polymorphism, Genetic / Q000187:drug effects*; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D001241:Aspirin