title: No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARdelta and PPARgamma act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma.
abstract: OBJECTIVE
  Regular continuous non-steroidal anti-inflammatory drug (NSAID) use has been associated with a reduction in risk of colorectal cancer. Our objective was to investigate whether or not a number of the polymorphic genes involved in the metabolism of NSAIDs, including cytochrome P450 s (CYPs), act as modifiers of this protective effect.
  
  
  METHODS
  As part of a multi-centre case-control study, 478 colorectal cancer patients and 733 controls (433 matched case-control pairs) answered questions on NSAID use. These individuals were then genotyped for common polymorphisms in P450 CYP2C8, P450 CYP2C9, UDP-glucuronosyl transferase (UGT)1A6 and peroxisome proliferator-activated receptor isoforms delta and gamma (PPARdelta and PPARgamma).
  
  
  CONCLUSIONS
  Our study confirmed the reduction in risk of colorectal cancer with regular NSAID use (odds ratio (OR) = 0.73, 95% confidence interval (CI) (0.56, 0.95)) but showed that none of the polymorphic genes studied appeared to modify the protective effect of regular NSAID use.
authors.affiliation: Biomedical Research Centre, Ninewells Hospital & Medical School, Dundee, UK.
authors.forename: Louise E
authors.initials: LE
authors.lastname: McGreavey
authors.forename: Faye
authors.initials: F
authors.lastname: Turner
authors.forename: Gillian
authors.initials: G
authors.lastname: Smith
authors.forename: Katherine
authors.initials: K
authors.lastname: Boylan
authors.forename: D
authors.initials: D
authors.lastname: Timothy Bishop
authors.forename: David
authors.initials: D
authors.lastname: Forman
authors.forename: C
authors.initials: C
authors.lastname: Roland Wolf
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barrett
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics* / Q000517:prevention & control; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D020022:Genetic Predisposition to Disease; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D047494:PPAR delta / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics; D011110:Polymorphism, Genetic; D020011:Protective Agents / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D047494:PPAR delta; D047495:PPAR gamma; D020011:Protective Agents; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase