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.
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.
McGreavey
Louise E
LE
Biomedical Research Centre, Ninewells Hospital & Medical School, Dundee, UK.
Turner
Faye
F
Smith
Gillian
G
Boylan
Katherine
K
Timothy Bishop
D
D
Forman
David
D
Roland Wolf
C
C
Barrett
Jennifer H
JH
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
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