COX-2 polymorphisms -765G-->C and -1195A-->G and colorectal cancer risk.
OBJECTIVE
To determine the possible modulating effect of the COX-2 polymorphisms, -765G-->C and -1195A-->G, on the risk of colorectal cancer (CRC) in a Dutch population.


METHODS
This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -765G-->C and -1195A-->G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression.


RESULTS
The -765GG genotype was associated with an increased risk of developing CRC (OR, 1.45; 95% CI, 1.03-2.04). No significant difference was observed in the genotype distribution of the -1195A-->G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls (OR 0.44; 95% CI, 0.22-0.85). When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls (OR((AG/AC)) 0.78; 95% CI, 0.57-1.06).


CONCLUSIONS
The -765GG genotype is associated with an increased risk of developing CRC and the GG/AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G-->C and -1195A-->G in the development of CRC in a Dutch population.
Hoff
Juliët H
JH
Department of Gastroenterology, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands.
te Morsche
Rene H M
RH
Roelofs
Hennie M J
HM
van der Logt
Elise M J
EM
Nagengast
Fokko M
FM
Peters
Wilbert H M
WH
D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D016172:DNA Fingerprinting; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human