Brief Articles
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World J Gastroenterol. Sep 28, 2009; 15(36): 4561-4565
Published online Sep 28, 2009. doi: 10.3748/wjg.15.4561
COX-2 polymorphisms -765G→C and -1195A→G and colorectal cancer risk
Juliët H Hoff, Rene HM te Morsche, Hennie MJ Roelofs, Elise MJ van der Logt, Fokko M Nagengast, Wilbert HM Peters
Juliët H Hoff, Rene HM te Morsche, Hennie MJ Roelofs, Elise MJ van der Logt, Fokko M Nagengast, Wilbert HM Peters, Department of Gastroenterology, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands
Author contributions: Nagengast FM, van der Logt EMJ and Peters WHM designed the research and included the patients, Hoff JH, te Morsche RHM and Roelofs HMJ performed the analyses; van der Logt EMJ and te Morsche RHM were responsible for the data analysis; Hoff JH and Peters WHM wrote the paper.
Correspondence to: Wilbert HM Peters, PhD, Department of Gastroenterology, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands. w.peters@mdl.umcn.nl
Telephone: +31-24-3616316 Fax: +31-24-3540103
Received: April 21, 2009
Revised: August 26, 2009
Accepted: September 2, 2009
Published online: September 28, 2009
Abstract

AIM: 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).

CONCLUSION: 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.

Keywords: Colorectal carcinoma; Cyclooxygenase-2; Genetic polymorphism