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.