Genetic polymorphisms of cyclooxygenase-2 and colorectal adenoma risk: the Self Defense Forces Health Study

Cyclooxygenase (COX) is a key enzyme in the formation of prostaglandins, and an inducible isoform of COX, COX-2, has been implicated in colorectal carcinogenesis. This study investigated the relation of COX-2 polymorphisms (-1195G>A, -765G>C and 8160A>G) to colorectal adenomas in a case-control study of male officials in the Self Defense Forces (SDF). The study subjects were 455 cases of colorectal adenoma and 1052 controls with no polyps who underwent total colonoscopy. Genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method with genomic DNA extracted from the buffy coat. Statistical adjustment was made for age, hospital, rank in the SDF, body mass index (BMI), cigarette smoking, and alcohol intake. A statistically non-significant decrease in the risk of colorectal adenomas was observed for the AA versus GG genotype of -1195G>A polymorphism and for the GC versus GG genotype of -765G>C polymorphism. None had the -765CC genotype in either the case or control groups. No effect modification of overweight, smoking or alcohol use was observed for either -1195G>A or -765G>C polymorphism. The variant allele of the 8160A>G polymorphism was extremely rare. A haplotype of -1195G, -765G and 8160A alleles was associated with a modest increase in the risk (adjusted odds ratio [OR] 1.38, 95% confidence interval [CI] 0.99-1.91), and the increase was more evident for distal adenomas (adjusted OR 1.57, 95% CI 1.04-2.38). Another haplotype of -1195A, -765C and 8160A alleles showed an adjusted OR of 0.22 (95% CI 0.06-0.88). These findings add to evidence for the role of COX-2 in colorectal carcinogenesis and warrant further studies focusing on haplotypes.