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Aberrant arachidonic acid metabolism by cyclooxygenase (COX)-2 and 12-lipoxygenase (LOX) has implicated in carcinogenesis. Genetic polymorphisms inCOX-2and12-LOXmight therefore affect susceptibility to colorectal cancer (CRC). To examine this hypothesis, genotypes ofCOX-2–1290A&gt;G, –1195G&gt;A, –765G&gt;C and12-LOX261Arg&gt;Gln polymorphisms were determined in 1000 CRC patients and 1300 controls. Increased risk of developing CRC was associated with theCOX-2–1195GA [adjusted odds ratio (OR) = 1.24, 95% confidence interval (CI) = 1.00–1.54] and –1195AA (adjusted OR = 1.77, 95% CI = 1.38–2.25) genotypes compared with the –1195GG genotype. Similarly, the increased risk for CRC was also associated with theCOX-2–765GC genotype (adjusted OR = 1.73, 95% CI = 1.23–2.43) compared with the –765GG genotype. Consistent with the results of genotype analyses, the ORs for the A_1195-C_765-containing haplotypes were significantly higher than those for the G_1195-G_765-containing haplotypes (P&lt; 0.01). Furthermore, the –1195A allele was further associated with advanced CRC, with adjusted ORs of Dukes D CRC against Dukes A CRC being 2.43 (95% CI = 1.15–4.97) and 2.66 (95% CI = 1.23–5.74) for the –1195GA and –1195AA genotypes, respectively. The increased risk of CRC was also associated with the12-LOX261Gln/Gln genotype compared with the Arg/Arg genotype (adjusted OR = 1.38, 95% CI = 1.09–1.74). Together, these observations indicate that inherited polymorphisms in arachidonic acid-metabolizing enzymes may confer susceptibility to CRC.

carcinogenesis

Associations of functional polymorphisms in               cyclooxygenase-2               and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer