The -765C Allele of the Cyclooxygenase-2 Gene as a Potential Risk Factor of Colorectal Cancer: A Meta-Analysis

Abstract

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the world. Human colorectal carcinogenesis is a complex, multistep and multigenetic process. Cyclooxygenase-2 (COX2), a key enzyme in arachidonic acid metabolism, is overexpressed in several epithelial malignancies including colorectal cancer. COX2 expression can be induced by pro-inflammatory and mitogenic stimuli. The -765G/C polymorphism of the COX2 gene promoter has been reported to affect CRC susceptibility, but recent studies have demonstrated conflicting results. To shed light on these inconclusive findings, we performed a meta-analysis for assessing the involvement of COX2 -765G/C polymorphisms at the onset of colorectal carcinoma. Literature-based searching was guided to gather data and either fixed-effect or random-effect model was used to pool the odds ratio (OR) according to the test of heterogeneity. The 10 eligible case-control studies included 3,322 colorectal cancer cases and 5,166 controls. Overall, no evidence has indicated that individuals carrying GC+CC genotypes had significantly increased colorectal cancer risk compared with GG genotype [OR = 1.06, 95% confidence interval (95% CI) = 0.94-1.20]. However, stratified analysis with ethnicity indicated that individuals carrying GC+CC genotypes had an increased risk of colorectal cancer (OR = 1.40, 95% CI = 1.11-1.76) among Asian population. In conclusion, although not all bias could be eliminated, the -765C allele of the COX2 gene may be a potential risk factor for colorectal cancer in Asians.