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.

The -765G>C Polymorphism in the Cyclooxygenase-2 Gene and Digestive System Cancer: a Meta-analysis

“…These results indicated that this polymorphism may contribute to cancer risks. Consistent with the previous meta-analysis (Cao et al, 2010;Liang et al, 2011;Wang et al, 2013), we found significant increased risk -765G>C polymorphism with digestive system cancer, strongly suggesting that this polymorphism may contribute to digestive system cancer pathogenesis and help to explain individual differences of host susceptibility.…”

Intestinal PTGS2 mRNA Levels, PTGS2 Gene Polymorphisms, and Colorectal Carcinogenesis

“…However, the validity of this meta-analysis is unclear as we noted that for several of the papers analysed, the allele frequencies of G- and A-alleles of PTGS2 A-1195G do not match the allele frequencies in the original papers [33], [34]. Our results are also in accordance with another meta-analysis showing that there is no evidence that the genotype at PTGS2- 765 influences risk of colorectal cancer except in populations of Asian descent [35]. However, the results obtained in the present study are in contrast with results from the Danish prospective Diet, Cancer and Health cohort, where we found that high PTGS2 mRNA level-associated PTGS2 variant alleles were associated with lower risk of CRC [36].…”

Cyclooxygenase-2 Promoter 765C Increase of Digestive Tract Cancer Risk in the Chinese Population: a Meta-analysis

“…Among 9 articles, genotype GC, GC+CC had significantly increased cancer susceptibility risk, researched by Tan et al (2007), Xu et al (2008), Tang et al (2009), Zhao et al (2009), Zhang et al (2011. At present, a meta-analysis included 3322 colorectal cancer cases and 5166 controls (Cao et al, 2010) was inconsistent with our meta-analysis, which the -765C allele of the COX-2 gene may be a potential risk factor for colorectal cancer in Asians. In recent study, Akkız et al (2011) showed that COX-2 -765 C allele carriers had lower susceptibility to liver cancer, but in this research, we did not find this relationship.…”