The genetic variant of COX-2 acts as a potential risk factor of colorectal cancer: evidence from a meta-analysis based on 13461 individuals

Yan Pan, Song Gao, Qi Qi, Luming Liu
2015 Integrative Molecular Medicine  
Cyclooxygenase-2 (COX-2) plays a crucial role in colorectal carcinogenesis. Accumulating studies investigating the association between COX-2 genetic variants (-765G>C, -1195G>A, and 8473T>C) and colorectal cancer (CRC) susceptibility generated conflicting results. To explore the potential correlation, we conducted a meta-analysis based on eligible case-control epidemiological studies. Databases of Medline, Embase and CNKI were screened for eligible papers focusing on the relationship between
more » ... -2 polymorphisms and CRC risk. The pooled odds ratio (OR) and 95% confidence interval (95% CI) was calculated to estimate the significance of such an association. A total of twelve studies for -765G>C, eight studies for COX-2 -1195G>A, and seven studies for 8473T>C were enrolled in this meta-analysis. On the whole, -1195 A allele carriers presented increased incidence rate of CRC compared with G allele carriers (OR=1.227, 95% CI=1.060-1.419, P OR =0.006). The result was consistent in subgroup analysis of sample size ≥500 (OR=1.232, 95% CI=1.064-1.426, P OR =0.005). As for -765C allele, an associated higher CRC risk was observed only in Asian descents under the heterozygote and dominant model (OR=1.477, 95% CI=1.148-1.898, POR=0.002; OR=1.451, 95% CI=1.146-1.747, P OR =0.001, respectively). In contrast, no linkage was defined between 8473T>C polymorphism and CRC susceptibility under all four genetic models. Considering the interactive influence of gene background and environmental factors on CRC, the smokers with -765GG genotype had a 1.761-fold greater risk to develop CRC. In summary, -1195G>A polymorphism contributed to CRC susceptibility worldwide whereas -765G>C was a potential CRC risk factor only in Asian population. Smokers with -765GG genotype would be more susceptible to CRC development. Large-sample, well-matched studies with consideration of gene-gene and gene-environment interaction are awaited to validate the findings. Pan Y (2015) The genetic variant of COX-2 acts as a potential risk factor of colorectal cancer: evidence from a meta-analysis based on 13461 individuals Volume 2(6): 440-448
doi:10.15761/imm.1000184 fatcat:5cijotvapjhwhlc75rixlenk5y