Association between rs20417 polymorphism in cyclooxygenase-2 and gastric cancer susceptibility Evidence from 15 case-control studies

Objective: Previous studies have reported an association between cyclooxygenase-2 (COX-2) polymorphism and gastric cancer (GC) susceptibility, but their results are controversial. This meta-analysis was intended to evaluate the relationship between the COX-2 rs20417 polymorphism and GC susceptibility in different ethnic groups. Methods: We searched PubMed, EMBASE, Web of Knowledge, and the Chinese Biomedical Database (CBM) for relevant case-control studies published up to October 6, 2018, which reported an association between the COX-2 rs20417 polymorphism and gastric cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association. Results: 15 papers detailing case-control studies were included in the analysis, which included a total of 2848 GC cases and 4962 healthy controls. The meta-analysis results indicated that the COX-2 rs20417 polymorphism was associated with increased GC susceptibility under allele (G vs C: OR=1.67, 95% CI=1.19-2.35, P=.003), heterozygous (GG vs CG: OR=1.44, 95% CI=1.03-2.02, P=.034), dominant (GC+ CC vs GG: OR=1.66, 95% CI=1.18-2.34, P=.004), homozygous (GG vs CC: OR=2.20, 95% CI=1.07-4.54, P=.033), and recessive models (CC vs GG+ CG: OR=2.05, 95% CI=1.09-3.85, P=.025). An analysis of ethnic subgroups revealed that the COX-2 rs20417 polymorphism was significantly associated with GC susceptibility in Asians under all 5 models (G vs C: OR=2.22, 95% CI=1.66-2.96, P<. 001; GG vs CC: OR=4.29, 95% CI=1.94-9.50, P<. 001; GG vs CG: OR=1.86, 95% CI=1.34-2.58, P<. 001; CC vs GG+ CG: OR=3.73, 95% CI=1.92-7.24, P<. 001; GC+ CC vs GG: OR=2.20, 95% CI=1.65-2.93, P<. 001). Helicobacter pylori positive patients suffered a high risk of GC, compared to H pylori negative patients under the dominant model (OR=3.09, 95% CI=1.80-5.32, P<. 001). Conclusion: This meta-analysis of 15 case-control studies provides strong evidence that the COX-2 rs20417 polymorphism increases the risk of GC susceptibility in general populations, especially in Asians. Helicobacter pylori positive patients and those with the COX-2 rs20417 polymorphism had a higher risk of developing GC.