Association between rs20417 polymorphism in cyclooxygenase-2 and gastric cancer susceptibility: Evidence from15 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.