Cyclooxygenase-2 gene polymorphisms and susceptibility to hepatocellular carcinoma: A meta-analysis based on 10 case-control studies

Objective: The association between cyclooxygenase-2 (COX-2) gene polymorphisms and hepatocellular carcinoma (HCC) has been widely reported, but the results are still controversial. To clarify the effect of COX-2 -1195G/A (rs689466), -765G/C (rs20417), and +8473T/C (rs5275) polymorphisms on HCC risk, a meta-analysis was performed. Materials and Methods: The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature, Wanfang, and Chinese National Knowledge Infrastructure databases were systematically searched to identify potential studies published up to October 10, 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of association. A total of eight studies with 2060 HCC cases and 2610 controls for -1195G/A, six studies with 1295 cases and 2193 controls for -765G/C, and four studies with 1477 cases and 1747 controls for +8473T/C were included in this meta-analysis. Results: Overall, the COX-2 -1195G/A, and +8473T/C polymorphisms were both significantly associated with an increased risk of HCC (rs689466 GA + AA vs. GG: OR = 1.390, P = 0.006, 95% CI: 1.099-1.759, I-2 = 50.7%, P-heterogeneity = 0.048; rs5275 CC vs. TT + TC: OR = 1.484, P = 0.041, 95% CI: 1.017-2.165, I-2 = 0.0%, P-heterogeneity = 0.416). In the subgroup analyses stratified by ethnicity, the COX-2 -1195G/A, -765G/C, and +8473T/C were all associated with an increased HCC risk in Asian populations (rs689466 A vs. G: OR = 1.346, P = 0.001, 95% CI: 1.137-1.595, I-2 = 0.0%, P-heterogeneity = 0.869; rs20417 CC vs. GG + GC: OR = 3.069, P = 0.013, 95% CI: 1.265-7.447; rs5275 CC vs. TT + TC: OR = 1.626, P = 0.020, 95% CI: 1.079-2.452, I 2 = 0.0%, P-heterogeneity = 0.495). Conclusions: Our meta-analysis suggests that -1195G/A, -765G/C, and + 8473T/C in COX-2 may contribute significantly to HCC risk.