COX-2 rs5275 and rs689466 polymorphism and risk of lung cancer: A PRISMA-compliant meta-analysis.

Background: Cyclooxygenase-2 (COX-2) is an inducible enzyme that mediates the synthesis of prostaglandin, which plays an important role in the inflammation response. The overexpression of COX-2 in lung cancer has been found in several studies, suggesting that COX-2 contributes to carcinogenesis. There are many previous case-control studies focused on the association between COX-2 polymorphism and lung cancer risk, however, the conclusion remained controversial.

Objectives: We performed this meta-analysis to evaluate the association between COX-2 rs5275 and rs689466 polymorphism and susceptibility to lung cancer.

Methods: A systematic literature research was conducted on PubMed, Embase, Cochrane Library, OVID, Web of Science, and Google Scholar up to November 30, 2017. The quality of studies was assessed by Newcastle-Ottawa scale. We combined odds ratios (ORs) and 95% confidence intervals (CIs) in 5 different genetic models for evaluation under a fixed-effect model or random-effect model. Subgroup analysis was performed according to source of control, ethnicity, pathological types, and smoking status. Sensitivity analysis and publication bias were also conducted.

Results: Eventually, 14 eligible studies were included in our meta-analysis. We found rs5275 gene polymorphism decreased the risk of lung cancer under heterozygote model (OR: 0.91, 95% CI: 0.84-0.98, P = .02). COX-2 rs689466 gene polymorphism was also related to a significantly reduced risk under allele (OR: 0.88, 95% CI: 0.82-0.95, P = .001), homozygote (OR: 0.81, 95% CI: 0.68-0.95, P = .01), heterozygote (OR: 0.81, 95% CI: 0.72-0.91, P < .001), and dominant model (OR: 0.81, 95% CI: 0.72-0.91, P < .001), except for recessive model. Subgroup analysis suggested a similar association in Asians, but not in Caucasians. Polymorphism of rs5275 was strongly associated with a reduced risk of lung adenocarcinoma according to stratified analysis by pathological types. Egger test identified no significant publication bias.

Conclusions: Our meta-analysis demonstrated that COX-2 rs5275 and rs689466 polymorphism significantly decrease the risk of lung cancer in Asians but not in Caucasians, indicating COX-2 could serve as a potential diagnostic marker for lung cancer.