COX-2 Rs5275 And Rs689466 Polymorphism And Risk Of Lung Cancer:a Meta-analysis

Background: Cyclooxygenase-2(COX-2)is an inducible enzyme that mediates the synthesis of prostaglandin,which plays an important part in the inflammation response.The over-expression of COX-2 in lung cancer has been found in several studies,suggesting that COX-2 contributes to carcinogenesis.Previous case-control studies focused on the association between COX-2 polymorphism and lung cancer risk have been published,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 literature research was conducted on Pub Med,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)and95% confidence intervals(CIs)in five 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=0.02).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=0.001),homozygote(OR: 0.81,95% CI: 0.68-0.95,P=0.01),heterozygote(OR: 0.81,95% CI:0.72-0.91,P<0.001)and dominant model(OR: 0.81,95% CI: 0.72-0.91,P<0.001),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 accoding to stratified analysis by pathological types.Egger's 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.