Association Of PLCE1 Rs2274223 A>G Polymorphism And Risk Of Developing Esophageal Cancer And Gastric Cancer:a Systematic Review And Meta-analysis

Background/Object:In recent years,the phospholipase C epsilon 1(PLCE1)rs2274223 polymorphism has been extensively investigated as a potential risk factor for upper gastrointestinal cancers,including esophageal squamous cell carcinoma(ESCC)and gastric carcinoma(GC).However,the results of previous studies have been inconsistent.Methods:A meta-analysis of 23 case-control studies was conducted including 12,596 cases and 13,263 controls with genotyped PLCE1 rs2274223 polymorphism.Odds ratios(OR)with 95% confidence intervals(95% CI)were employed to assess the association of the PLCE1 rs2274223 polymorphisn with the susceptibility to ESCC/GC using allelic model,homozygote model,heterozygote model,dominant model and recessive model.Results:A total of 21 eligible articles,which contained 23 studies were identified in the final meta-analysis.Among the 23 studies,11 reported on ESCC with 4,082 cases and 5,913 controls,12 reported on GC with 8487 cases and 7350 controls.All of the studies followed the Hardy-Weinberg equilibrium(HWE),except for the cases from Umar’s research.Among the studies,15 studies were conducted on the Asian individuals,6 on Caucasian population,1 on South African Black population,and 1 on South African Mixed Ancestry population.In ESCC,the overall result showed that the polymorphism was significantly associated with the increased risk of ESCC(G vs.A: OR = 1.22,95% CI = 1.08-1.37;GG vs.AA: OR = 1.50,95% CI = 1.15-1.96;GA vs.AA: OR = 1.28,95% CI = 1.17-1.41;GG/GA vs.AA: OR = 1.31,95% CI = 1.16-1.48;GG vs.GA/AA: OR = 1.35,95% CI = 1.06-1.70).Stratification analysis showed that significantly increased risk was only discovered for the Asian subgroup(G vs.A: OR = 1.38,95% CI = 1.19-1.59;GG vs.AA: OR = 2.03,95% CI = 1.53-2.70;GA vs.AA: OR = 1.38,95% CI = 1.24-1.54;GG/GA vs.AA: OR = 1.47,95% CI = 1.30-1.66;GG vs.GA/AA: OR = 1.74,95% CI = 1.36-2.24),but not for Caucasians,South African Black population and South African Mixed Ancestry population.In GC,the overall result showed that the polymorphism was significantly associated with the increased risk of ESCC in allelic model,homozygote model,dominant model and recessive model(G vs.A: OR = 1.14,95% CI = 1.02-1.27;GG vs.AA: OR = 1.27,95% CI = 1.03-1.57;GG/GA vs.AA: OR = 1.31,95% CI = 1.12-1.52;GG vs.GA/AA: OR = 1.21,95% CI = 1.02-1.45).Stratification analysis showed significantly increased risk was only discovered for the Asian subgroup in allelic model,homozygote model,and recessive model(G vs.A: OR = 1.72,95% CI = 1.02-1.34;GG vs.AA: OR = 1.38,95% CI = 1.07-1.77;GG vs.GA/AA: OR = 1.31,95% CI = 1.07-1.61),but not for Caucasians.Conclusion: In ESCC,the overall result showed that the polymorphism was significantly associated with the increased risk of ESCC.Stratification analysis showed that significantly increased risk was only discovered for the Asian subgroup,but not for Caucasians,South African Black population and South African Mixed Ancestry population.In GC,the overall result showed that the polymorphism was significantly associated with the increased risk of ESCC in allelic model,homozygote model,dominant model and recessive model.Stratification analysis showed significantly increased risk was only discovered for the Asian subgroup in allelic model,homozygote model,and recessive model,but not for Caucasians.