Association Of PLCE1 And MTORC1 Genetic Variations With Gastric Cancer Risk And Prognosis

Part I: Association of mTORC1 genetic variations with gastric cancer prognosisObjective Nowadays,mTOR signaling pathway is one of the research hotspots.Gene variations in this pathway play a significant role in development of gastric cancer.Some investigations demonstrated that mTORC1 polymorphisms were associated with the risk of gastric cancer.However,no research reported associations between mTORC1 genetic variations and gastric cancer prognosis.We first assess the correlation of mTORC1 genetic variations with gastric cancer prognosis.Method Patients with operation in xinhua hospital affiliated to Shanghai jiaotong university school of medicine and first diagnosed with gastric cancer were collected.We use TaqMan method for eight candidate loci genotyped.Kaplan-Meier survival analysis and univariate and multivariate Cox regression analysis were used to analyze the association between candidate genes polymorphisms and prognosis of gastric cancer.Results Our study contains 197 subjects.We have not observed the association between any candidate loci polymorphism in mTORC1 and gastric cancer prognosis.In the combined analysis of the four SNPs in Raptor gene,our results indicated patients with ? 2 risk genotypes had significantly increased death risk(adjusted HR=1.77,95% CI=1.02-3.09),compared with those having zero or one risk genotype.This death risk effect was more evident in subgroups of female,lymph node metastasis and TNM stage III+IV.When combined all eight SNPs,we found patients with >3 risk genotypes had significantly increased mortality risk(adjusted HR=2.40,95% CI=1.29-4.44),compared with those with ?3 genotypes.In the stratified analysis,the subgroups of age?65,male,non-drinkers,tumor size ? 4 cm,non-cardia cancer,depth of invasion T3+T4,lymph node metastasis,TNM stage III+IV,vascular invasion,lymphatic vessel invasion and perineural invasion had more evident mortality risk.Conclusion In conclusion,these findings demonstrate that genetic variations in mTORC1 genes may collectively influence gastric cancer prognosis.More studies with larger sample size and appropriate design are warranted.Part II: Association between PLCE1 rs2274223 A>G polymorphism and gastric cancer risk: proof from a meta-analysisObjective Phospholipase C epsilon 1(PLCE1)plays an important role in cell growth,differentiation and oncogenesis.As genome-wide association studies(GWASs)strategy is putting forward,an increasing number of individual studies have investigated the association between PLCE1 rs2274223 polymorphism and gastric cancer(GC),but the conclusions are inconclusive.To obtain a comprehensive conclusion,we performed a meta-analysis to systematically estimate the effects of PLCE1 rs2274223 A > G polymorphism on the susceptibility to cancer.Method We identified all eligible case-control studies from Pubmed,The New England Journal of Medcine,China National Knowledge Infrastructure(CNKI)and Wan Fang database.We use allelic,homozygote,heterozygote,dominant and recessive as the models.The genetic association between the PLCE1 rs2274223 polymorphism and the risk of gastric cancer was evaluated by the pooled odds ratios(OR)and 95% confidence interval(CI).If the P value of the Z test was less than 0.05,we considered the pooled OR statistically significant.When there existed significant heterogeneity(P <0.10),the random-effects model was used.Otherwise,the fixed effects model was used.Sensitivity analyses and publication bias were performed to measure the stability of the resultsResults A total of 5 eligible articles were identified in the final meta-analysis,which contained 6 studies and involved 6813 cases and 5666 controls.Overall,the PLCE1 rs2274223 polymorphism was not associated with the risk of gastric cancer in all genetic models.Stratification analysis by genotyping methods showed that rs2274223 was significantly associated with the risk of GC using Taq Man(G vs.A: OR=1.20,95% CI=1.04-1.39;GA vs.AA: OR=1.27,95% CI=1.12-1.44;GG/GA vs.AA: OR=1.28,95% CI=1.10-1.49).Sensitivity analyses and publication bias were not observed significant differences.Conclusion This meta-analysis demonstrated that there was no association between PLCE1 rs2274223 A>G polymorphism and the risk of gastric cancer.However,due to the limitation of the meta-analysis,the conclusion might be not conclusive which need more studies to confirm.