Association Of AP1S1 Polymorphisms With Risk And Survival Of Esophageal Squamous Cell Carcinoma

Objective:To study about the effects of AP1S1 gene single nucleotide polymorphisms on esophageal squamous carcinoma hereditary susceptibility and survival time respectively.Methods:Part 1:we conducted a hospital-based case-control study in which blood samples were collected from 1315 patients with ESCC and 1043 control subjects.The AP1S1 rs4727480 G>A,rs4729666 C>T,rs35208462 C>T,rs6969685 C>T,rs77387752 C>T genotyping of the subjects was detected by LDR.Analyzed the effect of functional single nucleotide polymorphisms（SNPS）in AP1S1 on genetic susceptibility to ESCC.Part 2:We collated and analyzed the follow-up results of 288 patients with ESCC who received surgical treatment in People’s Hospital affiliated of Jiangsu University.And input relevant data in Excel.SPSS 20.0 software was used to analyze and calculate the checked data,the survival rate was estimated by non-parametric method,the survival rate was calculated by life table method and product limit method.AP1S1 gene polymorphism and survival time of patients was analyzed by Kaplan-Meier method.Results:Statistical analysis showed that（1）when AP1S1rs4729666AA homozygous genotype was used as the reference group,the risk of esophageal cancer of rs4729666 AB genotype was significantly reduced.When AP1S1rs6969685 AA homozygous genotype was used as the reference group,the risk of esophageal cancer of rsrs6969685 BB genotype was significantly reduced.（2）Further stratified analyses showed that there was reduced risk associated with AP1S1 rs4729666 polymorphism among patients who were men,smokers or aged>63.The AP1S1 rs35208462 polymorphism reduced the risk in non-smoking population.The AP1S1 rs77387752 polymorphism increased the risk in men or alcohol drinkers,while it reduced the risk in patients who were age>63y.（3）The genotyping results show that the haploid Ars_4727480 Crss_4729666 Trs_35208462 Crs_6969685 Crs_77387752 and Grs_4727480 Trs_4729666 Crs_35208462 Trs_6969685 Crs_77387752,reduce the risk of suffering from esophageal cancer.Grs_4727480 Crs_4729666Crs_35208462 Trs_6969685 Crs_77387752 increase the risk of suffering from esophageal cancer.（4）The 1-year,3-year and 5-year survival rates of patients were 88.5%,75.8%and 43.2%,respectively,with an average survival time of 56.3 months and a median survival time of 48.0 months.The results showed that there was no significant correlation between five polymorphisms and survival.Conclusion:The polymorphisms rs4729666 and rs77387752 of AP1S1 gene might influence the risk of esophageal cancer in Chinese population.And the specific influence relationship needs to be further verified.However,the genetic variation of rs4727480,rs35208462 and rs6969685 polymorphisms were not implicated with altered susceptibility of ESCC according to different age,gender,cigarette smoking and alcohol drinking status.The polymorphism of rs4729666,rs77387752,rs4727480,rs35208462,rs6969685 of AP1S1 gene were not significantly associated with survival time of patients with ESCC.Of course,these conclusions need to be verified in larger studies and larger-scale randomized controlled trials among different ethnic populations with validation design.