EREG Rs1460008 A>G?FEN1 Rs174538 G>A Polymorphisms Are Associated With Risk Of Esophageal Cancer In A Chinese Population

Objective:Esophageal cancer is associated with high mortality worldwide,especially in Asia.Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009.Its incidence demonstrates obvious racial differences.Esophageal cancer can be classified as squamous cell carcinoma(ESCC)or adenocarcinoma(EADC).ESCC has a high incidence in China and is associated with poor prognostic features.However,the incidence of ESCC is affected by interactions between genetic and environmental factors;we try to explore the potential association between ESCC and genetic factors.Design and methods:This study aimed to assess the genetic susceptibility to ESCC in relation to functional single nucleotide polymorphisms(SNPs)in the EREG?DEC1 and flap endonuclease-1(FEN 1).We collected blood samples from 629 patients with ESCC and 686 control subjects,and determined the EREG rs1460008 A>G?DEC1 rs4978620 T>C,rs2269700 T>C,rs3750505 G>A and FEN1 rs174538 G>A genotype using the ligation detection reaction method.Results:When the EREG rs1460008 AA homozygote genotype was used as the reference group,the GG genotype was not associated with the risk for ESCC;the AG genotype was associated with a significantly decreased risk for ESCC(AG vs.AA:adjusted OR 0.76,95%CI 0.60-0.96,P-0.020).Logistic regression analyses revealed that the DEC1 rs4978620 T>C,rs2269700 T>C and rs3750505 G>A polymorphisms were not associated with the risk of ESCC in all comparison models.EREG rs1460008 A>G SNP is associated with decreased risk of ESCC.In a recessive model using FEN1 rs174538 GG/AA genotypes as the reference group,neither the AA homozygote genotype(AA vs.GG/AA:adjusted OR=1.18,95%CI=0.83-1.68,p=0.355),nor the GA/AA homozygote genotype(GA/AA vs.GG/AA:adjusted OR=0.85,95%CI=0.68-1.07,p = 0.176)was associated with ESCC risk.However,when the FEN1 rs174538 GG homozygote genotype was used as the reference group,nither GA genotype nor AA genotype was associated with a borderline significant decreased risk of ESCC(GA vs.GG:adjusted OR = 0.81,95%CI=0.64-1.04,p=0.092),(AA vs.GG:adjusted OR = 1.05,95%CI = 0.72-1.53,p=0.802).The risk of ESCC was significantly reduced among individuals with FEN1 rs174538 GA genotypes and GA/AA genotypes<63 years old.Conclusions:We conducted a hospital based case-control study to evaluate the association between Epiregulin?DEC 1 and FEN 1 SNPs and the susceptibility of esophageal cancer.Our results demonstrated that Epiregulin rs1460008 A>G might be potential functional or causal SNPs for esophageal cancer.And functional polymorphisms in FEN1 rs174538 G>A might affect individual(<63 years old)susceptibility to ESCC.This preliminary information will provide the basis for further clinical studies,though more studies with larger sample sizes are needed to verify the results.