SNPs In MicroRNA Binding Site Of EGFR Signaling Pathway And Susceptibility To ESCC

Most patients are in advanced stages at the time of diagnosis because of a lack ofspecific symptoms during the early stages. Therefore, overall5-year survival rate ofesophageal squamous cell carcinoma (ESCC) cases remains low around30%.Epidermal growth factor receptor (EGFR) signaling pathway regulates cellproliferation，differentiation, apoptosis, migration, metabolism and angiogenesis,which are associated with tumor development. Polymorphism in microRNA bindingsite can disrupte or create a binding site. Almost more than90%of the EC is ESCC,therefore, the study of the association between the polymorphism in the binding siteof microRNA in the target gene and esophageal cancer is essential.ObjectiveTo investigate the association between the polymorphisms in the microRNAbinding site of genes in EGFR pathway and esophageal cancer susceptibility.MethodsIn this case-control study,494ESCC patients were recruited, and494age (±5years) and sex frequency matched cancer-free controls randomly selected from acensus were enrolled. After the collection of information of the cases and controls,genomic DNA was extracted from peripheral blood samples. The genotypes of rs712in kirsten rat sarcoma viral oncogene homolog(KRAS), rs8904in nuclear factor ofkappa light polypeptide gene enhancerin B-cells1-α（NFKBIA）, rs3738894in proteinkinase C, epsilon (PRKCE) and rs701848in phosphatase and tensin homolog (PTEN)were detected by using PCR-RFLP. χ2test was used to compare differences in thedistribution of age, sex, smoking, drinking and tumor family history between thecases and controls. The associations between each SNP and esophageal cancer riskwere estimated by computing odds ratios (ORs) and their95%confidence (95%CIs) using unconditional logistic regression analyses. Hardy–Weinberg equilibrium amongthe controls was analyzed by online SHEsis software (http://analysis.bio-x.cn/myAnalysis.php). Multifactor dimensionality reduction (MDR, V2.0Beta2) were usedto calculate the possibility of gene–environment and gene-gene interactions betweenthe four studied genotypes and ESCC.ResultsThe result of single loci analyses showed that rs712was associated withincreased risk of ESCC (adjusted OR,1.30,95%CI,1.00-1.69for TT+GT vs. GG).The analysis of rs701848showed that TT genotype and TT+CT genotype wereassociated with increased risk of ESCC (adjusted OR,1.56,95%CI,1.07-2.27for TTvs. CC; adjusted OR,1.41,95%CI,1.01-1.97for TT+CT vs. CC). Thegene-environment interactions analysis presented the interactions among rs3738894,and smoking history might be associated with ESCC risk.Conclusionsrs712in KRAS gene GT+TT genotype and rs701848in the PTEN TT genotypemight increase the ESCC risk. The gene-environment interactions analysis presentedinteraction of rs3738894and smoking might be associated with ESCC risk.