Single Nucleotide Polymorphisms in MicroRNA-Binding Site of Epidermal Growth Factor Receptor Signaling Pathway and Susceptibility to Esophageal Squamous Cell Carcinoma

Abstract

Background: Epidermal growth factor receptor (EGFR) signaling pathway plays a fundamental role in regulating cell proliferation, differentiation, apoptosis, migration, and so on, which are associated with tumor development, including the esophageal squamous cell carcinoma (ESCC). The single nucleotide polymorphisms (SNPs) of microRNA-binding sites with target genes in the EGFR pathway could lead to alteration in the combination of microRNA with target genes and contribute to the susceptibility of cancer. Methods: A case-control study including 494 ESCC patients and 494 controls was carried out to investigate the genetic susceptibility of 4 microRNA-binding site SNPs (rs712 in the binding site of KRAS to let-7, rs8904 in the binding site of NFBIA to mir-507, rs3738894 in the binding site of protein kinase C epsilon to mir-218, rs701848 in the binding site of phosphatase and tensin to mir-1304) as well as the interactions of gene-environment in the development of ESCC. Results: The results showed that compared with CC genotype, the individuals with TT and TT + CT genotypes of rs701848 were significantly associated with increased ESCC risk (OR adjusted 1.56, 95% CI 1.07–2.27 and 1.41, 1.01–1.97). The gene-Environment interaction between rs3738894 and smoking history was associated with the risk of esophageal cancer. Conclusions: Results of these analyses underline the support of the notion that SNPs in microRNA-binding site of EGFR signaling pathway play certain important roles in the susceptibility to ESCC.