Association of miRNA-related Genetic Polymorphisms and Prognosis in Patients with Esophageal Squamous Cell Carcinoma

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a deadly disease with a poor prognosis. The single nucleotide polymorphisms (SNPs) involved in microRNA (miRNA) functions are potential biomarkers for prognosis of various human cancers. We investigated the association of the miRNA-related SNPs with the prognosis of ESCC.Methods: A total of 504 patients with ESCC were enrolled. The genotypes of 18 miRNA-related SNPs were analyzed from the genomic DNA of peripheral leukocytes and were correlated with the prognosis of patients randomly assigned to a training set (n?=?129) or an independent replication set (n?=?375).Results: In the training group, only the rs4919510 SNP of the mir-608 gene was significantly associated with clinical outcome (CG vs. GG, hazard ratio [HR] 0.47, 95?% confidence interval [CI] 0.27–0.82, P?=?0.008 for death, HR 0.47, 95?% CI 0.29–0.77, P?=?0.002 for recurrence). The association for overall survival was confirmed in an independent replication group (CG vs. GG, HR 0.74, 95?% CI 0.56–0.97, P?=?0.031 for death). Two other SNPs, rs14035 of RAN and rs7813 of GEMIN4, showed a borderline significant association with the prognosis of ESCC. In a combined analysis, we demonstrated the cumulative effect of the mir-608, RAN, and GEMIN4 polymorphisms on the clinical outcome of ESCC (HR 1.40, 95?% CI 1.18–1.67, Ptrend?<?0.001 for mortality, HR 1.30, 95?% CI 1.10–1.53, Ptrend?=?0.002 for recurrence). The cumulative effect was more evident in patients receiving concurrent chemoradiotherapy.Conclusions: The hereditary genetic polymorphisms of mir-608, RAN, and GEMIN4 can serve as predictors for clinical outcome in ESCC patients treated with concurrent chemoradiotherapy. ? 2014, Society of Surgical Oncology.