Abstract 4194: The hereditary genetic polymorphism of mir-608 predicts the clinical outcome and expression of IL-6 in patients with esophageal squamous cell carcinoma .

Abstract

Abstract PURPOSE: To investigate the effect of the single nucleotide polymorphisms (SNPs) in microRNA-related genes on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: A total of 504 patients with a diagnosis of ESCC were enrolled in the study. The genotypes of miRNA-related SNPs were analyzed from the genomic DNA of peripheral leukocytes and were correlated with the clinical outcome of patients, which was first evaluated in a randomly assigned training set (n=129) and subsequently verified by a replication set (n= 375). RESULTS: In training group, the heterozygous CG genotype of mir-608 rs4919510 was associated with reduced risk for adverse clinical outcomes (HR [95% CI] =0.47 [0.27-0.82] for death; HR [95% CI] =0.47 [0.29-0.77] for recurrence). In contrast, both homozygous CC and GG genotypes showed unfavorable for prognosis. The associations were confirmed in an independent replication group (GG+CC vs. CG, HR [95% CI] =1.36 [1.07-1.73], P=0.013 for death; HR [95% CI] = 1.26 [1.00-1.59], P=0.048 for recurrence). The prognostic effect was more pronounced among patients with advanced tumor stages and in those treated with concurrent neoadjuvant chemo- radiotherapy (CCRT). Functional relevance of rs4919510 was correlated with the serum IL-6 levels. GG variant was significantly associated with IL-6 over-expression in advanced ESCC patients. CONCLUSION: The hereditary genetic variants in mir-608 can serve as an independent predictor for the clinical outcome of ESCC patients. The prognostic effect of rs4919510 may be partially mediated by impairing the ability in regulating IL-6 expression. Citation Format: Pei-Wen Yang, Ching-Yueh Hsieh, Yu-Ting Huang, Ya-Chuan Huang, Tzu-Hsuan Chiang, Jang-Ming Lee. The hereditary genetic polymorphism of mir-608 predicts the clinical outcome and expression of IL-6 in patients with esophageal squamous cell carcinoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4194. doi:10.1158/1538-7445.AM2013-4194