Evaluation of common genetic variants in pre-microRNA in susceptibility and prognosis of esophageal cancer

Meenakshi Umar, Rohit Upadhyay, Garima Prakash, Shaleen Kumar, Uday Chand Ghoshal, Balraj Mittal

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26 Citations (Scopus)

Abstract

Genetic variants in micro-RNAs (miRNA) have been shown to affect progression, diagnosis, and prognosis of various malignancies; however, their role in esophageal squamous cell carcinoma (ESCC) susceptibility is controversial. Therefore, we aimed to determine role of common genetic variants in cancer related pre-miRNA in susceptibility and survival outcome of north Indian ESCC patients. We genotyped four common polymorphisms in pre-miRNA: mir-196a-2C>T, mir-146aG>C, mir-499T>C, and mir-423C>A in 289 incident ESCC cases (including 153 follow-up cases) and 309 controls using PCR/PCR RFLP-based methods. Binary logistic regression was applied for risk estimation, while Kaplan-Meier and Cox Regression tests were performed for survival analysis. We observed that none of the pre-miRNA genetic variants were associated with ESCC or its clinical phenotypes independently, however, combined risk genotypes of four pre-miRNA polymorphisms increased risk of ESCC in dose-response manner (Ptrend=0.011). Specifically, patients with 2-4 risk genotypes of pre-miRNA polymorphisms had 1.4-fold higher risk of ESCC compared to patients with 0-1 risk genotypes (OR=1.43, 95% CI=1.02-1.09, P-value=0.037). The risk was more pronounced in ESCC cases with upper-third esophageal tumors. Moreover, cumulative but not independent effect of risk genotypes of pre-miRNA polymorphisms was observed on survival outcome of ESCC patients. Cases with 2-4 risk genotypes had significantly lower median survival (11.60 vs. 30.2 months) and 2.3-fold greater hazard of death compared to patients with 0-1 risk genotypes. In conclusion, the four studied common pre-miRNA polymorphisms cumulatively affect susceptibility and survival of ESCC patients in north Indian population.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalMolecular Carcinogenesis
Volume52
Issue numberSUPPL1
DOIs
Publication statusPublished - 1 Jan 2013

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Keywords

  • ESCC
  • Esophageal cancer
  • MiRNA
  • Polymorphism
  • Prognosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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