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

Mol Carcinog. 2013 Nov;52 Suppl 1:E10-8. doi: 10.1002/mc.21931. Epub 2012 Jun 12.

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. © 2012 Wiley Periodicals, Inc.

Keywords: ESCC; esophageal cancer; miRNA; polymorphism; prognosis.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / surgery
  • Case-Control Studies
  • Esophageal Neoplasms / etiology
  • Esophageal Neoplasms / mortality*
  • Esophageal Neoplasms / surgery
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Risk Factors
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • MicroRNAs