Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients

Carcinogenesis. 2015 Jan;36(1):82-6. doi: 10.1093/carcin/bgu224. Epub 2014 Nov 3.

Abstract

Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. It is routinely cured by a 5-fluorouracil (5-FU)-based chemotherapy which improves outcomes in patients. We investigated the effect of single nucleotide polymorphisms (SNPs) in two microRNA (miRNA)-encoding genes that have been previously reported as important in prognosis in patients with stage III CRC and treated with 5-FU-based chemotherapy. Two SNPs (rs4919510 in miR-608 and rs213210 in miR-219-1) were genotyped in 1083 CRC patients recruited in the Czech Republic to evaluate their effect on clinical outcomes. Carriers of the variant T allele in rs213210 and receiving 5-FU chemotherapy were associated with a significantly worse survival [hazard ratio (HR) = 2.18; 95% confidence interval (CI): 1.20-3.98; adjusted P = 0.01] and an increased risk of relapse (HR = 1.94; 95% CI: 1.16-3.25; adjusted P = 0.01). After further stratification for tumor grading, stage III patients carrying the G allele of rs4919510 and undergoing adjuvant chemotherapy were at decreased risk of relapse (HR = 0.44; 95% CI: 0.20-0.94; adjusted P = 0.03). The present study confirms that variations in miRNA-encoding genes may be an important factor for modulating CRC prognosis and predicting therapy response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / mortality
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Female
  • Fluorouracil / therapeutic use
  • Follow-Up Studies
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Survival Rate

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers, Tumor
  • MIRN219 microRNA, human
  • MIRN608 microRNA, human
  • MicroRNAs
  • Fluorouracil