Let-7 microRNA-binding-site Polymorphism in the 3'UTR of KRAS and Colorectal Cancer Outcome: A Systematic Review and Meta-Analysis

Cancer Med. 2014 Oct;3(5):1385-95. doi: 10.1002/cam4.279. Epub 2014 Jun 2.

Abstract

There is a small but growing body of literature regarding the predictive utility of a Let-7 microRNA-binding-site polymorphism in the 3'-untranslated region (UTR) of KRAS (KRAS-LCS6) for colorectal cancer outcome, although the results are conflicting. We performed a review and meta-analysis in an attempt to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on KRAS let-7 microRNA-binding site polymorphism (LCS6; rs61764370) and colorectal cancer outcome. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or estimated from each manuscript. Log HRs and log CIs were combined across studies using the inverse-variance weight to calculate fixed- and random-effects summary estimates and corresponding 95% CIs for overall and progression-free survival. We did not observe any significant association between overall or progression-free survival, neither when considering all colorectal cancer patients nor for subgroup analyses (metastatic, anti-EGFR [epidermal growth factor receptor] treatment, or KRAS wild type). There was substantial heterogeneity across studies, overall and among subgroups analyzed. We have found no clear evidence to support an association between the KRAS-LCS6 genotype and overall or progression-free survival among colorectal cancer patients, even after conducting subgroup analyses by stage and anti-EGFR treatment status. This information helps to clarify the confusing body of literature regarding the clinical implications of the KRAS-LCS6 genetic variant on colorectal cancer outcomes, indicating that it should not be used at the present time to personalize therapeutic strategies (PROSPERO registration number: CRD42013005325).

Keywords: Cetuximab; lcs6; prognosis; progression; rs61764370; survival.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Review
  • Systematic Review

MeSH terms

  • 3' Untranslated Regions*
  • Binding Sites*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality*
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Patient Outcome Assessment
  • Proportional Hazards Models
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / chemistry
  • ras Proteins / genetics*

Substances

  • 3' Untranslated Regions
  • KRAS protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • mirnlet7 microRNA, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins