title: Let-7 microRNA-binding-site polymorphism in the 3'UTR of KRAS and colorectal cancer outcome: a systematic review and meta-analysis.
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).
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Langevin
authors.forename: Brock C
authors.initials: BC
authors.lastname: Christensen
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D063868:Patient Outcome Assessment; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C487931:mirnlet7 microRNA, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: Cetuximab; lcs6; prognosis; progression; rs61764370; survival