Let‐7 microRNA‐binding‐site polymorphism in the 3′UTRofKRASand 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).