Association of a genetic variant in microRNA-146a with risk of colorectal cancer: a population-based case-control study in a Chinese population

INTRODUCTION:  MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate target gene expression at the post-transcriptional level. Although recent studies have indicated that miR-146a is involved in the tumorigenesis of various types of malignancies, few studies have investigated its role in colorectal cancer.

METHODS:  In the current study, we examined the expression of miR-146a in colorectal cancer tissue and adjacent normal controls using publicly available expression profiling data. We then conducted a population-based case-control study that included 554 colorectal cancer cases and 566 matched healthy controls to assess the association of a genetic variant (rs2910164) in miR-146a with colorectal cancer susceptibility.

RESULTS:  We observed decreased expression of miR-146a in rectal cancer tissue compared to adjacent normal controls (P<0.001). Association between miR-146a rs2910164 polymorphism and risk of colorectal cancer was detected with effect modification by alcohol drinking status (P for interaction = 0.010). Among non-alcohol drinkers, individuals with CC/CG genotype had an increased risk of developing colorectal cancer compared with those carrying GG genotype (OR=1.63, 95% CI: 1.07~2.47).

CONCLUSIONS:  Our findings indicate an association between miR-146a dysregulation and colorectal cancer, suggesting that miR-146a may play a role in colorectal carcinogenesis. Further large population-based prospective studies as well as mechanistic investigations are warranted to validate our findings.