Association Between the Functional miR-146a SNP rs2910164 and Risk of Digestive System Cancer: Updated Meta-analysis

Previous association studies have linked the functional miR-146a SNP rs2910164 with risk of digestive system cancer; however, the results of these studies are inconclusive and inconsistent. The objective of the following study is to provide an up-to-date and comprehensive meta-analysis of the association of miR-146a rs2910164 and digestive system cancer risk.

We searched the PUBMED/MEDLINE and Cochrane/EBM databases. The following inclusion criteria were used for the study selection: i) Case-control studies; ii) studies with reported allelic frequency/genotype data; and iii) studies with reported association with risk of a digestive system cancer. The following exclusion criteria were used: Review article, meta-analysis, case report and case series; studies evaluating relationships of miR-146a rs2910164 with outcomes other than cancer incidence, such as cancer morbidity or mortality. Study quality was assessed using the Newcastle-Ottawa Scale and publication bias assessed graphically and numerically using Begg's funnel plot and Egger's regression test and rank test. Outcome measure was the pooled odds ratios under the allelic frequency, dominant, recessive, and over-dominant models. Subgroup analysis was conducted for country of study origin.

No association of miR-146a rs2910164 with overall risk of digestive system cancer was identified. However, subgroup analysis showed an association with overall risk in the European population in the over-dominant model. Furthermore, miR-146a rs2910164 was associated with reduced risk of gastric cancer in the dominant model (pooled odds ratio=0.91, 95% confidence intervaI=0.83-0.99), increased risk of colorectal cancer under the recessive model and reduced risk of colorectal cancer under the over-dominant model in the European population. No significant within-study or publication biases were detected.

miR-146a rs2910164 was not associated with overall risk of digestive system neoplasms. However, the GG genotype and the CC genotype may be linked to higher risk of gastric cancer and colorectal cancer, respectively; and the CG genotype may be protective against digestive system neoplasms overall in the European population, especially for colorectal cancer.