There is merging evidence suggesting that the miR-146a polymorphism might be associated with susceptibility to digestive system cancer. However, previous published studies have failed to achieve a definitive conclusion. To address this issue, an updated meta-analysis was performed.

A comprehensive electronic search was conducted using the following source to identify the eligible studies: PubMed, Embase, China BioMedicine, the Cochrane Library, and Google Scholar. Odds ratios and its corresponding 95% confidence interval (CI) was used in the quantitative synthesis.

The database search identified 1344 eligible studies, of which 32 (comprising 12,541 cases and 15,925 controls) were included. The results indicate that the miR-146a rs2910164 polymorphism was significantly associated with increased risk of digestive system cancer in heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02–1.30, P=0.02), and recessive model (GG vs. GC+CC: OR=1.11, 95% CI: 1.04–1.17, P=0.006). Subgroup analysis by cancer site revealed increased risk in gastric cancer above heterozygote comparison (GG vs. GC: OR=1.13, 95% CI: 1.02–1.25, P=0.02), and recessive model (GG vs. GC+CC: OR=1.15, 95% CI: 1.04–1.26, P=0.006). Similarly, increased cancer risk was observed in hepatocellular carcinoma when compared with homozygote comparison (GG vs. CC: OR=1.21, 95% CI: 1.04–1.42, P=0.02), heterozygote comparison (GC vs. CC: OR=1.15, 95% CI: 1.02–1.29, P=0.02), and dominant model (GG+GC vs. CC: OR=1.16, 95% CI: 1.04–1.29, P=0.009). When stratified by ethnicity and quality score, increased cancer risks were also observed among Asians, Caucasians and high quality studies subgroup.

The current study revealed that miR-146a G/C genetic polymorphism was more likely to be associated with digestive system cancer risk.