Polymorphism of miRNA and esophageal cancer risk: an updated systemic review and meta-analysis

Background: Accumulating evidence has demonstrated that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) (referred to as miR-SNPs) participate in the process of carcinogenesis by altering the expression and structure of mature miRNAs. However, the associations between several previously reported miR-SNPs, including miR-196a2 rs11614913, miR-146a rs2910164, miR-34b/c rs4938723, and miR-423 rs6505162 and the susceptibility of esophageal squamous cell carcinoma (ESCC) remain controversial. We, therefore, performed a comprehensive meta-analysis to systemically evaluate the correlation of genetic polymorphisms in these four miRNAs with the risk of ESCC. Methods: Relevant studies were searched in PubMed and other electronic databases up to August 2018, supplemented by a manual search of references from retrieved articles. The pooled ORs with 95% CIs were calculated using a random-effects model. Results: A total of 22 studies from 13 published articles were included in the meta-analysis. All studies have a relatively high score of quality assessment. The pooled analysis indicated that individuals with the variant TT genotype of rs11614913 in miR-196a2 gene have a significantly decreased risk of ESCC compared with CC genotype (OR =0.83, 95% CI: 0.73-0.95). The decreased risk of ESCC was also shown in the recessive model (TT vs CT/CC: OR=0.86, 95%CI: 0.77-0.96) and allele model (T vs C: OR=0.93, 95%CI: 0.87-0.99). The significantly reduced risk of ESCC was also observed in the polymorphisms of the miR-34b/c rs4938723 locus. The similar tendency was presented in the subgroup of Chinese Han population when stratified by ethnicity. However, no significant associations were observed in the miR-146a rs2910164 and miR-423 rs6505162 with the susceptibility of ESCC in any genetic model. Conclusion: Our results suggested that the polymorphisms of miR-196a and miR-34b/c genes were related to the risk of ESCC, especially among Chinese. The findings of this study, however, need to be confirmed in further researches.