Significant Association Between Long Non-coding RNA H19 Polymorphisms and Cancer Susceptibility: A PRISMA-compliant Meta-analysis and Bioinformatics Prediction

Background: H19, a well-known long non-coding RNA, is involved in carcinogenesis and progression of multiple cancers. Molecular epidemiological research suggests that polymorphisms in H19 are associated with an increased risk of cancer, but the results are inconsistent. Thus, we performed a meta-analysis to estimate the associations between H19 polymorphisms and cancer susceptibility.

Methods: PubMed, Embase, and Web of Science databases were searched. Odds ratios with 95% confidence interval were applied to assess the association between H19 rs2107425, rs217727, rs2839698, rs2735971, rs3024270, and rs3741219 polymorphisms and cancer susceptibility in all 5 models. We also predicted the H19 secondary structure, as well as the generation and abolishment of miRNA binding sites on H19 through the selected SNPs.

Results: Eighteen related studies, involving 17,090 patients and 23,532 control samples, were analyzed. The pooled data showed that rs2839698 polymorphism was significantly associated with an increased cancer susceptibility. As for rs217727 and rs3024270 polymorphisms, similarly increased risks were found in specific genetic models and stratified groups. However, significant decreases in cancer risk were observed for rs2107425 and rs2735971 in the total population, as well as in subgroup analyses. In addition, no significant associations were found in all 5 models for rs3741219 polymorphism. Furthermore, RNAfold prediction revealed that the centroid secondary structure was markedly altered in rs217727 and rs2735971. We also identified that rs217727 G>A and rs2839689 G>A alleles could create and destroy miRNA binding sites on H19.

Conclusion: The results of our meta-analyses suggest that H19 polymorphisms may be associated with the risk of cancer development.