The influence of LncRNA H19 polymorphic variants on susceptibility to cancer: A systematic review and updated meta-analysis of 28 case-control studies

Objective: Although myriad researches upon the associations between LncRNA H19 polymorphic variants (rs2839698 G>A, rs217727 G>A, rs2107425 C>T, rs2735971 A>G and rs3024270 C>G) and the susceptibility to cancer have been conducted, these results remained contradictory and perplexing. Basing on that, a systematic review and updated meta-analysis was performed to anticipate a fairly precise assessment about such associations. Methods: We retrieved the electronic databases EMBASE, PubMed and Web of Science for valuable academic studies before February 28, 2021. Ultimately, 28 of which were encompassed after screening in this meta-analysis, and the available data was extracted and integrated. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) was used to evaluate such associations. For multi-level investigation, subgroup analysis derived from source of controls together with genotypic method was preformed. Results: Eventually, 28 articles altogether embodying 57 studies were included in this meta-analysis. The results illuminated that LncRNA H19 polymorphisms mentioned above were all irrelevant to cancer susceptibility. Nevertheless, crucial results were found concentrated in population-based control group when subgroup analysis by source of controls were performed in H19 mutation rs2839698 and rs2735971. Meanwhile, in the stratification analysis by genotypic method, apparent cancer risks were discovered by TaqMan method in H19 mutation rs2107425 and rs3024270. Then, trial sequential analysis demonstrated that the results about such associations were firm evidence of effect. Conclusion: Therefore, this meta-analysis indicated that LncRNA H19 polymorphisms were not associated with the susceptibility to human cancer. However, after the stratification analysis, inconsistent results still existed in different genotypic method and source of control. Thus, more high-quality studies on cancer patients of different factors were needed to confirm these findings.