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

Abstract

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.

Association of lncRNA H19 polymorphisms with cancer susceptibility: An updated meta-analysis based on 53 studies

“…Our combined studies demonstrated a clear increase in cancer risk associated with H19 rs2839698 polymorphism in the overall and Asian population group, which contradicts the results of Wang et al (2021) and Liu et al (2020b) found no association between the H19 rs2839698 polymorphism and cancer risk neither in the overall group nor in the ethnicity subgroup. The obvious alteration of estimates of effect could be due to increased sample size, given that the 13 newly included studies accounted for 27.18% of individuals.…”

“… Liu et al (2020b) found that rs217727 is associated with increased cancer risk in the overall and Asian populations. However, our updated meta-analysis is more supportive of Wang’s study that no effect was detected between rs217727 polymorphism and cancer susceptibility in the general population and ethnicity subgroup ( Wang et al, 2021 ). This difference may result from 18 new articles included in our study.…”

“…In the previous meta-analysis, no association was found between the rs2735971 polymorphism and cancer risk in any genetic models Wang et al, 2021). However, we added five recently published articles and deleted studies using overlapping data and small sample sizes, finding that the A allele or AA genotype is a potential genetic marker for gastrointestinal tumors.…”

“…Besides, H19 mutation may produce antisense RNA 91H accumulating in breast cancer cells and regulate the expression of insulin growth factor 2 (IGF2) ( Berteaux et al, 2008 ), thereby affecting oncogene and tumor suppressor gene expression. Previously, several meta-analyses have investigated the correlation between H19 polymorphisms and tumorigenesis, and no definitive conclusion has been drawn on this causal relationship ( Liu et al, 2020a ; Liu et al, 2020b ; Wang et al, 2021 ). Here, we look forward to obtaining more effective evidence to precisely estimate their association and draw a more reliable conclusion.…”

“…Both PCR-RFLP and TaqMan have high confidence in the analysis of gene polymorphism due to their respective merits ( Hubáček et al, 2015 ). In addition, Wang’ meta-analysis pointed out that there was a significant correlation between rs217727 polymorphism and the HB control group when subgroup analysis by a source of controls was performed ( Wang et al, 2021 ). Nevertheless, crucial results were found concentrated in the HB control group in the rs3741219 locus in our study.…”