Association of Three micro-RNA Gene Polymorphisms with the Risk of Cervical Cancer: A Meta-Analysis and Systematic Review

Abstract

\n Objective: Regulation of single nucleotide polymorphisms (SNP) in micro-RNA (miRNA) on the host cells may be one of the most important factors influencing the occurrence of cervical cancer based on the prevalence of HPV infection and the development of cervical cancer. In order to explore the contribution of miRNA polymorphism to the occurrence and development of cervical cancer, we conducted an analytical study. Methods: We selected the polymorphisms of three widely studied miRNAs (miRNA-146a rs2910164, miRNA-499 rs3746444 and miRNA-196a2 rs11614913). Then we conducted a meta-analysis (for the first time) to investigate their susceptibility to cervical cancer. Case control studies on the correlation between these three miRNAs and cervical cancer susceptibility were investigated by searching on from Pubmed, The Cochrane Library, Embase, CBM, CNKI, Wanfang database and VIP database. Basic characteristics were recorded and meta-analysis of the case studies was performed using STATA 15.1 software. Results: The miRNA-146a rs2910164 mutation significantly reduced the risk of cervical cancer in both recessive model (OR= 0.804, 95%CI= 0.652-0.992, P= 0.042；CC vs. CG+GG) and allelic model (OR= 0.845, 95%CI= 0.721-0.991, P= 0.038；C vs. G). There was no significant correlation between miRNA -499 rs3746444 and the risk of cervical cancer. The miRNA -196a2 rs11614913 mutation was significantly associated with a reduced risk of cervical cancer in homozygous model (OR= 0.641, 95%CI= 0.447-0.919, P= 0.016；TT vs. CC), dominant model (OR= 0.795, 95%CI= 0.636-0.994, P= 0.045；CT+TT vs. CC), recessive model (OR= 0.698, 95%CI= 0.532-0.917, P= 0.01；TT vs. CC+CT), and allelic models (OR= 0.783, 95%CI= 0.643-0.954, P= 0.015；T vs. C). Conclusion: In summary, this meta-analysis shows that the mutant genotypes of miRNA -146a rs2910164 and miRNA -196a2 rs11614913 are associated with a reduced risk of cervical cancer. Therefore, they may be two gene regulatory points for the prevention of cervical cancer.PROSPERO Registration number: CRD42021270079.