Meta-analysis of Hsa-mir-499 polymorphism (rs3746444) for cancer risk: evidence from 31 case-control studies

Abstract

BackgroundMicroRNAs (miRNAs) are a family of endogenous, small and non-coding RNAs that regulate gene expression negatively at the post-transcriptional level by suppressing translation or degrading target mRNAs, and are involved in diverse biological and pathological processes. Single nucleotide polymorphisms (SNPs) which are located in the miRNA-coding genes may participate in the process of development and diseases by altering the expression of mature miRNA. Recent studies investigating the association between hsa-mir-499 polymorphism (rs3746444) and cancer risk have yielded conflicting results.MethodsIn this meta-analysis, we conducted a search of case–control studies on the associations of SNP rs3746444 with susceptibility to cancer in electronic databases. A total of 31 studies involving 12799 cases and 14507 controls were retrieved and the strength of the association was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Hardy-Weinberg equilibrium (HWE) was assessed by the goodness-of-fit chi-square test in controls. Subgroup analyses were done by racial descent and cancer type. Publication bias of literatures was evaluated by visual inspection of funnel plots and the linear regression asymmetry test by Egger et al. Sensitivity analysis was conducted by excluding one study at a time to examine the influence of individual data set on the pooled ORs.ResultsOverall, significant association between rs3746444 polymorphism and susceptibility to cancer was identified in TC versus TT and TC/CC versus TT (dominant) models. In the stratified analyses, increased risks were found in Asians, but not in Caucasians in all comparison models tested. Moreover, significant association with an increased risk was found in Chinese population. Also, much higher significant association with increased cancer risks were found in Iranian population. In different cancer types, a decreased risk was found in esophageal cancer.ConclusionOur meta-analysis suggested that hsa-mir-499 rs3746444 T > C polymorphism is associated with the risk of cancer in Asians, mainly in Iranian and Chinese population. However, rs3746444 T > C polymorphism is negatively associated with the risk of esophageal cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-014-0126-1) contains supplementary material, which is available to authorized users.

MicroRNA Genetic Variation: From Population Analysis to Functional Implications of Three Allele Variants Associated with Cancer

“…Therefore, investigation of the relationship between genetic variants in noncoding genomic regions and gene function may help to improve our knowledge about the associations between genotypes and phenotypes. Previous studies in miRNA variation reported a high conservation of human miRNAs [Saunders et al., ; Quach et al., ]; and although several examples showing the association of miRNA genetic variants with disease have already been described [Jazdzewski et al., ; Hoffman et al., ; Jazdzewski et al., ; Xu et al., ; Xu et al., ; Lopez‐Valenzuela et al., ; Soldà et al., ; Chen et al., ; Fu et al., ; Hrdlickova et al., ; Wan et al., ; Xu et al., ; Zhou et al., ], there is still little information on the functional consequences that these genetic changes may have [Duan et al., ; Jazdzewski et al., ; Jazdzewski et al., ; Lopez‐Valenzuela et al., ; Ghanbari et al., ; Hill et al., ]. Here, we analyzed global genetic variation in miRNA regions among human populations and look for the functional differences between allele variants of three common miRNA SNVs that had repeatedly been associated with different types of cancer.…”

“…After an analysis of the global genetic variation in miRNAs, we thoroughly analyzed three miRNA SNVs associated with cancer [Chen et al., ; Fu et al., ; Wan et al., ; Xu et al., ; Zhou et al., ] located in the mature region of four miRNAs (two in the seed). miRNA overexpression experiments showed statistically significant differences in the expression between allele variants for all the analyzed SNVs, being the highest differences found in the cases of hsa‐miR‐146a‐3p and hsa‐miR‐196a‐3p (10.7 and 9.78, respectively).…”

Circulating miR-499 as a potential biomarker for acute myocardial infarction

“…miRNA-499a-5p, miR-499a-3p, miR499b are three family members exhibiting high sequence homology. Recent studies have shown that miRNA-499, which is highly conserved across species, inhibits cardiomyocyte progenitor cells proliferation and promotes cell differentiation (14). There is a positive feedback between the expression of miRNA-499 and some cardiac enriched transcription factors.…”

Cumulative evidence for association between genetic polymorphisms and esophageal cancer susceptibility: A review with evidence from meta‐analysis and genome‐wide association studies

“…For 51 SNPs identified by meta‐analysis, 38 SNPs had statistically significant association with EC or ESCC susceptibility . Meta‐analysis results showed that there were 27 SNPs associated with increased EC or ESCC risk, whereas 11 SNPs decreased the risk of EC or ESCC risk.…”