Abstract

BackgroundMicroRNAs (miRNAs) negatively regulate the 3′ untranslated region (3′-UTR) of coding genes by suppressing translation or degrading mRNAs, and they act as oncogenes or tumor suppressors. Recently, several studies investigated the association between pre-miR-27a rs895819 polymorphism and the risks of various cancers, but the results were inconsistent.Methodology/Principal FindingsWe conducted a meta-analysis of 13 studies that included 6501 cancer cases and 7571 controls to address this association. Overall, this meta-analysis showed that the pre-miR-27a rs895819 A/G polymorphism was not statistically associated with cancers risk in all genetic models. In the stratified analysis by cancer types, when compared with the ancestral A allele, individuals with the variant G allele was consistently associated with reduced risks of breast cancer (OR = 0.92, 95% CI = 0.85–0.99), renal cell cancer (OR = 0.81, 95% CI = 0.67–0.97) and nasopharyngeal cancer (OR = 0.84, 95% CI = 0.72–0.97). Inversely, individuals with the heterozygote AG was associated with an increased risk of digestive tract cancers compared with AA genotype (AG vs. AA: OR = 1.16, 95% CI = 1.01–1.32). In the stratified analysis by ethnicity, the pre-miR-27a rs895819 polymorphism showed statistically significant association with decreased risks of cancers in Caucasians (G vs. A allele: OR = 0.90, 95% CI = 0.83–0.97; AG vs. AA: OR = 0.84, 95% CI = 0.75–0.94; AG/GG vs. AA: OR = 0.85, 95% CI = 0.76–0.94) but not in Asians.Conclusion/SignificanceThis meta-analysis suggests that the pre-miR-27a rs895819 polymorphism may contribute to the susceptibilities of some specific-type of cancers, including breast cancer, renal cell cancer, nasopharyngeal cancer and digestive tract cancers, as well as the susceptibilities of cancers in Caucasians to some extent.

Highlights

  • MicroRNAs are RNAs that are 18–23 nucleotides long that participate in the transcriptional regulation of eukaryotic genes [1], which is associated with post-transcriptional modifications that lead to the mRNA’s degradation or the translational repression of the targeted genes [2]. miRNA genes are transcribed to a hairpin-shaped RNA form named pri-miRNA [3], which is processed by an endonuclease, Drosha, to form a pre-miRNA that is 60–70 nucleotides long [4]

  • Our research group provided this meta-analysis with a set of unpublished data regarding the association between rs895819 polymorphism and gastric cancer risk

  • A total of 13 case-control studies extracted from 11 articles and a set of our unpublished data that met our inclusion criteria were included in the final meta-analysis [18,19,20,21,22,23,24,37,38,39,40], which consisted of 6501 cancer cases and 7571 cancer-free controls

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Summary

Introduction

MicroRNAs (miRNAs) are RNAs that are 18–23 nucleotides long that participate in the transcriptional regulation of eukaryotic genes [1], which is associated with post-transcriptional modifications that lead to the mRNA’s degradation or the translational repression of the targeted genes [2]. miRNA genes are transcribed to a hairpin-shaped RNA form named pri-miRNA [3], which is processed by an endonuclease, Drosha, to form a pre-miRNA that is 60–70 nucleotides long [4]. The miR-27a rs895819 A/G polymorphism is located in the loop of the pre-miRNA, and the variation from A to G could cause a change in the minimum free energy (MFE). This SNP may affect the function of the miRNA to some extent. 13 datasets consisted of 6501 cases with cancers and 7571 controls were included in our study These data should be combined to expand our understanding of the pre-miR-27a rs895819 SNP, which may provide some evidence for the future research. Several studies investigated the association between pre-miR-27a rs895819 polymorphism and the risks of various cancers, but the results were inconsistent

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