Abstract
MicroRNA-27a is highly expressed in cancers and has been identified as an oncogenic microRNA. A genetic variant in pre-miR-27a (rs895819) with a transition of A to G has been demonstrated to be associated with cancer risk; however, the results of these studies remain conflicting rather than conclusive. Therefore, we performed a meta-analysis to derive a more precise estimation. Through searching PubMed or other databases up to March 2014 using the following MeSH terms and keywords, "miR-27a", "polymorphism" and "cancer", seventeen case-control studies were identified in this meta-analysis, including 7,813 cases and 9,602. Crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to investigate the association strength between rs895819 and the susceptibility of cancer. The results of the overall meta-analysis did not suggest any association between rs895819 polymorphism and cancer susceptibility, and this remained in Asians as a sub- group. In Caucasians, however, the rs895819 was associated with a reduced cancer risk in heterozygous (OR, 0.83; 95%CI, 0.75-0.93) and dominant models (OR, 0.84; 95%CI, 0.76-0.93), and the [G] allele of rs895819 showed a protective effect (OR, 0.90, 95%CI, 0.84-0.97). Further studies showed a significant association between the [G] allele of rs895819 and decreased risk of breast cancer (0.91; 95%CI, 0.85-0.98), and stratified analyses indicated a protective effect of the [G] allele in Caucasians (OR, 0.89; 95%CI, 0.82-0.98), younger breast cancer cases (OR, 0.87; 95%CI, 0.79-0.96), and in the group of unilateral breast cancer patients (OR, 0.90; 95%CI, 0.83-0.97). These findings suggest an association between pre-miR-27a polymorphism rs895819 and cancer risk in Caucasians. The protective effect of rs895819 [G] allele in younger breast cancer and in the group of unilateral breast cancer patients await further confirmation since the included studies in this meta-analysis were limited.
Highlights
MicroRNAs are a group of short noncoding, single-stranded RNAs with18-25 nucleotides in length, which post-transcriptionally inhibit gene expression by degradation of messenger RNA targets and block protein translations of these targets (Pasquinelli, 2012)
Characteristics of studies Twenty-five abstracts were retrieved through the search “miR-27a”, “polymorphism” and “cancer”, and eleven articles were identified as eligible studies (Sun et al, 2010; Yang et al, 2010; Catucci et al, 2012; Hezova et al, 2012; Shi et al, 2012; Zhang et al, 2012; Zhou et al, 2012; Wei et al, 2013; Zhang et al, 2013; Xiong et al, 2014; Yang et al, 2014)
We found that rs895819 polymorphism heterozygote (AG) was significantly correlated with reduced cancer risk in Caucasian (AG vs AA: odds ratios (ORs), 0.83; 95%confidence intervals (CIs), 0.75-0.93), and this association was further confirmed in dominant model (AG+GG vs AA: OR, 0.84; 95%CI, 0.76-0.93) (Table 2)
Summary
MicroRNAs (miRNAs) are a group of short noncoding, single-stranded RNAs with nucleotides in length, which post-transcriptionally inhibit gene expression by degradation of messenger RNA (mRNA) targets and (or) block protein translations of these targets (Pasquinelli, 2012). Since the initial discovery of miRNAs as essential regulators of development in the nematode Caenorhabditis elegans, thousands of miRNA genes have been identified in animal and plant genomes (Kozomara and GriffithsJones, 2011). It is well-known that miRNAs are implicated in many important biological processes such as cell proliferation, differentiation, migration, autophagy and apoptosis, etc., and disruption of miRNA function has been found to have relevance to tumorigenesis, and to neurological, cardiovascular, developmental and other diseases (Esteller, 2011). SNPs in miRNAs or their precursors are marked as novel genetic variations which may modify the cancer susceptibilities (Chen et al, 2008)
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