Abstract
BackgroundMicroRNAs (miRNAs) negatively regulate the gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between single nucleotide polymorphism (SNP) in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies.Methodology/Principal FindingsAn updated meta-analysis based on 15 independent case-control studies consisting of 4999 cancer patients and 7606 controls was performed to address this association. It was found that miR-196a2 polymorphism significantly elevated the risks of digestive system cancers (CT vs. TT, OR = 1.25, 95% CI = 1.07–1.45; CC vs. TT, OR = 1.38, 95% CI = 1.13–1.67; CC/CT vs. TT, OR = 1.29, 95% CI = 1.10–1.50; CC vs. CT/TT, OR = 1.14, 95% CI = 1.01–1.30; C vs. T, OR = 1.15, 95% CI = 1.05–1.26). We also found that variant in miR-196a2 increased the susceptibility of colorectal cancer (CRC) (CT vs. TT, OR = 1.23, 95% CI = 1.04–1.44; CC vs. TT, OR = 1.32, 95% CI = 1.08–1.61; CC/CT vs. TT, OR = 1.25, 95% CI = 1.07–1.46; C vs. T, OR = 1.15, 95% CI = 1.05–1.28), while the association in recessive model (CC vs. CT/TT, OR = 1.16, 95% CI = 0.98–1.38) showed a marginal significance. Additionally, significant association between miR-196a2 polymorphism and increased risk of hepatocellular cancer (HCC) was detected. By stratifying tumors on the basis of site of origin, source of controls, ethnicity and allele frequency in controls, elevated cancer risks were observed.Conclusion/SignificanceOur findings suggest the significant association between miR-196a2 polymorphism and increased susceptibility of digestive system cancers, especially of CRC, HCC and Asians. Besides, C allele may contribute to increased digestive cancer risks.
Highlights
MicroRNAs are endogenous, small non-coding and have a length of 18–25 nucleotides RNAs. miRNAs can interact with messenger RNAs by binding to 39 un-translated regions (UTRs) and lead to the degradation or translational repression of mRNAs
Conclusion/Significance: Our findings suggest the significant association between miR-196a2 polymorphism and increased susceptibility of digestive system cancers, especially of colorectal cancer (CRC), hepatocellular cancer (HCC) and Asians
To improve the efficiency of metaanalysis on digestive cancers and reduce the potential betweenstudy heterogeneity which might derive from various cancers in diverse systems, we focused on digestive system cancers only and added more recent publications on CRC [14,15,16] and HCC [17] in this study
Summary
MicroRNAs (miRNAs) are endogenous, small non-coding and have a length of 18–25 nucleotides RNAs. miRNAs can interact with messenger RNAs (mRNAs) by binding to 39 un-translated regions (UTRs) and lead to the degradation or translational repression of mRNAs. Studies revealed that miRNAs played key roles in various biological processes including cell growth regulation, differentiation, apoptosis and tumorigenesis [1,2,3]. SNPs in miRNAs are marked as novel genetic variations which may modify the cancer susceptibilities [8]. Metaanalysis on breast cancer, lung cancer and other cancers revealed that rs11614913 was a functional SNP and had potential ability to modify the cancer risks [9,10,11,12,13]. The association between single nucleotide polymorphism (SNP) in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies
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