Abstract
BackgroundSingle nucleotide polymorphisms (SNPs) occurred in pre-microRNAs or targets of microRNAs (miRs) may contribute to cancer risks. Since 2007, many studies have investigated the association between common SNPs located on hsa-miR-499 (rs3746444) and cancer risks; however, the results were inconclusive.Methodology/Principal FindingsWe conducted a meta-analysis of 12 studies that included 5765 cases and 7076 controls to identify the strength of association. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, individuals with the variant AG (OR = 1.215, 95% CI: 1.027, 1.437; Pheterogeneity<0.01) and AG/GG (OR = 1.227, 95% CI: 1.046, 1.439; Pheterogeneity<0.01) genotypes were associated with a significantly increased risk of cancer than those with wild AA genotype. Sub-group analysis revealed that the variant AG (OR = 1.411, 95% CI: 1.142, 1.745; Pheterogeneity = 0.01) and AG/GG (OR = 1.413, 95% CI: 1.163, 1.717, Pheterogeneity = 0.01) genotypes still showed an increased risk of cancer in Asians; however, a trend of reduced risk of cancer was observed in Caucasians (AG vs. AA: OR = 0.948, 955 CI: 0.851, 1.057, Pheterogeneity = 0.12; AG/GG vs. AA: OR = 0.959, 95% CI: 0.865, 1.064; Pheterogeneity = 0.19). Meta-regression showed that ethnicity (p = 0.048) and sample size (p = 0.02) but not cancer types (p = 0.89) or source of control (p = 0.97) were the sources of heterogeneity.ConclusionsThese meta-analysis results suggest that hsa-miR-499 polymorphism rs3746444 is associated with a significantly increased risk of cancer, especially in Asian populations.
Highlights
MicroRNAs are a kind of non-coding RNAs, about,22 nucleotides in length
It is reported that a single miRNA could bind to mRNAs of about 200 genes, miRNAs play an important role in gene regulation [3,4] and are involved in physiologic and pathologic processes [1], including tumorigenesis [5], proliferation [6], apoptosis [7], and metabolism [8]
Common single nucleotide polymorphisms (SNPs) in premiRNAs and cancer risk has been investigated by case-control studies in the last decade, and some common SNPs in premiRNAs have been demonstrated with an increased cancer risk, such as hsa-miR-196a2 rs11614913 [11,12] and hsa-miR-146a rs2910164 [11,13] polymorphisms
Summary
MicroRNAs (miRNAs) are a kind of non-coding RNAs, about ,22 nucleotides in length. Mature miRNAs target the 39 untranslated region of mRNA, leading to mRNA degradation or suppression of translation [1,2]. Common single nucleotide polymorphisms (SNPs) in premiRNAs and cancer risk has been investigated by case-control studies in the last decade, and some common SNPs in premiRNAs have been demonstrated with an increased cancer risk, such as hsa-miR-196a2 rs11614913 [11,12] and hsa-miR-146a rs2910164 [11,13] polymorphisms Another common SNP in premiRNA, rs3746444 in hsa-miR-499 (A.G), was studied in several kinds of cancer, such as breast cancer [14,15,16], liver cancer [17], cervical squamous cell cancer [18], and gastric cancer [19]. Since 2007, many studies have investigated the association between common SNPs located on hsa-miR-499 (rs3746444) and cancer risks; the results were inconclusive
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