Abstract
BackgroundOwing to inconsistent and inconclusive results, we performed a meta-analysis to derive a more precise estimation of the association between miR-499 rs3746444 polymorphism and cancer risk.Methodology/Principal FindingsA systematic search of the Pubmed, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) databases was performed with the last search updated on May 6, 2012. The odds ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of the association. A total of 15 independent studies including 7,188 cases and 8,548 controls were used in the meta-analysis. In the present meta-analysis, we found a significant association between miR-499 rs3746444 polymorphism and cancer risk in the overall analysis (G versus A: OR = 1.10, 95%CI 1.01–1.19, P = 0.03; GG+AG versus AA: OR = 1.15, 95%CI 1.02–1.30, P = 0.02; GG versus AG+AA: OR = 1.07, 95%CI 0.89–1.28, P = 0.50; GG versus AA: OR = 1.13, 95%CI 0.98–1.31, P = 0.09; AG versus AA: OR = 1.16, 95%CI 1.02–1.33, P = 0.03). In the subgroup analysis by ethnicity, miR-499 rs3746444 polymorphism was significantly associated with cancer risk in Asian population. In the subgroup analysis by cancer types, miR-499 rs3746444 polymorphism was significantly associated with breast cancer.Conclusions/SignificanceThis meta-analysis suggests a significant association between miR-499 rs3746444 polymorphism and cancer risk. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.
Highlights
Cancer remains a major cause of mortality worldwide [1]
Identification of eligible studies To examine the association between miR-499 rs3746444 polymorphism and cancer risk, a systematic search of the US National Library of Medicine’s Pubmed database, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) was performed with the last search updated on May 6, 2012
We found a significant association between miR-499 rs3746444 polymorphism and cancer risk in the allelic contrast, dominant model and heterozygote comparison (G versus A: odds ratio (OR) = 1.10, 95% confidence interval (95%CI) 1.01–1.19, P = 0.03; GG+AG versus AA: OR = 1.15, 95%CI 1.02–1.30, P = 0.02; GG versus AG+AA: OR = 1.07, 95%CI 0.89–1.28, P = 0.50; GG versus AA: OR = 1.13, 95%CI 0.98–1.31, P = 0.09; AG versus AA: OR = 1.16, 95%CI 1.02– 1.33, P = 0.03)
Summary
Cancer remains a major cause of mortality worldwide [1]. Based on a new edition of the World Cancer Report from the International Agency for Research on Cancer, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008 [2]. The increased incidence rate and mortality rate lead researchers to speculate that dietary, infectious, cultural, environmental and/or genetic factors might be implicated in the etiology of the disease. There is clear evidence that genetic factors play an important role in individual predisposition to cancer [3]. MiRNAs are considered as key regulatory element in gene expression networks, which can influence many biological processes including cell differentiation, proliferation, apoptosis and tumorigenesis [5]. SNPs residing within the miRNA genes could potentially alter various biological processes by influencing the miRNA biogenesis and altering target selection [6]. Previous studies have demonstrated that altered expressions of miRNAs play critical roles in cancer development [7,8]. SNPs in miRNAs may in turn influence the individual susceptibility to cancers. Owing to inconsistent and inconclusive results, we performed a meta-analysis to derive a more precise estimation of the association between miR-499 rs3746444 polymorphism and cancer risk
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