title: Meta-analysis of Hsa-mir-499 polymorphism (rs3746444) for cancer risk: evidence from 31 case-control studies.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are a family of endogenous, small and non-coding RNAs that regulate gene expression negatively at the post-transcriptional level by suppressing translation or degrading target mRNAs, and are involved in diverse biological and pathological processes. Single nucleotide polymorphisms (SNPs) which are located in the miRNA-coding genes may participate in the process of development and diseases by altering the expression of mature miRNA. Recent studies investigating the association between hsa-mir-499 polymorphism (rs3746444) and cancer risk have yielded conflicting results.
  
  
  METHODS
  In this meta-analysis, we conducted a search of case-control studies on the associations of SNP rs3746444 with susceptibility to cancer in electronic databases. A total of 31 studies involving 12799 cases and 14507 controls were retrieved and the strength of the association was estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Hardy-Weinberg equilibrium (HWE) was assessed by the goodness-of-fit chi-square test in controls. Subgroup analyses were done by racial descent and cancer type. Publication bias of literatures was evaluated by visual inspection of funnel plots and the linear regression asymmetry test by Egger et al. Sensitivity analysis was conducted by excluding one study at a time to examine the influence of individual data set on the pooled ORs.
  
  
  RESULTS
  Overall, significant association between rs3746444 polymorphism and susceptibility to cancer was identified in TC versus TT and TC/CC versus TT (dominant) models. In the stratified analyses, increased risks were found in Asians, but not in Caucasians in all comparison models tested. Moreover, significant association with an increased risk was found in Chinese population. Also, much higher significant association with increased cancer risks were found in Iranian population. In different cancer types, a decreased risk was found in esophageal cancer.
  
  
  CONCLUSIONS
  Our meta-analysis suggested that hsa-mir-499 rs3746444 T > C polymorphism is associated with the risk of cancer in Asians, mainly in Iranian and Chinese population. However, rs3746444 T > C polymorphism is negatively associated with the risk of esophageal cancer.
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People's Republic of China. chenchen@tjh.tjmu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People's Republic of China. yangsl_1984@126.com.|Department of Internal Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. yangsl_1984@126.com.
authors.forename: Shenglan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People's Republic of China. sandip_schaugai@hotmail.com.
authors.forename: Sandip
authors.initials: S
authors.lastname: Chaugai
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People's Republic of China. newswangyan@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine and the Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People's Republic of China. dwwang@tjh.tjmu.edu.cn.
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: C548683:MIRN499 microRNA, human; D035683:MicroRNAs