title: DNMT1, DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis.
abstract: BACKGROUND
  Increasing studies showed that abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs (DNMT1, DNMT3A and DNMT3B) were associated with occurrence or decrease of various tumors. However, the associations between DNMTs variations and gastric cancer (GC) risk were still conflicting. We aimed to assess the effect of DNMTs polymorphisms on the susceptibility to GC.
  
  
  METHODS
  Firstly, we did a meta-analysis for 7 SNPs (rs16999593, rs2228611, rs8101866 in DNMT1, rs1550117, rs13420827 in DNMT3A, rs1569686, rs2424913 in DNMT3B). Four genetic models (homozygote, heterozygote, dominant and recessive model) were used. Moreover, a meta-sensitivity and subgroup analysis was performed to clarify heterogeneity source. Lastly, 17 SNPs that couldn't be meta-analyzed were presented in a systematic review.
  
  
  RESULTS
  20 studies were included, 13 studies could be meta-analyzed and 7 ones could not. Firstly, a meta-analysis on 13 studies (3959 GC cases and 5992 controls) for 7 SNPs showed that GC risk increased in rs16999593 (heterozygote model: OR 1.36, 95%CI 1.14-1.61; dominant model: OR 1.36, 95%CI 1.15-1.60) and rs1550117 (homozygote model: OR 2.03, 95%CI 1.38-3.00; dominant model: OR 1.20, 95%CI 1.01-1.42; recessive model: OR 1.96, 95%CI 1.33-2.89) but decreased in rs1569686 (dominant model: OR 0.74, 95%CI 0.61-0.90). The remaining SNPs were not found associated with GC risk. Furthermore, the subgroup analysis indicated that for rs1550117 and rs1569686, the significant associations were particularly found in people from Chinese Jiangsu province (rs1550117, OR 1.77, 95%CI 1.25-2.51; rs1569686, OR 0.48, 95%CI 0.36-0.64) and that PCR-RFLP was a sensitive method to discover significant associations (rs1550117, OR 1.77, 95%CI 1.25-2.51; rs1569686, OR 0.49, 95%CI 0.37-0.65). Lastly, a systematic review on 7 studies for 17 SNPs suggested that rs36012910, rs7560488 and rs6087990 might have a potential effect on GC initiation.
  
  
  CONCLUSIONS
  This meta-analysis demonstrated that rs16999593 and rs1550117 could contribute to GC risk and that rs1569686 might be a protective factor against gastric carcinogenesis. By using these SNPs as biomarkers, it is feasible to estimate the risk of acquiring GC and thus formulate timely preventive strategy.
authors: Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
authors: Hongjia
authors: H
authors: Li
authors: Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
authors: Wen
authors: W
authors: Li
authors: Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
authors: Shanshan
authors: S
authors: Liu
authors: Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
authors: Shaoqi
authors: S
authors: Zong
authors: Fudan University School of Public Health, Shanghai 200032, China.
authors: Weibing
authors: W
authors: Wang
authors: Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
authors: Jianlin
authors: J
authors: Ren
authors: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Qi
authors: Q
authors: Li
authors: Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China. Electronic address: fghou555@126.com.
authors: Fenggang
authors: F
authors: Hou
authors: Oncology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China. Electronic address: stevenshi_qi@hotmail.com.
authors: Qi
authors: Q
authors: Shi
mesh_terms: D000483:Alleles; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics*; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human
keywords: DNA methyltransferase; Gastric cancer; Meta-analysis; Single nucleotide polymorphism; Systematic review