DNMT1, DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis.
DNMT1, DNMT3A and DNMT3B Polymorphisms Associated With Gastric Cancer Risk: A Systematic Review and Meta-analysis.
复制标题
与胃癌风险相关的 DNMT1、DNMT3A 和 DNMT3B 多态性：系统评价和荟萃分析
DOI：
10.1016/j.ebiom.2016.10.028
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发表时间：
2016-11
期刊：
影响因子：
11.1
通讯作者：
Shi Q
中科院分区：
文献类型：
--
作者：
Li H;Li W;Liu S;Zong S;Wang W;Ren J;Li Q;Hou F;Shi Q
越来越多的研究表明，DNMTs（DNMT 1、DNMT 3A和DNMT 3B）单核苷酸多态性（SNPs）的异常改变与多种肿瘤的发生或减少有关。然而，DNMT变异与胃癌（GC）风险之间的关系仍然相互矛盾。我们的目的是评估DNMTs多态性对GC易感性的影响。首先，对DNMT 1中的rs 16999593、rs 2228611、rs 8101866，DNMT 3A中的rs 1550117、rs 13420827，DNMT 3B中的rs 1569686、rs 2424913等7个SNPs进行Meta分析。采用纯合子、杂合子、显性和隐性4种遗传模型。此外，进行了元敏感性和亚组分析，以澄清异质性来源。最后，在系统评价中列出了17个无法进行荟萃分析的SNP。纳入20项研究，13项研究可以进行荟萃分析，7项研究不能进行荟萃分析。首先，对13项研究进行荟萃分析，7个SNPs的3959例GC病例和5992例对照显示，rs 16999593位点的GC风险增加，（杂合子模型：OR 1.36，95%CI 1.14-1.61;显性模型：OR 1.36，95%CI 1.15-1.60）和rs 1550117（纯合子模型：OR 2.03，95%CI 1.38-3.00;显性模型：OR 1.20，95%CI 1.01-1.42;隐性模型：OR 1.96，95%CI 1.33-2.89），但rs 1569686（优势模型：OR 0.74，95%CI 0.61-0.90）。其余SNPs与GC风险无关。此外，亚组分析表明，对于rs 1550117和rs 1569686，在中国江苏省人群中发现了显著关联（rs1550117，OR 1.77，95%CI 1.25-2.51; rs 1569686，OR 0.48，95%CI 0.36-0.64），PCR-RFLP是发现显著关联的敏感方法（rs1550117，OR 1.77，95%CI 1.25-2.51; rs1569686，OR 0.49，95%CI 0.37-0.65）。最后，对17个SNPs的7项研究进行的系统评价表明，rs36012910，rs7560488和rs6087990可能对GC启动有潜在影响。这项荟萃分析表明，rs 16999593和rs 1550117可能有助于胃癌的风险，rs 1569686可能是一个保护因素，对胃癌的发生。利用这些SNPs作为生物标志物，可以评估胃癌的发病风险，从而制定及时的预防策略。DNMT 1、DNMT 3A和DNMT 3B基因多态性与胃癌的发生有关，其中rs 16999593和rs 1550117可能与胃癌的发生有关，rs 1569686可能是胃癌发生的保护因子。DNMTs基因多态性在江苏地区人群中尤为显著。PCR-RFLP是发现DNMTs多态性的敏感方法。遗传因素在GC风险中起着至关重要的作用。DNMTs基因与多种肿瘤的发生或减少有关。但DNMTs对胃癌的作用尚不清楚。现在我们的结果证明，两个和一个DNMT的变化与GC相关，表明从增加到减少的影响范围。利用这些变异作为生物标志物，可以估计获得GC的风险，从而制定及时的预防策略。
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. 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. 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. 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. DNMT1, DNMT3A and DNMT3B polymorphisms are associated with gastric cancer (GC) risk, in which rs16999593 and rs1550117 might contribute to GC and rs1569686 could be a protective factor against carcinogenesis. Significant DNMTs polymorphisms were particularly found in people from Chinese Jiangsu province. PCR-RFLP was a sensitive method to discover significant DNMTs polymorphisms. Research in context Genetic factors play a crucial role in GC risk. DNMTs genes were associated with occurrence or decrease of various tumors. But the effects of DNMTs on gastric cancer (GC) were not clear. Now our results proved that two and one variations in DNMTs were associated with GC, indicating a range of effects from the increased to the reduced. By using these variations as biomarkers, it is feasible to estimate the risk of acquiring GC and thus formulate timely preventive strategy.