Neves Marco, Ribeiro Joana, Medeiros Rui, Sousa Hugo
Molecular Oncology and Viral Pathology Group, Research Centre (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
Faculty of Medicine of University of Porto, Alameda Prof. Hernâni Monteiro, Porto, Portugal.
Porto Biomed J. 2016 Nov-Dec;1(5):164-172. doi: 10.1016/j.pbj.2016.10.005. Epub 2016 Nov 21.
Single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs) modulate protein expression and affect DNA methylation.Aberrant DNA methylation, have been associated with gastric carcinogenesis.DNMT2 rs11254413 is associated with protection for GC development.DNMT3A rs7560488, DNMT3A rs36012910 and, specially, DNMT1 rs16999593 are associated with increased susceptibility for GC development.
Epigenetics alterations, including aberrant DNA methylation, have been associated with gastric carcinogenesis. Single nucleotide polymorphisms (SNPs) in DNA methyltransferases (DNMTs) may influence protein expression and therefore affect DNA regulation and susceptibility for Gastric Cancer (GC).We have performed a systematic review and meta-analysis involving 11 studies and a total of 24 SNPs in DNMTs were analyzed. According to literature, only 4 SNPs, DNMT1 rs16999593, DNMT2 rs11254413 and DNMT3A rs7560488 and DNMT3A rs36012910, were associated with GC. DNMT1 rs16999593 and DNMT3A rs7560488C allele and DNMT3A rs36012910 G allele showed an increased risk for GC. On the other hand, DNMT2 rs11254413 G allele presented a protective effect for GC. Additionally, the meta-analysis evaluated the SNPs analyzed in more than one study ( = 6). Results revealed that only DNMT1 rs16999593 had a statistically significant association with GC development (OR = 1.31; 95% CI = 1.08-1.60; = 0.006 for TC + CC genotypes).Our study suggests that DNMT2 rs11254413, DNMT3A rs7560488, DNMT3A rs36012910 and, specially, DNMT1 rs16999593 may have an association with GC development. Nevertheless, further studies are need using different populations to clarify this association with GC risk.
DNA甲基转移酶（DNMTs）中的单核苷酸多态性（SNPs）可调节蛋白质表达并影响DNA甲基化。异常的DNA甲基化与胃癌发生有关。DNMT2 rs11254413与胃癌发生的保护作用相关。DNMT3A rs7560488、DNMT3A rs36012910，特别是DNMT1 rs16999593与胃癌发生易感性增加相关。
表观遗传学改变，包括异常的DNA甲基化，与胃癌发生有关。DNA甲基转移酶（DNMTs）中的单核苷酸多态性（SNPs）可能影响蛋白质表达，从而影响DNA调控及胃癌（GC）易感性。我们进行了一项系统评价和荟萃分析，纳入11项研究，共分析了DNMTs中的24个SNPs。根据文献，仅4个SNPs，即DNMT1 rs16999593、DNMT2 rs11254413、DNMT3A rs7560488和DNMT3A rs36012910与胃癌有关。DNMT1 rs16999593、DNMT3A rs7560488的C等位基因以及DNMT3A rs36012910的G等位基因显示胃癌风险增加。另一方面，DNMT2 rs11254413的G等位基因对胃癌有保护作用。此外，荟萃分析评估了在不止一项研究中分析的SNPs（n = 6）。结果显示，仅DNMT1 rs16999593与胃癌发生有统计学显著关联（OR = 1.31；95%CI = 1.08 - 1.60；TC + CC基因型的P = 0.006）。我们的研究表明，DNMT2 rs11254413、DNMT3A rs7560488、DNMT3A rs36012910，特别是DNMT1 rs16999593可能与胃癌发生有关。然而，需要使用不同人群进行进一步研究以阐明这种与胃癌风险的关联。
