Department of Pathology and Forensic Medicine-Genetic Section, Universidade Federal do Ceará, Rua Alexandre Baraúna, 949, Porangabussu, CEP 60183-630, Fortaleza, Brazil.
Virchows Arch. 2010 Dec;457(6):627-33. doi: 10.1007/s00428-010-0996-3. Epub 2010 Oct 19.
MTHFR C677T and Helicobacter pylori infection are believed to play critical roles in the DNA methylation process, an epigenetic feature frequently found in gastric cancer. The aim of this study was to verify the associations between the MTHFR C677T polymorphism and the methylation status of three gastric cancer-related genes. The influence of H. pylori strains was also assessed. DNA extracted from 71 gastric tumor samples was available for MTHFR C677T genotyping by PCR-RFLP, promoter methylation identification by MS-PCR and H. pylori detection and posterior subtyping (cagA and vacA genes) by PCR. In the distal tumors, a positive correlation was found between the methylation of CDKN2A and the allele T carriers (r=0.357; p=0.009). Considering the eldest patients (age ≥60 years old), this correlation was even higher (r=0,417; p=0.014). H. pylori infection by highly pathogenic strains (cagA+/vacAs1m1) was also found correlated to promoter methylation of CDKN2A and the allele T carriers in distal tumors (r=0.484; p=0.026). No significant correlation was verified between MTHFR C677T genotype and promoter methylation status when we analyzed the general sample. DNA methylation in CDKN2A associated to the MTHFR 677T carrier is suggested to be a distal tumor characteristic, especially in those 60 years old or older, and it seems to depend on the infection by H. pylori cagA/vacAs1m1 strains.
亚甲基四氢叶酸还原酶 C677T 突变和幽门螺杆菌感染被认为在 DNA 甲基化过程中起关键作用，而 DNA 甲基化是胃癌中常见的一种表观遗传特征。本研究旨在验证 MTHFR C677T 多态性与三种胃癌相关基因的甲基化状态之间的关联，并评估幽门螺杆菌菌株的影响。从 71 个胃癌肿瘤样本中提取的 DNA 可用于聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行 MTHFR C677T 基因分型、MS-PCR 进行启动子甲基化鉴定以及 PCR 进行幽门螺杆菌检测和后亚分型（cagA 和 vacA 基因）。在远端肿瘤中，CDKN2A 的甲基化与等位基因 T 携带者之间存在正相关（r=0.357；p=0.009）。考虑到年龄较大的患者（年龄≥60 岁），这种相关性甚至更高（r=0.417；p=0.014）。高致病性菌株（cagA+/vacAs1m1）引起的幽门螺杆菌感染也与远端肿瘤中 CDKN2A 的启动子甲基化和等位基因 T 携带者相关（r=0.484；p=0.026）。当我们分析总样本时，未发现 MTHFR C677T 基因型与启动子甲基化状态之间存在显著相关性。CDKN2A 的 DNA 甲基化与 MTHFR 677T 携带者相关，这似乎是远端肿瘤的一个特征，尤其是在 60 岁或以上的患者中，并且似乎依赖于 cagA/vacAs1m1 菌株引起的幽门螺杆菌感染。
