Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers
Higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers
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DOI：
10.1158/1055-9965.epi-06-0436
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发表时间：
2006-11-01
影响因子：
3.8
通讯作者：
Saito, Daizo
中科院分区：
文献类型：
--
作者：
Nakajima, Takeshi;Maekita, Takao;Saito, Daizo
背景资料：幽门螺杆菌感染可诱导胃粘膜CpG岛甲基化，在幽门螺杆菌活动后，CpG岛甲基化水平降低。幽门螺杆菌感染停止。非癌性胃粘膜H.幽门螺杆菌阴性的胃癌患者的甲基化水平高于幽门螺杆菌阴性的胃癌患者。幽门阴性的健康个体。在这里，使用的情况下，多个胃癌，我们分析是否较高的甲基化水平与胃癌的高风险。方法：26名健康志愿者（HV），30例与单一高分化胃癌（S例），32例与多个高分化胃癌（M例）被招募。H. pylori感染情况用培养法进行分析。采用实时甲基化特异性PCR方法检测7个CpG岛的甲基化水平。在幽门螺杆菌阴性个体中，FLNc和HAND1甲基化水平按HV、S例和M例的顺序呈现显著增加趋势（P < 0.01，斯皮尔曼秩序检验）。M组FLNc甲基化水平显著高于S组（P < 0.01，t检验）。即使通过胃萎缩程度调整，FLNc甲基化水平仍保持显著增加趋势（P = 0.03）。相反，H. pylori阳性者在三组均有不同程度的增加。pylori阴性的个体中，胃粘膜中甲基化水平在单个胃癌病例中显著升高，并且在多个胃癌病例中更高。甲基化水平的定量分析是胃癌的一个有前途的风险标志物。
Background: Helicobacter pylori infection potently induces methylation of CpG islands in gastric mucosae, which is considered to decrease to a certain level after active H. pylori infection discontinues. Noncancerous gastric mucosae of H. pylori-negative cases with a gastric cancer had higher methylation levels than those of H. pylori-negative healthy individuals. Here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers.Methods: Twenty-six healthy volunteers (HV), 30 cases with a single well-differentiated gastric cancer (S cases), and 32 cases with multiple well-differentiated gastric cancers (M cases) were recruited. H. pylori infection status was analyzed by the culture method. Methylation levels were quantified by real-time methylation-specific PCR of seven CpG islands.Results: In H. pylori-negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P < 0.01, Spearman's rank-order test). Furthermore, the FLNc methylation level of M cases was significantly higher than that of S cases (P < 0.01, t test). Even adjusted by the extent of gastric atrophy, the FLNc methylation level retained a significant increasing trend (P = 0.03). In contrast, methylation levels in H. pylori -positive individuals were increased to various degrees in all the three groups.Conclusions: In H. pylori-negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. Quantitative analysis of methylation levels is a promising risk marker for gastric cancers.