评价饮食因素、CagA 阳性幽门螺杆菌感染与胃癌组织中 RUNX3 启动子高甲基化之间的关系。
Evaluation of the relationship between dietary factors, CagA-positive Helicobacter pylori infection, and RUNX3 promoter hypermethylation in gastric cancer tissue.
机构信息
Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Cheongju 361-763, South Korea.
出版信息
World J Gastroenterol. 2013 Mar 21;19(11):1778-87. doi: 10.3748/wjg.v19.i11.1778.
AIM
To evaluate the relationship among Helicobacter pylori (H. pylori) infection, CagA status, and dietary factors with RUNX3 promoter hypermethylation.
METHODS
Gastric cancer tissue samples were collected from 184 South Korean patients. All patients were interviewed following a semi-quantitative food frequency questionnaire. The average frequencies of intake and portion sizes of 89 common food items were documented, and total intakes of calories, nutrients, vitamins, and minerals were calculated for each subject. DNA was extracted from gastric cancer tissue samples, and amplification of the HSP60 gene was performed to detect H. pylori infection. Nested polymerase chain reaction (PCR) was used to detect the presence of the CagA gene. RUNX3 gene expression was measured by reverse transcription-PCR, and RUNX3 methylation status was evaluated by methylation-specific PCR. The odds ratios (ORs) and 95%CI associated with RUNX3 promoter hypermethylation status were estimated for each of the food groups, lifestyle factors, and the interaction between dietary and lifestyle factors with CagA status of H. pylori infection.
RESULTS
Overall, 164 patients (89.1%) were positive for H. pylori DNA, with the CagA gene detected in 59 (36%) of these H. pylori-positive samples. In all, 106 (57.6%) patients with gastric cancer demonstrated CpG island hypermethylation at the RUNX3 promoter. RUNX3 expression was undetectable in 52 (43.7%) of the 119 gastric cancer tissues sampled. A high consumption of eggs may increase the risk of RUNX3 methylation in gastric cancer patients, having a mean OR of 2.15 (range, 1.14-4.08). A significantly increased OR of 4.28 (range, 1.19-15.49) was observed with a high consumption of nuts in patients with CagA-positive H. pylori infection. High intakes of carbohydrate, vitamin B1, and vitamin E may decrease the risk of RUNX3 methylation in gastric cancer tissue, particularly in CagA- or H. pylori-negative infection, with OR of 0.41 (0.19-0.90), 0.42 (0.20-0.89), and 0.29 (0.13-0.62), respectively. A high consumption of fruits may protect against RUNX3 methylation.
CONCLUSION
These results suggest that the CagA status of H. pylori infection may be a modifier of dietary effects on RUNX3 methylation in gastric cancer tissue.
目的
评估幽门螺杆菌（H. pylori）感染、CagA 状态与饮食因素与 RUNX3 启动子甲基化之间的关系。
方法
从 184 名韩国患者中收集胃癌组织样本。所有患者均接受半定量食物频率问卷访谈。记录 89 种常见食物的平均摄入量和份量，并为每位受试者计算热量、营养素、维生素和矿物质的总摄入量。从胃癌组织样本中提取 DNA，并进行 HSP60 基因扩增以检测 H. pylori 感染。采用巢式聚合酶链反应（PCR）检测 CagA 基因的存在。通过逆转录-PCR 测量 RUNX3 基因的表达，并通过甲基化特异性 PCR 评估 RUNX3 甲基化状态。对与 RUNX3 启动子高甲基化状态相关的每种食物组、生活方式因素以及饮食与 H. pylori 感染的 CagA 状态之间的相互作用的比值比（OR）和 95%置信区间进行了估计。
结果
总体而言，164 名患者（89.1%）的 H. pylori DNA 呈阳性，其中 59 名（36%）H. pylori 阳性样本中检测到 CagA 基因。共有 106 名（57.6%）胃癌患者 RUNX3 启动子发生 CpG 岛高甲基化。在 119 个取样的胃癌组织中，52 个（43.7%）RUNX3 表达无法检测到。高鸡蛋摄入量可能会增加胃癌患者 RUNX3 甲基化的风险，其平均 OR 值为 2.15（范围为 1.14-4.08）。在 CagA 阳性 H. pylori 感染患者中，坚果的高摄入量可显著增加 4.28（范围为 1.19-15.49）的 OR。高碳水化合物、维生素 B1 和维生素 E 的摄入量可能会降低胃癌组织中 RUNX3 甲基化的风险，特别是在 CagA 阴性或 H. pylori 阴性感染中，OR 值分别为 0.41（0.19-0.90）、0.42（0.20-0.89）和 0.29（0.13-0.62）。高水果摄入量可能有助于预防 RUNX3 甲基化。
结论
这些结果表明，H. pylori 感染的 CagA 状态可能是饮食对胃癌组织中 RUNX3 甲基化影响的修饰因子。
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