Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang, China.
Helicobacter. 2019 Oct;24(5):e12650. doi: 10.1111/hel.12650. Epub 2019 Jul 30.
Peripheral blood leukocyte DNA methylation status has been proposed to be a surrogate marker for evaluating susceptibility to gastric cancer (GC). Helicobacter pylori (H pylori) infection, smoking, and alcohol consumption are known to induce gene methylation. A case-control study was performed to investigate the interactions between the methylation of two candidate genes and H pylori infection, smoking, and alcohol consumption in the risk of GC.
A total of 400 GC cases and 402 controls were included in this study. The methylation status of WT1 and IGF2 was semiquantitatively determined by using methylation-sensitive high-resolution melting assays. H pylori IgG antibodies were detected by ELISA method.
Based on the area under the curve (AUC), 0% methylated DNA and 0.5% methylated DNA were used as the cutoff values for WT1 and IGF2, respectively. WT1 methylation was significantly associated with increased GC risk (OR = 1.65, 95% CI = 1.09-2.51, P = .019), especially in males (OR = 1.80, 95% CI: 1.10-2.95, P = .019) and older individuals (≥60 years) (OR = 2.03, 95% CI: 1.15-3.57, P = .014). A significant combination was observed between WT1 methylation and H pylori infection, alcohol consumption, and smoking for the risk of GC (OR = 2.28, 95% CI = 1.47-3.55, P = .003, OR = 2.19, 95% CI = 1.37-3.51, P = .001, OR = 2.21, 95% CI = 1.39-3.51, P = .001, respectively). However, no association between IGF2 methylation and the risk of GC was found in this study.
WT1 methylation may serve as a new potential biomarker for GC susceptibility and can combine with H pylori infection, smoking, and alcohol consumption to influence GC risk.
外周血白细胞 DNA 甲基化状态被认为是评估胃癌（GC）易感性的替代标志物。已知幽门螺杆菌（H pylori）感染、吸烟和饮酒会诱导基因甲基化。本病例对照研究旨在探讨两个候选基因甲基化与 H pylori 感染、吸烟和饮酒在 GC 发病风险中的相互作用。
本研究共纳入 400 例 GC 病例和 402 例对照。采用甲基化敏感高分辨率熔解曲线分析半定量检测 WT1 和 IGF2 的甲基化状态。采用 ELISA 法检测 H pylori IgG 抗体。
基于曲线下面积（AUC），将 0%甲基化 DNA 和 0.5%甲基化 DNA 分别作为 WT1 和 IGF2 的截断值。WT1 甲基化与 GC 风险增加显著相关（OR=1.65，95%CI=1.09-2.51，P=0.019），尤其是在男性（OR=1.80，95%CI：1.10-2.95，P=0.019）和年龄较大（≥60 岁）个体中（OR=2.03，95%CI：1.15-3.57，P=0.014）。WT1 甲基化与 H pylori 感染、饮酒和吸烟对 GC 发病风险的显著组合（OR=2.28，95%CI=1.47-3.55，P=0.003，OR=2.19，95%CI=1.37-3.51，P=0.001，OR=2.21，95%CI=1.39-3.51，P=0.001）。然而，本研究未发现 IGF2 甲基化与 GC 风险之间存在关联。
WT1 甲基化可能成为 GC 易感性的一个新的潜在生物标志物，并且可以与 H pylori 感染、吸烟和饮酒相结合影响 GC 风险。
