Epigenetic epidemiology of gastric cancer

为了确定血液白细胞DNA的甲基化状态是否可以作为癌症易感性的替代标志物，我们定量测定了299例胃癌病例和299例年龄和性别匹配的对照组中IGF-2和TUSC 3的甲基化水平。胃癌患者外周血白细胞DNA中IGF 2甲基化水平显著低于健康对照组，且随着IGF 2甲基化水平的降低，胃癌发生的危险性有明显增加的趋势。IGF 2高甲基化患者的生存率明显高于IGF 2低甲基化患者，提示IGF 2甲基化水平不仅可作为胃癌易感性的预测指标，而且可作为胃癌预后的预测指标。与此相反，血液白细胞DNA中的TUSC 3甲基化水平在病例中高于健康对照，但差异不显著。分析了参与者过去的生活方式和临床病理特征与甲基化水平的任何关系。随着年龄的增长和吸烟，IGF 2和TUSC 3甲基化在血液白细胞DNA中分别减少和增加。H.幽门螺杆菌抗体与血液白细胞DNA中TUSC 3的高甲基化状态显著相关。提示白细胞DNA中IGF-2和TUSC 3甲基化水平可作为胃癌易感性的一个重要替代指标。

To determine whether or not the methylation status of blood leukocyte DNA can be used as a surrogate marker of the liability for cancer, we quantitatively determined the methylation levels of IGF-2 and TUSC3 in 299 gastric cancer cases, and 299 age- and gender-matched controls. The IGF2 methylation levels in blood leukocyte DNA of the cases were significantly lower than those of the healthy controls and there was a significant trend of increasing gastric cancer risk with decreasing methylation level of IGF2. Patients with hypermethylated IGF2 in blood leukocyte DNA showed a significantly better survival rate than those with hypomethylated IGF2, indicating that the IGF2 methylation level in blood leukocyte DNA can be a predictive marker not only of the liability for but also of the prognosis of gastric cancer. In contrast, the TUSC3 methylation level in blood leukocyte DNA was higher in the cases than in the healthy controls, but the difference was not significant. The past lifestyle and clinicopathological characteristics of the participants were analyzed as to any relationship with the methylation level. With aging and smoking, methylation of IGF2 and TUSC3 decreased and increased in blood leukocyte DNA, respectively. The presence of H. pylori antibodies was significantly associated with a higher methylation status of TUSC3 in blood leukocyte DNA. These results indicate that the methylation levels of IGF-2 and TUSC3 in blood leukocyte DNA may be used as an important surrogate marker of the liability for gastric cancer.