Epigenetic epidemiology of gastric cancer

为了确定血白细胞DNA甲基化状态是否可以作为癌症易感性的替代标志，我们定量检测了299例胃癌患者和299例年龄和性别匹配的对照组IGF-2和TUSC3的甲基化水平。患者外周血白细胞DNA中IGF2甲基化水平明显低于健康对照组，且随着IGF2甲基化水平的降低，患胃癌的危险性有明显增加的趋势。血白细胞DNA中IGF2高甲基化患者的生存率明显高于低甲基化IGF2患者，提示血白细胞DNA中IGF2甲基化水平不仅可以预测胃癌的易感性，而且可以预测其预后。病例组外周血白细胞DNA中TUSC3甲基化水平高于健康对照组，但差异无统计学意义。分析参与者过去的生活方式和临床病理特征，以确定是否与甲基化水平有关。随着年龄的增长和吸烟，血白细胞DNA中IGF2和TUSC3的甲基化水平分别降低和升高。幽门螺杆菌抗体的存在与血白细胞DNA中TUSC3的甲基化状态显著相关。提示血白细胞DNA中IGF-2和TUSC3的甲基化水平可作为判断胃癌易感性的重要替代指标。

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.