Epigenetic epidemiology of gastric cancer

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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.