Fig. 1.

Reflection of past exposure to carcinogens in genetic and epigenetic alterations. a Reflection in the mutational signature. Exposure to a carcinogen induces a specific mutation signature (adapted from Alexandrov et al.⁷). b Reflection in methylated gene profiles. A different set of genes are aberrantly methylated depending on the tissue types and possibly on the inducers. Unexpressed genes are different among tissues, and specific genes are susceptible to methylation induction in individual tissues, such as Genes A, B, and C in the esophagus, Genes D, E, F, and G in the stomach, and Genes H, I, J, K, and L in the liver. Even among liver-specific susceptible genes, genes are methylated reflecting the cause of inflammation, such as Genes H and I by HBV infection, Genes J and K by HCV infection, and Gene L by alcohol