By analyzing normal esophageal mucosa, esophageal dysplasia, and ESCC, Guo et al. also found clear evidence of accumulated methylation events during ESCC progression, which included accumulation of promoter region methylation of genes MGMT, p16, BRCA1, MLH1, CDH1, RARβ2, DAPK, and APC (28, 71). This evidence concerns the gene CDH1 and esophageal squamous cell carcinoma.