Tobacco chewing had 4.84, 5.69, 5.28 and 6.27 folds increased risk, and smoking had 5.14, 2.67, 2.63 and 2.84 folds risk of ESCC with promoter hypermethylation of p16, DAPK, GSTP1 and BRCA1 genes respectively. The gene discussed is DAPK1; the disease is esophageal squamous cell carcinoma.