In addition, we observed that the rate of PTCH1 mutation was significantly higher in ESCC in smokers compared with that in nonsmokers (P=0.030, one-sided Fisher's exact test), while the rates of TP53, EP300, PTCH1, NOTCH3, TGFBR2 and ZNF750 mutations were significantly higher in ESCC in drinkers than that in non-drinkers (all P<0.05, one-sided Fisher's exact test). Here, NOTCH3 is linked to esophageal squamous cell carcinoma.