In normal esophageal squamous epithelium, variants in NOTCH1-3, FAT tumor suppressor homolog 1, zinc finger protein 36 like 2, protein phosphatase, Mg2+/Mn2+ dependent 1D, checkpoint kinase 2, and paired box gene 9 were more common than in ESCC. Here, CHEK2 is linked to esophageal squamous cell carcinoma.