In this study, we first examined the association between 18 potentially disruptive genetic variants of 17 genes, including alcohol dehydrogenase 4 (ADH4) and checkpoint kinase 2 (CHEK2), and ESCC risk in a Hangzhou population of 617 patients matched with 534 controls. The gene discussed is CHEK2; the disease is esophageal squamous cell carcinoma.