Since 2009, there have been 2 genome-wide association (GWA) studies reporting functional variants that were significantly associated with susceptibility to esophageal cancer in the Japanese population.24,25 The first GWA study identified 4q21-23 and 12q24 as susceptibility loci, in which 2 functional variants in ADH1B and ALDH2 showed significant associations with ESCC risk (Table 3).24ADH1B and ALDH2 are crucial in the metabolism of alcohol. This evidence concerns the gene ADH1B and esophageal squamous cell carcinoma.