Following the first study [12], which was conducted in the Japanese population, case control studies in Japan and Taiwan have consistently demonstrated a strong link between the risk of esophageal squamous cell carcinoma (Figure 3) and alcohol consumption in low-activity ALDH2 heterozygotes, with odds ratios (ORs) ranging from 3.7 to 18.1 after adjustment for alcohol consumption. Moreover, most studies show ORs of over 10 for increased risk in heterozygotes who are heavy drinkers [13,14]. An independent meta-analysis has also confirmed an increased risk, even among moderate drinking heterozygotes [11]. In the Japanese and Taiwanese studies, a strikingly high proportion (58%–69%) of the excessive risk for esophageal cancer is attributable to drinking by low-activity ALDH2 heterozygous individuals [13,14].
