AIM: To investigate the association between the genetic polymorphisms of ADH2 and ALDH2, lifetime alcohol consumption and esophageal cancer risk in the Taiwanese men. METHODS: Between August 2000 and June 2003, 134 pathologically-proven esophageal squamous cell carcinoma male patients and 237 male controls were recruited from Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital in southern Taiwan. ADH2 and ALDH2 polymorphisms were genotyped using PCR-RFLP. RESULTS: Compared to those with ADH2*2/*2, individuals with ADH2*l/*2 and ADH2*1/*1 had 2.28-and 7.14-fold, respectively, increased risk of developing esophageal cancer (95%CI = 1.11-4.68 and 2.76-18.46) after adjusting for alcohol consumption and other covariates. The significant increased risk was also noted among subjects with ALDH2*l/*2 (adjusted OR (AOR) = 5.25, 95%CI = 2.47-11.19), when compared to those with ALDH2*1/*1. The increased risk of esophageal cancer was made greater, when subjects carried both ADH2*1/*1 and ALDH2*1/*2, compared to those with ADH2*1/*2 or ADH2*2/*2 and ALDH2*1/*1 (AOR = 36.79, 95%CI = 9.36-144.65). Furthermore, we found a multiplicative effect of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk. CONCLUSION: Our findings suggest that polymorphisms of ADH2 and ALDH2 can modify the influence of alcoholic consumption on esophageal cancer risk. A: To investigate the association between the genetic polymorphisms of ADH2 and ALDH2, lifetime alcohol consumption and esophageal cancer risk in the Taiwanese men. METHODS: Between August 2000 and June 2003, 134 pathologically-proven esophageal squamous cell carcinoma male patients and 237 male controls were recruited from Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital in southern Taiwan. ADH2 and ALDH2 polymorphisms were genotyped using PCR-RFLP. RESULTS: Compared to those with ADH2 * 2 / * 2, individuals with ADH2 * 1 / * 2 and ADH2 The significant increased risk was also noted (* 95% CI = 1.11-4.68 and 2.76-18.46) after adjusting for alcohol consumption and other covariates. * 1 / * 1 had 2.28-and 7.14-fold, respectively, increased risk of developing esophageal cancer among subjects with ALDH2 * 1 / * 2 (adjusted OR (AOR) = 5.25, 95% CI = 2.47-11.19), when compared to those with ALDH2 * 1 / * 1. The increased risk of esophageal cancer was made greater when subjects carried bot ADH2 * 1 / * 1 and ALDH2 * 1 / * 2, compared to those with ADH2 * 1 / * 2 or ADH2 * 2 / * 2 and ALDH2 * 1 / * 1 (AOR = 36.79, 95% CI = 9.36 - 144.65). Furthermore, we found a multiplicative effect of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk. CONCLUSION: Our findings suggest that polymorphisms of ADH2 and ALDH2 can modify the influence of alcoholic consumption on esophageal cancer risk.