Alcohol and aldehyde dehydrogenase gene polymorphisms and oropharyngolaryngeal, esophageal and stomach cancers in Japanese alcoholics

Alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) gene po lymorphisms play roles in ethanol metabolism, drinking behavior and esophag eal carcinogenesis in Japanese; however, the combined influence of ADH2 and ALDH2 genotypes on other aerodigestive tract cancers have not been investi gated. ADH2/ALDH2 genotyping was performed on lymphocyte DNA samples from J apanese alcoholic men (526 cancer-free; 159 with solitary or multiple aerod igestive tract cancers, including 33 oropharyngolaryngeal, 112 esophageal, 38 stomach and 22 multiple primary cancers in two or three organs). After a djustment for age, drinking and smoking habits, and ADH2/ALDH2 genotypes, t he presence of either ADH2*1/2*1 or ALDH2*1/2*2 significantly increased the risk for oropharyngolaryngeal cancer [odds ratios (ORs), 6.68 with;ADH2*1/ 2*1 and 18.52 with ALDH2*1/2"2] and esophageal cancer (ORs, 2.64 and 13.50, respectively). For patients with both ADH2*1/2*1 and ALDH2*1/2*2, the risk s for oropharyngolaryngeal and esophageal cancers were enhanced in a multip licative fashion (OR = 121.77 and 40,40, respectively). A positive associat ion with ALDH2*1/2*2 alone was observed for stomach cancer patients who als o had oropharyngolaryngeal and/or esophageal cancer (OR = 110.58), but it w as not observed for those with stomach cancer alone. Furthermore, in the pr esence of ALDH2*1/2"2, the risks for multiple intra-esophageal cancers (OR = 3.43) and for esophageal cancer with oropharyngolaryngeal and/or stomach cancer (OR = 3.95) were higher than the risks for solitary intra-esophageal cancer and for esophageal cancer alone, but these tendencies were not obse rved for ADH2*1/2*1 genotype, Alcoholics' population attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0 % for oropharyngolar yngeal cancer and 63.9% for esophageal cancer.