Chinese alcoholic patients with esophageal cancer are genetically different from alcoholics with acute pancreatitis and liver cirrhosis

OBJECTIVE: It is a mystery why some alcoholic patients acquire certain orga n-specific complications of alcoholism, whereas other alcoholic patients ac quire different ones. The aim of this study was to investigate the differen ces among Chinese alcoholic patients with esophageal cancer, acute pancreat itis, and liver cirrhosis by studying the genetic polymorphisms of ADH2, AD H3, ALDH2, and P4502E1. METHODS: Liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALD H2 loci and the 5'-flanking region of the P4502E1. Using the polymerase cha in reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the polymorphism of the above-mentioned alcohol metabolizing gen es in 59 alcoholics with carcinoma of the esophagus (alcoholic esophageal C a), 87 acute alcoholic pancreatitis patients, 116 alcoholics with liver cir rhosis (alcoholic cirrhosis), 19 alcoholics with both liver cirrhosis and a cute pancreatitis (alcoholic P plus C), and 241 nonalcoholic patients. RESULTS: The results showed that the allele frequency of ALDH2*2 was signif icantly higher in the alcoholic esophageal Ca group than in the alcoholic p ancreatitis and alcoholic cirrhosis groups. The allele frequency of ADH2*1 was significantly higher in the alcoholic esophageal Ca patients than in no nalcoholic control groups. The ALDH2*2 was significantly lower in alcoholic groups (except the alcoholic esophageal Ca group) than in nonalcoholic con trol groups. The allele frequencies of ADH2*1 and ALDH2*2 are higher in alc oholic patients with esophageal Ca than alcoholic patients without it. The genotype distribution of P4502E1, detected by RsaI and PstI, was not differ ent among alcoholic patients with different organ diseases. CONCLUSIONS: The allele frequency of ADH2*1 and ALDH2*1 are different among subpopulations of alcoholics, suggesting that alcoholic patients with diff erent specific types of organ damage are genetically different. The Chinese alcoholic patients with the ADH2*1 and ALDH2*2 allele are more susceptible to esophageal Ca. (Am J Gastroenterol 2000;95:2958-2964. (C) 2000 by Am. C oll. of Gastroenterology).