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 organ-specific complications of alcoholism, whereas other alcoholic patients acquire different ones. The aim of this study was to investigate the differences among Chinese alcoholic patients with esophageal cancer, acute pancreatitis, and liver cirrhosis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1.


METHODS
Liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we determined the polymorphism of the above-mentioned alcohol metabolizing genes in 59 alcoholics with carcinoma of the esophagus (alcoholic esophageal Ca), 87 acute alcoholic pancreatitis patients, 116 alcoholics with liver cirrhosis (alcoholic cirrhosis), 19 alcoholics with both liver cirrhosis and acute pancreatitis (alcoholic P plus C), and 241 nonalcoholic patients.


RESULTS
The results showed that the allele frequency of ALDH2*2 was significantly higher in the alcoholic esophageal Ca group than in the alcoholic pancreatitis and alcoholic cirrhosis groups. The allele frequency of ADH2*1 was significantly higher in the alcoholic esophageal Ca patients than in nonalcoholic control groups. The ALDH2*2 was significantly lower in alcoholic groups (except the alcoholic esophageal Ca group) than in nonalcoholic control groups. The allele frequencies of ADH2*1 and ALDH2*2 are higher in alcoholic patients with esophageal Ca than alcoholic patients without it. The genotype distribution of P4502E1, detected by RsaI and PstI, was not different 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 different 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.
Chao
Y C
YC
Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Wang
L S
LS
Hsieh
T Y
TY
Chu
C W
CW
Chang
F Y
FY
Chu
H C
HC
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics; D000437:Alcoholism / Q000235:genetics* / Q000473:pathology; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D001706:Biopsy; D002681:China; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008099:Liver / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic
D007527:Isoenzymes; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase