Alcohol-related cancers and aldehyde dehydrogenase-2 in Japanese alcoholics

Abstract

Aldehyde dehydrogenase-2 (ALDH2) eliminates most of the acetaldehyde produced during alcohol metabolism. In some drinkers, a mutant ALDH2 allele contributes to diminished activity of the enzyme, dramatically increasing the risk for esophageal cancer. This study was designed to evaluate the ALDH2 gene polymorphism as a predictor of the development of cancers prevalent in Japanese alcoholics. We performed ALDH2 genotyping on lymphocyte DNA samples from Japanese alcoholic men (487 cancer-free; 237 with cancer, including 34 oropharyngolaryngeal, 87 esophageal, 58 stomach, 46 colon, 18 liver, 7 lung, 9 other sites, and 19 multiple primary cancers in two or three organs). The frequencies of the mutant ALDH2*2 allele were significantly higher in alcoholics with oropharyngolaryngeal (52.9%), esophageal (52.9%), stomach (22.4%), colon (21.7%) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (78.6%), than in cancer-free alcoholics (9.0%). After adjustment for age, daily alcohol consumption and amount of cigarette smoking, significantly increased risks (odds ratios) in the presence of the ALDH2 *2 allele were found for oropharyngolaryngeal (11.14), esophageal (12.50), stomach (3.49), colon (3.35), lung (8.20) and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (54.20) but not for liver or other cancers. These results suggest a general role of acetaldehyde, a recognized animal carcinogen, in the development of human cancers.

Removal of acetaldehyde from saliva by a slow‐release buccal tablet of L‐cysteine

“…6,7 Asian heavy drinkers with a genetically deficient aldehyde dehydrogenase (ALDH2) enzyme do show a markedly increased risk for GI-tract cancers. 8 Our recent findings demonstrate that Asians with this mutant ALDH2 have 2-3 times higher salivary acetaldehyde levels after a moderate dose of ethanol than Asians with the normal ALDH2 enzyme. 7 When this observation is combined with the earlier epidemiologic data, our results provide strong evidence for the local carcinogenic action of acetaldehyde produced from alcohol in the saliva by either oral microbes or in the salivary glands.…”

“…Significantly increased risks (odds ratios) in the presence of ALDH2 deficiency gene have been found for oropharyngolaryngeal (11.1), esophageal (12.5), stomach (3.5), colon (3.49) and lung (8.2), and esophageal cancer concomitant with oropharyngolaryngeal and/or stomach cancer (54.2) but not for liver or other cancers. 8 Also, individuals who are homozygous for the fast alcohol-metabolising alcohol dehydrogenase (ADH3) enzyme have increased risk of alcohol-related oral cancer. 35 The plausible explanation for this association is the abnormally high salivary acetaldehyde concentration after alcohol intake among individuals with ALDH2 deficiency or individuals possessing ADH3*1,1 ge-FIGURE 1 -In vivo acetaldehyde levels (mean Ϯ SEM) in oral saliva of 9 volunteers with placebo or L-cysteine-containing buccal drug formulation after a dose of alcohol (0.8 g/kg of body weight).…”

Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress

“…Individuals who accumulate acetaldehyde due to polymorphism and/or mutations in the gene coding for enzymes responsible for acetaldehyde generation and detoxification have been shown to have an increased cancer risk (Yokoyama et al, 1998). In this context it is interesting that in Caucasians polymorphism of alcohol dehydrogenase 1C (ADH1C) exists and that the allele ADH1C*1 encodes for an enzyme with a high capacity to generate acetaldehyde.…”

Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population

“…3 Most studies, conducted mainly in Japan, have revealed associations between the ADH2 or ALDH2 polymorphism and esophageal cancer risk. [4][5][6][7][8] Chao et al 9 found that Chinese alcoholic patients with the ADH2 G and ALDH2 A alleles were more susceptible to esophageal cancer. Wu et al 10 also found a multiplicative effect of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk, but those were only found in Taiwanese males.…”