The ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) genotypes were independently and significantly higher in esophageal cancer patients than in healthy controls.
To determine the effects of ALDH2 and ADH2 genotypes in genetically based cancer susceptibility, lymphocyte DNA samples from 668 Japanese alcoholic men more than 40 years of age (91 with and 577 without esophageal cancer) were genotyped and the results were expressed as odds ratios (ORs).
Alcoholics' population attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0% for oropharyngolaryngeal cancer and 63.9% for esophageal cancer.
The association of lifestyle habits and polymorphism of ADH2 and ALDH2 genes with the risk of esophageal cancer in Thai population was investigated in a hospital-based case-control study: 202 cases and 261 controls.
For individuals with both ALDH2*1/2*2 and ADH2*1/2*1, the risk of esophageal cancer was enhanced in a multiplicative fashion (OR = 30.12), whereas for those with either ALDH2*1/2*2 or ADH2*1/2*1 alone the ORs were 7.36 and 4.11.
A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers.
After adjusting for age, drinking and smoking habits, BMI and ALDH2/ADH2 genotypes, macrocytosis of MCV > or =106 fl was associated with increased risk for esophageal cancer (OR = 2.75).
Inactive ALDH2 encoded by ALDH2*1/2*2 and the low-activity form of alcohol dehydrogenase (ADH)-2 encoded by ADH2*1/2*1 enhance the risk for esophageal cancer in Japanese light to heavy drinkers, a significant association that emphasizes the importance of screening tests for inactive ALDH2 based on alcohol flushing.
Compared to Zoroastrians, Turkomans had higher frequency of four alleles that are speculated to favor carcinogenesis (CYP1A1 m1, CYP1A1 m2, CYP2A6*9, and ADH2*1); these results are consistent with an influence of these allele variants on the population risk of EC.
Compared with individuals carrying both ALDH2 G/G and ADH2 A/A alleles and with a cumulative amount of alcohol consumption <2.5 (kg * years), drinkers carrying both ALDH2 A and ADH2 G alleles and with a cumulative amount of alcohol consumption > or =2.5 (kg * years) showed a significantly elevated risk of esophageal cancer (OR=53.15, 95% CI: 4.24-666.84).
ADH1B*1/*1 increased the risk of esophageal cancer among never/rare [1.56 (0.93-2.61)], moderate [2.71 (1.37-5.35)], and heavy drinkers [3.22 (2.27-4.57)].
Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles.
Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2(*)1/(*)2) and less-active alcohol dehydrogenase-1B (ADH1B(*)1/(*)1) increase the risk of esophageal cancer in East Asian drinkers, and esophageal cancer multiplicity is strongly associated with ALDH2(*)1/(*)2. p53 alterations are key molecular events in multifocal carcinogenesis in the esophagus.