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).
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.
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.
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.
Alcoholics' population attributable risks due to ADH2/ALDH2 polymorphisms were estimated to be 82.0% for oropharyngolaryngeal cancer and 63.9% for esophageal cancer.
Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.
The key findings of the earlier studies were that variations (i.e., polymorphisms) in the DNA sequences of the genes encoding alcohol dehydrogenase 1B (i.e., the ADH1B gene), aldehyde dehydrogenase 2 (i.e., the ALDH2 gene), and other alcohol-metabolizing enzymes mediate the risk for alcoholism; moreover, these polymorphisms also have an impact on the risk of alcohol-related cancers, such as esophageal cancer.
Genetic polymorphisms of the alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genes are associated with the risk of esophageal cancer.
Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.
Associations between ADH1B genotypes and the risk of esophageal cancer were estimated by computing the odds ratios (ORs) and their 95% confidence intervals (CIs) using logistic regression analyses for crude ORs and adjusted ORs when adjusting for age, gender, and tobacco use status.
The ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) genotypes were independently and significantly higher in esophageal cancer patients than in healthy controls.
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.
Furthermore, Arg/Arg genotype of ADH1BArg47His variant combined with drinking, smoking and males appeared to show a high risk in patients with esophageal cancer.
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).
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).