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Yukawa Y.,Kyoto University | Muto M.,Kyoto University | Hori K.,Kyoto University | Nagayoshi H.,Environmental Quality Management | And 3 more authors.
Cancer Science | Year: 2012

The acetaldehyde associated with alcoholic beverages is an evident carcinogen for the esophagus. Genetic polymorphisms of the alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genes are associated with the risk of esophageal cancer. However, the exact mechanism via which these genetic polymorphisms affect esophageal carcinogenesis has not been elucidated. ADH1B*2 is involved in overproduction of acetaldehyde due to increased ethanol metabolism into acetaldehyde, and ALDH2*2 is involved in accumulation of acetaldehyde due to the deficiency of acetaldehyde metabolism. Acetaldehyde can interact with DNA and form DNA adducts, resulting in DNA damage. N 2-ethylidene-2′-deoxyguanosine (N 2-ethylidene-dG) is the most abundant DNA adduct derived from acetaldehyde. Therefore, we quantified N 2-ethylidene-dG levels in blood samples from 66 Japanese alcoholic patients using liquid chromatography/electrospray tandem mass spectrometry, and investigated the relationship between N 2-ethylidene-dG levels and ADH1B and ALDH2 genotypes. The median N 2-ethylidene-dG levels (25th percentile, 75th percentile) in patients with ADH1B*1/*1 plus ALDH2*1/*1, ADH1B*2 carrier plus ALDH2*1/*1, ADH1B*1/*1 plus ALDH2*1/*2, and ADH1B*2 carrier plus ALDH2*1/*2 were 2.14 (0.97, 2.37)/10 7 bases, 2.38 (1.18, 2.98)/10 7 bases, 5.38 (3.19, 6.52)/10 7 bases, and 21.04 (12.75, 34.80)/10 7 bases, respectively. In the ALDH2*1/*2 group, N 2-ethylidene-dG levels were significantly higher in ADH1B*2 carriers than in the ADH1B*1/*1 group (P < 0.01). N 2-ethylidene-dG levels were significantly higher in the ALDH2*1/*2 group than in the ALDH2*1/*1 group, regardless of ADH1B genotype (ADH1B*1/*1, P < 0.05; ADH1B*2 carriers, P < 0.01) N 2-ethylidene-dG levels in blood DNA of the alcoholics was remarkably higher in individuals with a combination of the ADH1B*2 and ALDH2*2 alleles. These results provide a new perspective on the carcinogenicity of the acetaldehyde associated with alcoholic beverages, from the aspect of DNA damage. © 2012 Japanese Cancer Association. Source

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