Open AccessCombination of ADH 1 B *2/ ALDH 2*2 polymorphisms alters acetaldehyde‐derived DNA damage in the blood of J apanese alcoholics
Author(s) -
Yukawa Yoshiyuki,
Muto Manabu,
Hori Kimiko,
Nagayoshi Haruna,
Yokoyama Akira,
Chiba Tsutomu,
Matsuda Tomonari
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02360.x
Subject(s) - acetaldehyde , chemistry , biochemistry , microbiology and biotechnology , biology , ethanol
The acetaldehyde associated with alcoholic beverages is an evident carcinogen for the esophagus. Genetic polymorphisms of the alcohol dehydrogenase 1 B ( ADH 1 B ) and aldehyde dehydrogenase 2 ( ALDH 2 ) 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. ADH 1 B *2 is involved in overproduction of acetaldehyde due to increased ethanol metabolism into acetaldehyde, and ALDH 2*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‐d G ) is the most abundant DNA adduct derived from acetaldehyde. Therefore, we quantified N 2 ‐ethylidene‐d G levels in blood samples from 66 J apanese alcoholic patients using liquid chromatography/electrospray tandem mass spectrometry, and investigated the relationship between N 2 ‐ethylidene‐d G levels and ADH 1 B and ALDH 2 genotypes. The median N 2 ‐ethylidene‐d G levels (25th percentile, 75th percentile) in patients with ADH 1 B *1 /* 1 plus ALDH 2*1 /* 1 , ADH 1 B *2 carrier plus ALDH 2*1 /* 1 , ADH 1 B *1 /* 1 plus ALDH 2*1 /* 2 , and ADH 1 B *2 carrier plus ALDH 2*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 ALDH 2*1 /* 2 group, N 2 ‐ethylidene‐d G levels were significantly higher in ADH 1 B *2 carriers than in the ADH 1 B *1 /* 1 group ( P < 0.01). N 2 ‐ethylidene‐d G levels were significantly higher in the ALDH 2*1 /* 2 group than in the ALDH 2*1 /* 1 group, regardless of ADH 1 B genotype ( ADH 1 B *1 /* 1 , P < 0.05; ADH 1 B *2 carriers, P < 0.01) N 2 ‐ethylidene‐d G levels in blood DNA of the alcoholics was remarkably higher in individuals with a combination of the ADH 1 B *2 and ALDH 2*2 alleles. These results provide a new perspective on the carcinogenicity of the acetaldehyde associated with alcoholic beverages, from the aspect of DNA damage.