Combination of ADH1B*2/ALDH2*2 polymorphisms alters acetaldehyde-derived DNA damage in the blood of Japanese alcoholics

被引:41
作者
Yukawa, Yoshiyuki [1 ]
Muto, Manabu [1 ]
Hori, Kimiko [1 ]
Nagayoshi, Haruna [2 ]
Yokoyama, Akira [3 ]
Chiba, Tsutomu [1 ]
Matsuda, Tomonari [2 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Kyoto, Japan
[2] Kyoto Univ, Res Ctr Environm Qual Management, Otsu, Shiga, Japan
[3] Natl Hosp Org, Kurihama Alcoholism Ctr, Dept Internal Med, Yokosuka, Kanagawa, Japan
来源
CANCER SCIENCE | 2012年 / 103卷 / 09期
关键词
ALDEHYDE DEHYDROGENASE-2; GENETIC POLYMORPHISMS; PANCREATIC-CANCER; ADDUCTS; ETHANOL; RISK; N-2-ETHYLDEOXYGUANOSINE; ESOPHAGEAL; CELLS; CARCINOGENESIS;
D O I
10.1111/j.1349-7006.2012.02360.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. N2-ethylidene-2'-deoxyguanosine (N2-ethylidene-dG) is the most abundant DNA adduct derived from acetaldehyde. Therefore, we quantified N2-ethylidene-dG levels in blood samples from 66 Japanese alcoholic patients using liquid chromatography/electrospray tandem mass spectrometry, and investigated the relationship between N2-ethylidene-dG levels and ADH1B and ALDH2 genotypes. The median N2-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)/107 bases, 2.38 (1.18, 2.98)/107 bases, 5.38 (3.19, 6.52)/107 bases, and 21.04 (12.75, 34.80)/107 bases, respectively. In the ALDH2*1/*2 group, N2-ethylidene-dG levels were significantly higher in ADH1B*2 carriers than in the ADH1B*1/*1 group (P similar to<similar to 0.01). N2-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 similar to<similar to 0.05; ADH1B*2 carriers, P similar to<similar to 0.01) N2-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.
引用
收藏
页码:1651 / 1655
页数:5
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