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

被引:39
|
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
相关论文
共 50 条
  • [1] GENETIC POLYMORPHISMS OF ADH1B AND ALDH2 AND THEIR PHENOTYPES IN JAPANESE ALCOHOLIC MEN
    Yokoyama, A.
    [J]. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2018, 42 : 60A - 60A
  • [2] Gender Differences in the Effects of ADH1B and ALDH2 Polymorphisms on Alcoholism
    Kimura, Mitsuru
    Miyakawa, Tomohiro
    Matsushita, Sachio
    So, Mirai
    Higuchi, Susumu
    [J]. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2011, 35 (11) : 1923 - 1927
  • [3] THE EFFECTS OF GENETIC POLYMORPHISMS OF ADH1B AND ALDH2 ON PHARMACOKINETICS OF ETHANOL
    Kang, G.
    Ahn, B.
    Kim, S.
    Bae, K.
    Jeong, S.
    Yoon, J.
    Kim, J.
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 2011, 89 : S85 - S86
  • [4] Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium
    Yusuke Amanuma
    Shinya Ohashi
    Yoshiro Itatani
    Mihoko Tsurumaki
    Shun Matsuda
    Osamu Kikuchi
    Yukie Nakai
    Shin’ichi Miyamoto
    Tsunehiro Oyama
    Toshihiro Kawamoto
    Kelly A. Whelan
    Hiroshi Nakagawa
    Tsutomu Chiba
    Tomonari Matsuda
    Manabu Muto
    [J]. Scientific Reports, 5
  • [5] GENETIC POLYMORPHISMS OF ADH1B AND ALDH2 AFFECT ALCOHOL ELIMINATION RATES AND SALIVARY ACETALDEHYDE LEVELS IN INTOXICATED JAPANESE ALCOHOLIC MEN
    Kamada, Y.
    Yokoyama, A.
    Imazeki, H.
    Hayashi, E.
    Kitagawa, Y.
    [J]. ALCOHOL AND ALCOHOLISM, 2015, 50
  • [6] Effects of ADH1B and ALDH2 Genetic Polymorphisms on Alcohol Elimination Rates and Salivary Acetaldehyde Levels in Intoxicated Japanese Alcoholic Men
    Yokoyama, Akira
    Kamada, Yoko
    Imazeki, Hiromi
    Hayashi, Emiko
    Murata, Shigenori
    Kinoshita, Kenji
    Yokoyama, Tetsuji
    Kitagawa, Yoshinori
    [J]. ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2016, 40 (06) : 1241 - 1250
  • [7] Genetic polymorphisms of ADH1B, ADH1C and ALDH2 in Turkish alcoholics: lack of association with alcoholism and alcoholic cirrhosis
    Vatansever, Sezgin
    Tekin, Fatih
    Salman, Esin
    Altintoprak, Ender
    Coskunol, Hakan
    Akarca, Ulus Salih
    [J]. BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES, 2015, 15 (02) : 37 - 41
  • [8] Effect of the allelic variants of aldehyde dehydrogenase ALDH2*2 and alcohol dehydrogenase ADH1B*2 on blood acetaldehyde concentrations.
    Peng G.S.
    Yin S.J.
    [J]. Human Genomics, 3 (2) : 121 - 127
  • [9] The risk prediction for esophageal cancer by drinking, smoking, and the polymorphisms of ALDH2 and ADH1B
    Ito, Hidemi
    Oze, Isao
    Hosono, Satoyo
    Watanabe, Miki
    Tanaka, Hideo
    Matsuo, Keitaro
    [J]. CANCER RESEARCH, 2015, 75
  • [10] The prognostic effect of ADH1B and ALDH2 in lung adenocarcinoma
    Zhang, Ying
    Ma, Jinan
    Du, Hongchun
    Shi, Ying
    Willis-Owen, Saffron A. G.
    Moffatt, Miriam F.
    Zhang, Youming
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (16)