2012年9月
Combination of ADH1B*2/ALDH2*2 polymorphisms alters acetaldehyde-derived DNA damage in the blood of Japanese alcoholics
CANCER SCIENCE
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- 巻
- 103
- 号
- 9
- 開始ページ
- 1651
- 終了ページ
- 1655
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1349-7006.2012.02360.x
- 出版者・発行元
- WILEY-BLACKWELL
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.
- リンク情報
- ID情報
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- DOI : 10.1111/j.1349-7006.2012.02360.x
- ISSN : 1347-9032
- PubMed ID : 22703580
- Web of Science ID : WOS:000308208300007