論文

査読有り
2012年9月

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

CANCER SCIENCE
  • Yoshiyuki Yukawa
  • ,
  • Manabu Muto
  • ,
  • Kimiko Hori
  • ,
  • Haruna Nagayoshi
  • ,
  • Akira Yokoyama
  • ,
  • Tsutomu Chiba
  • ,
  • Tomonari Matsuda

103
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
DOI
https://doi.org/10.1111/j.1349-7006.2012.02360.x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22703580
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000308208300007&DestApp=WOS_CPL
ID情報
  • DOI : 10.1111/j.1349-7006.2012.02360.x
  • ISSN : 1347-9032
  • PubMed ID : 22703580
  • Web of Science ID : WOS:000308208300007

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