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Genetic polymorphisms of alcohol dehydrogense-1B and aldehyde dehydrogenase-2, alcohol flushing, mean corpuscular volume, and aerodigestive tract neoplasia in Japanese drinkers.
- Source :
-
Advances in experimental medicine and biology [Adv Exp Med Biol] 2015; Vol. 815, pp. 265-79. - Publication Year :
- 2015
-
Abstract
- Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1%) and head and neck SCC (1.0%). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (≈180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0% of 4,879 alcoholics had a history of (4.0%) or newly diagnosed (1.0%) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7% of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5% of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV≥106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia.
- Subjects :
- Aldehyde Dehydrogenase, Mitochondrial
Asian People
Ethanol metabolism
Flushing genetics
Genotype
Humans
Alcohol Dehydrogenase genetics
Alcohol Drinking adverse effects
Aldehyde Dehydrogenase genetics
Digestive System Neoplasms etiology
Erythrocyte Indices
Esophageal Neoplasms etiology
Flushing chemically induced
Polymorphism, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0065-2598
- Volume :
- 815
- Database :
- MEDLINE
- Journal :
- Advances in experimental medicine and biology
- Publication Type :
- Academic Journal
- Accession number :
- 25427912
- Full Text :
- https://doi.org/10.1007/978-3-319-09614-8_15