title: Roles of defective ALDH2 polymorphism on liver protection and cancer development.
abstract: Because serum transaminases elevate alcohol dose dependently as a consequence of liver injury, they serve as useful biological markers of excessive drinking. However, these markers are inadequate in individuals with a defective allele of the aldehyde dehydrogenase 2 gene, ALDH2*2, because they show a different correlation with the amount of ethanol. For example, the serum alanine aminotransferase (ALT) level could become even lower than the baseline after alcohol intake in ALDH2*2 carriers. In fact, multiple studies suggest that ALDH2*2 is a hepato-protective factor in healthy individuals. Importantly, excessive drinking is particularly dangerous in carriers of ALDH2*2 because the risk of alcohol-related cancer is much higher than that for ALDH2*1/*1 carriers. Without recognizing the genotype interaction on serum transaminase, the opportunity to warn people about potential cancer risks is missed owing to incorrect interpretation. This is particularly important in East Asian countries where approximately half of the population carries the ALDH2*2 allele. To date, the mechanism of liver protection from ethanol load in individuals with ALDH2*2 has not been fully elucidated. However, some reasonable mechanisms have been suggested by experimental studies, including remodelling of detoxifying systems. Further studies to uncover the whole mechanism are anticipated.
authors.affiliation: Department of Social Medicine, Saga University School of Medicine, Saga, 849-8501, Japan. matsumoa@cc.saga-u.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumoto
authors.affiliation: Department of Clinical Pharmacy, University of Colorado School of Pharmacy, 12850 E. Aurora, Denver, CO, 80045, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Thompson
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, 06520-8034, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Molecular Biology, Hamamatsu University School of Medicine, Hamamatsu, 431-3125, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kitagawa
authors.affiliation: Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, 06520-8034, USA.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Vasiliou
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000503:physiopathology; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D063646:Carcinogenesis / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D000637:Transaminases / Q000097:blood*
chemical_list: D015415:Biomarkers; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000637:Transaminases
keywords: ALDH2; Alcohol; Cancer; Gene polymorphism; Serum transaminase