ALDH2-deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde

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http://hdl.handle.net/10138/198902

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Lachenmeier , D W & Salaspuro , M 2017 , ' ALDH2-deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde ' , Regulatory Toxicology and Pharmacology , vol. 86 , pp. 128-136 . https://doi.org/10.1016/j.yrtph.2017.02.024

Title: ALDH2-deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde
Author: Lachenmeier, Dirk W.; Salaspuro, Mikko
Contributor: University of Helsinki, Department of Medicine
Date: 2017-06
Language: eng
Number of pages: 9
Belongs to series: Regulatory Toxicology and Pharmacology
ISSN: 0273-2300
URI: http://hdl.handle.net/10138/198902
Abstract: Humans are cumulatively exposed to acetaldehyde from various sources including alcoholic beverages, tobacco smoke, foods and beverages. The genetic-epidemiologic and biochemical evidence in ALDH2-deficient humans provides strong evidence for the causal relationship between acetaldehyde-exposure due to alcohol consumption and cancer of the upper digestive tract. The risk assessment has so far relied on thresholds based on animal toxicology with lower one-sided confidence limit of the benchmark dose values (BMDL) typically ranging between 11 and 63 mg/kg bodyweight (bw)/day dependent on species and endpoint. The animal data is problematic for regulatory toxicology for various reasons (lack in study quality, problems in animal models and appropriateness of endpoints - especially cancer - for transfer to humans). In this study, data from genetic epidemiologic and biochemical studies are reviewed. The increase in the daily exposure dose to acetaldehyde in alcohol-consuming ALDH2-deficients vs. ALDH2-actives was about twofold. The acetaldehyde increase due to ALDH2 inactivity was calculated to be 6.7 mu g/kg bw/day for heavy drinkers, which is associated with odds ratios of up to 7 for head and neck as well as oesophageal cancer. Previous animal toxicology based risk assessments may have underestimated the risk of acetaldehyde. Risk assessments of acetaldehyde need to be revised using this updated evidence. (C) 2017 The Authors. Published by Elsevier Inc.
Subject: Acetaldehyde
Genetic epidemiology
ALDH2
Cancer
Alcohol
Ethanol
SQUAMOUS-CELL CARCINOMA
ALDEHYDE DEHYDROGENASE 2
ALCOHOL-METABOLIZING ENZYMES
UNDERESTIMATED RISK-FACTOR
TEREPHTHALATE PET BOTTLES
ESOPHAGEAL CANCER-RISK
SALIVARY ACETALDEHYDE
ETHANOL-METABOLISM
TOBACCO-SMOKE
ORAL-CANCER
3121 General medicine, internal medicine and other clinical medicine
317 Pharmacy
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