The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption
Open accessAbstract
A Primer on the Genetics of Alcohol MetabolismEthanol is first metabolized primarily by alcohol dehydrogenase (ADH) into acetaldehyde (Figure 2), a mutagen and animal carcinogen that causes DNA damage and has other cancerpromoting effects [5][6][7].Acetaldehyde is subsequently metabolized to acetate, mainly by the enzyme ALDH2 [8].In East Asian populations there are two main variants of ALDH2, resulting from the replacement of glutamate (Glu) at position 487 with lysine (Lys) [9].The Glu allele (also designated ALDH2*1) encodes a protein with normal catalytic activity, whereas the Lys allele (ALDH2*2) encodes an inactive protein.As a result, Lys/ Lys homozygotes have no detectable Funding: The authors received no specific funding for this article.
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Genetic variations in the aldehyde dehydrogenase 2 gene affect the risk relationship between alcohol consumption and oral cavity and oesophageal cancer.
“Specifically, genetic variations in the aldehyde dehydrogenase 2 gene have been shown to affect the risk relationship between alcohol consumption and oral cavity and oesophageal cancer 175, 181, 183.”
From The relationship between different dimensions of alcohol use and the burden of disease—an update (2017) · cites this paper as [181]
The risk relationship between alcohol consumption and the development of cancer is modified by genetic variations in the carbon metabolism pathway and the ethanol-acetaldehyde metabolic pathways.
“The risk relationship between alcohol consumption and the development of cancer has been shown to be modified by genetic variations in the carbon metabolism pathway and the ethanol–acetaldehyde metabolic pathways 181, 182.”
From The relationship between different dimensions of alcohol use and the burden of disease—an update (2017) · cites this paper as [181]
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- Authors
- Brooks, P. J., Enoch, M.-A., Goldman, D., Li, T.-K., & Yokoyama, A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Brooks, Philip J
- Yokoyama, Akira
- Venue
- PLoS Medicine
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-03-24
- Volume
- 6
- Issue
- 3
- Pages
- e1000050
- ISSN
- 1549-1277 (ISSN-L)
- 1549-1676
- PMC
- PMC2659709
- OpenAlex
- W2007801750
- Cited by
- 480
- References
- 36
- Citations by year
- 2026: 15 · 2025: 29 · 2024: 34 · 2023: 35 · 2022: 32 · 2021: 38 · 2020: 28 · 2019: 34 · 2018: 32 · 2017: 37 · 2016: 22 · 2015: 25 · 2014: 23 · 2013: 25 · 2012: 19
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Medicine (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000083)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- esophageal cancer, alcohol consumption, ALDH2 polymorphism, alcohol dehydrogenase, acetaldehyde, East Asian populations
- MeSH terms
- Aldehyde Dehydrogenase, Mitochondrial, Acetaldehyde, Adult, Alcohol Drinking, Ethanol, Alcoholism, Aldehyde Dehydrogenase, Carcinoma, Squamous Cell, DNA Damage, Esophageal Neoplasms, Asia, Eastern, Flushing, Humans, Middle Aged, Patient Education as Topic, Surveys and Questionnaires, Risk Factors, Social Behavior, Genetic Predisposition to Disease, Early Diagnosis, Asian People
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