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. 2009 Mar 24;6(3):e50.
doi: 10.1371/journal.pmed.1000050.

The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer From Alcohol Consumption

Free PMC article

The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer From Alcohol Consumption

Philip J Brooks et al. PLoS Med. .
Free PMC article


Philip Brooks and colleagues discuss evidence linking the alcohol flushing response (predominantly due to ALDH2 deficiency) with a much higher risk of esophageal cancer from alcohol consumption.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Figure 1
Figure 1. The Alcohol Flushing Response
Facial flushing in a 22-year-old ALDH2 heterozygote before (left) and after (right) drinking alcohol. The individual pictured in this figure has given written consent for publication of his picture using the PLoS consent form.
Figure 2
Figure 2. The Ethanol Metabolic Pathway and the Role of the ALDH2 Variants in Acetaldehyde Accumulation
It should be noted that ADH is also polymorphic, and genetic variants in ADH1B interact with the ALDH2 variant to modify risk [13].
Figure 3
Figure 3. A Late-Stage Squamous Cell Carcinoma of the Esophagus in a 51-Year-Old Male with a Known History of Flushing and Alcohol Drinking
Figure 4
Figure 4. Chemical Structures of Deoxyguanosine, the DNA Base That Is the Target for Acetaldehyde, As Well As the Acetaldehyde-Derived DNA Lesions Referred To in Table 1 The atoms in red represent the acetaldehyde-derived chemical modifications.
Figure 5
Figure 5. Odds Ratios for Esophageal Cancer at Different Amounts of Alcohol Consumption In Relation To the Flushing Response
Alcohol consumption amounts: low, 1–8.9 units/week; moderate, 9–17.9 units/week; high, ≥18 units/week; where 1 unit = 22 g of ethanol. The referent (OR = 1) is never/rare drinkers (<1 unit/week) of either genotype. Odds ratios were adjusted for age, frequency of drinking strong alcohol beverages, pack-years of smoking, and intake of fruit and green-yellow vegetables, based on a multiple logistic regression model. Error bars are 95% confidence intervals. The graph is based on the data in [25].

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