"Esophageal Cancer Risk Up to 35 Times Higher"—A Surprising Finding About People Whose Faces Do Not Flush When They Drink [Health Talk]

[Financial News] People whose faces flush when they drink are known to face a higher risk of cancer. However, a study has found that people with the most dangerous combination of genes do not develop facial flushing even after drinking.

According to a study published in the July issue of the international journal Cancer Medicine, a research team at Kurihama Medical Center of the National Hospital Organization of Japan analyzed the relationship between alcohol-related cancer histories and alcohol dehydrogenase 1B gene and ALDH2 genotypes in 5,214 Japanese men who were first diagnosed with alcohol dependence at the hospital between 2005 and 2020. The participants were aged 20 to 79, with an average age of 53.3.
The alcohol dehydrogenase 1B gene and ALDH2 each play a role in the process of breaking down alcohol. The alcohol dehydrogenase 1B gene produces an enzyme that converts alcohol into acetaldehyde. The slower this enzyme works, the longer alcohol remains in the body.
ALDH2 produces an enzyme that breaks acetaldehyde down into harmless substances. People with an inactive form of this enzyme develop flushing in the face and body when they drink.
Of the 5,214 participants, 385 (7.38%) reported a history of alcohol-related cancer. Stomach cancer was the most common, affecting 204 people (3.91%), followed by colorectal cancer in 80 (1.53%), esophageal cancer in 73 (1.40%), head and neck cancer in 55 (1.05%), and liver cancer in 31 (0.59%).
Most of the cancers were treated when alcohol dependence had already progressed considerably or afterward. Stomach cancer was different. More than half—51.5%—had already received treatment before their alcohol dependence progressed.
The risks varied clearly by genotype. Compared with patients carrying the fast-metabolizing form of the alcohol dehydrogenase 1B gene, those carrying the slow-metabolizing form had a 1.99-fold higher risk of head and neck cancer and a 3.05-fold higher risk of esophageal cancer. Their risk of stomach cancer was 0.65 times as high, meaning it was lower.
ALDH2 showed a similar pattern. Compared with patients carrying the active form, those with the inactive form had an 8.63-fold higher risk of head and neck cancer, an 11.35-fold higher risk of esophageal cancer, and a 1.54-fold higher risk of stomach cancer.

The gap widened further among people carrying both risk genotypes. The 264 patients (5.1% of the total) who had both the slow-metabolizing form of the alcohol dehydrogenase 1B gene and the inactive form of ALDH2 faced up to a 17-fold higher risk of head and neck cancer and a 35-fold higher risk of esophageal cancer than those without both variants.
When the research team reexamined 649 patients with inactive ALDH2, 52% of those who also had the slow-metabolizing form of the alcohol dehydrogenase 1B gene said they had never experienced facial flushing even after drinking. That was more than twice the rate among those with the fast-metabolizing form of the alcohol dehydrogenase 1B gene (23%).
The research team explained that people with the slow-metabolizing form of the alcohol dehydrogenase 1B gene produce acetaldehyde gradually, so the warning response of flushing in the face and body is relatively less pronounced. In other words, the warning signal may disappear in the group at the highest risk.
The research team explained, "When the two risk genotypes overlap, not only does the body's warning response become weaker, but the length of time that alcohol and acetaldehyde remain in the body at high concentrations also increases." It added, "This may lead people to drink more, further increasing their cancer risk."
However, this study did not prove a causal relationship. That is because the participants were limited to patients who had received treatment for alcohol dependence.
The research team also noted that some errors may be possible because cancer histories and the timing of treatment were determined based on patients' accounts.
[email protected] Minseo Seong Reporter