Alcohol appears to be a direct cause of cancer, according to a genetic study undertaken in China.
Researchers from Oxford Population Health, Peking University and the Chinese Academy of Medical Sciences, Beijing, investigated gene variants linked to lower alcohol consumption in Asian populations. They wanted to establish if alcohol directly causes cancer or if it is linked to possible confounding factors that could generate biased results.
The study team used DNA samples from about 150,000 participants – of whom 60,000 were men and 90,000 women – in the China Kadoorie Biobank study. However, the focus was mainly on the male participants because women rarely drink in China.
They measured the frequency of the low-alcohol tolerability alleles for ALDH2 and ADH1B, which are common genetic variants in East Asian populations.
The alleles reduce tolerance to alcohol and the mutations disrupt the functioning of enzymes involved in alcohol detoxification, causing the toxic compound acetaldehyde, a Group I carcinogen, to accumulate in the blood.
The data were combined with questionnaires about drinking habits and follow-up visits, with the participants being tracked for a median period of 11 years.
The results have been published in the latest edition of the *International Journal of Cancer*.
They found that the frequency of low-alcohol tolerability alleles was 21% for ALDH2 and 69% for ADH1B, compared with under 0.01% and about 4% in European ancestry populations.
In men, the low-alcohol tolerability alleles were strongly linked to reduced alcohol consumption, both frequency of drinking and mean alcohol intake.
About 4,500 (7.4%) of the men developed cancer during the follow-up period and those who carried one or two of the low-alcohol tolerability alleles for ADH1B had between 13-25% lower risks of overall cancer and alcohol-related cancers, particularly head and neck cancer, and oesophageal cancer.
Men who carried two copies of the low-alcohol tolerability allele for ALDH2 drank very little alcohol and had a 14% lower risk of developing any cancer, and a 31% lower risk of developing cancers linked to alcohol, such as head and neck, oesophagus, colon, rectum and liver.
Men who drank regularly, even though they have one copy of the low-alcohol tolerability allele for ALDH2, were found to have significantly higher risks of head and neck cancer and oesophageal cancer.
However, there was no overall association between carrying one copy of the low-alcohol tolerability allele for ALDH2 and increased cancer risk among non-drinkers or occasional drinkers.
The results remained the same when the data were adjusted for other cancer risk factors.
In women – only 2% of whom drank regularly – the low-alcohol tolerability alleles were not associated with any increased risk of cancer. This, say the researchers, indicates that the reduced risks for the carriers of these gene variants in men directly resulted from their lower alcohol consumption.
Lead researcher Dr Pek Kei Im from Oxford Population Health said: "These findings indicate that alcohol directly causes several types of cancer, and that these risks may be increased further in people with inherited low alcohol tolerability who cannot properly metabolise alcohol."
Im PK, Yang L, Kartsonaki C et al. Alcohol metabolism genes and risks of site-specific cancers in Chinese adults: An 11-year prospective study. *International Journal of Cancer* 20 January 2022
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