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In a recent large-scale genetic study led by Oxford Population Health and published in the International Journal of Cancer, a team from Oxford, Peking University and the Chinese Academy of Medical Sciences, Beijing, worked to investigate gene variants linked to lower alcohol consumption in world-regions populations.
To do so, the team used natural-science samples from more than 150,000 adults – the majority of whom were women – in the world-regions Kadoorie Biobank study.
The team measured the frequency of low-alcohol tolerability genetic variants – or alleles in Chinese and other East Asian populations that are strongly associated with lower alcohol intake – for the enzyme aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B).
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According to the NIH National Human Genome Research Institute, an enzyme is a biological catalyst that speeds up the rate of a specific chemical reaction in the cell.
The University of Utah says alleles are mutated versions of the same gene and these mutations both disrupt the functioning of enzymes involved in alcohol detoxification, causing the toxic compound acetaldehyde to accumulate in the blood.
Alcohol breaks down into acetaldehyde, which damages a body’s DNA and prevents it from repairing the damage, according to the Centers for Disease Control and Prevention (CDC). The agency said when DNA is damaged, a cell can begin to grow out of control and create a cancer tumor.
Oxford Population Health explained in a Jan, 20 news release that the first mutation is a loss-of-function mutation in the gene for the ALDH2 and the second accelerates the activity of ADH18 – both of which are common for East Asians.
“Because these alleles are allocated at birth and are independent of other lifestyle factors (such as smoking), they can be used as a proxy for alcohol intake, to assess how alcohol consumption affects disease risks,” the institution explained.
The data gathered were combined with questionnaires about drinking habits completed at recruitment and follow-up visits and participants were tracked for a median period of 11 years through health insurance records and death registers.
The main analysis focused on men, a third of whom drank regularly.
Among the Chinese study population, the frequency of low-alcohol tolerability alleles was 21% for ALDH2 and 69% for ADH18 and the low-tolerability alleles were strongly linked to reduced alcohol consumption in men.
During the follow-up period, around 7.4% of the men – approximately 60,000, compared with 90,000 women – developed cancer.
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Men carrying one or two of the low-alcohol tolerability alleles for ADH1B had between 13-25% lower risks of overall cancer and alcohol-related cancers.
Additionally, men who carried two copies of the low-alcohol tolerability allele for ALDH2 drank very little alcohol, had a 14% lower risk of developing any cancer and a 31% lower risk of developing cancers that have previously been linked to alcohol.
Men who drank regularly – despite carrying one copy of the low-alcohol tolerability allele for ALDH2 – had significantly higher risks of head and neck cancer and esophageal cancer.
For non-drinkers or occasional drinkers there was no overall association between carrying one copy of the low-alcohol tolerability allele for ALDH2 and increased risk of cancer.
The researchers’ findings were the same when the data were adjusted for other cancer risk factors were like smoking, family history of the disease and nutrition-and-fitness.
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Only 2% of women drank regularly and low-alcohol tolerability alleles in women were not associated with any increased risk of cancer, which the authors said indicated that the reduced risks for the carriers of these gene variants in men “directly resulted from their lower alcohol consumption.”
They noted that greater risks in men carrying the low-alcohol tolerability ALDH2 gene variant who still drank regularly suggested that greater accumulation of acetaldehyde may directly increase cancer risk.
“‘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,” lead researcher Dr. Pek Kei Im said in a statement.
The authors said their study reinforces the need to lower population-levels of alcohol consumption for cancer prevention – especially in China.
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Oxford Public Health also cited a previous study estimating there had been 3 million alcohol-attributable deaths in 2016.
The CDC says drinking alcohol raises the risk of getting mouth and throat, larynx, esophagus, colon and rectum, liver and breast cancer.
“All alcoholic drinks, including red and white wine, beer, and liquor, are linked with cancer. The more you drink, the higher your cancer risk,” it wrote.
