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Oxford researchers say they have confirmed that alcohol is a direct cause of cancer, emphasising how their findings reinforce the need to lower levels of alcohol consumption in the population for cancer prevention.
Worldwide alcohol is responsible for an estimated 3 million deaths each year, with over 400,000 of these being from cancer. The authors point out that with alcohol consumption rising, particularly in rapidly developing countries such as China, there is an “urgent need to understand how alcohol affects disease risks in different populations”.
According to a UK Government report sales of alcohol in the UK between 2019 and 2020 – before and during the pandemic – increased by 25%. The authors of this report warned that before the pandemic there were already increased alcohol-related hospital admissions and deaths, and that “the pandemic seems to have accelerated these trends”.
‘Difficult to Establish Whether Alcohol Directly Causes Cancer’
For their study, published in the International Journal of Cancer, the researchers, from Oxford Population Health, Peking University and the Chinese Academy of Medical Sciences, Beijing, used DNA samples from over 150,000 Chinese people who are part of the China Kadoorie Biobank Study. This is a long-term prospective study involving more than half a million participants recruited between 2004 and 2008 from ten diverse areas across China, including both rural and urban regions, with data collected by questionnaire and physical measurements, and blood samples taken for long-term storage.
Cancer Research UK states that drinking alcohol increases the risk of seven different types of cancer – breast, bowel, oral, oesophageal, laryngeal, pharyngeal, and liver. The researchers commented in their study that it has been “difficult to establish whether alcohol directly causes cancer, or if it is linked to possible confounding factors – such as smoking and diet – that could generate biased results”. They also raised the uncertainty that it was also unclear whether alcohol is linked to other types of cancer, including lung and stomach cancers.
Mutations Disrupt Alcohol Detoxification
To try and answer these unknowns, the researchers used a genetic approach, investigating gene variants linked to lower alcohol consumption in Asian populations.
Two common alleles disrupt the functioning of enzymes involved in alcohol detoxification – a loss of function mutation in the gene for the enzyme aldehyde dehydrogenase 2 (ALDH2), and a mutation that accelerates the activity of alcohol dehydrogenase 1B (ADH1B) – causing the toxic compound acetaldehyde, a recognised carcinogen, to accumulate in the blood. Both mutations are common in East Asians but rare in European ancestry populations.
Using the DNA samples the researchers measured the frequency of the low-alcohol tolerability alleles for ALDH2 and ADH1B finding that among the Chinese study population, the frequency of low-alcohol tolerability mutations was 21% for ALDH2 and 69% for ADH1B – this compares, they said, with <0.01% and around 4% respectively in European ancestry populations.
These two mutations reduce alcohol tolerability and are strongly associated with lower alcohol intake because they cause an unpleasant ‘flushing’ effect. The researchers stated that “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 data were combined with questionnaires about drinking habits completed by participants at recruitment and subsequent follow-up visits, with participants being tracked for a median period of 11 years.
The researchers pointed out that since women rarely drink alcohol in China, the main analysis focused on men, a third of whom drank regularly, that is, most weeks.
Greater Cancer Risk in Regular Drinking Men with Low Alcohol Tolerability
In their results the researchers said of the 150,722 adults enrolled (mean age 52.1 years, 40% men) from 10 areas in China during 2004-2008, after just over 11 years’ follow-up 9339 individuals had developed cancer.
In men, the low-alcohol tolerability alleles were strongly linked to reduced alcohol consumption, both frequency of drinking and mean alcohol intake. Those 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, particularly head and neck cancer, and oesophageal cancer. Overall, 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 that have previously been linked to alcohol.
For men who drank regularly, despite carrying one copy of the low-alcohol tolerability allele for ALDH2 they had significantly higher risks of head and neck cancer and oesophageal 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 cancer risk.
Lead researcher Dr Pek Kei (Becky) 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.”
The researchers said the results remained the same when the data were adjusted for other cancer risk factors, such as smoking, diet, physical activity, body mass, and family history of cancer.
In women – of whom only 2% drank regularly – these low-alcohol tolerability alleles were not associated with any increased risk of cancer, indicating, the researchers said, “that the reduced risks for the carriers of these gene variants in men directly resulted from their lower alcohol consumption”.
They went on to say that the significantly greater risks seen in men carrying the low-alcohol tolerability ALDH2 gene variant who still drank regularly “suggests that greater accumulation of acetaldehyde may directly increase cancer risk”.
Senior researcher Dr Iona Millwood from Oxford Population Health said: “Our study reinforces the need to lower population levels of alcohol consumption for cancer prevention, especially in China where alcohol consumption is increasing despite the low alcohol tolerability among a large subset of the population.”
Study Confirms Alcohol Carcinogenic but Adds Little to Existing Knowledge
Commenting on the study Prof Darren Griffin, Professor of Genetics, University of Kent, said the study, “reports that certain genetic variants predispose a higher risk of head and neck, oesophageal, and lung cancers” and that its design “inherently isolates the fact that it is alcohol consumption (not other lifestyle factors) that seem to cause the cancer”.
Whilst agreeing that the study findings support the evidence that alcohol is carcinogenic to humans, Dr Michael Jones, senior staff scientist in Genetics and Epidemiology at The Institute of Cancer Research, London, said: “It is important to note that the study was conducted in China, where the types of alcoholic drink and the pattern of drinking may be different to consumption elsewhere in the world. In other words, results could differ across populations.”
A view echoed by Dr Stephen Burgess, statistician at the MRC Biostatistics Unit, University of Cambridge, said: “Further research is needed to determine whether a similar harmful effect of alcohol on cancer holds in European ancestry populations.”
Prof Paul Pharoah, Professor of Cancer Epidemiology, University of Cambridge, pointed out that the study is “a well-conducted study that has been carefully analysed”. However, he said that the results “do not add much to what we already know,” reiterating that, “limiting alcohol consumption is one of many ways to live a healthier lifestyle that helps reduce cancer risk”.
Créditos: Comité científico Covid