The widespread acknowledgement that alcohol is a potent carcinogen has not deterred many to stop consuming it. While some said that alcohol in limited quantities is good for the body, others argued saying poison is poison. In a new study conducted on mice, it is now becoming clear why alcohol and its metabolic products are dangerous to the body – they cause damage to DNA which increases the chances of developing a cancer. The results of this study were published online in the journal Nature on January 3.
Inside the body, alcohol is oxidised into toxic acetaldehyde which is converted into acetate by an enzyme called aldehyde dehydrogenase (ALDH2). If this enzyme doesn’t work properly, it leads to the incomplete processing of acetaldehyde that is dangerous to be accumulating in the body.
In this study, researchers injected ethanol (the main component of alcoholic beverages) into mice and observed mice lacking ALDH2 showed increased amounts of DNA breaks and these breaks were exacerbated in mice that also lacked another gene called FANCD2 that helps to repair these breaks.
The researchers clearly demonstrated that incomplete processing of alcohol and acetaldehyde by the body causes damage to DNA. This happens either when the enzyme ALDH2 is malfunctioning. Almost 540 million people carry a polymorphic ALDH2 gene that is associated with sensitivity to alcohol and an increased risk for esophageal cancer. Another scenario I can imagine this happening is when there is too much alcohol for the enzyme to handle even though it is fully functioning.
The body’s second line of defence in the absence of ALDH2 is to repair the breaks caused by aldehydes. Homologous recombination is a process by which DNA breaks are repaired inside the cells with help from proteins like FANCD2. When this is also hampered, breaks are not repaired and cells use a haphazard method called non-homologous end joining to repair the breaks, which can cause errors in the DNA sequence – mutations. These mutations can accumulate eventually arising into cancer. They can also cause premature-ageing like symptoms, abnormal development and bone-marrow failure.
Therefore, this research provides a simple plausible explanation for the established epidemiological link between alcohol consumption and enhanced cancer risk.
- J. I. Garaycoechea, et al. Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells. Nature (2018). https://dx.doi.org/doi:10.1038/nature25154.
- International Agency for Research on Cancer, WHO. List of Classifications by cancer sites with sufficient or limited evidence in humans, Volumes 1 to 120. IARC Monographs (2017).