19 January 2018

How alcohol Leads to cancer

Alcohol increases the risk of cancer by damaging the DNA of stem cells

Marina Astvatsaturyan, Echo of Moscow

The association of alcohol consumption with an increased risk of developing certain types of cancer has been known for a long time, but it was unclear exactly how it acts on the cells of the body, causing their malignant degeneration.

British researchers from the Laboratory of Molecular Biology of the Medical Research Council (MRC Laboratory of Molecular Biology) in Cambridge, observing irreversible genetic changes produced by alcohol in mice, in particular, found that the alcohol metabolite acetaldehyde formed endogenously can damage DNA in blood stem cells. And although it is generally believed that blood cancer is not associated with alcohol consumption, stem cells contained in the blood allow scientists to study what happens to the DNA inside them.

For example, having established that alcohol consumption can lead to chromosomal rearrangements and irreversible changes in the DNA sequence of blood stem cells, Cambridge researchers have identified a mechanism that may be involved in other stem cells, including stem cells in those tissues that are known to be susceptible to the carcinogenic effects of alcohol. These are the tissues of the breast, liver and gastrointestinal tract.

The breaks in the DNA double chain caused by acetaldehyde and the associated genetic phenomena are described in an article published in early January by Professor Ketan Patel's group in the journal Nature (Garaycoechea et al., Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells).

According to the authors, combining the transplantation of monitored hematopoietic stem cells with genome-wide sequencing, they saw that the damage occurring in stem cells leads to deletions (loss of genome sections) and permutations, which indicate that there was a certain process of repair, or restoration of DNA continuity. Moreover, although deletion of the p53 protein saves hematopoietic stem cells exposed to aldehyde, it does not affect the nature or degree of genomic instability.

It is important to note here that the p53 protein is one of the oncosuppressors – factors that normally suppress the formation of malignant tumors. Speaking about the natural mechanisms of protecting the body from damage caused by alcohol, Patel and co-authors, in particular, pay attention to the fact that DNA repair systems do not always work, and some people carry mutations in these systems, and this means that their cells cannot restore their DNA effectively. Another nuance noted by the authors is the correlation between poor alcohol tolerance and an increased risk of alcohol-induced DNA damage, and therefore the development of certain forms of cancer.

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