Inflammation, genomic instability and cancer
Inflammation is also associated with a phenomenon known as “genomic instability”, caused by the accumulation of genetic and epigenetic alterations. Sometimes this is instability at the level of single nucleotides (the building blocks that form DNA), which leads to the appearance of somatic point mutations; at other times it is instability at the chromosome level, which involves the loss or gain of whole chromosomes, or the amplification of genes or other changes that can lead to the loss or gain of parts of chromosomes or to the generation of new genes.
For its part, inflammation is associated with mutations or the silencing of genes coding for proteins involved in correcting the errors that can occur during DNA replication (the so-called mismatch repair). In this way it promotes a form of genetic instability known as “microsatellite instability”. But that is not all. Inflammation also promotes chromosomal instability and the generation of double-strand DNA damage.
Genomic instability is an important feature of cancer cells. Most tumors develop it at one of the stages of their progression, and not only that: it could be one of the factors that contribute to their appearance. Indeed, it is enough for a very small fraction of the cells that, in the whole organism, have developed genomic instability not to be eliminated for them to proliferate and give rise to a tumor.
Both point mutations and chromosomal alterations have been associated with cancer. Only in a limited number of cases are they hereditary mutations transmitted through germ cells; more often, they are acquired, non-heritable mutations that occur in specific tissues. As they accumulate progressively, they can lead to the development of a tumor, and their presence is a sign of a certain genomic instability.
Genomic instability should not, however, be considered a marker of the risk of developing a tumor. Rather, it is associated with the prodromal stage of cancer development, that is, the phase, which generally lasts several years, during which cells progressively accumulate somatic mutations in clinically healthy individuals who show no symptom or sign of cancer but who might show, besides genomic instability, levels of inflammation markers that indicate a chronic low-grade inflammatory state.
Scientific content reviewed by the Bioscience Institute Scientific Board. · Last updated
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