How Does Chronic Inflammation Lead To Cancer?

Electron microscope image of a single human lymphocyte

Although inflammation has rather a bad reputation, it is a vital process which allows us to effectively fight off infection. Like many things however, there appears to be a balancing act, and when inflammation becomes maladaptive and persistent – it does more harm than good.

One of the deadliest diseases in history, Spanish flu, claimed millions of lives and was particularly deadly to young, healthy individuals precisely because it turned immune systems into overdrive, causing a fatal ‘cytokine storm’. Just as an innocuous allergy can lead to anaphylactic shock and death, it seems that in the process of destroying adversaries, immune responses can sometimes go too far, creating collateral damage which can set the stage for later cancerous developments. 

As a part of the inflammatory response, the immune system uses chemical warfare – attacking the enemy with substances including hydrogen peroxide, nitric oxide and hypochlorous acid (found in household bleach).

“The presence of a foreign pathogen activates the immune response, which tries to fight off the bacteria, but in this process it also damages some of the normal cells,”

Work at MIT has identified a lesion present in inflamed tissues called 5-chlorocytosine (5ClC). This lesion, an altered version of the normal DNA base cytosine, seems to be created by hypochlorous acid. When researchers tested this further, they found that this lesion causes an incorrect DNA base to be paired with about 5% of the time. This essentially means the alteration is mutagenic – increasing the internal rate of mutation. 

The formation of 5-chlorocytosine in DNA (panel 2) drives the formation of C:G-to-T:A mutations, which have ties to cancer. Image credit: Jose-Luis Olivares/MIT.

“They found the lesions were very persistent in DNA, meaning we don’t have a repair system to take them out.. 5-chlorocytosine is intrinsically miscoding during DNA replication and it could give rise to significant frequencies of C-to-T mutation, a type of mutation that is frequently observed in human cancers,””

Understanding mechanisms like this which can contribute to cancer formation should help pave the way for more targeted treatment in the future.

Read more at Neuroscience News