For those suffering with liver, colon or stomach cancer, one of the highest risks patients face is that of inflammation. Generally caused by viral or bacterial infection, this kind of problem can cause otherwise healthy cells to turn cancerous, and make the disease more aggressive as cancer grows.
But how do such infections provoke cells to turn cancerous?
A new study conducted by the Massachusetts Institute of Technology (MIT) focuses on the chemical and genetic changes which occur as inflammation and infection progresses --and potentially leads to the growth of cancerous cells.
Funded by the National Cancer Institute, the study -- which will appear in the online edition of Proceedings of the National Academy of Sciences this week -- collated data on a variety of genetic and chemical changes through animal experimentation.
Tracking the changes in the livers and colons of mice infected with the bacteria Helicobacter hepaticus, a pathogen which causes stomach ulcers and cancer in human hosts, the scientists hope that improving their knowledge of the changes could result in preventative drug developments.
Peter Dedon, an MIT professor of biological engineering and an author of the paper, said:
"If you understand the mechanism, then you can design interventions. For example, what if we develop ways to block or interrupt the toxic effects of the chronic inflammation?"
If a body becomes infected with a pathogen, then its natural response is to instigate inflammation. However, if this carries on for too long, tissues become damaged.
Inflammation itself is the release of cells called macrophages and neutrophils. These cells engulf bacteria and dead cells. As part of the process, potent chemicals are released to destroy the bacteria, which unfortunately also diffuses into tissue and causes damage to healthy cells.
This process is the key. If the chemicals are released for too long, it causes otherwise healthy cells to become cancerous -- and 16 percent of new cancer cases worldwide are due to inflammation.
In the study, the MIT researchers analyzed the infected mice, and found that over 20 weeks, the mice developed chronic liver and colon infections -- some of which led to colon cancer.
Through this time period, a dozen types of different damage rates to DNA, RNA and proteins were recorded. Not only this, but they also examined the extent of tissue damage and which genes were affected -- some turning on or off -- as the infections intensified.
In the colon, but not the liver, neutrophils released acids that damaged proteins, DNA and RNA. It kills bacteria, but also damages epithelial cells found in the colon. The levels of damaged DNA and RNA were found to correlate with the severity of inflammation. This, in turn, could be used to predict the risk of chronic inflammation in patients -- and therefore how at risk they are of cancer growth.
However, they found that in the liver, DNA repair became more active than in the colon. Even though the colon was also under DNA attack, it did not respond so well to bodily regeneration.
"It's possible that we have kind of a double whammy [in the colon]. You have this bacterium that suppresses DNA repair, at the same time that you have all this DNA damage happening in the tissue as a result of the immune response to the bacterium," Dedon says.
This key finding, that the liver and colon responded differently to infections, once explored further, could result in the development of tailored drugs to adapt to each separate bodily response.
In future studies, the scientists plan to investigate cancer development further -- in particular, why cells experience increases in some kinds of DNA damage.