Link Between Chronic Inflammation And Cancer Confirmed

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Main Category: Cancer / Oncology
Also Included In: Immune System / Vaccines;  Infectious Diseases / Bacteria / Viruses
Article Date: 09 Jun 2008 - 0:00 PDT

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According to scientists at the Massachussets Institute of Technology, chronic inflammation of the intestine or stomach has been linked to DNA damage and thus increased cancer risk. These results were released on June 2, 2008 in the Journal of Clinical Investigation (JCI).

Inflammation can be caused by many factors, including infectious agents such as Helicobacter pylori and Hepatitis C, which are already known to increase cancer risk in the stomach and liver, respectively. The inflammatory response produces cytokines, the chemicals in the immune response that encourage cell proliferation and suppress apoptosis, which can also contribute to an increased risk of cancer. In most normal situations, damage induced to DNA during an inflammatory response is repaired by the cell's internal error correction system -- but if this is not functioning properly, there is a higher chance that mutation will occur, increasing the risk of cancer. Knowing the connection between these factors and cancer can help doctors better guide patients who might be at risk for inflammation induced cancers. "That variation could influence the susceptibility of individuals and how they are going to respond to a chronic inflammation response," said senior author Leona Samson, director of the CEHS.

By performing two separate studies, the team discovered that chronic inflammation in mice generally increased the development of tumors. This was tested additionally using mice who were already less able to repair DNA damage and thus more susceptible to cancerous mutations. While this was long hypothesized, these studies help confirm the idea that inflammation can be linked to cancer. "It's something that was expected but it was never formally proven," said lead author Lisiane Meira, research scientist in MIT's Center for Environmental Health Sciences (CEHS).

In the JCI study, colon inflammation was induced using a chemical compound that mimics a human colitis. This induced a higher rate of cancer. According to Meira: "Lo and behold, the DNA repair deficient mice were more susceptible."

A second study, in collaboration with James Fox, director of the Division of Comparative Medicine at MIT, and one of his students, Chung-Wei Lee, meant to solidify the first. In this, mice were infected with H. pylori, and those lacking the proper DNA repair mechanisms were more likely to have pre-cancerous regions in the stomach. The latter study is further related to another piece published by Fox, which showed that treating infection with this bacterium quicly could prevent cancer development. 

These results indicate that individuals who are less able to perform DNA damage with chronic inflammation, such as ulcerative colitis, are more susceptible to cancer than others, according to Meira. However, there is another effect of inflamation that they postulate might influence this -- during the inflammatory response to infection, immune cells like macrophages and neutrophils excrete oxygen and nitrogen species that might damage DNA.

DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice
Lisiane B. Meira, James M. Bugni, Stephanie L. Green, Chung-Wei Lee, Bo Pang, Diana Borenshtein, Barry H. Rickman, Arlin B. Rogers, Catherine A. Moroski-Erkul, Jose L. McFaline, David B. Schauer, Peter C. Dedon, James G. Fox and Leona D. Samson
J. Clin. Invest.  doi:10.1172/JCI35073.
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Written by Anna Sophia McKenney
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