Variations in two genes related to inflammation may be a major risk factor for developing lung cancer, according to a team of scientists from the National Cancer Institute and the University of Texas M. D. Anderson Cancer Center. The effect of these genes is especially strong among heavy smokers, suggesting that the inflammatory response is important in modulating the damage caused by tobacco smoke.

Their study, published in the July 1 issue of Cancer Research, a publication of the American Association for Cancer Research, is the first to pinpoint the mechanism by which damage to the lung might trigger an overzealous inflammatory response by the immune system, leading to lung cancer. The variants, or polymorphisms, were found in genes for interleukin 1A and interleukin 1B, two signaling molecules that immune system cells secrete in response to infection or tissue damage.

Our findings help explain how heavy smoking, for example, combines with a genetic predisposition to create a besieged environment within the lungs, said lead author Eric Engels, M.D., MPH, researcher at the Viral Epidemiology Branch of the NCIs Division of Cancer Epidemiology and Genetics. Essentially, sustained inflammation alters the microenvironment of the lung tissue, damaging cells and altering DNA.

Inflammation is part of the immune systems arsenal to combat the effects of infection and cell damage. However, prolonged or intense inflammation could lead to conditions within the lung environment that foster cancer, Engels said. Previous studies have shown that diseases associated with lung damage, such as tuberculosis and asthma, increase the risk of developing lung cancer. Likewise, exposure to tissue-damaging substances like silica and asbestos, inhaled into the lungs, has also been shown to increases lung cancer risk.

Inflammation has long been thought to be a factor in many cancers, including lung cancer, and could provide an explanation how d
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Contact: Greg Lester
lester@aacr.org
267-646-0554
American Association for Cancer Research
3-Jul-2007