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 NCI 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.
The polymorphisms were found in genes for interleukin (IL)1A and IL1B, two signaling molecules that immune system cells secrete in response to infection or tissue damage.
“Essentially, sustained inflammation alters the microenvironment of the lung tissue, damaging cells and altering DNA,” reports lead author, Eric Engels, M.D., researcher at the viral epidemiology branch of the NCI’s division of cancer epidemiology and genetics.
To examine the relationship between inflammation and lung cancer risk, the researchers compared differences in genes related to inflammation between more than 1,500 lung cancer patients and 1,700 controls. More than 80% of the cancer patients in the study were current or former smokers.
Among the 59 variations in 37 inflammation-related genes studied, the researchers discovered that some variants in the genes for IL1A and 1B are found more frequently in patients with lung cancer and especially among heavy smokers.
The effect was most profound in polymorphisms in IL1B. The IL1B protein is an integral part of the chemical cascade by which cell signals moderate the response to inflammation. Variations in the gene may lead to greater expression of the protein, which is more likely to turn on the cascade and sustain the damaging effects of inflammation. Over time, the constant damage of inflammation could lead to genetic damage and cancer, according to Dr. Engel.
The study is published in the July 1 issue of Cancer Research.