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Assessment model gauges lung cancer risk based on medical history and genetics
Heavy smokers with emphysema history who carry MMP-1 and MPO alleles increase their risk of lung cancer 11-fold.
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Researchers at the University of Texas MD Anderson Cancer Center are developing a risk assessment model that they hope will result in earlier detection of lung cancer in those smokers identified to be most at risk.
Using this prototype model, which was discussed at the 97th Annual Meeting of the American Association for Cancer Research in Washington, researchers already have calculated that a subset of heavy smokers who have emphysema and possess inefficient DNA repair capacity have as much as 11 times the risk of developing lung cancer.
“Our goal is to develop an instrument that can help physicians estimate risk for developing lung cancer, like the Gail model does for breast cancer, or the Framingham model used to predict heart disease,” said the study’s first author, Matthew Schabath, PhD, a postdoctoral researcher in the department of epidemiology.
Assessing risk
The analysis is based on research that compared the medical history and DNA repair capacity profiles of 2,134 lung cancer patients treated at MD Anderson with the same data from 2,295 matched healthy individuals.
The prototype model is designed to first evaluate risk using only medical history, if that is all that is available, or a combination of medical history and whether the patients express two polymorphic genes: matrix metalloproteinase-1 (MMP-1) and myeloperoxidase (MPO). In this study, the researchers used a laboratory test that calculates how efficiently subjects’ lymphocytes in a test tube repair damage from a tobacco carcinogen. In the future, more cost effective and simpler laboratory analyses need to be developed to represent the activity of genes involved in the repair processes, researchers said.
Results
They found that heavy smokers who have a previous history of emphysema exhibit nearly a four times increased risk of lung cancer than light smokers without emphysema.
The risk of developing lung cancer increases to nearly 11-fold if a patient with the same medical history also carries the MMP-1 and MPO alleles.
Clinical variables that appear to protect against lung cancer development are also being incorporated into the model, Schabath said in a press statement. For example, they have estimated that individuals with a history of allergies have a 29% reduced risk of lung cancer.
Such individuals, who also exhibit efficient DNA repair capacity, have a 56% reduced risk of developing lung cancer, compared with people who do not have allergies with poor DNA repair genes.
Allergies are believed to stimulate an immune response in lungs that help fight initial tumor development, Schabath said in a press statement.
Classifying cancer
The model is a work in progress, according to senior author Margaret Spitz, MD, professor and chair of the department of epidemiology. “It appears to be reasonably accurate in that we can correctly classify over 78% of lung cancer cases,” she said, adding that additional variables such as genetic variations in important pathways and more environmental risk factors will be added.
“Early detection is key to successful treatment of any cancer, and this model is designed to help physicians identify and screen those patients most at risk for lung cancer,” Spitz added.
For more information:
- Schabath MB, Wei Q, Wu X, et al. Prior respiratory disease, DNA repair capacity, and inflammation-related genotypes modify lung cancer risk. Abstract 5663. Presented at: 97th Annual Meeting of the American Association for Cancer Research; April 1-5, 2006; Washington.