Assessment Model Gauges Lung Cancer Risk

DNA Repair Ability and Medical History Are Considered

Physicians have little to help them predict development of lung cancer in their patients. Even a history of heavy smoking does not help, since only a fraction of lifetime smokers develops the cancer.

M. D. Anderson researchers are developing a risk assessment model that they hope will result in early detection of lung cancer in smokers identified to be most at risk.

Using this prototype model, presented last month at the annual meeting of the American Association for Cancer Research (AACR), 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," says the study's first author, Matthew Schabath, Ph.D., a postdoctoral researcher in M. D. Anderson's Department of Epidemiology.

DNA repair ability, health history are indicators

The analysis is based on research that compared the medical history and DNA repair capacity profiles of 2,134 lung cancer patients treated at M. D. Anderson with the same data from 2,295 healthy individuals.

The prototype model is designed to first evaluate risk using only medical history, or a combination of medical history and genetic information.

Researchers drew blood from participants and used a laboratory test to calculate how efficiently lymphocytes repair damage from tobacco. In the future, simpler and more cost-effective laboratory analyses need to be developed to represent the activity of genes involved in the repair process.

Using the model, the researchers found data related to:

Emphysema- Heavy smokers with a previous history of emphysema (a chronic lung condition occurring in heavy smokers) exhibit nearly a four-fold increased risk of lung cancer than light smokers without emphysema.

Emphysema and DNA repair- The risk of developing lung cancer increases to nearly 11-fold if a patient with the same history of emphysema also has an inefficient DNA repair capacity.

Allergies- Individuals with a history of allergies (defined by a prior history of hay fever) have a 29% reduced risk of lung cancer.

Allergies and DNA repair- People with a history of allergies and who exhibit efficient DNA repair capacity have a 56% reduced risk of developing lung cancer, compared with people without allergies and who have inefficient DNA repair genes.

The model is a work in progress, says senior author Margaret Spitz, M.D., professor and chair of the Department of Epidemiology. "It appears to be reasonably accurate in that we can correctly classify more than 78% of lung cancer cases," she says, adding that additional variables such as genetic variations and other environmental risk factors will be added in the future.

"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."