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Test Spots Genetic Damage Done by Smoking
Date:9/5/2007

It could lead to earlier detection, treatment of lung cancer, study says

WEDNESDAY, Sept. 5 (HealthDay News) -- An experimental lung cancer screening test designed to look for precancerous genetic damage could help better identify patients at risk for the disease, while opening up the possibility for earlier diagnoses and preventive treatments, a new study suggests.

The procedure enabled the researchers to screen people for evidence of chromosomal abnormalities in the lungs that are found among virtually all lung cancer patients. More than 80 percent of patients who did not yet have lung cancer -- but whose smoking placed them at high-risk -- were found to have such disease biomarkers.

"We were able to see precancerous genetic changes in the bronchial cells lining the airways of the lungs in both high-risk smokers and in patients who have lung cancer in another part of the lung," said lead author Dr. Wilbur A. Franklin, a professor of pathology at the University of Colorado Health Sciences Center.

Reporting in the September issue of the American Journal of Respiratory and Critical Care Medicine, the authors cautioned that they are not yet certain that the genetic changes they identified will always lead to lung cancer. However, they said the prospect of such an association was fuel for further research.

Lung cancer is the leading cancer killer in the United States, causing more fatalities than colon, breast, and prostate cancer combined, the researchers noted.

They added that genetic markers for lung cancer risk are good targets for screening interventions, given that once chromosomal abnormalities occur, they are considered irreversible -- even among smokers who kick the habit.

Franklin and his team used two laboratory techniques -- spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) -- to check the chromosomal status of lung tissue among 71 people. Fourteen of the study participants had already been diagnosed with lung cancer, 43 were considered at high-risk for the disease because they were smokers, and another 14 people were healthy men and women who'd never smoked.

Chromosomal abnormalities were found in 100 percent of the cancer patients and 82 percent of the high-risk smokers.

The researchers also established a so-called chromosomal abnormality index (CAI) to illustrate the extent of genetic damage. They found that while non-smokers had CAI readings of less than 1 percent, high-risk smokers had reading above 10 percent, and cancer patients topped 15 percent.

The researchers said it's not yet known when such potential genetic "markers" for future lung cancer develop or what constitutes the initial "genetic hit" that triggers chromosomal changes.

Still, they were able to identify four chromosomes -- numbers 5, 7, 8, and 18 -- that were most often affected among both cancer patients and the high-risk smokers.

Franklin emphasized that the technology his team used would not be practical for widespread medical use outside of a research setting. But he said he hoped the study is a "small step" forward in the effort to develop widely available screening options that could offer patients at risk of lung cancer a chance at earlier and more effective treatment.

"Ultimately, the point is to identify those patients who are likely to go on to get cancer before they get it," he said. "And, ultimately, we'd like to develop chemo prevention drugs that would target these high-risk individuals."

Franklin said he expects a biomarker screening technique for lung cancer to be available in the "not too distant future."

Dr. Timothy Winton, an associate professor of surgery and division director of thoracic surgery at the University of Alberta and the University of Alberta Hospital in Edmonton, Canada, called the new study a "very interesting" effort to harness modern technology to get a jump on lung cancer diagnoses.

"This is an attempt to look inside the cell at a very early genetic change level to get useful insights into the damage that's been done and the risk that is associated with it," he said. "It's an extension of a series of screening studies ongoing for decades to catch cancer at a very early stage, so it can be cured by surgery or surgery plus chemotherapy.

"It's also further strong evidence that not smoking is one of the major things that people can do to protect themselves from lung cancer," Winton added. "Because the message here is that smoking leads to genetic abnormalities, which go on to lead potentially to cancer. And very few people that do not smoke get lung cancer."

More information

For additional information on lung cancer, visit the American Cancer Society.



SOURCES: Wilbur A. Franklin, M.D., professor, pathology, University of Colorado Health Sciences Center, Aurora; Timothy Winton, M.D., associate professor, surgery, and division director, thoracic surgery, University of Alberta and University of Alberta Hospital, Edmonton, Canada; September 2007 American Journal of Respiratory and Critical Care Medicine


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