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Sputum Samples May Predict Lung Cancer

By Pippa Wysong, Access Excellence

Albuquerque, NM (05/26/06) - A non-invasive test currently under investigation may be able to predict who will get lung cancer as much as 18 months before people show any other signs of the disease. And to do the test, all people have to do is provide a sputum sample.alt

"We're trying to develop a non-invasive test that uses sputum to assay cells that are exfoliated from the lungs," said Steven Belinsky, PhD, director of the lung cancer program at the Lovelace Respiratory Research Institute in Albuquerque, New Mexico. He was the lead author of a study on the topic published in the March 15 edition of Cancer Research. The University of Colorado Cancer Center Sputum Screening Cohort Study, a long-term cohort study was designed to find out whether lung cancer could be predicted using cells present in sputum samples. The project began in 1993.

Currently, screening for lung cancer relies on use of x-rays which can reveal tumors once they are already present. The hope is to develop a test that will help predict who will get tumors before they are evident, and several research groups are investigating the use of sputum samples. Once people at risk are identified, treatments and strategies to prevent progression could be started earlier.

"When people cough not only do they bring up mucus, but they bring up cells from the lungs," Dr. Belinsky told Access Excellence. Earlier studies have shown that some genes undergo fairly specific alterations in lung cancer. These altered genes are present in sputum.

Sputum samples were taken from people who were at very high risk – smokers who already had chronic obstructive pulmonary disease (COPD) or emphysema. Some of the people, 98 cases, developed lung cancer. The others, a total of 92 patients, had not developed cancer at the time of the study and are being used as matched controls. From the samples, researchers identified six genes that are of special interest and are associated with the development of cancer.

"Looking at sputum samples that were collected three to 18 months before the person had any clinical symptoms of lung cancer, we were able to predict that 65 per cent of these people would have lung cancer," Dr. Belinsky said. However, the test also predicted lung cancer in close to 35% of the non-lung cancer controls, showing that the test is not quite ready for use.

At present, the test looks for six genes known to undergo specific changes during different stages of lung cancer development. The test is used to determine whether the genes have been methylated or not -- that is, whether a portion of the genes have methyl molecules attached to them. When this happens, the genes no longer function normally and cancer results.

People in the study who had three or more methylated genes had a 6.5 fold increased risk for developing lung cancer. It also showed that methylation became more prevalent as the time to lung cancer diagnosis decreased.

"We have developed a way to test for that -- whether the gene is methylated or not methylated," Dr. Belinksy said. In future, there may be drugs that will reduce the methylation process and return gene function to normal. Researchers hope to refine the test and include testing of additional genes known to undergo changes. Eventually, it is hoped the test will be able to predict at least 80% of cases and would be useful in clinical settings.


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