Study Finds Genetic Aberrations Linked To Lung Cancer; Could Help In Early Diagnosis

Led by Ming You, a professor of molecular virology, immunology and medical genetics, the researchers found 14 genes that are over-expressed - meaning they are too active - in lung cells stricken by cancer. They also identified 12 genes that are under-expressed (not active enough) in these cells.

You and his colleagues reported their findings in a recent issue of the journal Neoplasia. About half of the 26 genes pinpointed in the study have never been linked to lung cancer before.

"In the past five years, lung cancer has killed more people in the U.S. than breast cancer, prostate cancer and colon cancer combined," You said. "We must find methods for early detection of the disease."

For the study, You and his colleagues analyzed samples of cancerous lung tissue taken from patients who had died of the ailment. (Some of these victims had been heavy smokers and one had suffered exposure to asbestos.) The researchers compared the samples to normal lung tissue from the same patients.

Using standard tests, the researchers found that the level of certain proteins in the tumor cells was higher than normal. They traced the increased level of these proteins to the over-expression of 14 genes. In the same way, the researchers traced the low level of another set of proteins to 12 genes that were under-expressed in the tumor cells.

Among the genes identified in the study are ones that regulate intra-cellular communication, cell growth and apoptosis, or programmed cell death. The list includes some known oncogenes - genes that promote cancer when they go into overdrive - and some known tumor-suppressor genes, which fail to check tumor growth when they are under-expressed.

"The over-expression and under-expression of certain genes in lung cells may directly contribute to the initiation or progression of lung cancer," You said. "Alternately, the abnormal expression of these genes may be secondary effects of the tumor development process."

The next step in You's research will be to find out which of the 26 genes identified in this study start behaving abnormally at a relatively early stage in the onset of lung cancer.

"In order to find diagnostic markers for the disease, we need to identify genes that show aberrant behavior before it is too late for treatment," You said.

Successful treatment of lung cancer hinges on early diagnosis - more so than in other cancers - because the continuous flow of blood through the lungs makes the disease very easy to spread inside the body. Most diagnostic methods of today don't do a very good job of spotting lung tumors at a treatable stage, You said.

"We estimate that about 20 percent of the genes identified in our study show signs of alteration at a very early stage of tumor development," You said. To spot these early changes, the researchers plan to analyze lung tissue samples from patients who have been diagnosed at an early stage of their illness - through positron emission tomography (PET) or other imaging techniques.

Equipped with a profile of genetic aberrations that are linked to early tumor growth, it would be possible to distinguish potentially dangerous nodules in a patient's lung from the benign ones. "If you know which lesions are likely to become cancerous, you could start treating them right away," You said. "That would give you enough lead time to halt the progression of the illness."

The research was funded by the National Cancer Institute.