Test for lung cancer looks for discomforting quiet among protective genes

Sep 18, 2007

When it is quiet – “almost too quiet” – in movies, it is a sign that something is about to go wrong for the good guys. This holds true for the genes that protect against lung cancer, as researchers at the University of Toledo in Toledo, Ohio, have learned. They identified a panel of 15 genes that could serve to predict cancer; if enough of their collective activity becomes quiet – almost too quiet -- it could mean they are being suppressed by other factors in the cell, a step that may lead to cancer.

According to lead researcher, James C. Willey, M.D., a test for these genes, in normal cells sampled via bronchoscopy, could serve as a technique to identify those individuals genetically at risk for lung cancer. In a study of 49 subjects, Dr. Willey and his colleagues were able to correctly identify the individuals with cancer 96 percent of the time. Dr. Willey presents the team’s findings today in Atlanta, Georgia at the American Association for Cancer Research’s second International Conference on Molecular Diagnostics in Cancer Therapeutic Development.

“Smoking causes about 90 percent of all lung cancer cases, yet only about 10 to 15 percent of heavy smokers will develop lung cancer,” said Dr. Willey, an associate professor of medicine and molecular biology at the University of Toledo’s College of Medicine. “We are looking for new techniques that will allow us to pick out the 10 to 15 percent of individuals at highest risk for lung cancer from the enormous pool of current and former smokers.”

While advances in screening tools like high resolution coaxial tomography (HRCT) enable increasingly effective early detection of lung cancer, scanning all present or former heavy smokers is problematic and costly when, due to genetic makeup, 85 to 90 percent of them are at low risk despite smoking history, Dr. Willey said. Therefore, Willey believes that a screen to identify the 10 to 15 percent of high risk individuals should increase the accuracy of further HRCT screening. “In America alone, there are more than 40 million present or former heavy smoking individuals,” Dr. Willey said.

To determine which genes are active in lung cancer, Dr. Willey and his colleagues look for levels of messenger RNA transcripts -- instructions copied from DNA that direct cells to create specific proteins. Previously, the researchers had published findings demonstrating that genes responsible for protecting lung cells from damage caused by cigarette smoke or environmental toxins are sub-optimally regulated in the normal lung cells of individuals who develop lung cancer. In this study, Dr. Willey and his colleagues put their theories to the clinical test by measuring transcript abundance (TA) of 15 genes that encode protective antioxidant and DNA repair proteins in lung airway cells taken from 25 people with lung cancer and 24 people without the disease.

Their previous research allowed them to determine the threshold levels of TA for each gene – the point at which the amount of mRNA transcripts would indicate a tendency toward cancer. In this study, they used the threshold levels as a basis to assign a value of one or zero to each of the targeted genes for an individual subject, with “zero” indicating normal TA.

If the sum total of a subject’s target genes was greater than or equal to seven, the genes could collectively serve as a biomarker for lung cancer, the researchers found. Their results yielded one false negative and seven false positives among the 49 individuals assessed. According to Dr. Willey, they believe that a positive result in a subject without lung cancer may not actually be false positive, but rather could mean that the person is at an increased risk for lung cancer, which might arise later.

These results justify a larger, prospective study to determine whether this biomarker will be useful in predicting risk for lung cancer in current and former smokers. “Overall, the study showed a high degree of accuracy for picking out lung cancer patients,” said Dr. Willey.

Source: American Association for Cancer Research

Explore further: Researchers find chemotherapy after bladder cancer surgery improved survival

add to favorites email to friend print save as pdf

Related Stories

Canada looks east-west to ship oil after Keystone veto

2 hours ago

After US President Barack Obama vetoed a bill to expedite construction of the Keystone XL pipeline Tuesday, petroleum producers are expected to turn to Canadian routes to ship oil internationally, but hurdles ...

Internet access limited in developing world

2 hours ago

Most people in the developing world do not use the Internet, with access limited by high costs, poor availability and a lack of relevant content, a Facebook report said Tuesday.

Manhattan Project physicist Ralph Nobles dies at 94

2 hours ago

(AP)—Ralph Nobles, a nuclear physicist who worked on the Manhattan Project and later led efforts to save thousands of acres of San Francisco Bay wetlands from development, died following complications of pneumonia, according ...

In Japan, robot dogs are for life - and death

2 hours ago

Incense smoke wafts through the cold air of the centuries-old Buddhist temple as a priest chants a sutra, praying for the peaceful transition of the souls of the departed.

US sees little severe weather so far in 2015

2 hours ago

(AP)—While a big chunk of the nation deals with snow and ice, the U.S. is poised to end January and February with the fewest bouts of severe weather in decades.

Recommended for you

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.