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Research Shows Gene-Based Test Can Prioritize Smokers For Lung Cancer CT Screening

November 10, 2010

Targeting highest risk smokers could make CT screening more cost effective, study finds

New research shows a gene-based test for lung cancer risk can help identify which smokers are most likely to benefit from CT screening for lung cancer, according to results of a study presented today at the American Association of Cancer Research’s Ninth Annual Conference on Frontiers in Cancer Prevention Research.

In studies that included 1,216 lung cancer cases and 1,200 controls gathered from smokers and ex-smokers in three countries, the Respiragene̢Ң gene-based predisposition test accurately identified a subgroup of very high risk smokers (20 percent of the at-risk population) who accounted for just over 50 percent of all lung cancer cases.

The study results demonstrate that is possible to identify those individuals with a regular smoking history most likely to develop lung cancer ““ before symptoms emerge ““ and prioritize them for closer medical attention, including low-dose CT screening, a technology that can find cancers early enough to cure them, researchers said.

“The medical challenge to understand who is most likely to develop lung cancer has become even more urgent with the recent evidence that a regular screening program with CT scans of smokers can save lives,” said Dr. Robert Young, Associate Professor of Medicine and Molecular Genetics at the University of Auckland, who presented the genetic test study results. “Now that the broad benefit of screening for lung cancer has been confirmed, there’s a pressing need to better target screening resources on those individuals who are most at risk from this disease.”

An announcement on November 4th by the National Lung Screening Trial that low dose CT screening was shown to save lives in its 53,000 person study brings wide hope that deaths from the country’s leading cancer killer can be significantly reduced. Lung cancer will kill 157,000 Americans in 2010, and fewer than half of individuals will survive 12 months after diagnosis. Up to 90 percent of the diagnoses will be in current and former smokers, a group now estimated to include 80 million Americans.

But the breakthrough also poses serious medical management dilemmas due to the potential cost of screening millions of smokers and the possible harm of accumulated radiation exposure and false positives from imaging which may, in turn, spur more invasive procedures such as lung biopsies for ultimately non-cancerous lesions. Without better patient targeting, CT screening of smokers or ex-smokers aged 50 and over only picks up cancers in only 1 to 2 percent of those scanned.

“Using Respiragene to prioritize current and former smokers for CT scanning would significantly improve the number of early stage lung cancer cases found per scans administered,” said Dr. Young.

About the Research

Researchers used the Respiragene test on 1,216 confirmed lung cancer cases in cohorts gathered in New Zealand, Spain and the United Kingdom. The test incorporates 20 genetic markers associated with smoking-related lung damage and propensity to lung cancer, along with a smoker’s age, family history, and diagnosis of chronic obstructive pulmonary disease (COPD) to derive a predictive risk score on a 1-12 scale whereby higher scores correlate with higher lifetime risk of developing lung cancer, compared to other smokers.

In the group analysis, current or former smokers with a Respiragene score of 6 or higher, representing 20 percent of the group, identified more than 50 percent of those with lung cancer. With the test featuring a specificity level over 80 percent (i.e. a false positive rate of only 20 percent), this sub-group is at very high risk of getting lung cancer and would likely gain the most benefit from closer surveillance and active screening, including regular CT scans. By increasing the pick-up rate of lung cancer per number of persons scanned, the cost-effectiveness of CT screening can be substantially improved, the study found.

“We are very excited by the possibility that advances in genetics, which allow us to better understand why some smokers are more likely to get lung cancer than others, can now help reduce deaths through effective screening tests like CT,” said Dr. Young.

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