Irreversible inhalation. Smoking may damage some genes in the lungs beyond repair.

Smoke Clears, But Gene Damage Remains

Doctors may now be able to explain why ex-smokers retain a lifelong risk for lung cancer. Researchers have discovered that the onslaught of cigarette smoke causes 97 genes to malfunction. Kicking the habit lets most genes return to normal function over time, but some are damaged forever.

Cigarette smoke is the leading cause of cancer deaths worldwide. Frustratingly, although lung cancer responds well to treatment if caught early, there is currently no screening test available for the disease--doctors simply don't know what to look for yet. However, thanks to advances in genome data collection, that may change.

In search of early markers of lung cancer, pulmonary and critical care physicians Avrum Spira and Jerome Brody of the Boston Medical Center sampled bronchial tube epithelial cells from 85 people. The study, reported in the 21 June issue of the Proceedings of the National Academy of Sciences, included 34 smokers, 18 former smokers, and 23 people who had never smoked. The team isolated RNA from the cells and looked for patterns in gene expression. Ultimately, the team identified 97 genes that function differently in smokers. Cell detoxification, airway inflammation control, and tumor suppression were dampened while cancer-causing gene activity increased. As expected, gene expression was most severely affected in the heaviest smokers. The team found no difference in gene function based on age or gender.

To their surprise, however, the team discovered that in ex-smokers most of the dampened genes returned to normal levels of gene expression within 2 years. But some of the tumor suppression genes didn't recover and remained forever altered. Encouraged by the study results, the team suggests that it may now be technologically possible to screen for cancer by checking expression levels of bronchial airway cell genes.

"The snapshot of gene expression in smokers, ex-smokers, and nonsmokers is just fascinating," says pathologist Brad Rodu of the University of Alabama in Birmingham. The results of this study "give researchers a road map for a new approach to lung cancer studies," he adds, calling the work a "wonderful first step." If the pattern is verified by a larger study, Rodu says, doctors could one day catch cancers early and begin treatment at the beginning stages of the disease. Spira hopes ultimately to develop a less invasive test using throat epithelial cells, which are easier to access than bronchial tube cells.

Spira's Web site