Smokers whose lungs appear to be clear are in fact harboring airway cells that show early signs of impairment similar to that found in lung cancer, researchers have discovered. Physical examinations, lung function tests, and chest x-rays are not sensitive enough to pick up these very early changes, leading patients to mistakenly believe that they have incurred no smoking-related lung damage.

Activation of the human embryonic stem cell (hESC)–signature genes has been observed in various epithelial cancers, explained a team led by Ronald G. Crystal, MD, in a Stem Cells paper. These genes are normally expressed in developing embryos, but are also activated in the most aggressive lung cancers.

In their own study of airway epithelial cells from 21 healthy nonsmokers and 31 smokers with no symptoms of lung disease and with normal x-ray and chest findings, Dr. Crystal and colleagues found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers, with a pattern similar to that activated in all major types of lung cancer found in humans.

“We were surprised to see that the smokers were expressing these very primitive human embryonic stem cell genes,” Crystal affirmed in a separate statement. “These genes are not normally functioning in the healthy lung.”

As Crystal noted, smoking strips lung cells of some of their genetic programming, and they take on the appearance of more primitive cells. “It doesn’t necessarily mean you will develop cancer, but the soil is fertile to develop cancer.”