The a1ATD carrier rate among 1,443 genotyped patients with lung cancer was 13.4 percent, compared to 7.8 percent among unrelated control participants.

All a1ATD gene carriers were at a similarly greater risk of developing lung cancer, regardless of smoking status. Those who had never smoked were at a 2.2-fold higher risk; light smokers had a twofold greater risk; and moderate to heavy smokers had a 2.3-fold increased risk. Although there's no absolute definition, less than 20 pack-years of smoking cigarettes is defined as light; more than 40 pack-years as heavy. A pack-year is the number of packs of cigarettes smoked per day multiplied by the number of years the person has smoked.


A history of COPD increased lung cancer risk significantly for light, moderate and heavy smokers, but affected those who had never smoked the most - an almost sixfold increased risk.

Increased lung cancer risk among a1ATD carriers is independent of a family history of lung or other cancers.

The estimated attributable risk for a1ATD carriers in this study among those who never smoked and among heavy smokers was 11 percent to 12 percent, suggesting that the genetic disorder might explain a significant proportion of lung cancer in the general population. The majority of study participants were of European descent, the population in which this genetic disorder is common.

Although the study helps explain why people who have never smoked can develop lung cancer, it doesn't mean that people who don't have the gene won't develop lung cancer, says Dr. Yang. "Smoking remains the overwhelming risk factor for lung cancer development."

The study was funded by grants from the National Institutes of Health. Co-authors include Zhifu Sun, M.D., Michael Krowka, M.D., Marie-Christine Aubry, M.D., William Bamlet,, Jason Wampfler, Stephen Thibodeau, Ph.D., Jerry Katzmann, Ph.D., Mark Allen, M.D., David Midthun, M.D., Randolph Marks, M.D., and Mariza de Andrade, Ph.D.

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