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Common Genetic Variant Tied to Lung Cancer Risk
Date:5/27/2008

It may explain why some nonsmokers contract the disease, study says

TUESDAY, May 27 (HealthDay News) -- A common genetic variant increases the risk of lung cancer, even in nonsmokers, researchers report.

The findings -- that certain forms of the alpha1-antitrypsin gene double someones risk of developing lung cancer, regardless of whether he or she ever smoked -- could help explain why some nonsmokers develop the disease, said study author Dr. Ping Yang, of the Mayo Clinic.

The study also sheds light on why some smokers never develop lung cancer while others do, added William Phelps, scientific program director at the American Cancer Society.

"Part of the reason may be changes like this that are fairly common in the population," he said. "It is a common mutation that adds a modest amount of risk."

Alpha1-antitrypsin (AT) gene deficiencies are among the most common genetic disorders in the United States, affecting at least 10 million Americans. An estimated 11 percent to 12 percent of lung cancer patients in the study carried the defective gene variants, said the study authors, who published their findings in the May 26 issue of Archives of Internal Medicine.

According to Yang, the link between AT deficiency (ATD) and lung cancer involves another disease called chronic obstructive pulmonary disease (COPD). People with COPD are at greater risk of lung cancer, and the diseases often coexist in families, suggesting a genetic link. People with two abnormal copies of the AT gene develop early onset emphysema and ultimately COPD. But those with just one bad copy often have no symptoms at all, the study authors said.

"These carriers may be more vulnerable to carcinogen-containing tobacco smoke than non-carriers in developing lung cancer, especially when their alpha1-AT levels are compromised under physiological stress or have sub-clinical lung tissue damage," Yang explained.

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