More Genetic Clues to Lung Cancer's Cause

One mutation occurs more often in nonsmokers with the disease

TUESDAY, March 1, 2005 (HealthDay News) -- Researchers say they've identified two gene mutations key to the development of lung cancer, with one occuring more often in people who've never smoked.

Experts and physicians have long suspected that an individual smoker's genes help determine who gets lung cancer. In this latest study of lung cancer patients from the United States, Japan, Taiwan and Australia, researchers at the University of Texas Southwestern Medical Center found that mutations in a specific domain of the epidermal growth factor receptor (EGFR) gene were more common in people who'd never smoked (51 percent) than in smokers (10 percent).

These mutations were also more common in cases of adenocarcinomas (40 percent) than in other forms of lung cancer (3 percent), in people of East Asian ancestry (30 percent) than in other ethnic groups (8 percent), and in females (42 percent) than in males (14 percent), they report.

A second gene mutation also predisposed individuals to lung cancer, but only in the absence of the EGFR mutation, they add. Mutations in a gene called KRAS occurred in 8 percent of lung cancers, but the variant was not found in any lung cancers that already had an EGFR mutation.

The findings "support the hypothesis that at least two distinct molecular pathways" determine the development of either the EGFR-type cancer, or the KRAS malignancy, the study authors wrote.

The findings also suggest that something outside of exposure to secondhand smoke might be to blame for many of the lung cancers seen in nonsmokers, according to the researchers.

Last week, two groups of researchers reported that a second gene mutation in EGFR explains why some lung cancer tumors become resistant to treatment with the newest cancer drugs.

More information

The U.S. National Cancer Institute has more about lung cancer.

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