Studies have found that the epidermal growth factor receptor (EGFR) gene is mutated in many nonsmall-cell lung cancers and that these mutations are associated with increased sensitivity to gefitinib (Iressa) or erlotinib (Tarceva), tyrosine kinase (TK) inhibitors that target EGFR. Recent studies have found that EGFR gene mutations are more common among females, patients from Japan, never smokers, and patients with adenocarcinomas, which are the same groups that have the highest response rates to TK inhibitors. However, little is known about how EGFR gene mutations affect lung cancer development.

To examine the role of EGFR gene mutations in the development of lung cancer, Adi F. Gazdar, M.D., of the University of Texas Southwestern Medical Center in Dallas, and colleagues searched for these mutations in primary lung tumors from patients in Japan, Taiwan, the United States, and Australia. They also examined these mutations in DNA from nonmalignant lung tissue from many of the lung cancer patients and from other epithelial cancer tissues.

In lung cancer patients, mutations in the TK domain of the EGFR gene were more common in never smokers than in smokers (51% versus 10%), adenocarcinomas versus other types of lung cancer (40% versus 3%), in patients of East Asian ancestry than in other ethnicities (30% versus 8%), and in females versus males (42% versus 14%). Mutation status was not associated with age at diagnosis, clinical stage, the presence of certain histologic features, or overall survival, and they were not found in any normal tissue or tissue from other cancer types. EGFR TK domain mutations are the first known mutation to occur in never smokers. In
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Contact: Sarah L. Zielinski
jncimedia@oupjournals.org
301-841-1287
Journal of the National Cancer Institute
1-Mar-2005