What is the role of genetics in the pathophysiology of non–small cell lung cancer (NSCLC)?

Updated: Jul 15, 2021
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Advanced molecular techniques have identified amplification of oncogenes and inactivation of tumor suppressor genes in NSCLC. The most important abnormalities detected are mutations involving the ras family of oncogenes. The ras oncogene family has 3 members: H-ras, K-ras, and N-ras. These genes encode a protein on the inner surface of the cell membrane with guanosine triphosphatase activity and may be involved in signal transduction.

Studies performed on mice suggest the involvement of ras mutations in the molecular pathogenesis of NSCLC. Studies in humans suggest that ras activation contributes to tumor progression in persons with lung cancer. The ras gene mutations occur almost exclusively in adenocarcinoma and are found in 30% of such cases. These mutations were not identified in adenocarcinomas that developed in persons who do not smoke. The K-ras mutation appears to be an independent prognostic factor.

Studies are ongoing to develop management plans according to the presence or absence of ras gene mutations.

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