Non-Small Cell Lung Cancer - Causes

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Genetic Mutations

Genetic mutations that cause cancer generally occur in two types of genes:

• Tumor-suppressor genes, which prevent cells from endlessly copying themselves
• Proto-oncogenes, which encourage cells to keep making copies of themselves [when a proto-oncogene changes (becomes mutated), it is then called an oncogene]

Damage to either type of gene can cause a mutation that results in uncontrolled division of cells. This uncontrolled division forms tumors.

It is unlikely that a single specific abnormality causes all lung cancer. It probably takes a variety of mutations to start the devastating chain of events leading to cancer. The following mutations are among those under investigation:

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• EGFR mutations: EGFR (epidurmal growth factor receptor gene) is a family of genes that can mutate and promote tumor growth. This gene mutation is often implicated in non-smokers. In the same gene family, HER2 is another gene under study that plays a role in regulating cell growth
• BPDE-caused mutations: The chemical BPDE, a byproduct of tobacco smoke, is involved with a number of genetic mutations, including those to an oncogene called K-ras and to three tumor-suppressor genes known as p53, PPP2R1B, and p16. (Tumors that contain the p53 mutation may also be more resistant to chemotherapy.)
• Rb mutations: Another important contributor to lung cancer is a genetically defective protein called retinoblastoma (Rb), which is associated with very aggressive tumors. Low levels of the normal Rb gene may sometimes predict aggressive cancer, especially in patients with small cell lung cancer.
• Abnormalities in the FHIT gene: Such abnormalities may cause the cells lining the lung to become more vulnerable to the effects of tobacco smoke and other cancer-causing substances.
• Alpha1-antitrypsin mutations: People who carry a common variation in the gene for alpha1-antitrypsin -- a substance that normally protects the walls of the alveoli in the lungs -- are 70% more likely to develop lung cancer than those without the mutation, regardless of whether they smoke.
• Many other gene mutations have been implicated including IL8, SNP, PIB, LKB1 and TITF1. Scientists continue to explore the complex relationship between various genes that play a role in cell production and what environmental factors give rise to cancer.
• Medical centers are beginning to test tumors for specific gene mutations affecting tumor growth. The hope is that an accurate "genetic fingerprint" can help doctors prescribe the most effective and appropriate treatment options.

Review Date: 07/01/2010
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org).