What causes non-small cell lung cancer?
We don’t know what causes each case of lung cancer. But we do know many of the risk factors for these cancers (see “What are the risk factors for non-small cell lung cancer?”) and how some of them cause cells to become cancerous.
Tobacco smoking is by far the leading cause of lung cancer. About 80% of lung cancer deaths are caused by smoking, and many others are caused by exposure to secondhand smoke.
Smoking is clearly the strongest risk factor for lung cancer, but it often interacts with other factors. Smokers exposed to other known risk factors such as radon and asbestos are at even higher risk. Not everyone who smokes gets lung cancer, so other factors like genetics likely play a role as well (see below).
Lung cancer in non-smokers
Not all people who get lung cancer are smokers. Many people with lung cancer are former smokers, but many others never smoked at all.
Lung cancer in non-smokers can be caused by exposure to radon, secondhand smoke, air pollution, or other factors. Workplace exposures to asbestos, diesel exhaust, or certain other chemicals can also cause lung cancers in some people who don’t smoke.
A small portion of lung cancers occur in people with no known risk factors for the disease. Some of these might just be random events that don’t have an outside cause, but others might be due to factors that we don’t yet know about.
Lung cancers in non-smokers are often different in some ways from those that occur in smokers. They tend to occur at younger ages. Lung cancers in non-smokers often have certain gene changes that are different from those in tumors from smokers. In some cases, these changes can be used to guide treatment.
Gene changes that may lead to lung cancer
Scientists know how some of the risk factors for lung cancer can cause certain changes in the DNA of lung cells. These changes can lead to abnormal cell growth and, sometimes, cancer. DNA is the chemical in our cells that makes up our genes, which control how our cells function. We usually look like our parents because they are the source of our DNA. But DNA also can influence our risk for developing certain diseases, including some kinds of cancer.
Some genes help control when cells grow, divide to make new cells, and die:
- Genes that help cells grow, divide, or stay alive are called oncogenes.
- Genes that help keep cell division under control or cause cells to die at the right time are called tumor suppressor genes.
Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.
Inherited gene changes
Some people inherit DNA mutations (changes) from their parents that greatly increase their risk for developing certain cancers. But inherited mutations alone are not thought to cause very many lung cancers.
Still, genes do seem to play a role in some families with a history of lung cancer. For example, people who inherit certain DNA changes in a particular chromosome (chromosome 6) are more likely to develop lung cancer, even if they don’t smoke or only smoke a little.
Some people seem to inherit a reduced ability to break down or get rid of certain types of cancer-causing chemicals in the body, such as those found in tobacco smoke. This could put them at higher risk for lung cancer.
Other people inherit faulty DNA repair mechanisms that make it more likely they will end up with DNA changes. People with DNA repair enzymes that don’t work normally might be especially vulnerable to cancer-causing chemicals and radiation.
Researchers are developing tests that may help identify such people, but these tests are not yet used routinely. For now, doctors recommend that all people avoid tobacco smoke and other exposures that might increase their cancer risk.
Acquired gene changes
Gene changes related to lung cancer are usually acquired during life rather than inherited. Acquired mutations in lung cells often result from exposure to factors in the environment, such as cancer-causing chemicals in tobacco smoke. But some gene changes may just be random events that sometimes happen inside a cell, without having an outside cause.
Acquired changes in certain genes, such as the TP53 or p16 tumor suppressor genes and the K-RAS or ALK oncogenes, are thought to be important in the development of non-small cell lung cancer. Changes in these and other genes may also make some lung cancers more likely to grow and spread than others. Not all lung cancers share the same gene changes, so there are undoubtedly changes in other genes that have not yet been found.
Last Medical Review: 08/15/2014
Last Revised: 02/08/2016