Do we know what causes non-small cell lung cancer?

Smoking

Tobacco smoking is by far the leading cause of lung cancer. About 80% of lung cancer deaths are caused directly by smoking, and many others are caused by exposure to secondhand smoke. Smokers exposed to other known risk factors such as radon and asbestos are at even higher risk.

Lung cancer in non-smokers

Still, not all people who get lung cancer are smokers. Many people with lung cancer are former smokers, but many others never smoked at all. Some of the causes for lung cancer in non-smokers were described in the section called "What are the risk factors for non-small cell lung cancer?" These include exposure to radon, which accounts for about 20,000 cases of lung cancer each year, and exposure to secondhand smoke.

Workplace exposures to asbestos, diesel exhaust, or certain other chemicals can also cause lung cancers in some people who do not smoke. A small portion of lung cancers occur in people with no known risk factors for the disease, so there must be other factors that we don't yet know about.

Genetic factors seem to play a role in at least some of these cancers. Lung cancers in non-smokers are often different in some ways from those that occur in smokers. They tend to occur at younger ages, often affecting people in their 30s or 40s (while in smokers the average age at diagnosis is over 70). The cancers that occur 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 therapy.

Gene changes that may lead to lung cancer

Scientists have begun to understand how the known risk factors for lung cancer may produce certain changes in the DNA of cells in the lungs, causing them to grow abnormally and form cancers. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look. It also can influence our risk for developing certain diseases, such as some kinds of cancer.

Some genes contain instructions for controlling when cells grow and divide. Genes that promote cell division are called oncogenes. Genes that slow down cell division 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. However, inherited mutations 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, 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 may inherit faulty DNA repair mechanisms that make it more likely they will end up with DNA changes. Every time a cell prepares to divide into 2 new cells, it must make a new copy of its DNA. This process is not perfect, and copying errors sometimes occur. Cells normally have repair enzymes that proofread the DNA to help prevent this. People with repair enzymes that don't work as well 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 reliable enough for routine use. 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 external cause.

Acquired changes in certain genes, such as the p53 or p16 tumor suppressor genes and the K-RAS oncogene, 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 likely to grow and spread more rapidly 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.