What Causes 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 Lung Cancer Risk Factors) and how some of them cause cells to become cancer.

Smoking

Smoking tobacco 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. People who smoke and are exposed to other known risk factors such as radon and asbestos are at an even higher risk. Not everyone who smokes gets lung cancer, so other factors like genetics probably play a role as well (see below).

Causes in people who don't smoke

Not all people who get lung cancer smoke. Many people with lung cancer formerly smoked, but many others never smoked at all. And it is rare for someone who has never smoked to be diagnosed with small cell lung cancer (SCLC), but it can happen. 

Lung cancer in people who don't smoke 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 develop 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 people who don't smoke are often different from those that occur in people who do. They tend to develop in younger people and often have certain gene changes that are different from those in tumors found in people who smoke. In some cases, these gene 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. DNA, which comes from both our parents, affects more than just how we look. It 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 control 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. Changes in many different genes are usually needed to cause lung cancer.

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.

Some non-small cell lung cancers (NSCLCs) make too much EGFR protein (which comes from an abnormal EGFR gene). This specific gene change is seen more often with adenocarcinoma of the lung in young, non-smoking, Asian women, but the excess EGFR protein has also been seen in more than 60% of metastatic NSCLCs.

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 a person's lifetime 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 RB1 tumor suppressor gene, are thought to be important in the development of SCLC. Acquired changes in genes such as the p16 tumor suppressor gene and the K-RAS oncogene, are thought to be important in the development of NSCLC. Changes in the TP53 tumor suppression gene and to chromosome 3 can be seen in both NSCLC and SCLC. Not all lung cancers share the same gene changes, so there are undoubtedly changes in other genes that have not yet been found.