Is non-small cell lung cancer hereditary?

Overview

• A hereditary family history of lung cancer is one of the many risk factors for developing non-small cell lung cancer. About 8% of lung cancers are thought to be inherited or linked to gene changes, but smoking and air pollution remain the primary causes of lung cancer.
• The risk of lung cancer in those with a family history of cancer among first-degree relatives (mother, father, brother/sister, children) is increased by roughly 50% compared to those without a family history.
• A family history increases the risk of lung cancer in both smokers and non-smokers.

Lung cancer risk may be due to inherited genes among family members or it may be due to shared exposures (like smoking, household second-hand smoke, diet, indoor and outdoor air pollution, or radon in the home).

If you have previously had non-small cell lung cancer, you also have a greater chance of developing it again.

What are the top risk factors for lung cancer?

Causes of lung cancer include:

• smoking cigarette and tobacco
• toxins like radon or asbestos
• heavy metals such as arsenic, beryllium, and uranium
• exposure to cancer causing chemicals or asbestos
• radiation (especially to the chest area)
• family history of cancer (inherited risk)
• second-hand smoke
• personal history of previous lung cancer
• alcohol consumption
• other diseases such as tuberculosis (TB) and chronic obstructive pulmonary disease (COPD)
• indoor and outdoor air pollution (for example: diesel exhaust)
• gene changes that can alter lung cells and cause cancer

Not everyone with one of these causes will develop lung cancer. Some people with one or more risk factors may never develop cancer, too. On the other hand, people with no known risk factors may be diagnosed with lung cancer.

In 2021, the American Cancer Society estimated that there were:

• over 235,000 new cases of lung cancer
• close to 132,000 deaths from lung cancer

Do gene mutations cause non-small cell lung cancer?

DNA helps to make up our genes. DNA mutations, which can be inherited or acquired, can affect our risk for developing some kinds of cancer. Certain risk factors may lead to changes in the DNA of lung cells, causing abnormal cell growth and cancer.

Inherited mutations

You can have an inherited risk for lung cancer. You may inherit gene changes from your parents, but this risk factor alone is not thought to contribute to many lung cancers. Gene changes that cause lung cancer are thought to primarily be due to acquired changes.

Researchers have also found inherited changes, such as those to chromosome 6, are more likely to lead to lung cancer, even in people who do not smoke. Some people may have trouble eliminating cancer-causing toxins, such as those found in tobacco smoke or air pollution, due to an inherited risk. People may also inherit genes that lead to faulty DNA repair enzymes.

Some patients with adenocarcinoma of the lung (a common type of NSCLC) make too much of a protein called EGFR due to a faulty gene. This seems to be prevalent in young, non-smoking, Asian women and has also been seen in more than 60% of NSCLCs that have spread (metastatic).

Learn more: Which drugs are used to treat non-small cell lung cancer (NSCLC)?

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Acquired mutations

Gene mutations lead to permanent changes in your DNA. Most lung cancers are due to acquired mutations that happen during your lifetime, not from inherited gene changes.

Acquired gene mutations may be due to environmental or lifestyle factors, such as air pollution or tobacco smoke from cigarettes. Mutations that are acquired can also just happen randomly in a cell without a known cause.

Tumor suppressor genes and oncogenes help control cell division, growth and death of the cell. Changes in these genes may be important in the development of non-small cell lung cancer. For example, acquired changes in the p16 or TP53 tumor suppressor gene, chromosome 3, and the K-RAS oncogene can be important in NSCLC. Researchers continue to find new gene changes through studies. Your doctor may be able to test you for certain gene changes that can help to guide treatment.

Smoking cigarette tobacco is the leading cause of lung cancer and leads to a 13 times higher risk for lung cancer than non-smokers. Cigars and pipe smoking are almost as likely to cause lung cancer as cigarettes. Secondhand smoke is thought to lead to over 7,000 deaths per year in the U.S. Having multiple risk factors can further increase your risk.

Do studies show that genetic changes lead to lung cancer?

Studies in twins have found that a combination of environmental and genetic influences may influence the development of lung cancer.

• Several research studies looking at monozygotic (genetically identical) and dizygotic (sharing half of the segregating genes) twins suggest that environmental and lifestyle factors and smoking habits (but not genetics) contribute to the onset of lung cancer.
• However, a large study in 45,000 monozygotic and dizygotic twins found that they had a 7.7- and 6.7-fold increased risk of lung cancer, respectively, due to a combined effect of genetics and the environment.

A family history of lung cancer is common in patients with non-small cell lung cancer (NSCLC) who have never smoked.

• In one study, researchers found there was a link between NSCLC in families with an EGFR mutated tumor when compared to ALK or KRAS mutated tumors.
• Patients with EGFR mutated tumors had a higher percentage of family history of lung cancer (22%) than other tumor types. In some cases, gene changes can be used to guide treatment.

Other cancers that are commonly associated with a hereditary pattern include: breast, colon, bladder and ovarian cancers.

Related: Pembrolizumab (Keytruda) vs. nivolumab (Opdivo): How do they compare?

Can people who don't smoke get non-small cell lung cancer?

In the U.S. the total numbers of lung cancer diagnoses are going down, but the rate of lung cancer in non-smokers is increasing. Most people who have never smoked get the non-small cell lung cancer (NSCLC) type (instead of small cell lung cancer.) Non-small cell lung cancers can have genetic mutations, but new immunotherapies for treatment have been developed that can target these mutations.

Smoking cigarette tobacco is the leading cause of lung cancer and leads to 13 times higher risk for lung cancer than non-smokers. Cigars and pipe smoking are almost as likely to cause lung cancer as cigarettes. Secondhand smoke is thought to lead to over 7,000 deaths per year in the U.S. Having multiple risk factors, whether they are genetic or acquired, can further increase your risk.