Several genes within the body can mutate and lead to non-small cell lung cancer (NSCLC). The genes that these mutations can occur with include epidermal growth factor receptor (EGFR), TP53, and KRAS.

There are two types of mutations that can affect people’s genes: somatic and germline.

Somatic mutations occur due to external factors, such as exposure to chemicals, toxins, or other agents. By contrast, germline mutations are hereditary.

This article explores the gene mutations related to NSCLC, whom they affect, what the risk factors are, and more.

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Genes provide the genetic makeup of cells. They determine every aspect of how each cell functions, including when to reproduce and when to die off.

When genes mutate, they can cause issues within the cell. In the case of cancer, mutations lead to uncontrollable cell growth, and the functions they affect include turning off the cell’s ability to die off or divide at the correct time, and turning on the cell’s ability to divide, reproduce, or grow.

When either of these mutations occurs, cancer can develop.

According to a 2020 survey, the mutations leading to NSCLC most commonly affect the following genes:

  • EGFR
  • TP53
  • KRAS
  • MET
  • anaplastic lymphoma kinase (ALK)
  • ROS1
  • BRAF


EGFR is a protein present on the outside of the cell that helps the cell divide and grow. According to research, up to 23% of all NSCLC cases involve the EGFR gene mutation.


TP53 is a gene responsible for helping suppress damaged cells and preventing cancer. It produces a protein called p53 that naturally targets and eliminates potentially problematic cells.

Research has shown that the TP53 gene mutation is present in about 50% of NSCLC cases. Despite its high rate of occurrence, not all doctors believe testing for it is important, because there are currently no targeted therapies to address the mutation.


The KRAS gene mutation mainly affects individuals who have smoked, and it accounts for about 30% of all NSCLC cases.


Of all people living with NSCLC, about 5% have a MET gene mutation. This mutation is often more aggressive than NSCLC cases where the mutation is not present.


The ALK gene mutation affects about 5% of all individuals living with NSCLC.

Similar to other genes, it is responsible for the growth and division of cells. Also, it is more common among those who do not smoke and young people.


About 1–2% of individuals living with NSCLC have the ROS1 gene mutation. The mutation primarily affects young people who do not smoke.


The BRAF gene mutation is common in individuals who used to or currently smoke. It affects about 3–4% of those with NSCLC.

Gene mutations can affect anyone, although some are more common in certain groups of people.

For instance, the KRAS and BRAF gene mutations both occur more frequently in people who used to or currently smoke. By contrast, the ROS1 and ALK gene mutations tend to affect younger individuals who do not smoke.

A person who has a parent with a genetic mutation also has a higher likelihood of inheriting a mutation from one of their parents.

People at risk of developing an inherited form of NSCLC should contact a doctor about when and how often they should get screenings.

Research suggests that people who have inherited gene mutations from their parents have a higher risk of developing NSCLC than others.

While experts still do not fully understand the mutations, which is due to the prevalence of smoking-related risk factors, a person with an inherited gene mutation may have a higher chance of successful treatment with targeted therapies.

According to the American Cancer Society, the most common risk factor for developing NSCLC is smoking.

However, several other factors can increase a person’s risk of having NSCLC in their lifetime, including exposure to:

  • radon
  • secondhand smoke
  • air pollution
  • asbestos
  • diesel exhaust

Chemical exposure, as well as inherited or acquired gene mutations, can also play a role.

The Lung Cancer Foundation of America recommends that people who have received a NSCLC diagnosis get genetic or biomarker testing. These tests look at the gene mutation responsible, which can allow a doctor to provide targeted, more effective treatment for the person.

A biomarker test involves a biopsy. How a doctor carries out the biopsy will vary and can include the use of a long needle, bronchoscope, or other tools.

Once the doctor has removed the tissue, they will send the sample to a laboratory for testing to look for the presence of mutations.

The amount of time it takes to receive test results can depend on the sample size, the laboratory, and the office taking the sample. If results are required quickly, a doctor may request a rush order to get them as fast as possible.

Treatment for NSCLC can depend on which genes have become affected.

A person with a genetic mutation may qualify for targeted therapies. These therapies can help address the exact issue causing the cells to grow uncontrollably.

Standard treatments can also vary based on the stage of the cancer. Some common treatment options include:

Treating NSCLC with targeted drug therapy is a newer treatment approach with promising results. Consequently, these types of therapies are undergoing clinical trials to determine how effective and safe they are in the general population.

Clinical trials involve several stages to test the effectiveness and safety of medications.

There are three main stages. The first stage generally involves the smallest number of participants, while tests in the third stage are often larger and closer to the release of the medication for prescription use.

Clinical trials regularly look for participants. A person interested in taking part in a clinical trial may wish to consult a doctor about any studies they believe the person may be eligible for.

Individuals may also look for recruiting trials on the National Cancer Institute website. They will need to contact a doctor before signing up for a trial. It is also advisable to check for information about costs and length of the trial before signing up.

Genetic mutations, both inherited and acquired, account for several cases of NSCLC.

When a doctor finds the genetic mutation responsible, they may be able to use targeted therapy to better treat the cancer.

A person who receives a lung cancer diagnosis should contact a doctor about undergoing tests for genetic mutations. They may also wish to consider discussing signing up for a clinical trial.