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How Genetic Mutations Affect Your Lung Cancer Risk
DNA gives your cells instructions based on the order of its nucleotides. When these building blocks are out of sequence or damaged, a gene mutation may be created. Mutations in lung cells can cause an overgrowth of cells that turn into cancer.
“These mutations can keep lung cells from responding to cues that normally would control their growth and survival,” says Katerina Politi, PhD, a researcher and the scientific director of the Center for Thoracic Cancers at Yale Cancer Center in New Haven, Connecticut.
The body doesn’t always inherit gene mutations. It can also acquire them. Inherited mutations come from the DNA you got from your parents, while acquired mutations happen randomly or due to exposure to radiation and chemicals. Mutations can also affect different genes, such as the Kirsten rat sarcoma virus (KRAS) and epidermal growth factor receptor (EGFR) genes. These mutations are often called biomarkers.
KRAS Mutations in Lung Cancer
KRAS genes typically receive and send information that leads to cell growth, and a mutation can mean that cells grow too much, developing into cancer. The KRAS mutation in lung cancer is one of the most common, especially in adenocarcinoma, a type of non-small cell lung cancer.
About 25 percent of all patients diagnosed with lung cancer have a KRAS mutation, a number that goes up to 30 percent for lung adenocarcinomas.
“KRAS mutations are associated with more aggressive tumor behavior and resistance to standard therapies,” says Michael Menefee, MD, a medical oncologist at the Cleveland Clinic in Ohio.
Depending on the stage at diagnosis, the survival rate could be anywhere from eight months to four years, according to research. Treatment has advanced for some KRAS mutation types, however.
Approved treatments for KRAS-positive lung cancer include these methods:
Two KRAS inhibitors, a type of targeted therapy, are approved for patients with the KRAS G12C mutations:
- sotorasib (Lumakras)
- adagrasib (Krazati)
The G12C mutation is the most common KRAS mutation among people with lung cancer, Dr. Menefee says, adding that “there are additional mutations in KRAS for which novel therapies are being developed.”
EGFR Mutations in Lung Cancer
The EGFR gene helps cells grow and multiply. When it mutates, it can promote abnormal cell growth.
Overall, EGFR mutations appear in about 10 to 15 percent of lung cancers diagnosed in the United States, and researchers estimate that nonsmokers with the EGFR mutation have about a 30 percent chance of developing lung cancer.
EGFR-related lung cancer is more common in these groups:
- People who have never smoked
- People assigned female at birth
- People with adenocarcinoma
- Young adults with lung cancer
- People of Asian descent
“There are different types of EGFR mutations, some of which impact prognosis and therapeutic decisions,” Menefee says.
Management and treatment of this mutation has advanced in recent years, he says. Treatment may include these options:
- EGFR inhibitors such as osimertinib (Tagrisso), afatinib (Gilotrif), erlotinib (Tarceva), and lazertinib (Lazcluze)
- Antibody-based targeted therapy such as amivantamab (Rybrevant)
- Combination therapies such as chemotherapy with osimertinib, or lazertinib with amivantamab
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