The hidden role of genetics in lung cancer

Many people believe lung cancer is solely caused by smoking cigarettes, but that’s just part of the story.

While tobacco use is the leading cause, a surprising number of cases occur in people who have never smoked a cigarette in their life. In addition to second-hand smoke or other environmental factors, genetics can play a role.

According to Dr. Croix Fossum, a board-certified radiation oncologist with Sharp Community Medical Group and affiliated with Sharp Grossmont Hospital, “While it’s true that most lung cancers are associated with smoking, this perception can lead to the misbelief that lung cancer is exclusively a smoker’s disease, which is incorrect.”

About 20% of lung cancer cases occur in nonsmokers, and nearly half of those can be attributed to an inherited genetic predisposition that increases susceptibility to cancer development. In these instances, our genes influence risk by triggering abnormal cell growth and affecting how — or whether — the disease develops and progresses.

Why genetic awareness matters

One in 5 cancer deaths is due to lung cancer — more than colon, breast and prostate cancers combined — making it the deadliest form of cancer in the U.S. While smoking may be the primary cause, understanding the genetic factors could transform how lung cancer is detected and treated.

“Being aware of the genetic factors behind the disease may improve screening and prevention strategies and optimize treatment selection,” says Dr. Fossum. “Ultimately, it enhances outcomes.”

Knowledge of certain gene mutations can guide doctors toward targeted treatments and help identify individuals at higher risk who may benefit from earlier screening and preventive care, especially those who have never smoked. Understanding genetic factors may shape who is screened for lung cancer and how it’s treated, moving providers toward a more personalized, precise approach.

Inherited vs. acquired gene mutations

Genes influence our cancer risk in two ways:

• Inherited (germline) genetic factors are passed from parent to child and are present in all cells from birth. These mutations can significantly increase a person's lifetime risk of developing certain cancers.

• Acquired (somatic) mutations occur during a person’s lifetime in specific cells, often triggered by environmental factors, such as pollution, radiation, random DNA errors or smoking. These mutations are not inherited and are not passed on to children.

Several specific gene mutations, including EGFR, TP53, BRCA1/2, ATM, CHEK2 and MUTYH, have been associated with hereditary lung cancer risk. Identifying these mutations through genetic testing can reveal who might benefit most from early and frequent screening.

Who should consider testing?

Genetic testing may be especially valuable for individuals with a family history of hereditary cancer, particularly those diagnosed at a younger age, with multiple different types of cancer, or with a first-degree relative who has had lung cancer. Developing lung cancer before age 40 or 50 would be considered early, as it’s typically diagnosed around age 70.

Dr. Fossum notes that before testing, it’s important to understand the related emotional and ethical aspects. “Individuals considering genetic testing for hereditary lung cancer risk should be aware of several important emotional and ethical considerations, including psychological impact, implications for family members, privacy and potential for genetic discrimination,” he says.

He adds that these concerns are best addressed through expert genetic counseling and informed consent.

A decade of progress, detection and screening

Advances in genetic testing over the past ten years have significantly changed both the diagnosis and treatment of lung cancer, especially for nonsmokers.

“There are now medications that target cancers with specific gene mutations,” says Dr. Fossum. “Patients who are candidates for these treatments can live two to five times longer today than in previous decades.”

A low-dose screening lung CT (computed tomography) — especially in high-risk individuals, such as those with a smoking history — remains the gold standard for detecting the disease, greatly increasing chances for long-term survival. Dr. Fossum says the benefit for individuals who have never smoked or those with a genetic predisposition is less well-established, but emerging data suggests it could be valuable in selected high-risk groups.

If you’re a current or former smoker or have a strong family history of cancer, talk with your doctor about your individual risk factors and whether screening for lung cancer may be right for you.

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