How common is lung cancer in non-smokers?

Lung cancer is the leading cause of cancer-related death and the second most common cancer in the United States. Although smoking is a significant risk factor, Massachusetts General Hospital’s Dr. Jessica Lin emphasizes that “lung cancer can affect anyone with lungs,” not just people who smoke. Recent data shows that 1 in 4 lung cancer cases now occur in non-smokers. Experts are taking a look at some of the factors that may be contributing to the rise of lung cancer in non-smokers. Here’s what we know so far.

Environmental risk factors

When it comes to lung cancer in non-smokers, researchers have been examining the role of environmental and workplace exposures, including radon (a naturally occurring gas that can accumulate indoors), asbestos, and heavy metals.  Additionally, emerging findings suggest worsening air pollution could contribute to an increased risk of lung cancer. In this data, results revealed that non-smokers living in heavily polluted areas were more likely to have increased driver mutations in their lung cancer tumors. As air quality declines in many regions, so may the risk of developing lung cancer, even among those who have never smoked.

Genetic changes in non-smokers

In some non-smokers with lung cancer, the disease may be linked to genetic drivers. These are changes in the DNA within cells that develop over time, not inherited from family members, and they often respond well to targeted therapies. Some acquired changes occur in genes including EGFR, ALK, and ROS1.

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What is EGFR-positive lung cancer?

About 10–15% of non-small cell lung cancers (NSCLCs) are EGFR-positive, and approximately 50% of non-smokers with NSCLC have an EGFR mutation. There are many subtypes of EGFR-mutated lung cancers, each with different treatment options. If you’ve been told that your lung cancer has an EGFR mutation, Dr. Lin suggests to “learn what kind of EGFR mutation it is because that affects what the optimal treatment is for the next step.” For example, Dr. Lin notes that while osimertinib works well for EGFR exon 19 deletion and EGFR L858R mutation, it’s not as effective for other EGFR mutations.

What is ALK-positive lung cancer?

Georgetown University’s thoracic oncologist Dr. Stephen V. Liu says, “ALK-positive refers to a cancer that has an ALK fusion or a chromosomal rearrangement within the ALK gene. We don’t know what is causing it. We’re still trying to figure that out, including why we’re seeing more of these cancers in recent years. This is a cancer that can spread quickly and tends to spread to the brain.”

About 5% of NSCLCs are ALK-positive and 10-15% of non-smokers with NSCLC have an ALK alteration. For these patients, ALK inhibitors are typically the preferred treatments. According to Dr. Liu, these targeted therapies “work very quickly and work for almost everyone.” Although largely effective, Dr. Liu emphasizes that resistance to treatment can occur and the time to resistance is still part of ongoing research.

What is ROS1-fusion positive NSCLC? 

About 1-2% of lung cancers have a ROS1 fusion. Although it’s not as common as ALK-positive and EGFR-positive NSCLC, Dr. Liu advises testing every lung cancer for ROS1 because “if we miss the ROS1 fusion, we’d default to standard treatment, immunotherapy, which largely doesn’t work for these cancers.” When lung cancer has a ROS1 fusion, it uses the ROS1 signal to grow and spread. That’s why ROS1 inhibitors are often used to block this signal. “When we see a ROS1 fusion–positive lung cancer, we know we can treat it by blocking that ROS1 signal,” says Dr. Liu. “These targeted drugs are very effective and we think better tolerated and more effective than chemotherapy.” 

How do you know if your lung cancer has a genetic alteration?

Biomarker testing is the tool your care team uses to find out whether your cancer has a genetic alteration. It’s a critical step in creating a personalized, effective treatment plan. If it hasn’t been done, University of Central Florida’s Dr. Martin F. Dietrich says, “that’s a major missing piece of information. [Biomarker testing] needs to be done as a top priority in selecting treatments. Patients so unanimously deserve genetic testing on a comprehensive basis, really looking for the entire array of abnormalities that can be seen on the genetic level.”

Testing isn’t just important at the time of a diagnosis, Dr. Dietrich notes that retesting can also help track changes in the tumor over time and inform next steps if resistance or changes develop.

What does this mean for you?

With up to 40% of lung cancer patients not receiving DNA testing, Palomar Health’s Dr. Hardeep Phull believes testing should be automatic and “just part of the process.” So, why isn’t it? Dr. Phull explains that it’s taking a while for insurance companies to catch on because it requires sending the tissue off. “Many hospital systems don’t own DNA sequencers,” he adds. 

If you haven’t received biomarker testing, Dr. Lin strongly recommends asking your doctor about it. She emphasizes that biomarker testing allows your care team to tailor a treatment plan that matches the specific genetic makeup of your cancer, opening the door to more effective, targeted treatments with fewer side effects, better outcomes, and enhanced quality of life.

If you’d like to learn more about targeted therapies, tune into Chapter 1 of “Precision Minute” with Dr. Stephen V. Liu.