Lung cancer, the second-most common cancer in the U.S., is often associated with smoking — but even those who have never had a cigarette could be at risk of the deadly disease.

While it’s true that those who smoke face a much higher risk, up to 20% of lung cancers affect people who have never smoked or have smoked fewer than 100 cigarettes in their lifetime, according to the U.S. Centers for Disease Control and Prevention (CDC).

Despite this, the US Preventive Services Task Force (USPSTF) does not recommend lung cancer screening for those who have never smoked, as the agency states the risks may outweigh the potential benefits.

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Most lung cancers fall into two groups: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), according to the American Cancer Society.

NSCLC, which encompasses about 80% to 85% of all lung cancers, includes adenocarcinoma (common in non-smokers), squamous cell carcinoma and large cell carcinoma. 

The remaining lung cancers are classified as SCLC, a more aggressive type that tends to spread faster and has a poorer prognosis. 

Mohamed Abazeed, M.D., Ph.D., chair of radiation oncology and the William N. Brand Professor at the Northwestern University Feinberg School of Medicine in Chicago, agrees that the share of lung cancers diagnosed in never-smokers is increasing, particularly among women and patients of Asian ancestry. 

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“While overall incidence is declining due to reduced smoking rates, the relative share of never-smokers is growing and is reflected in clinical practice, where we increasingly diagnose patients without a traditional smoking history,” he told Fox News Digital.

Dr. Lauren Nicola, a practicing radiologist and chief medical officer at Reveal Dx in North Carolina, said she is also seeing an increase in the rate of newly diagnosed lung cancer in non-smokers, particularly among women and younger adults.

The main factor driving up the share of non-smokers among lung cancer patients, according to Abazeed, is the successful drive to reduce tobacco consumption in the U.S. 

“Other factors include improvements in imaging and broader use of CT scans that have enhanced early-stage tumor detection,” he noted. 

“It is estimated that about 8% of lung cancers are inherited or occur because of a genetic predisposition.”

“Evolving environmental factors may also be contributing to this change, with pollutants potentially driving lung inflammation, which in turn has been implicated in cancer development.”

Modifiable risk factors

Some of the biggest non-smoking risk factors for lung cancer include ambient air pollution and secondhand smoke, according to Abazeed.

Exposure to thoracic radiation (high-energy radiation in the chest area) — along with occupational hazards like radon, asbestos and diesel exhaust — can also increase the risk.

Lifestyle-related inflammation, which is often linked to poor diet and sedentary behavior, can also play a role, Nicola noted.

“Some of these, like radon and air quality, can be addressed at the household or policy level,” Abazeed said. 

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“Lifestyle interventions — such as exercise, diet and avoidance of indoor pollutants — may play a modest protective role.”

Both doctors pointed out that former smokers, especially those who smoked more often and for longer periods of time, remain at elevated risk even decades after quitting.

“The greater the number of pack-years, the higher the risk,” said Nicola. “Risk declines over time after quitting, but never returns to the baseline of a never-smoker.”

Genetic risk factors

Some people inherit a higher risk of developing lung cancer due to their DNA.

“It is estimated that about 8% of lung cancers are inherited or occur because of a genetic predisposition,” Abazeed told Fox News Digital. 

“Inherited predisposition is an area of active investigation, particularly in younger patients or those with a strong family history.”

Having a first-degree relative with lung cancer roughly doubles the risk of developing the disease, even after controlling for smoking exposure, according to Nicola.

“Up to 50% of all chest CTs will detect at least one pulmonary nodule.”

“Cancers in non-smokers are more often associated with specific genetic mutations and genomic profiles,” she said. “This suggests that these malignancies have a different underlying biology compared to tumors in smokers.”

Screenings in question

Current U.S. screening guidelines call for annual low-dose CT scans for high-risk individuals based on age and smoking history, Abazeed reiterated. 

The USPSTF recommends screening for “adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years.”

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“There is a growing interest in expanding eligibility to include non-smoking risk factors,” Abazeed noted. “Evidence is accumulating that could potentially change current population-wide guidelines.”

There are some potential risks linked to expanding screening, experts say, including the potential for overdiagnosis and false positives.

“The problem with screening everyone for lung cancer is that up to 50% of all chest CTs will detect at least one pulmonary nodule,” Nicola noted. “The vast majority of these nodules are benign, but a small percentage will turn out to be cancer.”

Based primarily on the size of the nodule, the clinician may recommend follow-up imaging or biopsy. 

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“New tools are being developed that can help us better characterize the malignancy risk of a nodule, which will decrease the potential for harm associated with overdiagnosis in screening,” Nicola said.