Health & Wellness

Never-Smokers: Why Are They Being Diagnosed More Frequently with Lung Cancer?

Apr. 4, 2021

“Never-smokers,” or those who are medically defined as those who have smoked less than 100 cigarettes during their lifetime, now account for an increasingly larger portion of lung cancer cases.  

Why is this happening and how can “never-smokers” protect themselves from being diagnosed with this deadly disease?

Christopher Radchenko, MD medical director of the UC Health Incidental Pulmonary Nodule Program and assistant professor in the Department of Internal Medicine at the University of Cincinnati College of Medicine, provides answers to the questions below, and is available to discuss and clarify information about this topic.

Are never-smokers at (higher) risk for being diagnosed with lung cancer?

Exposure to tobacco smoke is the primary etiologic factor responsible for lung cancer, however, the rate of lung cancer in never-smokers is significant. It’s estimated that in the U.S., 19% of women with lung cancer had never smoked, compared to 9% of men with the disease.

The age-adjusted incidence rate for lung cancer in never-smokers ages 40 to 79 ranges from 11.2 to 13.7 per 100,000 person-years for men, and from 15.2 to 20.8 per 100,000 person-years for women. These incidence rates are similar to those for myeloma in men or cervical cancer in women in the U.S.

Are more never-smokers receiving a lung cancer diagnosis? If so, why?

Emerging data supports the notion that lung cancer in never-smokers is distinct enough from an epidemiologic and biologic standpoint to be considered a separate disease entity. As the number of never-smokers in the U.S. and other countries rise, the issue of lung cancer in this group is becoming more critical.

What does current research say about never-smokers and lung cancer?

A higher percentage of women with lung cancer are never-smokers compared to men. The risk of lung cancer in never-smokers differs by race/ethnicity. Studies in California found that in women, 46% of all lung cancer in Asian/Pacific Islanders was in never-smokers compared to 25% in Hispanics, 11% in African Americans and 10% in non-Hispanic whites. These findings were echoed by another study looking at lung cancer in women, where 71% of lung cancer in Asian/Pacific Islanders was in never-smokers compared to 35% in Hispanic women and 40% in non-Hispanic whites. Furthermore, lung cancer may occur at a younger age in never-smokers.

Multiple studies have shown an association between lung cancer in never-smokers and a family history of lung cancer. In a case-control study of 257 lung cancer cases among never-smokers, lung cancer was significantly more common among those with a positive family history (7.2 odds ratio). Analysis from the Environment and Genetics in Lung Cancer Etiology study, the relative risk (RR) of lung cancer associated with a positive family history, adjusted for age, gender, residence, education and smoking status, was 1.57.

Studies are finding specific mutations that are associated with higher rates of non-small cell lung cancer (NSCLC) in never-smokers. The best understood are mutations are in the epidermal growth factor receptor (EGFR), for which targeted therapies are available.

Do environmental factors (e.g., air pollution, pollutants in the home such as hair spray, air fresheners) have anything to do with this increase?

Pertinent risk factors for never-smokers are many, some of which aren’t completely understood or elucidated, including the impact of hair spray, air fresheners and marijuana exposure on lung cancer. Environmental exposures pertinent to development of lung cancer in never-smokers include asbestos, chromium, arsenic, organic dust, solvents, paints or thinners.

Secondhand smoke is an important risk factor with studies suggesting that approximately 15-35% of lung cancer among never-smokers is due to secondhand smoke.

Radon is a gaseous decay product of uranium-238 and radium-226, and is commonly present in soil, rock and groundwater. Exposure to radon within the home may play a role in the development of lung cancer in never-smokers.

Various dietary factors have been studied, however, none are clearly implicated. Higher intake of fruits and vegetables may be protected against lung cancer. Higher consumption of red meat was found to have higher relative risk for developing lung cancer in never-smokers, and higher consumption of fish may protect against lung cancer in never-smokers. A separate study in the U.S. reported a reduced risk of lung cancer in those with the healthiest dietary patterns (high consumption of fruits/vegetables and of low-fat foods). The consumption of low-moderate amounts of alcohol was potentially protective against lung cancer.

Indoor pollutants, such as vapors from cooking oil and smoke from burning coal, have been linked to lung cancer. Outdoor air pollution is also associated with lung cancer risk. In the Cancer Prevention Study-II, there was a 15-27% increase in lung cancer mortality in never-smokers for increasing concentrations of air pollution. Exposure to diesel exhaust was associated with an increased risk of lung cancer in pooled analyses of studies. Furthermore, in a study using nitrogen dioxide as a marker of air pollution, traffic-related air pollution was linked to increased lung cancer mortality.

What does this mean for lung cancer screening guidelines?

The U.S. Preventative Services Task Force (USPSTF) has recently expanded screening eligibility criteria to adults ages 50-80 years, who have a 20 pack per year smoking history and currently smoke or have quit within the past 15 years. However, lung cancer screening does not capture the never-smoker patient population at risk of lung cancer as they do not meet eligibility criteria.

What do those who are never-smokers need to know about reducing their risk of a lung cancer diagnosis?

To reduce the risk of developing lung cancer, it is most important to avoid smoking and reduce secondhand smoke exposure. If in an environment with possible exposures, it is important to wear appropriate personal protective equipment or avoid the exposure altogether. Commonly, people will have their basements checked for radon, and if levels are increased, install a radon mitigation system. Finally, adjusting your dietary intake to include higher amounts of fruits and vegetables with low-fat foods may reduce your risk of developing lung cancer. 

NOTE: Clinical references for this content are available upon request.