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Lung Cancer in Non-Smokers

Reviewed by: HU Medical Review Board | Last reviewed: January 2017.

While most cases of lung cancer are linked to smoking tobacco, as many as 20 percent of deaths caused by lung cancer occur in people who do not smoke or use any other form of tobacco (approximately 16,000 to 24,000 Americans every year). Although anti-smoking campaigns implemented in the 1980’s have led to a decrease in smoking-related lung cancers, rates of lung cancer are up among non-smokers.

At the World Conference on Lung Cancer in 2015, two studies demonstrated an increase of lung cancer cases among never-smokers. One study showed that during a 6-year period, the incidence of never-smokers diagnosed with non-small cell lung cancer (NSCLC) increased from 13 percent to 28 percent. The second study showed increases from 8.9 percent in 1990-1995 to 19.5 percent in 2011-2013.1-3

Demographics of never-smokers

Among never-smokers, women have a higher incidence of lung cancer than men, but men are more likely to die from lung cancer than women. Women seem to be more susceptible to developing lung cancer but less likely to die from it. The death rate from lung cancer is approximately 25 percent higher in men than in women who have never smoked.4

Early detection can save lives

Early detection of lung cancer is important because the cancer is much more treatable and the prognosis is better when it is found in its earliest stages. However, early detection is challenging in the non-smoking population. In one study, 52 percent of patients had no clear symptoms. Thirty-four percent of patients presented with a cough, but 36 percent of the lung cancer diagnoses occurred due to incidental imaging, such as a chest x-ray taken for another reason.3

Risk factors for lung cancer in non-smokers

While avoiding tobacco smoke is the number one way to reduce the risk of developing lung cancer, researchers have identified several other factors that can increase the risk of developing lung cancer among non-smokers:

Radon gas

Radon is a colorless, tasteless, and odorless gas that is produced by decaying uranium. It occurs naturally in soil and rock, and underground miners have a high risk of exposure to radon. Exposure to radon increases a person’s risk of developing lung cancer, and radon exposure is estimated to be the second-leading cause of lung cancer.2,5

Secondhand smoke

Nonsmokers are 20-30 percent more likely to develop lung cancer if they are exposed to secondhand smoke at home or at work. Secondhand smoke, also known as environmental tobacco smoke (ETS), includes both the smoke exhaled from a smoker and the smoke from a lighted cigarette, pipe, cigar or hookah.2,5

Air pollution

Air pollution has long been considered to be a health risk and to increase the risk for lung cancer. The effect of low levels of air pollution exposure over time are difficult to measure, but some studies have shown that people who live in urban areas have a 10-40 percent increase in lung cancer deaths than those in rural areas.6

Workplace carcinogens

Carcinogens are substances that are known to cause cancer or increase the risk of developing cancer. Lung cancer can be caused due to exposures to carcinogens in the workplace, including asbestos, uranium, and coke from iron manufacturing.5

Genetic mutations

There is a genetic component to the development of lung cancer, as the incidence of lung cancer is greater in those with a family history of the disease, with or without smoking or exposure to environmental carcinogens. One meta-analysis (assessment of multiple studies to combine data) that leveraged data from 32 studies demonstrated a 2-fold increased risk for lung cancer in people with a family history of the disease.6

Differences in lung tumors in non-smokers

Clinical studies have proven that lung tumors in non-smokers are often different at a molecular level (specific mutations or changes in the cancer cells) and respond differently to targeted therapy than lung cancers in smokers. The majority of lung cancers that are adenocarcinomas – cancers that begin in the cells that line the alveoli (the air sacs) – occur in lifelong non-smokers. Centrally-located (in the lung) small-cell carcinomas are rare among non-smokers.1,4

There are several genetic differences in the lung cancers that affect non-smokers compared to the lung cancers that affect smokers. Mutations in the KRAS gene are predominantly present in smokers, and mutations in EGFR are generally related to the lung cancers found in never-smokers. These genetic differences help provide identifying features for targeted therapy to individual patients.4

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