• Article reviewed by Dr Misako Nagasaka, Oncologist, UCI Health

When people think of lung cancer, smoking is typically the first – and often only – risk factor that comes to mind. It’s the well-known villain, responsible for around 80%-90% of lung cancer deaths in the United States. 

Tobacco smoke contains over 7,000 chemicals, many of which are highly toxic, with at least 70 recognized carcinogens (like benzene, formaldehyde, and arsenic), and each puff exposes lung cells to this hazardous mix of chemicals, which can lead to DNA damage and promote tumor growth over time.

But is someone really safe if they have never smoked a day in their lives?

The short answer is, no.

About 20,000 to 40,000 of all lung cancer cases in the US each year are detected among non-smokers (or people who have smoked less than 100 cigarettes in their lifetime) – a reality that all too often flies under the radar.

“The fact that lung cancer can occur regardless of smoking history, is an aspect of lung cancer care that is most often overlooked or underfunded by the medical community,” says UCI Health oncologist Dr Misako Nagasaka, who focuses on providing patient care, conducting clinical research, and contributing to advancements in the field of oncology, particularly regarding lung cancer treatments and therapies. “Screening for never smokers is a step forward that holds the most potential for the next decade.”

In this blog, we will explore the lesser-known, non-smoking causes of lung cancer and shed light on the factors contributing to its development in individuals without a smoking history. Understanding these risk factors is crucial – not just for prevention, but also for awareness that lung cancer doesn’t always follow the smoking stereotype.

 

# 1: Radon

Radon exposure is the top environmental cause of lung cancer in the United States and the leading cause of the disease among non-smokers. According to the Environmental Protection Agency (EPA), radon exposure is responsible for approximately 21,000 lung cancer deaths annually in the country, with about 2,900 of these cases occurring in people who have never smoked. 

Radon is a colorless, odorless, radioactive gas naturally produced by the decay of uranium in soil, rock, and water. When radon is released from the ground, it can seep into homes and buildings through cracks in foundations, floors, and walls. 

This infiltration is most common in basements and lower-level rooms, where air pressure differences can draw radon gas inside. Once indoors, radon levels can accumulate to concentrations that significantly increase the risk of lung cancer.

 

The primary danger from radon exposure lies in its radioactive decay products, which emit alpha particles. When inhaled, these particles become lodged in the lung tissue, where they continuously emit radiation that damages the DNA of lung cells. Over time, this radiation exposure can lead to mutations and increase the likelihood of cancerous growths. Studies confirm that radon exposure correlates with a significantly increased risk of lung cancer, with risk proportional to radon concentration levels and duration of exposure. 

Certain regions in the United States have naturally higher radon levels due to geological factors. Areas in the Midwest, Appalachian regions, and parts of the Northeast are known for higher radon concentrations, but elevated levels have been found in every state. 

Homes with high radon levels are not restricted to specific areas and may occur anywhere, underscoring the need for universal testing. 

In response, the EPA recommends that all homes, especially those in high-risk zones, be tested for radon. A radon level of 4 picocuries per liter (pCi/L) or higher is considered hazardous, though levels below this threshold still carry some risk.

The risks of radon exposure become even more pronounced for individuals exposed over extended periods, such as those who spend a lot of time indoors or have lived in the same home for decades without mitigation efforts. The EPA and the American Cancer Society emphasize that awareness and mitigation are essential steps for at-risk populations, and installing radon mitigation systems, such as ventilation systems that reduce indoor radon levels, can effectively reduce radon concentration in homes by up to 99%. 

While testing for radon has become more accessible, awareness remains low. The Surgeon General, alongside the EPA, advises testing all homes, schools, and workplaces, particularly in radon-prone areas. Radon is a critical yet under-acknowledged factor in lung cancer prevention, and widespread radon testing could prevent thousands of lung cancer cases each year by enabling mitigation efforts that directly reduce radon exposure.

What non-smokers can do to reduce lung cancer risks from radon in their homes

(Applies to people who are actively smoking as well)

• Test For Radon: Start with a radon test kit, which can be purchased online or at home improvement stores. The EPA recommends testing all homes, especially those in high-risk areas. Short-term tests can provide immediate results, while long-term tests offer a more accurate picture of radon levels.

• Use A Mitigation System: If elevated radon levels are detected (4 picocuries per liter or higher), consider installing a radon mitigation system. The most common method is a soil suction system, which draws radon gas from beneath the house and vents it outside, away from windows and doors. Professional radon mitigators can assess your home and recommend the best system.

• Improve Ventilation: Increasing air circulation can help reduce radon levels. Use exhaust fans in bathrooms and kitchens to enhance airflow. Additionally, opening windows and doors when weather permits can help dilute radon concentrations indoors.

• Monitor Indoor Air Quality: Using air purifiers with HEPA filters can help reduce airborne particulates and improve the general environment within your home.

• Seal Off Cracks And Openings: Seal cracks in floors and walls, around service pipes, and at joints to minimize radon entry points. Use caulk, expandable foam, or other sealants specifically designed for this purpose to ensure a tight seal.

• Install a Radon-Resistant Foundation: If building a new home, consider incorporating radon-resistant construction techniques. This includes features such as a gas-permeable layer beneath the foundation, plastic sheeting, and venting systems to channel radon outside before it enters the home.

• Consult Professionals: For complex situations or persistent high radon levels, consult professionals who specialize in radon testing and mitigation. Their expertise can provide tailored solutions based on your specific home environment.

• Educate Yourself and Others: Help increase awareness about radon risks within your community. Share information and resources on radon testing and mitigation with friends and family, as this collective knowledge can promote healthier living environments.

 

# 2: Occupational Hazards

Exposure to certain carcinogens in the workplace significantly contributes to lung cancer among non-smokers. Industries such as construction, mining, and manufacturing put workers at higher risk due to exposure to substances like asbestos, silica dust, and diesel exhaust.

• Asbestos: Historically used in construction materials, asbestos fibers can be inhaled and trapped in the lungs, leading to lung cancer or mesothelioma. 

When asbestos fibers are inhaled, they can become lodged in the lung tissue, where they may remain for years. The body attempts to eliminate these foreign fibers through immune responses, leading to chronic inflammation. This persistent inflammation can result in cellular changes, DNA damage, and eventually, malignant transformations. Studies have shown that asbestos fibers induce oxidative stress and inflammation, both of which are key contributors to cancer development.

Duration of exposure is a factor as well, and those exposed for extended periods have a significantly increased likelihood of developing lung cancer. The higher the concentration of asbestos fibers in the air, the higher the risk, especially if manual handling of asbestos materials is involved.

Due to the known dangers of asbestos exposure, regulatory agencies, including the Occupational Safety and Health Administration (OSHA), have implemented guidelines to protect workers. These regulations mandate monitoring of air quality in workplaces and limiting permissible exposure levels. Despite these measures, the legacy of asbestos use means that many workers remain at risk, especially in older buildings and industries where asbestos was commonly used before its dangers were widely recognized.

• Silica: Silica, specifically crystalline silica, is a common occupational hazard, putting non-smokers at risk for lung cancer. Silica is a natural mineral found in various forms, with quartz being the most prevalent. It is extensively used in industries such as construction, mining, and manufacturing, where it is often present in materials like sand, concrete, and stone.

The International Agency for Research on Cancer (IARC), which is part of the World Health Organization, classifies crystalline silica as Group 1, meaning it is carcinogenic to humans. 

When these particles are inhaled, they can penetrate deep into the lungs, leading to inflammation and scarring of lung tissue, a condition known as silicosis. This chronic lung disease is characterized by the progressive formation of fibrotic nodules that can impede lung function and lead to respiratory distress. Research has demonstrated that the inflammatory process initiated by silica exposure can cause DNA damage and promote cellular mutations, thereby increasing the risk of lung cancer over time.

• Diesel Exhaust: Diesel exhaust is produced when diesel fuel is burned in engines, releasing a mixture of gasses and fine particulate matter known as diesel particulate matter (DPM). This particulate matter contains a range of harmful substances, including known carcinogens like polycyclic aromatic hydrocarbons (PAHs), benzene, and formaldehyde. Inhalation of diesel exhaust over extended periods is strongly linked to respiratory diseases and increased lung cancer risk for non-smokers.

Research shows that DPM particles are especially concerning because they are small enough to bypass the body’s natural filtration system in the respiratory tract, reaching deep into the alveoli, the air sacs within the lungs where gas exchange occurs. Here, these particles can cause oxidative stress, inflammation, and immune responses, all of which are associated with cancer development.

A major study conducted by the National Cancer Institute (NCI) and the National Institute for Occupational Safety and Health (NIOSH) analyzed data from more than 12,000 workers in the mining industry and found that those with high exposure to diesel exhaust had three times the risk of lung cancer compared to those with lower exposure levels. The risk is also dose-dependent, meaning that the more diesel exhaust a worker is exposed to over time, the higher their risk for lung cancer.

What non-smokers can do to reduce lung cancer risk from occupational hazards

(Applies to people who are actively smoking as well)

• Personal Decontamination: Thoroughly wash hands, face, and any exposed skin after working with hazardous materials.

• Respirators: Use approved respirators (NIOSH-approved) suited to the specific hazard (such as asbestos-rated or particulate respirators) when working in areas with airborne particles.

• Protective Clothing: Wear disposable or specialized work clothing to prevent contamination, especially when handling asbestos or working in high-dust areas.

• Wet Cutting And Handling: Wet down materials like concrete or tiles before cutting to minimize silica dust; wet asbestos-containing materials when removing them.

• Avoid Dry Sweeping Or Compressed Air For Cleaning: Use wet cleaning methods or HEPA-filtered vacuums instead of sweeping to reduce airborne dust.

• Reduce Exposure Duration: Rotate tasks among employees to limit individual exposure times to hazardous environments.

• Lung Health Monitoring: Participate in routine health screenings, including lung function tests, to detect early signs of respiratory issues or lung cancer.

• Medical Surveillance Programs: Join employer-provided surveillance programs if working in industries with high exposure to these hazards to monitor health over time.

 

# 3: Air Pollution

Air pollution is a complex mixture containing particulate matter (PM), nitrogen oxides (NOx), sulfur dioxide (SO2), volatile organic compounds (VOCs), and polycyclic aromatic hydrocarbons (PAHs), many of which have been identified as carcinogens. Particulate matter, particularly PM2.5 (particles smaller than 2.5 micrometers), is especially concerning. PM2.5 particles can penetrate deep into the lungs and remain lodged in lung tissue, initiating inflammation and oxidative stress, both of which are strongly linked to cancer development.

What non-smokers can do to reduce lung cancer risk from air pollution
(Applies to people who are actively smoking as well)

• Limit Exposure To Indoor Pollutants: Avoid using wood-burning stoves and fireplaces, which can emit harmful smoke and pollutants indoors. Consider alternatives, like electric fireplaces, if you need additional warmth.

• Choose Clean Energy Appliances: Gas stoves and appliances can release pollutants like nitrogen dioxide and carbon monoxide. When possible, switch to electric alternatives, and always ensure proper ventilation when using gas stoves, ovens, or heaters.

• Use Masks On High Pollution Days: During periods of poor air quality, especially if outdoor activity is necessary, use N95 or similar masks to reduce inhalation of fine particulate matter (PM2.5) and other harmful pollutants.

• Minimize Car Use: Limit time in heavy traffic, where air quality tends to be worse. Opt for carpooling, public transportation, cycling, or walking. Switching to walking or biking in lower-traffic areas not only reduces your exposure to pollutants but also contributes to lower emissions.

• Plant Indoor And Outdoor Vegetation: Some plants are known to help filter air pollutants, improving indoor air quality. Consider adding indoor plants like spider plants, peace lilies, and Boston ferns, which absorb certain toxins from the air.

• Advocate For Cleaner Air Policies: Engage with local policies that support reduced emissions from factories, transportation, and other major sources of air pollution. Supporting legislation and programs for clean air can have a broader impact on air quality and public health.

 

# 4: Genetic Predisposition

Genetic predisposition refers to the increased likelihood of developing a disease based on an individual’s genetic makeup. In this section, we will explore how hereditary factors contribute to the risk of lung cancer, highlighting specific genetic mutations and their implications.

• Key Genetic Factors: Mutations in the EGFR (epidermal growth factor receptor) gene are prevalent in lung adenocarcinoma, particularly among non-smokers. 

Studies indicate that these mutations are more common in Asian populations compared to Caucasians. EGFR mutations are also more common in females and non-smokers, suggesting a significant genetic predisposition in these groups.

Kirsten rat sarcoma viral oncogene (KRAS) mutations are associated with more aggressive forms of lung cancer, especially lung adenocarcinoma. While KRAS mutations are found in both smokers and non-smokers, they are generally more common in smokers.

The mechanisms by which KRAS mutations contribute to lung cancer development are still being researched, and while they are implicated in tumor progression, it is important to note that they are often associated with poorer prognosis.

• Hereditary Cancer Syndromes: In addition to individual mutations, certain hereditary cancer syndromes increase lung cancer risk. For example: the Li-Fraumeni Syndrome.

Caused by mutations in the TP53 gene, Li-Fraumeni Syndrome significantly increases the risk of various cancers, including lung cancer. Individuals with this syndrome may develop lung cancer at a younger age and often without a significant smoking history.

While Familial Adenomatous Polyposis (FAP) is primarily associated with colorectal cancer due to mutations in the APC gene, it is less commonly linked to lung cancer. The main risks for lung cancer in individuals with FAP are generally considered to be lower compared to other cancers like colorectal and gastrointestinal cancers. However, there may be an increased risk for other types of cancers due to the syndrome, but it is not a primary association.

What non-smokers can do to reduce lung cancer risk from genetic predisposition

(Applies to people who are actively smoking as well)

• Regular Health Screenings: Non-smokers with a family history of lung cancer should consider regular health screenings, including low-dose computed tomography (CT) scans, particularly if they meet criteria based on age and family history. 

Early detection is crucial in improving treatment outcomes. The American Cancer Society recommends discussing screening options with a healthcare provider to tailor a plan that considers personal risk factors.

• Genetic Counseling and Testing: Individuals with a family history of lung cancer may benefit from genetic counseling and testing. Understanding specific genetic mutations can inform personalized risk assessments and management strategies, and genetic counselors can provide insights into preventive measures and the significance of findings.

• Maintain a Healthy Diet: A diet rich in fruits, vegetables, and whole grains can help bolster the immune system and provide essential nutrients that may be of help in reducing cancer risk. Antioxidants found in colorful fruits and vegetables can combat oxidative stress and may protect against cellular damage associated with cancer development. Studies have shown that a diet high in fruits and vegetables correlates with a lower risk of various cancers, including lung cancer.

• Regular Physical Activity: Engaging in regular physical activity can improve overall health and may lower cancer risk. Exercise helps maintain a healthy weight, reduces inflammation, and improves lung function. The American Heart Association recommends at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous activity each week.

• Avoid Secondhand Smoke: Even as non-smokers, individuals should actively avoid environments where they may be exposed to secondhand smoke. Secondhand smoke contains numerous carcinogens that can increase lung cancer risk. Advocating for smoke-free environments in homes and public spaces is vital for personal health and the health of others.

 

# 5: Previous Radiation Therapy

Radiation therapy, a common treatment for various cancers, can inadvertently increase the risk of developing secondary malignancies, including lung cancer. While this risk is particularly relevant for patients who have undergone treatment for cancers in nearby regions – such as breast, head and neck, or esophageal cancers – understanding the mechanisms and implications of radiation exposure is crucial for both patients and healthcare providers.

Radiation therapy works by delivering high-energy rays to targeted cancer cells, aiming to damage their DNA and inhibit their ability to proliferate. However, this treatment can also affect surrounding healthy tissues, leading to mutations that may manifest as secondary cancers over time. Specifically, the lungs are sensitive to radiation due to their complex cellular structure and the high oxygen levels present in lung tissue, which can exacerbate radiation damage.

The latent period between radiation exposure and the development of lung cancer can range from several years to decades, depending on various factors, including the dose of radiation, the area treated, and individual genetic susceptibility. Studies have indicated that patients who receive high doses of radiation to the thoracic region are at a greater risk of developing lung cancer compared to the general population.

Factors influencing risk include:

• Radiation Dose: Higher doses of radiation correlate with an increased risk of lung cancer. Research indicates that patients receiving doses greater than 30 Gy (Gray) to the chest area face significantly elevated risks of secondary lung malignancies.

• Age at Exposure: Younger patients are generally at a higher risk for developing radiation-induced cancers. Those who receive radiation therapy during adolescence or early adulthood may be particularly vulnerable, as their cells are still rapidly dividing, increasing the chances of mutations leading to cancer.

• Cumulative Effects: Patients who undergo multiple radiation treatments for various cancers may experience a cumulative effect, further increasing their risk. For instance, those treated for breast cancer may later develop lung cancer due to prior exposure to radiation in the chest area during their initial treatment.

What non-smokers can do to reduce lung cancer risk from previous radiation therapy

(Applies to people who are actively smoking as well)

• Regular Screening: Engaging in regular health check-ups that may include imaging studies, such as low-dose CT scans, can aid in the early detection of lung cancer. Healthcare providers should consider the patient’s radiation history when recommending screening protocols.

• Lifestyle Modifications: Patients should adopt a healthy lifestyle that includes a balanced diet, regular exercise, and smoking cessation. These factors can help mitigate overall cancer risk and improve lung health.

• Genetic Counseling: Individuals with significant cancer histories may benefit from genetic counseling to assess their risk for various cancers, including lung cancer, and to develop personalized monitoring strategies.

 

# 6: Hormonal Factors

One of the most critical hormonal influences is estrogen, which has been shown to play a role in lung cancer pathogenesis. Research indicates that estrogen receptors are present in lung tissues, and their activation can promote cellular proliferation and tumor growth. This connection suggests that fluctuations in estrogen levels, particularly during menopause or hormone replacement therapy, may increase vulnerability to lung cancer among non-smoking women.

Additionally, the interplay between sex hormones and genetic predisposition cannot be overlooked. Certain polymorphisms in genes related to hormone metabolism can influence an individual’s susceptibility to lung cancer. For example, variations in genes responsible for estrogen metabolism may lead to increased levels of active estrogen in the lungs, potentially heightening cancer risk. This genetic variability underscores the importance of understanding hormonal influence in the context of lung cancer, particularly for non-smokers who may not typically be considered at risk.

Moreover, androgens also play a role in lung cancer risk, particularly in men. Testosterone and its metabolites have been implicated in the modulation of lung tissue response to environmental carcinogens, which may contribute to tumor development. Although the direct relationship between androgens and lung cancer in non-smokers is less established than that of estrogen, emerging studies suggest that hormonal balance is a significant factor that warrants further investigation.

What non-smokers can do to reduce lung cancer risk from hormonal factors

(Applies to people who are actively smoking as well)

• Maintain a Healthy Weight: Obesity has been linked to various cancers, including lung cancer. Maintaining a healthy weight through a balanced diet and regular exercise can help regulate hormonal levels, including estrogen, which may reduce cancer risk. Emphasizing a diet rich in fruits, vegetables, whole grains, and lean proteins can support overall health and hormonal balance.

• Monitor Hormonal Therapies: For individuals considering hormone replacement therapy (HRT) or similar treatments, it is crucial to consult healthcare professionals about the potential risks and benefits. Understanding personal risk factors and opting for the lowest effective dose for the shortest duration can help minimize any associated cancer risks.

• Regular Physical Activity: Engaging in regular physical activity has been shown to positively influence hormone levels and metabolic processes. Exercise can help lower estrogen levels in the body, which may be beneficial for reducing the risk of hormone-related cancers. Aim for at least 150 minutes of moderate-intensity aerobic activity each week, alongside strength training exercises.

Conclusion

The landscape of lung cancer risk is complex and multifaceted. As we deepen our understanding of these causes, it becomes imperative to advocate for stricter regulations on air quality and industrial emissions, as well as to promote awareness around the risks associated with passive exposure. 

Furthermore, ongoing research into the genetic markers of lung cancer will play a critical role in identifying at-risk individuals, enabling earlier detection and intervention. By fostering a comprehensive approach that encompasses education, prevention, and research, we can make significant strides in reducing lung cancer incidence among non-smokers and ultimately save lives.