For more than a decade, fine particulate matter (PM2.5) pollution has been widely recognized as a carcinogen, and large epidemiologic studies have demonstrated notable links between PM2.5 exposure and lung cancer. To this end, Renelle Myers, MD, FRCPC, recently spoke with the CHEST Physician publication about ongoing work being done to identify populations who are at high risk of lung cancer due to PM2.5 exposure.
Dr. Myers is Clinical Associate Professor of Medicine at the University of British Columbia and Interventional Respirologist at Vancouver General Hospital. She is the medical lead for the British Columbia (BC) Cancer Smoking Cessation Program and leads the Breathomics Lab at the BC Cancer Research Institute, where her team is studying noninvasive breath tests for the early detection of lung cancer and other diseases.
CHEST Physician: What is important to understand about lung cancer risk in 2025, and how does PM2.5 fit into that picture?
Dr. Myers: We can’t really talk about PM2.5 and lung cancer without talking about people who have never used tobacco. We’re seeing an increase in lung cancer in that population. Lung cancer was thought to be a disease only for people who used tobacco, but we need to reframe our thinking. If you have lungs, you can get lung cancer!
In British Columbia, Canada, where I practice, 33% of patients with lung cancer presenting to our tertiary care cancer center are people who never smoked. Much work is ongoing to evaluate the environmental factors such as PM2.5 and the association with lung cancers in people who have never used tobacco.
CHEST Physician: What are some of the questions you or others are attempting to answer?
Dr. Myers: Our group is looking at creating a risk prediction model to identify people with light or no smoking history who are at higher risk of lung cancer. We will incorporate lifetime PM2.5 exposure, as well as other environmental exposures such as secondhand smoke and indoor cooking exposures, and traditional risk factors.
By collecting a detailed residential address history and using satellite and ground measurement PM2.5 data, we can calculate a person’s cumulative PM2.5 exposure in a 10-kilometer by 10-kilometer radius. We found a high association between lung cancer in patients who had never smoked and a history of high PM2.5 exposure.1 Compared with the patients who had used tobacco, those who had not were significantly younger, more frequently female, and more frequently Asian, and the majority of the cohort lived outside of Canada for much of their life before their cancer diagnosis. Of the lung cancers, 92% were adenocarcinoma, and a high percentage were epidermal growth factor receptor-positive. Our finding supported the work done by Professor Charles Swanton’s Lung Adenocarcinoma Promotion by Air Pollutants, published in Nature, proposing that PM2.5 promotes lung cancer by acting on cells that harbor preexisting oncogenic mutations in healthy lung tissue.2
There remain many unanswered questions about exposure type as well as intensity and duration of exposure. Around North America and the globe, there is an increase in wildfires and urban fires, which cause short but very intense exposure to PM2.5. We know that a lifetime exposure of high PM2.5 is associated with lung cancer, but what about these shorter, intense periods? A recent Canadian study, looking at long-term exposure to wildfires and cancer incidence, highlighted that individuals living within a 50-kilometer distance of burn areas displayed consistent elevations in the incidence of both lung cancer and brain tumors compared with cohort members who were never exposed to wildfires.3 Work in this area is ongoing.
CHEST Physician: What needs to be done to further identify high-risk populations?
Dr. Myers: We know that lung cancer screening saves lives through early detection. We simply cannot do population-wide low-dose CT screening. We first need to define the people who never smoked but who are at risk and validate with prospective, large, multicenter, randomized controlled trials to prove the benefit of low-dose CT screening in this population.
National Cancer Institute work on the incidence and mortality of lung cancer in the US population projected a steady increase in the incidence of nontobacco-related lung cancer, which may outpace current smoking-related lung cancer incidence in the coming years. This highlights the importance and urgency of the work to define who to screen, beyond people with smoking history.
There are several nonsmoking-related lung cancer screening trials currently enrolling participants, including one out of New York University—the New York Female Asian Nonsmoker Screening Study—as well as our BC Cancer Lung Health Check for Never Smokers Pilot. These studies will help inform larger trial design.
Lung cancer kills more people than breast, prostate, and colon cancers combined. Yet, there’s stigma around it because it’s associated with smoking. This stigma is reflected in research funding, which limits the speed and capacity of this work.
CHEST Physician: What could one possible path forward look like?
Dr. Myers: One of the areas my lab is working on is finding a biomarker that will indicate an increased risk of lung cancer in this population with a history of never to light smoking. We are looking at breath as a biomarker.4 Breath is an attractive biomarker, as it is noninvasive and point-of-care, and potentially widely deployable. If a breath biomarker can be the first step to indicate increased risk of lung cancer, then patients can go on to low-dose CT screening. We have multiple ongoing studies for breath biomarker discovery in this population.
CHEST Physician: In light of what we know, what can clinicians start doing now?
Dr. Myers: We continue to work in this area, but, in the meantime, nonsmoking-related lung cancer needs to be on the differential of all physicians. We need to shift the mindset to include lung cancer in patients who never smoked, especially younger Asian women with a family history of lung cancer who are presenting with respiratory symptoms such as cough. This population is diagnosed at a later stage; our previous work demonstrated that approximately 60% of the cohort of people who never smoked were diagnosed at stage III or IV, with 40% at stage IV. Last week, I performed a bronchoscopy for tissue diagnosis and staging on a 31-year-old woman, who arrived at the appointment with her 10-month-old baby. She had never smoked and had a 4-cm right upper lobe mass, which was adenocarcinoma.
We need to change our thinking process. If a 60-year-old patient with a 30-pack-year smoking history came in with a chronic cough, lung cancer would be very high on the differential; but this young woman had presented for more than two years with a chronic cough. No chest imaging was done until she had hemoptysis because she was deemed low risk for lung cancer given her age and smoking status.
The other key piece is public education about the harms of air pollution, particularly PM2.5. Each summer across North America, we are faced with increasing wildfires causing high levels (more than 300 micrograms per cubic meter) of PM2.5 that can last for several months in certain areas. We need the public to be aware that exposure to this is dangerous. Breathing in this level of PM2.5 can exacerbate your asthma, can cause COPD exacerbations, and may increase your risk of lung cancer. PM2.5 is a carcinogen. There are apps that track the level of PM2.5 in most areas across North America and notify users during high levels to take precautions, including avoiding outdoor exercise, wearing a mask outdoors, closing the windows, etc.
The health of our environment is important for the health of our population. It’s on us to educate the public and empower people with the knowledge to make the choices to protect themselves.
References
1. Myers R, Brauer M, Dummer T, et al. High-ambient air pollution exposure among never smokers versus ever smokers with lung cancer. J Thorac Oncol. 2021;16(11):1850-1858. doi:10.1016/j.jtho.2021.06.015
2. Hill W, Lim EL, Weeden CE, et al. Lung adenocarcinoma promotion by air pollutants. Nature. 2023;616(7955):159-167. doi:10.1038/s41586-023-05874-3
3. Korsiak J, Pinault L, Christidis T, Burnett RT, Abrahamowicz M, Weichenthal S. Long-term exposure to wildfires and cancer incidence in Canada: a population-based observational cohort study. Lancet Planet Health. 2022;6(5):e400-e409. doi:10.1016/S2542-5196(22)00067-5
4. UBC Faculty of Medicine. Can your breath be used to detect lung cancer? The University of British Columbia. February 12, 2024. https://www.med.ubc.ca/news/can-your-breath-be-used-to-detect-lung-cancer/