A Dalhousie University-led research project could break new ground when it comes to identifying lung cancer risk in people who’ve never smoked.
An estimated one in five Canadians diagnosed with lung cancer are so-called never-smokers (smoked fewer than 100 cigarettes in their lifetime). They are at increased risk due to environmental factors like radon gas, arsenic, and air pollution.
Atlantic Canadians and residents in the territories have the highest incidence and mortality rates of lung cancer in the country. It’s also one of six cancers identified as having the lowest survival rate.
“When you think about the mortality that comes along with lung cancer… it’s certainly a lot of people that we don’t think about that get lung cancer who had never smoked,” Dr. Robin Urquhart said in an interview.
Urquhart, an associate professor at Dalhousie University’s Department of Community Health and Epidemiology, is leading the five-year project. National in scope, it’s expected to provide information about environmental exposures that increase lung cancer risk and to improve early detection efforts across the country.
Over the course of five years, the multidisciplinary team of researchers will identify biological risk markers related to radon, arsenic, and air pollution. They’ll also develop an air pollution monitoring system to learn more about how it affects cells and elevates cancer risk.
Survival rates could rise dramatically
The project recently received $5 million in funding from the Canadian Cancer Society.
“The thing about lung cancer is that it’s actually a really good candidate for screening, because basically about 70% of all lung cancers are actually diagnosed at an advanced stage right now. So, it’s really low survival rates,” Urquhart said.
“But if you actually diagnosed lung cancer at an earlier stage, survival rates rise quite dramatically. We can actually save a lot of people’s lives if we detect them earlier. And so how would you detect them earlier? Lung cancer screening programs.”
The problem, Urquhart said, is that in provinces where lung cancer screening programs for people at high risk exist or are being implemented, risk assessments only consider a person’s age and smoking history.
“We can actually increase survival to over 80% if it is detected in early stages… And for sure, people who smoke and meet that high risk criteria should be screened as well,” she said.
“But we also know that there are other causes or contributors to lung cancer and those are largely environmental. The number one cause of lung cancer in never-smokers in Canada is radon.”
Climate change impact
Health Canada notes that in addition to being the number one cause of lung cancer after smoking, an estimated 16% of lung cancers are from radon exposure. This results in more than 3,000 lung cancer deaths a year in Canada, a country whose residents are among the most radon-exposed in the world.
A 2021 article published in the journal Nature found that lung cancer in those who’ve never smoked is now the seventh leading cause of cancer-linked death on earth. The authors noted it’s also increasing in prevalence.
“The impact at a population level of radon, arsenic, and air pollution is going to increase in the future. And that is in part because of climate change. Just think about the wildfires in BC. That’s just going to increase,” Urquhart said.
“When I was putting this grant together, I saw some graphs looking at the changes in air pollution over time in BC. It’s unbelievable… And certainly in northern Canada, thawing permafrost, fine permafrost, that’s going to result in increased radon exposure. Climate change is going to impact human health so much, but certainly in terms of lung cancer as well.”
Determining radon and arsenic exposure
Urquhart is also the scientific director of Atlantic PATH, sometimes referred to as the toenail study. The longitudinal project involves following more than 36,000 people in Atlantic Canada over decades to understand the development of cancer. Participants have given toenail, blood, urine, and saliva samples.
Those samples can and will be used for this project to help researchers better understand radon or arsenic exposure that people may have had over their lifetime.
“We have those samples from healthy people, although they may have developed cancer later,” she said.
Halifax is also home to the QEII Lung Tumour Bank, one of the largest human lung tumour banks in the country. Consenting patients with lung cancer allow their tissue to be stored there for future study. Researchers working on the new project will have access to that and to the Atlantic PATH samples.
Urquhart said samples will be used to examine environmental exposures of radon and arsenic in healthy people and in those who’ve already developed lung cancer. This will help researchers better understand what those exposures are doing at the cellular level — more specifically, how they’re damaging the cell and putting it at a higher risk of lung cancer development.
“The plan is all of these different pieces of data, whether we’re looking at residential exposure like air, water, or whether we’re looking at people’s bio samples, that we will be able to actually calculate, based on all the research we’re doing, a person’s personalized lung cancer risk based on environmental exposure,” Urquhart said.
“Today we can calculate a person’s lung cancer risk based on their smoking history. It’s the same thing based on your chronic arsenic exposure or your chronic radon exposure so that we can actually use that in screening programs.”
Biomarkers and early detection
Screening programs currently only look at age and smoking because there’s not yet a way to calculate lung cancer risk based on environmental exposures. Urquhart said the intent of the research project is that five years from now, their work will make that possible.
“If you’ve got certain markers in your body that say, ‘I’m at high risk,’ and maybe we can do that through non-invasive means, like get a person’s toenail… we can say, ‘You know what? You’re in a high risk group. You need to be screened just like somebody who has this smoking history and age,’” she said.
“The idea is to really focus on that 20% that we know are never-smokers. Cancer development is an interplay of a lot of different things, but we know the biggest contributors are arsenic and radon in that population.”
If they can tell based on a biomarker that someone is at high risk for lung cancer due to chronic exposure, Urquhart said they can ensure those people are screened.
“It really is similar to the other screening programs. The goal would be the same — to detect early, to look at markers, whatever they are,” Urquhart said.
“Think about the colorectal screening programs. And if you’re thinking about breast screening and mammography, they’re looking for changes in the breast that would indicate that there’s a cancer. We’re hoping to find them earlier.”
Developing tool to measure residential air pollution
Another project component involves the development of a monitoring system for air pollution. Urquhart said our knowledge of the interplay between air pollution and lung cancer development lags behind that of radon and arsenic.
A biomedical engineer on the research team has already created a prototype for a tool to measure residential air pollution.
“Air pollution, it’s particles. We’re breathing these little tiny microparticles into our lungs. We always thought that it’s the particle itself in a sense that is causing the inflammation and all those things that are going on at the cellular level. There’s a little bit of work out there that’s saying it might not be the particle size that’s really doing it. It’s probably actually what’s on the particle,” Urquhart said.
“Basically, the particles from forest fire smoke might impact your lungs a bit differently than diesel exhaust, or from cooking. What’s interesting with this is we’re going to design this instrument, have people actually collect air pollution in their homes.”
Researchers will then use the tool to determine the content of air pollution inside homes.
“Then in the lab we can look at it and say, ‘OK, so what does forest fire smoke do to your lung cells versus what does cooking fumes do,’ or something like that,” Urquhart said.
“So, we are going to actually measure household air pollution by designing this monitoring system… Air pollution now is monitored for the most part with these huge machines that are put on top of buildings. It’s not measuring your own individual or residential air pollution. In the end, it can be like a radon detector that you put in your home.”
‘A bit of a breakthrough’
Urquhart said focusing on never-smokers and environmental carcinogens is critical, given the importance of early detection and survival.
“It is a growing population of people who are diagnosed with lung cancer and who have poor outcomes. And we need to do something about that,” she said. “I think it is really transformative… It is a bit of a breakthrough.
Urquhart’s passion for cancer research is rooted in her upbringing in rural Newfoundland. She said she grew up with cancer “all around” her. The first person with whom she was close to die in her life was an aunt who died of lung cancer.
Both her parents died of pancreatic cancer when they were in their thirties, and one of her uncles is currently living with lung cancer.
“The idea of cancer itself and trying to improve survival from cancer and improve other outcomes also, it’s been something that has led my whole career,” she said.
“We do actually have to do something about this because this research can actually translate into improved outcomes. We know lung cancer can be cured for most people if it’s detected early… I feel like cancer’s been something that’s impacted my life, including lung cancer, since my earliest memories. I’m just passionate about trying to improve outcomes.”
By the end of the project’s five-year span, Urquhart said they intend to be able to calculate a person’s lung cancer risk based on environmental exposures. They’ll use that information to pilot screening programs across the country for never-smokers who are determined to have an increased risk due to chronic long term exposures.