One of the hot topics at the VCCC Alliance Research Conference was the role of air pollution in cancer and the biological responses that trigger it. Our Program Communications Manager, Michelle Henderson, spoke to international guest speaker Professor Charles Swanton from the Francis Crick Institute about his groundbreaking research.
In April this year, research showing the role air pollution plays in the development of cancer was published in the journal Nature. Led by UK researcher Professor Charles Swanton, the study found a significant association between microparticles – particulate matter measuring less than 2.5 micrometres or PM2.5 – in air pollution and lung cancer cases in populations across four different countries. Further research in pre-clinical models revealed how this was happening – the microparticles were sparking an inflammatory response in cells that had existing DNA damage. In short, air pollution wasn’t causing cellular damage leading to cancer, it was the inflammatory response acting on pre-existing DNA mutations.
With Australia entering what some are predicting to be a severe bushfire season, and catastrophic bushfires in the northern hemisphere this year during their summers, what are the implications of this type of air pollutant for our health?
Q: Are bushfires implicated in air pollution and can they have the same impact in driving cancer?
CS: “The truth is, we don’t know how long you need to be exposed (to air pollution) for. Some of the exposures you get if you are close to a bushfire are very much higher to what you’d experience daily in a city with high levels of air pollution.
“What we don’t know is whether acute, very high exposure would have the same impact as chronic, low exposure. I think these epidemiological studies need to be done.
“What we did show in our paper was an association between lung cancer incidence and increasing PM2.5 levels, with an analysis suggesting that three years of this exposure may be sufficient to increase the risk of developing lung cancer with a particular genetic mutation. That doesn’t mean it couldn’t be less time or higher exposures, we just didn’t have the data to investigate these relationships. The key question is whether shorter, bigger exposures can mimic longer, smaller exposures, we just don’t know. It’s an important scientific question.
“I certainly think it is reasonable to be concerned about the potential (harmful impact of bushfire exposure promoting cancer growth). It’s not just lung cancer either. Pollution is associated with multiple other diseases in humans including neurodegenerative disease, premature low birth weight babies, diabetes, cardiovascular disease, strokes, vascular dementia, as well as Alzheimer’s.
“A study recently showed air pollution is responsible for 9 million deaths a year.”
Q: Are any other cancers being linked to air pollution?
CS: “There’s quite a lot of evidence for breast cancer now and one or two others including mesothelioma, head and neck, and nasopharyngeal cancers.”
Q: Are we hypothesising then that if you breathe these microparticles into your lungs that these can make their way to other organs?
CS: “Yes, we are beginning to see unpublished animal data that shows this. You can give these PM2.5 microplastics to mice, and they are taken up, if inhaled into the lung. A couple of weeks later, if you look for the particles (highlighted with fluorescence) you can find them in many organs.
Q: Hang on, microplastics? We’re breathing in microplastics?
CS: “We are. It is estimated that we consume about 5g of plastics a week in our diet and breathing. I’m concerned about it. A credit card’s worth of plastic a week.
“We think these small plastic particles have a similar impact to air pollution. They get into cells and they just sit there.
“We’ve got evidence when you give mice microplastics you get a similar response that we see for air pollution – it promotes lung cancer. The (microplastics) get into the brain, the heart, the kidneys, the liver, they get everywhere."
Q: This reminds me of antibiotics getting into the food chain globally and contributing to antibiotic resistance!
CS: “It's interesting that PM2.5s can carry antimicrobial resistance (AMR) genes and bacteria on them. And I think maybe microplastics can do the same thing. Air pollution has been shown to be associated with AMR across the globe and is thought to be a driver of AMR, because it contains bacterial-resistant plasmids that stick to surface of PMs and get into the cells.
Q: Are there other factors at play?
CS: “There’s a lot of data out there that shows we are all just a patchwork of mutant clones. So we know that these cancer genes, these cancer mutations, may be necessary for cancer initiation, but they are not sufficient on their own. You need another trigger. And that trigger at least in some cases is inflammation. It can be caused by a myriad of things, obesity probably, asbestos fibres, h. pylori (bacteria), air pollution, pancreatitis, inflammatory bowel disease… we’ve known for decades that inflammation is a risk factor for cancer. What we don’t know is what is that relationship between inflammation, cancer and these mutations which accumulate in our normal cells as we age. As they do so, occasionally a driver mutation will allow these normal cells to expand and out-compete their neighbours, despite the fact they look normal under the microscope with no evidence of cancer.
"I think what we are seeing is a rather nice merger of our understanding of the evolution of mutations in normal tissues that may just happen to hit a stem cell compartment with inflammation. Our work simply contributes to a body of evidence that brings the fields of inflammation, stem cell biology, epidemiology and cancer together."
Q: What is your research focusing on now?
CS: We’re spending a lot of time studying microplastics. We are trying to understand the mechanism, why it is these cells take up the air pollutants and what happens to them when they have done so and how they signal. Ultimately we want to try to block these signals without affecting the body’s ability to tackle infectious disease. We are looking at glioma, brain tumours, and also at Alzheimer’s disease because we know these particles get into the brain. There is a lot of evidence that air pollution is strongly associated with Alzheimer’s."
Q: Are some body tissues more vulnerable than others to these microparticles?
CS: We know that the blood vessels are very vulnerable. The incidence of cardiovascular disease goes up with pollution exposure. Macrophages are central to that process. The macrophages get congested, get into the lining of the blood vessels and cause plaques that rupture and result in heart attacks or strokes. We hypothesise that the brain and possibly the gut is sensitive to these microparticles too. These are the areas we are studying in the lab currently."
The VCCC Alliance is grateful to Professor Swanton for presenting his research at the Beyond the Breakthroughs conference. We look forward to following his future research.