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Cancer: How air pollution might promote some lung cancers (N&V) *UK SMC BRIEFING*
Fine particulate air pollution may promote the proliferation of existing lung cancer-specific genetic mutations, which leads to increased tumour progression, a study published in Nature suggests.
Increased exposure to pollution is associated with a higher incidence of lung cancer. A key driver of this is particulate matter (PM), especially fine particles that are 2.5 micrometres or smaller (PM2.5) and can travel deep into the lung. The interplay between environmental triggers and genetic mutations associated with lung cancer (such as mutations to the EGFR or KRAS genes, two of the most commonly mutated genes in non-small-cell lung cancer) is poorly understood.
Charles Swanton and colleagues investigated the relationship between PM2.5 exposure and frequency of lung cancer in 32,957 individuals with EGFR-mutant lung cancer from four countries (England, Taiwan, South Korea, and Canada). The authors report that exposure to increasing levels of PM2.5 are associated with an increasing estimated incidence of EGFR-mutant lung cancer. Data from 407,509 UK Biobank participants supported this association. The observations of a cohort of 228 individuals with lung cancer from Canada found a higher frequency of lung cancer cases after 3 years of high PM2.5 air pollutant exposure (73%) versus low exposure (40%). This association amongst the Canadian cohort was not observed over a 20-year period, which suggests that 3 years of exposure to high levels of pollution may be sufficient for these cancers to arise.
Mouse models were used to investigate the cellular processes that might underlie cancer progression in relation to air pollution. The authors find that PM2.5 seems to trigger an influx of immune cells and the release of interleukin-1β (a pro-inflammatory signalling molecule) in lung cells. This was seen to exacerbate inflammation and further drive tumour progression in both EGFR and KRAS models of cancer. Blocking interleukin-1β during PM2.5 exposure was shown to prevent EGFR-driven cancer development. The authors also identify alveolar type II (AT2) cells as the likely cells that initiate lung tumours in the presence of PM2.5.
Taken together, these results suggest that PM2.5 could act as a tumour promoter and further aggravate existing cancerous mutations. A new understanding of this relationship may open up avenues for disease prevention, as well as provide an argument in favour of initiatives to address air quality as a priority for public health.
An online press briefing, hosted by the UK Science Media Centre, will take place on Tuesday 04 April at 10:30am London time (BST) (7:30pm AEST).
In order to attend the press briefing you will need to pre-register by following the link.
Expert Reaction
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
Elena Schneider-Futschik is a pharmacist by training and leads the Respiratory Pharmacology Lab at the University of Melbourne, Biochemistry & Pharmacology.
Australia has quite low levels of outdoor air pollution compared to other countries. And levels of most pollutants including particulate matter are within the recommended limits. But levels can peak depending on the time of year and the weather or where exactly you are located.
This study has shown that fine particular matters travel deep into the lung. These environmental triggers together with certain genetic mutations are associated with the development of lung cancer. The authors studied this in almost 33,000 patients from four countries. They clearly show that these particular matters act as a tumour promotor. This is problematic as it is difficult for anyone to avoid air pollution completely, and this new data is very concerning. This should give our policy makers a push to address air quality and healthy lungs as a priority for public health measures.
Matthew Peters is a Professor of Respiratory Medicine at Macquarie University's Woolcock Institute of Respiratory Medicine
At the turn of the 20th century, primary lung cancer was extremely rare. Tobacco drove much of the subsequent increase, and this is waning to a significant extent, but there are gaps in reducing occupational and environmental carcinogen exposure.
Links between lung cancer and PM2.5 are known. High exposure reduces survival after apparently curative lung cancer surgery.
This paper adds a deep molecular genetic understanding of the pathway between PM2.5 exposure and expansion of tumour clones as a prelude to clinical cancer diagnosis. The frequent observation of lung cancer, with specific mutations such as in EGFR, in persons of Asian heritage is not just related to ethnicity/genetics but from the adverse environment.
In Australia, PM2.5 is lower than many foreign cities but there are localised high exposures around arterial roads, in mining areas and notably in the 'dormitory' suburban developments in southwestern Sydney.
The finding that as little as three years of PM2.5 exposure is enough to have a measurable adverse effect should lead to action now. These findings should drive rapid transition to transport energy sources that do not generate PM2.5 – EV and clean hydrogen.
Urban planners should look to these data and ask how we can justify siting childcare centres and the like on arterial roads and heavily trafficked smaller roads – especially where there may be stop-start truck movements.
Professor Hubertus Jersmann is a Respiratory Specialist at the Royal Adelaide Hospital and a Professor in the School of Medicine at University of Adelaide. He is a member of the Thoracic Society of Australia and New Zealand (TSANZ) and the Lung Foundation of Australia (LFA)
The only air that should enter our lungs is fresh, clean air.
Dusts and air pollution can make us ill, and can cause cancer too, even in non smokers. There is no safe level of exposure to air pollution.
Excellent lung health can only be achieved by cutting pollution by as much, and quickly, as possible; as well as aiming for a tobacco and vape-free environment and careful control of dust at work.
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