Australian respiratory physicians have called for air quality to be prioritised as evidence grows for the health impacts of air pollution including on lung cancer.

Research published in Nature [link here] said as little as three years of fine particulate matter exposure (PM_2.5) could increase the risk of developing EGFR-driven lung cancer.

The article reported on a consistent relationship ship between PM_2.5 levels and EGFR-driven lung cancer incidence in the UK, South Korea and Taiwan – three countries with different ranges of PM_2.5 air pollution and ethnicities.

“The relative rates of EGFR-driven lung cancer incidence (per 100,000 population), per 1 μg m–3 increment of PM_2.5 levels were 0.63 (P = 0.0028) in England, 0.71 (P = 0.0091) in South Korea and 1.82 (P = 4.01 × 10 –6 ) in Taiwan,” it said.

It also showed in Canadian data that EGFR-driven lung cancer cases were significantly higher after 3 years of high air pollutant exposure compared with low exposure.

The investigators said that interaction tests between ever-smoking status and PM_2.5 exposure levels suggested that smoking and high PM_2.5 levels may have a combined effect on lung cancer risk (P= 0.049).

A similar relationship was noted for lip and oropharyngeal cancer, and mesothelioma.

The article also provided experimental data suggesting that PM_2.5 triggers an influx of immune cells and the release of interleukin-1β 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 PM_2.5 exposure was shown to prevent EGFR-driven cancer development.”

It also noted that the monoclonal antibody canakinumab which targets IL-1β has been shown to reduce lung cancer incidence in the cardiovascular prevention trial CANTOS.

“Taken together, these results suggest that PM_2.5 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,” it concluded.

Professor Matthew Peters, Professor of Respiratory Medicine at Macquarie University Hospital and head of Respiratory Medicine at Concord Hospital, said Australia’s air quality was better than many countries.

However localised high exposures around arterial roads, in mining areas and notably in ‘dormitory’ suburban developments such as in southwestern Sydney, should be of concern.

“The finding that as little as three years of PM_2.5 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 PM_2.5 – EV and clean hydrogen,” he said.

“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, a Senior Consultant in the Department of Thoracic Medicine at the Royal Adelaide Hospital and University of Adelaide, said 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.”

Dr Elena Schneider-Futschik, Head of the Cystic Fibrosis Pharmacology Laboratory at the University of Melbourne, said the evidence that fine particular matter can travel deep into the lung was compelling.

“These environmental triggers together with certain genetic mutations are associated with the development of lung cancer. 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 measure,” she said.

Senior investigator Professor Charles Swanton, from the Cancer Evolution and Genome Instability Laboratory in London’s Francis Crick Institute, has previously presented some of this work in the presidential address at the ESMO 2022 meeting [see the limbic‘s related story below].

Meanwhile, a study by the same TRACERx Consortium and also published in Nature [link here] has explored the evolution of metastases in patients with NSCLC.

Amongst its findings, it found smoking at the time of primary tumour resection was an independent predictor of early metastatic divergence “…suggesting that smoking may provide the fuel for ongoing clonal sweeps after metastatic divergence, enabling cancer cells to continually adapt to their environment.”

“Consistent with previous findings, we also observed that platinum chemotherapy acts as a potent mutagen and contributes to tumour heterogeneity and evolution,” it said.