Particles associated with climate change may cause lung cancer in never-smokers
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Exposure to increased concentrations of airborne particulate matter appeared associated with increased risk for EGFR-mutated non-small cell lung cancer among never-smokers, according to study results presented at ESMO Congress.
Methodology
A mechanistic basis for NSCLC initiation in never-smokers is not known. Particulate matter (PM), an air pollutant often found in vehicle exhaust and smoke from fossil fuels, is known to be associated with risk for NSCLC. However, a direct cause and mechanism has not been identified, according to background provided in the abstract.
For this reason, Charles Swanton, MD, PhD, chief clinician at Cancer Research UK, and colleagues sought to examine the association between increased 2.5 µm PM (PM2.5) concentrations and cancer risk among 463,679 individuals residing in England, South Korea and Taiwan.
Researchers performed ultra-deep profiling of 247 normal lung tissue samples and assessed normal lung tissue from humans and mice after exposure to PM.
Key findings
Researchers identified an association between increased PM2.5 levels and an increased risk for EGFR-mutated NSCLC among the study cohort.
They specifically observed an increased risk for mesothelioma (HR = 1.19); lung cancer (HR = 1.16); anal cancer (HR = 1.23); small intestine cancer (HR = 1.3); glioblastoma (HR = 1.19); lip, oral cavity and pharynx (HR = 1.15) and laryngeal (HR = 1.26) carcinomas among samples in UK Biobank.
Moreover, in the absence of malignancy, 15% of normal lung tissue samples harbored driver mutations in EGFR and 53% harbored KRAS activating mutations.
“The same particles in the air that derive from the combustion of fossil fuels, exacerbating climate change, are directly impacting human health via an important and previously overlooked cancer-causing mechanism in lung cells,” Swanton said in a press release. “The risk [for] lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe. Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and these new data link the importance of addressing climate health to improving human health.”
Next steps
The next steps are to “discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” Swanton said in the release.
“I hope this might start to open up some doors in the context of molecular cancer prevention in high-risk populations,” he said during a presentation. “We have no choice over the air we breathe, and in North America, the poorest are often exposed to the highest levels of PM2.5, so how do we solve this societal problem?”
References :
- Scientists discover how air pollution may trigger lung cancer in never-smokers (press release). Available at: www.esmo.org/newsroom/press-releases/scientists-discover-how-air-pollution-may-trigger-lung-cancer-in-never-smokers. Published Sept. 10, 2022. Accessed Sept. 12, 2022.
- Swanton C, et al. Abstract LBA1. Presented at: European Society for Medical Oncology Congress; Sept. 9-13, 2022; Paris.
Perspective
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Edward S. Kim, MD, MBA, FACP, FASCO
Air pollution has historically been associated with aerodigestive cancers, including lung cancer, and other pulmonary ailments, including asthma. For those who smoke tobacco, the risks are higher and generally supersede the risk of air pollution.
For those who have minimal or never-smoking histories, the development of lung cancer is a bit more confusing. Certainly, exposure to a carcinogen occurs. However, a portion of people may have bronchial epithelium with low susceptibility to carcinogenic exposure, whereas some people may have higher susceptibility.
In this study, it seems that EGFR and KRAS mutations found in normal bronchial epithelial tissue have a higher susceptibility to cause cancer due to particulate matter. More studies will be needed, especially measuring the impact of air pollution and lung cancer susceptibility when other confounders, such as smoking or other biomarkers, are present.
How do we identify people who have EGFR and KRAS in their normal tissue? These people will have a higher propensity to potentially develop lung cancer.
New imaging modalities will need to be developed to help identify these biomarkers in normal tissue. Additionally, what is the true impact of less exposure to particulate matter, even in people with higher susceptibility? Should these individuals wear air filtration devices? What about foreign countries with less regulated air pollution standards? With air pollution existing at varying levels around the world, one needs to assess whether risk is conferred higher with shorter or longer exposure or depth of exposure into the airways and then determine what level of particulate matter is safe or safer for people who harbor these mutations. Further identification of these factors may allow strategies to prevent lung cancer in highly susceptible patients.
Perspective
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Tony S.K. Mok, MD, FRCPC, FASCO
This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for precancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1 beta inhibitors. We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find nonsmokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative.
We have known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. As consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate for tackling these issues — for both environmental and health reasons.
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Swanton C, et al. Abstract LBA1. Presented at: European Society for Medical Oncology Congress; Sept. 9-13, 2022; Paris.
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