Posted: Wednesday, October 5, 2022
Although the air pollutant particulate matter is known to be associated with an increased risk of non–small cell lung cancer (NSCLC), the mechanism behind its connection to NSCLC in patients who have never smoked remains elusive. Study results, presented during the Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract LBA1), suggested a mechanistic basis for lung cancer associated with particulate matter. The study authors provided evidence to limit air pollution and presented opportunities for molecular targeted cancer prevention.
“These results shed light on the etiology of EGFR-mutated lung cancer, particularly in never-smokers, and suggest that oncogenic mutations may be necessary but insufficient for tumor formation,” Charles Swanton, MBBS, PhD, of The Francis Crick Institute, London, and colleagues concluded.
The study authors evaluated more than 450,000 individuals to address the associations of increasing 2.5 µm particulate matter (PM2.5) concentrations with cancer risk. Ultra-deep profiling was performed on 247 normal lung tissue samples (normal lung tissue from humans and mice following exposures to particulate matter). Using mouse lung cancer models, the study authors investigated the consequences of airborne pollution on tumor promotion.
Higher levels of PM2.5 were associated with an increased risk of NSCLC with EGFR mutations in England, South Korea, and Taiwan. It was also associated with an increased risk of several cancers, including mesothelioma, lung, anal, small intestine, glioblastoma, lip, oral cavity and pharyngeal, and laryngeal cancers.
In the absence of malignancy, 18% to 33% of normal lung tissue samples harbored driver mutations in EGFR and KRAS. The study authors found that particulate matter increased tumor burden in three EGFR- or KRAS-driven lung cancer models in a dose-dependent manner. The study authors also uncovered an actionable inflammatory axis driven by interleukin-1b (IL-1b) in response to particulate matter. Anti–IL-1b therapy reduced particulate matter–induced tumor formation in mice and may show similar results in humans, suggesting a mechanistic basis driving lung cancer following exposure to particulate matter.
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.