Lung adenocarcinoma promotion by air pollutants

Abstract

Environmental carcinogenic exposures are major contributors to global disease burden yet how they promote cancer is unclear. Over 70 years ago, the concept of tumour promoting agents driving latent clones to expand was rst proposed. In support of this model, recent evidence suggests that human tissue contains a patchwork of mutant clones, some of which harbour oncogenic mutations, and many environmental carcinogens lack a clear mutational signature. We hypothesised that the environmental carcinogen, <2.5μm particulate matter (PM2.5), might promote lung cancer promotion through nonmutagenic mechanisms by acting on pre-existing mutant clones within normal tissues in patients with lung cancer who have never smoked, a disease with a high frequency of EGFR activating mutations. We analysed PM2.5 levels and cancer incidence reported by UK Biobank, Public Health England, Taiwan Chang Gung Memorial Hospital (CGMH) and Korean Samsung Medical Centre (SMC) from a total of 463,679 individuals between 2006-2018. We report associations between PM2.5 levels and the incidence of several cancers, including EGFR mutant lung cancer. We nd that pollution on a background of EGFR mutant lung epithelium promotes a progenitor-like cell state and demonstrate that PM accelerates lung cancer progression in EGFR and Kras mutant mouse lung cancer models. Through parallel exposure studies in mouse and human participants, we nd evidence that in ammatory mediators, such as interleukin-1 , may act upon EGFR mutant clones to drive expansion of progenitor cells. Ultradeep mutational pro ling of histologically normal lung tissue from 247 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 33% of normal tissue samples, respectively. These results support a tumour-promoting role for PM acting on latent mutant clones in normal lung tissue and add to evidence providing an urgent mandate to address air pollution in urban areas.

Structural Racism and Lung Cancer Risk

“…Multiple studies demonstrated that neighborhoods with high concentrations of African American or Hispanic patients have higher exposures to environmental carcinogens, including particulate matter less than 2.5 μg (PM 2.5 ), nitrogen oxide, benzenes, and carbon monoxide . The association of PM 2.5 , nitrogen oxide, and other pollutants with lung cancer risk is well established . Although we did not find a specific article that evaluated the direct link between the increased risk of environmental carcinogens that African American and Hispanic/Latino individuals experience with lung cancer risk, a secondary analysis of patients with lung cancer in a single center in California found an association between neighborhood PM 2.5 and an aggressive non–small cell lung cancer somatic ( TP53 ) mutation.…”

“…22,23,29,39,40 The association of PM 2.5 , nitrogen oxide, and other pollutants with lung cancer risk is well established. 44,45 Although we did not find a specific article that evaluated the direct link between the increased risk of environmental carcinogens that African American and Hispanic/Latino individuals experience with lung cancer risk, a secondary analysis of patients with lung cancer in a single center in California found an association between neighborhood PM 2.5 and an aggressive non-small cell lung cancer somatic (TP53) mutation. In this cohort, census block groups with higher minority populations had statistically higher PM 2.5 exposure levels.…”

Exploring Single-Cell Exposomics by Mass Spectrometry

“…Single-cell-type exposomics offers several applications with the potential to drive significant discoveries. For instance, one could conduct single-cell exposome analysis on different lung cell types to scrutinize their differential responses to particulate matter exposures . The expected findings could demonstrate that distinct cell types exhibit varying adaptive metabolic responses, underlining the importance of cell-specific analyses in deciphering complex pathophysiological processes.…”

Role of WSOCs and pH on Ammonium Nitrate Aerosol Efflorescence: Insights into Secondary Aerosol Formation

“…Atmospheric aerosols possess complex compositions of organic and inorganic components that dictate their phase and mixing states. With variations of the ambient relative humidity (RH), changes in aerosol water content led to phase transitions such as effloresce, deliquescence, and liquid–liquid phase separation. − Effloresced particles, formed via crystallization of dissolved salts upon water evaporation, can directly or indirectly affect the radiative forcing, cloud formation, and atmospheric chemistry due to the changes in physicochemical properties (e.g., morphology, size, refractive index). − Therefore, aerosol efflorescence plays a crucial role in atmospheric processes and has profound impact on climate, air quality, , and human health. − …”