{"entity":{"id":"paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023","kind":"paper","name":"Lung adenocarcinoma promotion by air pollutants","aka":[],"tldr":"Healthy lungs already carry cancer-causing mutations. This study argues that fine particles in polluted air do not create the mutation but wake it up, which is why lung cancer happens in people who never smoked.","summary":"Hill, Lim, Weeden and colleagues from the TRACERx consortium and the Francis Crick Institute, with Swanton as senior author, proposed that particulate matter of 2.5 micrometres or less promotes lung cancer by acting on cells that already carry oncogenic mutations in otherwise healthy lung tissue, rather than by causing those mutations.\n\nThe paper combines epidemiology across four within-country cohorts, functional mouse models and ultradeep sequencing of histologically normal lung. It revives the two-step initiation-and-promotion model of tumorigenesis proposed more than seventy years earlier, and gives it a molecular mechanism: an influx of macrophages, release of interleukin-1 beta and a progenitor-like state in EGFR-mutant alveolar type II cells.","asOf":"2026-09-25","links":[{"label":"Nature 2023","url":"https://doi.org/10.1038/s41586-023-05874-3"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37020004/"}],"tags":["lung-evidence"],"related":["paper-zhang-lung-cancer-never-smokers-nat-genet-2021","paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017","idea-prev-clean-air-never-smoker-endpoints"],"cancers":["lung-cancer","nsclc","lung-adenocarcinoma"],"sections":["prevention","early-detection"],"technologies":[],"targets":["egfr","kras"],"drugs":[],"companies":[],"institutions":["francis-crick"],"pathways":[],"terms":["driver-mutation"],"trials":[],"people":["charles-swanton"],"bottlenecks":["b-prevention-adoption","b-early-detection","b-tme-immunosuppression"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2023,"doi":"10.1038/s41586-023-05874-3","pmid":"37020004","authors":"Hill W, Lim EL, Weeden CE, et al.","paperType":"translational","findings":["A significant association between PM2.5 levels and the incidence of lung cancer across 32,957 EGFR-driven lung cancer cases in four within-country cohorts.","Air pollutants caused an influx of macrophages into the lung and release of interleukin-1 beta in mouse models, producing a progenitor-like state in EGFR-mutant alveolar type II epithelial cells.","Ultradeep mutational profiling of histologically normal lung from 295 individuals across 3 clinical cohorts found oncogenic EGFR driver mutations in 18 percent and KRAS driver mutations in 53 percent of healthy tissue samples."],"whatItMeans":"It reframes air quality as cancer policy rather than respiratory policy, and it explains the shape of lung cancer in never-smokers: the mutations are common and mostly silent, and what differs is whether something inflames the tissue enough to let one of them grow.","caveats":["The epidemiological association is observational; the causal chain is demonstrated in mice, not in people.","Interleukin-1 beta blockade has not been tested prospectively as lung cancer prevention in a population exposed to particulates.","Most lung cancer in never-smokers worldwide is not explained by PM2.5 alone; radon, secondhand smoke and cooking fuel exposure sit alongside it."],"changedPractice":false},"route":"/key-papers/paper-hill-lung-adenocarcinoma-air-pollutants-nature-2023/","neighbours":{"paper":[{"id":"paper-zhang-lung-cancer-never-smokers-nat-genet-2021","kind":"paper","name":"Genomic and evolutionary classification of lung cancer in never smokers","route":"/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/"},{"id":"paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017","kind":"paper","name":"Tracking the evolution of non-small-cell lung cancer","route":"/key-papers/paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017/"}],"idea":[{"id":"idea-prev-clean-air-never-smoker-endpoints","kind":"idea","name":"Evaluate clean-air policies using lung cancer in never-smokers","route":"/ideas/idea-prev-clean-air-never-smoker-endpoints/"},{"id":"idea-lung-never-smoker-disease-its-own-programme","kind":"idea","name":"Treat lung cancer in never-smokers as its own disease, with its own detection programme","route":"/ideas/idea-lung-never-smoker-disease-its-own-programme/"}],"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"section":[{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"},{"id":"prevention","kind":"section","name":"Prevention & Risk","route":"/fronts/prevention/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"}],"institution":[{"id":"francis-crick","kind":"institution","name":"The Francis Crick Institute","route":"/institutions/francis-crick/"}],"term":[{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"}],"person":[{"id":"charles-swanton","kind":"person","name":"Charles Swanton","route":"/people/charles-swanton/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-prevention-adoption","kind":"bottleneck","name":"Prevention we already have is not deployed","route":"/bottlenecks/b-prevention-adoption/"},{"id":"b-early-detection","kind":"bottleneck","name":"The hardest cancers are found late","route":"/bottlenecks/b-early-detection/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}]}}