Lung adenocarcinoma promotion by air pollutants

Abstract

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development1. Here we propose that environmental particulate matter measuring ≤2.5 μm (PM2.5), known to be associated with lung cancer risk, promotes lung cancer by acting on cells that harbour pre-existing oncogenic mutations in healthy lung tissue. Focusing on EGFR-driven lung cancer, which is more common in never-smokers or light smokers, we found a significant association between PM2.5 levels and the incidence of lung cancer for 32,957 EGFR-driven lung cancer cases in four within-country cohorts. Functional mouse models revealed that air pollutants cause an influx of macrophages into the lung and release of interleukin-1β. This process results in a progenitor-like cell state within EGFR mutant lung alveolar type II epithelial cells that fuels tumorigenesis. Ultradeep mutational profiling of histologically normal lung tissue from 295 individuals across 3 clinical cohorts revealed oncogenic EGFR and KRAS driver mutations in 18% and 53% of healthy tissue samples, respectively. These findings collectively support a tumour-promoting role for PM2.5 air pollutants and provide impetus for public health policy initiatives to address air pollution to reduce disease burden. Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Shown for reading. Its publisher allows quoting it, not republishing it.

References 74

1. 1.
   A New, Quantitative, Approach to the Study of the Stages of Chemical Carcinogenesis in the Mouse's Skin · 1947

   No notice
2. 2.

   Cogliano VJ, et al. Preventable exposures associated with human cancers. J Nat Cancer Inst. 2011;103:1827-1839.

   Not in our library10.1093/jnci/djr483

3. 3.

   Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers—a different disease. Nat Rev Cancer. 2007;7:778-790.

   Not in our library10.1038/nrc2190

4. 4.

   Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5:2892-2911.

   Not in our library

5. 5.

   Carrot-Zhang J, et al. Genetic ancestry contributes to somatic mutations in lung cancers from admixed Latin American populations. Cancer Discov. 2021;11:591-598.

   Not in our library10.1158/2159-8290.cd-20-1165

6. 6.

   Myers R, et al. High ambient air pollution exposure among never smokers versus ever smokers with lung cancer. J Thorac Oncol. 2021;16:1858.

   Not in our library10.1016/j.jtho.2021.06.015

7. 7.

   Particulate Matter (PM2.5 and PM10), Ozone, Nitrogen Dioxide, Sulfur Dioxide and Carbon Monoxide. 2021.

   Not in our library

8. 8.
   A Compendium of Mutational Signatures of Environmental Agents · 2019

   No notice
9. 9.

   Riva L, et al. The mutational signature profile of known and suspected human carcinogens in mice. Nat Genet. 2020;52:1189-1197.

   Not in our library10.1038/s41588-020-0692-4

10. 10.

    Moody S, et al. Mutational signatures in esophageal squamous cell carcinoma from eight countries with varying incidence. Nat Genet. 2021;53:1553-1563.

    Not in our library10.1038/s41588-021-00928-6

11. 11.

    Zhang T, et al. Genomic and evolutionary classification of lung cancer in never smokers. Nat Genet. 2021;53:1348-1359.

    Not in our library10.1038/s41588-021-00920-0

12. 12.

    Jamal-Hanjani M, et al. Tracking the evolution of non-small-cell lung cancer. N Engl J Med. 2017;376:2109-2121.

    Not in our library10.1056/nejmoa1616288

13. 13.

    Chen Y-J, et al. Proteogenomics of non-smoking lung cancer in East Asia delineates molecular signatures of pathogenesis and progression. Cell. 2020;182:226-244.

    Not in our library10.1016/j.cell.2020.06.012

14. 14.
    The evolution of lung cancer and impact of subclonal selection in TRACERx · 2023

    Corrected
15. 15.

    Takahashi H, Ogata H, Nishigaki R, Broide DH, Karin M. Tobacco smoke promotes lung tumorigenesis by triggering IKKμ- and JNK1-dependent inflammation. Cancer Cell. 2010;17:89-97.

    Not in our library10.1016/j.ccr.2009.12.008

16. 16.

    Im H-B, et al. South Korea Encyclopaedia Britannica.

    Not in our library

17. 17.

    Executive Yuan.

    Not in our library

18. 18.

    Huang Y, et al. Air pollution, genetic factors, and the risk of lung cancer: a prospective study in the UK Biobank. Am J Respir Crit Care Med. 2021;204:817-825.

    Not in our library10.1164/rccm.202011-4063oc

19. 19.

    McDaniel Mims B, Grisham MB. Humanizing the mouse immune system to study splanchnic organ inflammation. J Physiol. 2018;596:3915-3927.

    Not in our library10.1113/jp275325

20. 20.

    Hogg JC, Van Eeden S. Pulmonary and systemic response to atmospheric pollution. Respirology. 2009;14:336-346.

    Not in our library10.1111/j.1440-1843.2009.01497.x

21. 21.

    Sutherland KD, et al. Multiple cells-of-origin of mutant K-Ras-induced mouse lung adenocarcinoma. Proc Natl Acad Sci USA. 2014;111:4952-4957.

    Not in our library10.1073/pnas.1319963111

22. 22.
    Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration · 2020

    No notice
23. 23.
    Alveolar regeneration through a Krt8+ transitional stem cell state that persists in human lung fibrosis · 2020

    No notice
24. 24.

    Ryu MH, et al. Impact of exposure to diesel exhaust on inflammation markers and proteases in former smokers with chronic obstructive pulmonary disease: a randomized, double-blinded, crossover study. Am J Respir Crit Care Med. 2022;205:1046-1052.

    Not in our library10.1164/rccm.202104-1079oc

25. 25.

    Ryu MH. Effects of Traffic-Related Air Pollution Exposure on Older Adults with and without Chronic Obstructive Pulmonary Disease. 2021.

    Not in our library

26. 26.

    Nolan E, et al. Radiation exposure elicits a neutrophil-driven response in healthy lung tissue that enhances metastatic colonization. Nat Cancer. 2022;3:173-187.

    Not in our library10.1038/s43018-022-00336-7

27. 27.

    Dost AFM, et al. Organoids model transcriptional hallmarks of oncogenic KRAS activation in lung epithelial progenitor cells. Cell Stem Cell. 2020;27:663-678.

    Not in our library10.1016/j.stem.2020.07.022

28. 28.
    Contribution of Lung Macrophages to the Inflammatory Responses Induced by Exposure to Air Pollutants · 2013

    No notice
29. 29.

    Klughammer B, et al. Examining treatment outcomes with erlotinib in patients with advanced non-small cell lung cancer whose tumors harbor uncommon EGFR mutations. J Thorac Oncol. 2016;11:545-555.

    Not in our library10.1016/j.jtho.2015.12.107

30. 30.

    Takano APC, et al. Pleural anthracosis as an indicator of lifetime exposure to urban air pollution: an autopsy-based study in Sao Paulo. Environ Res. 2019;173:23-32.

    Not in our library10.1016/j.envres.2019.03.006

31. 31.

    Mirsadraee M. Anthracosis of the lungs: etiology, clinical manifestations and diagnosis: a review. Tanaffos. 2014;13:1-13.

    Not in our library

32. 32.

    Kunzke T, et al. Patterns of carbon-bound exogenous compounds in patients with lung cancer and association with disease pathophysiology. Cancer Res. 2021;81:5862-5875.

    Not in our library10.1158/0008-5472.can-21-1175

33. 33.

    Deprez M, et al. A single-cell atlas of the human healthy airways. Am J Respir Crit Care Med. 2020;202:1636-1645.

    Not in our library10.1164/rccm.201911-2199oc

34. 34.
    An integrated cell atlas of the lung in health and disease · 2023

    No notice
35. 35.
    COSMIC: the Catalogue Of Somatic Mutations In Cancer · 2018

    No notice
36. 36.

    Su F, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366:207-215.

    Not in our library10.1056/nejmoa1105358

37. 37.

    Yoshida K, et al. Tobacco smoking and somatic mutations in human bronchial epithelium. Nature. 2020;578:266-272.

    Not in our library10.1038/s41586-020-1961-1

38. 38.

    Yokoyama A, et al. Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature. 2019;565:312-317.

    Not in our library10.1038/s41586-018-0811-x

39. 39.

    Diesel And Gasoline Engine Exhausts And Some Nitroarenes. 2014;105.

    Not in our library

40. 40.

    Outdoor Air Pollution. 2016;109.

    Not in our library

Cited by papers we hold 4

• Imperfect wound healing sets the stage for chronic diseases · 2024
  No notice
• Aging and cancer · 2024
  No notice
• Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets · 2024
  No notice
• An atlas of epithelial cell states and plasticity in lung adenocarcinoma · 2024
  Corrected

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.