Lung adenocarcinoma promotion by air pollutants

Hill, W. et al. (2023) Lung adenocarcinoma promotion by air pollutants. Nature, 616(7955), pp. 159-167. (doi: 10.1038/s41586-023-05874-3) (PMID:37020004)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dick, Dr Craig and Le Quesne, Professor John and Blyth, Professor Kevin
• Authors: Hill, W., Lim, E. L., Weeden, C. E., Lee, C., Augustine, M., Chen, K., Kuan, F.-C., Marongiu, F., Evans, E. J., Moore, D. A., Rodrigues, F. S., Pich, O., Bakker, B., Cha, H., Myers, R., van Maldegem, F., Boumelha, J., Veeriah, S., Rowan, A., Naceur-Lombardelli, C., Karasaki, T., Sivakumar, M., De, S., Caswell, D. R., Nagano, A., Black, J. R. M., Martínez-Ruiz, C., Ryu, M. H., Huff, R. D., Li, S., Favé, M.-J., Magness, A., Suárez-Bonnet, A., Priestnall, S. L., Lüchtenborg, M., Lavelle, K., Pethick, J., Hardy, S., McRonald, F. E., Lin, M.-H., Troccoli, C. I., Ghosh, M., Miller, Y. E., Merrick, D. T., Keith, R. L., Al Bakir, M., Bailey, C., Hill, M. S., Saal, L. H., Chen, Y., George, A. M., Abbosh, C., Kanu, N., Lee, S.-H., McGranahan, N., Berg, C. D., Sasieni, P., Houlston, R., Turnbull, C., Lam, S., Awadalla, P., Grönroos, E., Downward, J., Jacks, T., Carlsten, C., Malanchi, I., Hackshaw, A., Litchfield, K., Lester, J. F., Bajaj, A., Nakas, A., Sodha-Ramdeen, A., Ang, K., Tufail, M., Chowdhry, M. F., Scotland, M., Boyles, R., Rathinam, S., Wilson, C., Marrone, D., Dulloo, S., Fennell, D. A., Matharu, G., Shaw, J. A., Riley, J., Primrose, L., Boleti, E., Cheyne, H., Khalil, M., Richardson, S., Cruickshank, T., Price, G., Kerr, K. M., Benafif, S., Gilbert, K., Naidu, B., Patel, A. J., Osman, A., Lacson, C., Langman, G., Shackleford, H., Djearaman, M., Kadiri, S., Middleton, G., Leek, A., Hodgkinson, J. D., Totten, N., Montero, A., Smith, E., Fontaine, E., Granato, F., Doran, H., Novasio, J., Rammohan, K., Joseph, L., Bishop, P., Shah, R., Moss, S., Joshi, V., Crosbie, P., Gomes, F., Brown, K., Carter, M., Chaturvedi, A., Priest, L., Oliveira, P., Lindsay, C. R., Blackhall, F. H., Krebs, M. G., Summers, Y., Clipson, A., Tugwood, J., Kerr, A., Rothwell, D. G., Kilgour, E., Dive, C., Aerts, H. J. W. L., Schwarz, R. F., Kaufmann, T. L., Wilson, G. A., Rosenthal, R., Van Loo, P., Birkbak, N. J., Szallasi, Z., Kisistok, J., Sokac, M., Salgado, R., Diossy, M., Demeulemeester, J., Bunkum, A., Stewart, A., Frankell, A. M., Karamani, A., Toncheva, A., Huebner, A., Chain, B., Campbell, B. B., Castignani, C., Puttick, C., Richard, C., Hiley, C. T., Pearce, D. R., Karagianni, D., Biswas, D., Levi, D., Hoxha, E., Cadieux, E. L., Colliver, E., Nye, E., Gálvez-Cancino, F., Athanasopoulou, F., Gimeno-Valiente, F., Kassiotis, G., Stavrou, G., Mastrokalos, G., Zhai, H., Lowe, H. L., Matos, I. G., Goldman, J., Reading, J. L., Herrero, J., Rane, J. K., Nicod, J., Lam, J. M., Hartley, J. A., Peggs, K. S., Enfield, K. S. S., Selvaraju, K., Thol, K., Ng, K. W., Dijkstra, K., Grigoriadis, K., Thakkar, K., Ensell, L., Shah, M., Duran, M. V., Litovchenko, M., Sunderland, M. W., Dietzen, M., Leung, M., Escudero, M., Angelova, M., Tanić, M., Chervova, O., Lucas, O., Al-Sawaf, O., Prymas, P., Hobson, P., Pawlik, P., Stone, R. K., Bentham, R., Hynds, R. E., Vendramin, R., Saghafinia, S., López, S., Gamble, S., Ung, S. K. A., Quezada, S. A., Vanloo, S., Zaccaria, S., Hessey, S., Ward, S., Boeing, S., Beck, S., Bola, S. K., Denner, T., Marafioti, T., Mourikis, T. P., Watkins, T. B. K., Spanswick, V., Barbè, V., Lu, W.-T., Liu, W. K., Wu, Y., Naito, Y., Ramsden, Z., Veiga, C., Royle, G., Collins-Fekete, C.-A., Fraioli, F., Ashford, P., Clark, T., Forster, M. D., Lee, S. M., Borg, E., Falzon, M., Papadatos-Pastos, D., Wilson, J., Ahmad, T., Procter, A. J., Ahmed, A., Taylor, M. N., Nair, A., Lawrence, D., Patrini, D., Navani, N., Thakrar, R. M., Janes, S. M., Hoogenboom, E. M., Monk, F., Holding, J. W., Choudhary, J., Bhakhri, K., Scarci, M., Hayward, M., Panagiotopoulos, N., Gorman, P., Khiroya, R., Stephens, R. C. M., Wong, Y. N. S., Bandula, S., Sharp, A., Smith, S., Gower, N., Dhanda, H. K., Chan, K., Pilotti, C., Leslie, R., Grapa, A., Zhang, H., AbdulJabbar, K., Pan, X., Yuan, Y., Chuter, D., MacKenzie, M., Chee, S., Alzetani, A., Cave, J., Scarlett, L., Richards, J., Ingram, P., Austin, S., Lim, E., De Sousa, P., Jordan, S., Rice, A., Raubenheimer, H., Bhayani, H., Ambrose, L., Devaraj, A., Chavan, H., Begum, S., Buderi, S. I., Kaniu, D., Malima, M., Booth, S., Nicholson, A. G., Fernandes, N., Shah, P., Proli, C., Hewish, M., Danson, S., Shackcloth, M. J., Robinson, L., Russell, P., Blyth, K. G., Dick, C., Le Quesne, J., Kirk, A., Asif, M., Bilancia, R., Kostoulas, N., Thomas, M., DeGregori, J., Jamal-Hanjani, M., and Swanton, C.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Nature
• Publisher: Nature Research
• ISSN: 0028-0836
• ISSN (Online): 1476-4687
• Published Online: 05 April 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Nature 616(7955): 159-167
• Publisher Policy: Reproduced in accordance with the publisher copyright policy