Lung adenocarcinoma promotion by air pollutants.
Lung adenocarcinoma promotion by air pollutants.
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DOI：
10.1038/s41586-023-05874-3
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发表时间：
2023-04
期刊：
影响因子：
64.8
通讯作者：
Swanton C
中科院分区：
文献类型：
--
作者：
Hill W;Lim EL;Weeden CE;Lee C;Augustine M;Chen K;Kuan FC;Marongiu F;Evans EJ Jr;Moore DA;Rodrigues FS;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 DR;Nagano A;Black JRM;Martínez-Ruiz C;Ryu MH;Huff RD;Li S;Favé MJ;Magness A;Suárez-Bonnet A;Priestnall SL;Lüchtenborg M;Lavelle K;Pethick J;Hardy S;McRonald FE;Lin MH;Troccoli CI;Ghosh M;Miller YE;Merrick DT;Keith RL;Al Bakir M;Bailey C;Hill MS;Saal LH;Chen Y;George AM;Abbosh C;Kanu N;Lee SH;McGranahan N;Berg CD;Sasieni P;Houlston R;Turnbull C;Lam S;Awadalla P;Grönroos E;Downward J;Jacks T;Carlsten C;Malanchi I;Hackshaw A;Litchfield K;TRACERx Consortium;DeGregori J;Jamal-Hanjani M;Swanton C
对暴露于环境物质如何促进癌症形成缺乏完整的理解。70多年前，肿瘤发生被认为是一个两步过程：一个引发健康细胞突变的起始步骤，然后是引发癌症发展的启动子步骤。在这里，我们提出，已知与肺癌风险相关的环境颗粒物测量≤2.5 μm（PM2.5），通过作用于健康肺组织中预先存在致癌突变的细胞来促进肺癌。关注EGFR驱动的肺癌，这在从不吸烟者或轻度吸烟者中更常见，我们发现PM2.5水平与4个国家内队列中32，957例EGFR驱动的肺癌病例的肺癌发病率之间存在显著相关性。功能性小鼠模型显示，空气污染物导致巨噬细胞流入肺部并释放白细胞介素-1 β。这一过程导致EGFR突变型肺泡II型上皮细胞内的祖细胞样细胞状态，从而促进肿瘤发生。来自3个临床队列的295名个体的组织学正常肺组织的超深突变谱显示，分别在18%和53%的健康组织样本中存在致癌EGFR和KRAS驱动突变。这些发现共同支持PM2.5空气污染物的肿瘤促进作用，并为公共卫生政策措施提供动力，以解决空气污染问题，减少疾病负担。
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 development. 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.
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影响因子：
64.8
作者：
Frankell, Alexander M.;Dietzen, Michelle;Al Bakir, Maise;Lim, Emilia L.;Karasaki, Takahiro;Ward, Sophia;Veeriah, Selvaraju;Colliver, Emma;Huebner, Ariana;Bunkum, Abigail;Hill, Mark S.;Grigoriadis, Kristiana;Moore, David A.;Black, James R. M.;Liu, Wing Kin;Thol, Kerstin;Pich, Oriol;Watkins, Thomas B. K.;Naceur-Lombardelli, Cristina;Cook, Daniel E.;Salgado, Roberto;Wilson, Gareth A.;Bailey, Chris;Angelova, Mihaela;Bentham, Robert;Martinez-Ruiz, Carlos;Abbosh, Christopher;Nicholson, Andrew G.;Le Quesne, John;Biswas, Dhruva;Rosenthal, Rachel;Puttick, Clare;Hessey, Sonya;Lee, Claudia;Prymas, Paulina;Toncheva, Antonia;Smith, Jon;Xing, Wei;Nicod, Jerome;Price, Gillian;Kerr, Keith M.;Naidu, Babu;Middleton, Gary;Blyth, Kevin G.;Fennell, Dean A.;Forster, Martin D.;Lee, Siow Ming;Falzon, Mary;Hewish, Madeleine;Shackcloth, Michael J.;Lim, Eric;Benafif, Sarah;Russell, Peter;Boleti, Ekaterini;Krebs, Matthew G.;Lester, Jason F.;Papadatos-Pastos, Dionysis;Ahmad, Tanya;Thakrar, Ricky M.;Lawrence, David;Navani, Neal;Janes, Sam M.;Dive, Caroline;Blackhall, Fiona H.;Summers, Yvonne;Cave, Judith;Marafioti, Teresa;Herrero, Javier;Quezada, Sergio A.;Peggs, Karl S.;Schwarz, Roland F.;Van Loo, Peter;Miedema, Daniel M.;Birkbak, Nicolai J.;Hiley, Crispin T.;Hackshaw, Allan;Zaccaria, Simone;Jamal-Hanjani, Mariam;McGranahan, Nicholas;Swanton, Charles;Bajaj, Amrita;Nakas, Apostolos;Sodha-Ramdeen, Azmina;Ang, Keng;Tufail, Mohamad;Chowdhry, Mohammed Fiyaz;Scotland, Molly;Boyles, Rebecca;Rathinam, Sridhar;Wilson, Claire;Marrone, Domenic;Dulloo, Sean;Matharu, Gurdeep;Shaw, Jacqui A.;Riley, Joa;Primrose, Lindsay;Cheyne, Heather;Khalil, Mohammed;Richardson, Shirley;Cruickshank, Tracey;Gilbert, Kayleigh;Patel, Akshay J.;Osman, Aya;Lacson, Christer;Langman, Gerald;Shackleford, Helen;Djearaman, Madava;Kadiri, Salma;Leek, Angela;Hodgkinson, Jack Davies;Totten, Nicola;Montero, Angeles;Smith, Elaine;Fontaine, Eustace;Granato, Felice;Doran, Helen;Novasio, Juliette;Rammohan, Kendadai;Joseph, Leena;Bishop, Paul;Shah, Rajesh;Moss, Stuart;Joshi, Vijay;Crosbie, Philip;Gomes, Fabio;Brown, Kate;Carter, Mathew;Chaturvedi, Anshuman;Priest, Lynsey;Oliveira, Pedro;Lindsay, Colin R.;Clipson, Alexandra;Tugwood, Jonathan;Kerr, Alastair;Rothwell, Dominic G.;Kilgour, Elaine;Aerts, Hugo J. W. L.;Kaufmann, Tom L.;Szallasi, Zoltan;Kisistok, Judit;Sokac, Mateo;Diossy, Miklos;Demeulemeester, Jonas;Stewart, Aengus;Magness, Alastair;Rowan, Andrew;Karamani, Angeliki;Chain, Benny;Campbell, Brittany B.;Castignani, Carla;Weeden, Clare E.;Richard, Corentin;Pearce, David R.;Karagianni, Despoina;Levi, Dina;Hoxha, Elena;Larose Cadieux, Elizabeth;Nye, Emma;Gronroos, Eva;Galvez-Cancino, Felip;Athanasopoulou, Foteini;Gimeno-Valiente, Francisco;Kassiotis, George;Stavrou, Georgia;Mastrokalos, Gerasimos;Zhai, Haoran L.;Lowe, Helen L.;Matos, Ignacio;Goldman, Jacki;Reading, James L.;Rane, Jayant K.;Lam, Jie Min;Hartley, John A.;Enfield, Katey S. S.;Selvaraju, Kayalvizhi;Litchfield, Kevin;Ng, Kevin W.;Chen, Kezhong;Dijkstra, Krijn;Thakkar, Krupa;Ensell, Leah;Shah, Mansi;Vasquez, Marcos;Litovchenko, Maria;Werner Sunderland, Mariana;Leung, Michelle;Escudero, Mickael;Tanic, Miljana;Sivakumar, Monica;Kanu, Nnennaya;Chervova, Olga;Lucas, Olivia;Al-Sawaf, Othman;Hobson, Philip;Pawlik, Piotr;Stone, Richard Kevin;Hynds, Robert E.;Vendramin, Roberto;Saghafinia, Sadegh;Lopez, Saioa;Gamble, Samuel;Ung, Seng Kuong Anakin;Vanloo, Sharon;Boeing, Stefan;Beck, Stephan;Bola, Supreet Kaur;Denner, Tamara;Mourikis, Thanos P.;Spanswick, Victoria;Barbe, Vittorio;Lu, Wei-Ting;Hill, William;Wu, Yin;Naito, Yutaka;Ramsden, Zoe;Veiga, Catarina;Royle, Gary;Collins-Fekete, Charles-Antoine;Fraioli, Francesco;Ashford, Paul;Clark, Tristan;Borg, Elaine;Wilson, James;Procter, Alexander James;Ahmed, Asia;Taylor, Magali N.;Nair, Arjun;Patrini, Davide;Martinoni Hoogenboom, Emilie;Monk, Fleur;Holding, James W.;Choudhary, Junaid;Bhakhri, Kunal;Scarci, Marco;Hayward, Martin;Panagiotopoulos, Nikolaos;Gorman, Pat;Khiroya, Reena;Stephens, Robert C. M.;Wong, Yien Ning Sophia;Bandula, Steve;Sharp, Abigail;Smith, Sean;Gower, Nicole;Dhanda, Harjot Kaur;Chan, Kitty;Pilotti, Camilla;Leslie, Rachel;Grapa, Anca;Zhang, Hanyun;AbdulJabbar, Khalid;Pan, Xiaoxi;Yuan, Yinyin;Chuter, David;MacKenzie, Mairead;Chee, Serena;Alzetani, Aiman;Scarlett, Lydia;Richards, Jennifer;Ingram, Papawadee;Austin, Silvia;De Sousa, Paulo;Jordan, Simon;Rice, Alexandra;Raubenheimer, Hilgardt;Bhayani, Harshil;Ambrose, Lyn;Devaraj, Anand;Chavan, Hema;Begum, Sofina;Buderi, Silviu, I;Kaniu, Daniel;Malima, Mpho;Booth, Sarah;Fernandes, Nadia;Shah, Pratibha;Proli, Chiara;Danson, Sarah;Robinson, Lily;Dick, Craig;Kirk, Alan;Asif, Mo;Bilancia, Rocco;Kostoulas, Nikos;Thomas, Mathew
通讯作者：
Thomas, Mathew
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
23.9
作者：
Dost AFM;Moye AL;Vedaie M;Tran LM;Fung E;Heinze D;Villacorta-Martin C;Huang J;Hekman R;Kwan JH;Blum BC;Louie SM;Rowbotham SP;Sainz de Aja J;Piper ME;Bhetariya PJ;Bronson RT;Emili A;Mostoslavsky G;Fishbein GA;Wallace WD;Krysan K;Dubinett SM;Yanagawa J;Kotton DN;Kim CF
通讯作者：
Kim CF
DOI：
10.1152/ajplung.00232.2019
发表时间：
2019-09-01
影响因子：
4.9
作者：
Chan, Yik Lung;Wang, Baoming;Oliver, Brian Gregory George
通讯作者：
Oliver, Brian Gregory George
影响因子：
64.5
作者：
Chung, Katherine Minjee;Singh, Jaffarguriqbal;Muzumdar, Mandar Deepak
通讯作者：
Muzumdar, Mandar Deepak