Mutational signatures associated with tobacco smoking in human cancer

被引：870

作者：

Alexandrov, Ludmil B. ^{[1
,2
,3
]}

Ju, Young Seok ^{[4
]}

Haase, Kerstin ^{[5
]}

Van Loo, Peter ^{[5
,6
]}

Martincorena, Inigo ^{[7
]}

Nik-Zainal, Serena ^{[7
,8
]}

Totoki, Yasushi ^{[9
]}

Fujimoto, Akihiro ^{[10
,11
]}

Nakagawa, Hidewaki ^{[10
]}

Shibata, Tatsuhiro ^{[12
]}

Campbell, Peter J. ^{[7
,13
]}

Vineis, Paolo ^{[14
,15
]}

Phillips, David H. ^{[16
]}

Stratton, Michael R. ^{[7
]}

机构：

[1] Los Alamos Natl Lab, Theoret Biol & Biophys T 6, Los Alamos, NM 87545 USA

[2] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA

[3] Univ New Mexico, Ctr Comprehens Canc, Albuquerque, NM 87102 USA

[4] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon 34141, South Korea

[5] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England

[6] Univ Leuven, Dept Human Genet, B-3000 Louvain, Belgium

[7] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England

[8] Addenbrookes Hosp Natl Hlth Serv Trust, Dept Med Genet, Cambridge, England

[9] Natl Canc Ctr, Res Inst, Div Canc Genom, Chuo Ku, Tokyo, Japan

[10] RIKEN, Ctr Integrat Med Sci, Lab Genome Sequencing Anal, Tokyo, Japan

[11] Kyoto Univ, Grad Sch Med, Dept Drug Discovery Med, Kyoto 6068507, Japan

[12] Univ Tokyo, Ctr Human Genome, Inst Med Sci, Lab Mol Med,Minato Ku, Tokyo, Japan

[13] Univ Cambridge, Dept Haematol, Cambridge CB2 0XY, England

[14] Human Genet Fdn, I-10126 Turin, Italy

[15] Imperial Coll London, Ctr Environm & Hlth, Sch Publ Hlth, PHE,MRC,Dept Epidemiol & Biostat, Norfolk Pl, London W2 1PG, England

[16] Kings Coll London, MRC PHE Ctr Environm & Hlth, Analyt & Environm Sci Div, Franklin Wilkins Bldg,150 Stamford St, London SE1 9NH, England

来源：

SCIENCE | 2016年 / 354卷 / 6312期

基金：

英国惠康基金;

关键词：

LUNG-CANCER; PROTEIN ADDUCTS; HUMAN TISSUES; DNA; CARCINOGENS; LANDSCAPE; PATTERNS; EXPOSURE; HOTSPOTS; GENOMES;

D O I：

10.1126/science.aag0299

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Tobacco smoking increases the risk of at least 17 classes of human cancer. We analyzed somatic mutations and DNA methylation in 5243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clocklike mutational process. Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.

引用

页码：618 / 622

页数：5

共 32 条

[1]

Impact of Cigarette Smoking on Cancer Risk in the European Prospective Investigation into Cancer and Nutrition Study [J].

Agudo, Antonio ;

Bonet, Catalina ;

Travier, Noemie ;

Gonzalez, Carlos A. ;

Vineis, Paolo ;

Bueno-de-Mesquita, H. Bas ;

Trichopoulos, Dimitrios ;

Boffetta, Paolo ;

Clavel-Chapelon, Francoise ;

Boutron-Ruault, Marie-Christine ;

Kaaks, Rudolf ;

Lukanova, Annekatrin ;

Schuetze, Madlen ;

Boeing, Heiner ;

Tjonneland, Anne ;

Halkjaer, Jytte ;

Overvad, Kim ;

Dahm, Christina C. ;

Ramon Quiros, J. ;

Sanchez, Maria-Jose ;

Larranaga, Nerea ;

Navarro, Carmen ;

Ardanaz, Eva ;

Khaw, Kay-Tee ;

Wareham, Nicholas J. ;

Key, Timothy J. ;

Allen, Naomi E. ;

Trichopoulou, Antonia ;

Lagiou, Pagona ;

Palli, Domenico ;

Sieri, Sabina ;

Tumino, Rosario ;

Panico, Salvatore ;

Boshuizen, Hendriek ;

Buchner, Frederike L. ;

Peeters, Petra H. M. ;

Borgquist, Signe ;

Almquist, Martin ;

Hallmans, Goran ;

Johansson, Ingegerd ;

Gram, Inger T. ;

Lund, Eiliv ;

Weiderpass, Elisabete ;

Romieu, Isabelle ;

Riboli, Elio .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (36) :4550-4557

[2]

Understanding the origins of human cancer [J].

Alexandrov, Ludmil B. .

SCIENCE, 2015, 350 (6265) :1175a

[3]

Clock-like mutational processes in human somatic cells [J].

Alexandrov, Ludmil B. ;

Jones, Philip H. ;

Wedge, David C. ;

Sale, Julian E. ;

Campbell, Peter J. ;

Nik-Zainal, Serena ;

Stratton, Michael R. .

NATURE GENETICS, 2015, 47 (12) :1402-+

[4]

Mutational signatures: the patterns of somatic mutations hidden in cancer genomes [J].

Alexandrov, Ludmil B. ;

Stratton, Michael R. .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2014, 24 :52-60

[5]

Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[6]

Deciphering Signatures of Mutational Processes Operative in Human Cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Campbell, Peter J. ;

Stratton, Michael R. .

CELL REPORTS, 2013, 3 (01) :246-259

[7]

Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53 [J].

Denissenko, MF ;

Pao, A ;

Tang, MS ;

Pfeifer, GP .

SCIENCE, 1996, 274 (5286) :430-432

[8]

Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer [J].

Fujimoto, Akihiro ;

Furuta, Mayuko ;

Totoki, Yasushi ;

Tsunoda, Tatsuhiko ;

Kato, Mamoru ;

Shiraishi, Yuichi ;

Tanaka, Hiroko ;

Taniguchi, Hiroaki ;

Kawakami, Yoshiiku ;

Ueno, Masaki ;

Gotoh, Kunihito ;

Ariizumi, Shun-ichi ;

Wardell, Christopher P. ;

Hayami, Shinya ;

Nakamura, Toru ;

Aikata, Hiroshi ;

Arihiro, Koji ;

Boroevich, Keith A. ;

Abe, Tetsuo ;

Nakano, Kaoru ;

Maejima, Kazuhiro ;

Sasaki-Oku, Aya ;

Ohsawa, Ayako ;

Shibuya, Tetsuo ;

Nakamura, Hiromi ;

Hama, Natsuko ;

Hosoda, Fumie ;

Arai, Yasuhito ;

Ohashi, Shoko ;

Urushidate, Tomoko ;

Nagae, Genta ;

Yamamoto, Shogo ;

Ueda, Hiroki ;

Tatsuno, Kenji ;

Ojima, Hidenori ;

Hiraoka, Nobuyoshi ;

Okusaka, Takuji ;

Kubo, Michiaki ;

Marubashi, Shigeru ;

Yamada, Terumasa ;

Hirano, Satoshi ;

Yamamoto, Masakazu ;

Ohdan, Hideki ;

Shimada, Kazuaki ;

Ishikawa, Osamu ;

Yamaue, Hiroki ;

Chayama, Kazuki ;

Miyano, Satoru ;

Aburatani, Hiroyuki ;

Shibata, Tatsuhiro .

NATURE GENETICS, 2016, 48 (05) :500-+

[9]

Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers [J].

Govindan, Ramaswamy ;

Ding, Li ;

Griffith, Malachi ;

Subramanian, Janakiraman ;

Dees, Nathan D. ;

Kanchi, Krishna L. ;

Maher, Christopher A. ;

Fulton, Robert ;

Fulton, Lucinda ;

Wallis, John ;

Chen, Ken ;

Walker, Jason ;

McDonald, Sandra ;

Bose, Ron ;

Ornitz, David ;

Xiong, Donghai ;

You, Ming ;

Dooling, David J. ;

Watson, Mark ;

Mardis, Elaine R. ;

Wilson, Richard K. .

CELL, 2012, 150 (06) :1121-1134

[10]

Hainaut P, 2000, ADV CANCER RES, V77, P81

← 1 2 3 4 →