A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
In: Nature Nature, 2008, 452 (7187), pp.633-637. ⟨10.1038/nature06885⟩ Nature, Nature Publishing Group, 2008, 452 (7187), pp.633-637. ⟨10.1038/nature06885⟩; (2008)
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Zugriff:
Letter; International audience; Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually1. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 × 10$^{-10}$). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 × 10$^{-20}$ overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N′-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets
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A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
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| Autor/in / Beteiligte Person: | Foretova, Lenka ; Chen, Chu ; Lund, Eiliv ; Hainaut, Pierre ; Bencko, Vladimir ; Foglio, Mario ; Rasmuson, Torgny ; Ahrens, Wolfgang ; Janout, Vladimir ; Vatten, Lars J. ; Xinarianos, George ; Krokan, Hans E. ; Maiken Bratt Elvestad ; Simonato, Lorenzo ; Vineis, Paolo ; Heath, Simon ; Cassidy, Adrian ; Matsuda, Fumihiko ; Clavel-Chapelon, Françoise ; Talamini, Renato ; Boland, Anne ; Rudnai, Peter ; Mukeria, Anush ; Macfarlane, Gary J. ; Delepine, Marc ; Merletti, Franco ; Lechner, Doris ; Znaor, Ariana ; Bingham, Sheila ; Zelenika, Diana ; Benhamou, Simone ; Goodman, Gary E. ; Liu, Geoffrey ; Blanché, Hélène ; Mates, Dana ; Healy, Claire M. ; Hung, Rayjean J. ; H. Bas Bueno-de-Mesquita ; Szeszenia-Dabrowska, Neonilia ; Gut, Ivo ; Field, John K. ; Zaridze, David ; Lissowska, Jolanta ; Liloglou, Triantafillos ; Martinez, Carmen ; Skorpen, Frank ; Kjærheim, Kristina ; Trichopoulos, Dimitrios ; Holcatova, Ivana ; Hveem, Kristian ; Gaborieau, Valerie ; Brennan, Paul ; McKay, James ; Linseisen, Jakob ; Lagiou, Pagona ; Riboli, Elio ; Fabianova, Eleonora ; Hashibe, Mia ; McLaughlin, John R. ; Agudo, Antonio ; Conway, David I. ; Lowry, Ray ; Boffetta, Paolo ; Narod, Steven A. ; Lathrop, Mark ; School of Public Health ; Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC) ; Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO) ; Institute of Carcinogenesis ; Russian Cancer Research Centre ; Cancer Research Centre ; Department of Epidemiology ; Institute of Occupational Medicine ; The M Sklodowska-Curie Cancer Center ; Institute of Oncology ; National Institute of Environment Health ; Specialized Institute of Hygiene and Epidemiology ; Regional Authority of Public Health-Specialized State Health Institute ; Institute of Public Health ; Institute of Hygiene and Epidemiology ; Charles University [Prague] (CU)-1st Faculty of Medicine ; Masaryk Memorial Cancer Institute (MMCI) ; Department of Preventive Medicine [Univ Palacký] ; Faculty of Medicine and Dentistry [Univ Palacký] ; Palacky University Olomouc-Palacky University Olomouc ; Fred Hutchinson Cancer Research Center [Seattle] (FHCRC) ; Roy Castle Lung Cancer Research Programme ; University of Liverpool ; University of Liverpool-Cancer Research Centre ; Cancer Care Ontario ; Samuel Lunenfeld Research Institute ; Princess Margaret Hospital ; Ontario Cancer Institute ; Women's College Research Institute ; University of Toronto ; Norwegian University of Science and Technology [Trondheim] (NTNU) ; Norwegian University of Science and Technology (NTNU) ; Division of Cancer Epidemiology ; German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ) ; Nutrition, hormones et cancer: épidémiologie et prévention (E3N) ; Epidémiologie, sciences sociales, santé publique (IFR 69) ; Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Department of Epidemiology and Public Health ; Imperial College London ; Centre for Nutrition and Health (CVG) ; National Institute for Public Health and the Environment [Bilthoven] (RIVM) ; Institute of Community Medicine ; University of Tromsø (UiT) ; Andalusian School of Public Health [Granada] ; MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival ; University of Cambridge [UK] (CAM) ; Department of Radiation Sciences, Oncology ; University, Umeå ; Bremen Institute for Prevention Research and Social Medicine ; University of Bremen ; U794, INSERM ; CEPH ; Génomes et cancer (GC (FRE2939)) ; Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS) ; Department of Hygiene, Epidemiology and Medical Statistics ; University of Athens Medical School [Athens] ; Harvard School of Public Health ; Cancer Epidemiology Unit ; Université de Turin ; Cancer registry of Norway ; University of Oslo (UiO) ; Institut Català d'Oncologia ; Spain Institute of Oncology ; University of Aberdeen ; Aviano cancer center ; Aviano Cancer Center ; Department of Environmental Medicine and Public Health ; Università degli Studi di Padova = University of Padua (Unipd) ; University of Newcastle Dental School ; University of Newcastle, UK ; University of Glasgow Dental School ; University of Glasgow ; Croatian National Cancer Registry ; National Institute of Public Health ; Trinity College School of Dental Science ; Centre National de Génotypage (CNG) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA) ; Centre d'Etude du Polymorphisme Humain (CEPH) ; Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH) ; Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset ; Hung, R.J. ; McKay, J.D. ; Gaborieau, V. ; Boffetta, P. ; Hashibe, M. ; Zaridze, D. ; Mukeria, A. ; Szeszenia-Dabrowska, N. ; Lissowska, J. ; Rudnai, P. ; Fabianova, E. ; Mates, D. ; Bencko, V. ; Foretova, L. ; Janout, V. ; Chen, C. ; Goodman, G. ; Field, J.K. ; Liloglou, T. ; Xinarianos, G. ; Cassidy, A. ; McLaughlin, J. ; Liu, G. ; Narod, S. ; Krokan, H.E. ; Skorpen, F. ; Elvestad, M.B. ; Hveem, K. ; Vatten, L. ; Linseisen, J. ; Clavel-Chapelon, F. ; Vineis, P. ; Bueno-De-Mesquita, H.B. ; Lund, E. ; Martinez, C. ; Bingham, S. ; Rasmuson, T. ; Hainaut, P. ; Riboli, E. ; Ahrens, W. ; Benhamou, S. ; Lagiou, P. ; Trichopoulos, D. ; Holcátová, I. ; Merletti, F. ; Kjaerheim, K. ; Agudo, A. ; MacFarlane, G. ; Talamini, R. ; Simonato, L. ; Lowry, R. ; Conway, D.I. ; Znaor, A. ; Healy, C. ; Zelenika, D. ; Boland, A. ; Delepine, M. ; Foglio, M. ; Lechner, D. ; Matsuda, F. ; Blanche, H. ; Gut, I. ; Heath, S. ; Lathrop, M. ; Brennan, P. ; Savelli, Bruno ; Masaryk Memorial Cancer Institute ; Masaryk Memorial Cancer Institute (RECAMO) ; Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11) ; Universita degli Studi di Padova |
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| Quelle: | Nature Nature, 2008, 452 (7187), pp.633-637. ⟨10.1038/nature06885⟩ Nature, Nature Publishing Group, 2008, 452 (7187), pp.633-637. ⟨10.1038/nature06885⟩; (2008) |
| Veröffentlichung: | HAL CCSD, 2008 |
| Medientyp: | unknown |
| ISSN: | 0028-0836 (print) ; 1476-4687 (print) ; 1476-4679 (print) |
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