A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25

Rayjean J. Hung, James D. McKay, Valerie Gaborieau, Paolo Boffetta, Mia Hashibe, David Zaridze, Anush Mukeria, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Chu Chen, Gary Goodman, John K. Field, Triantafillos Liloglou, George Xinarianos, Adrian Cassidy, John McLaughlin, Geoffrey Liu, Steven Narod, Hans E. Krokan, Frank Skorpen, Maiken Bratt Elvestad, Kristian Hveem, Lars Vatten, Jakob Linseisen, Françoise Clavel-Chapelon, Paolo Vineis, H. Bas Bueno- de-Mesquita, Eiliv Lund, Carmen Martinez, Sheila Bingham, Torgny Rasmuson, Pierre Hainaut, Elio Riboli, Wolfgang Ahrens, Simone Benhamou, Pagona Lagiou, Dimitrios Trichopoulos, Ivana Holcátová, Franco Merletti, Kristina Kjaerheim, Antonio Agudo, Gary Macfarlane, Renato Talamini, Lorenzo Simonato, Ray Lowry, David I. Conway, Ariana Znaor, Claire Healy, Diana Zelenika, Anne Boland, Marc Delepine, Mario Foglio, Doris Lechner, Fumihiko Matsuda, Helene Blanche, Ivo Gut, Simon Heath, Mark Lathrop and Paul Brennan ()
Additional contact information
Rayjean J. Hung: International Agency for Research on Cancer (IARC)
James D. McKay: International Agency for Research on Cancer (IARC)
Valerie Gaborieau: International Agency for Research on Cancer (IARC)
Paolo Boffetta: International Agency for Research on Cancer (IARC)
Mia Hashibe: International Agency for Research on Cancer (IARC)
David Zaridze: Institute of Carcinogenesis, Cancer Research Centre, Moscow 115478, Russia
Anush Mukeria: Institute of Carcinogenesis, Cancer Research Centre, Moscow 115478, Russia
Neonilia Szeszenia-Dabrowska: Institute of Occupational Medicine
Jolanta Lissowska: M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
Peter Rudnai: National Institute of Environmental Health
Eleonora Fabianova: Specialized Institute of Hygiene and Epidemiology
Dana Mates: Institute of Public Health
Vladimir Bencko: Charles University in Prague, First Faculty of Medicine, Institute of Hygiene and Epidemiology
Lenka Foretova: Masaryk Memorial Cancer Institute
Vladimir Janout: Palacky University
Chu Chen: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
Gary Goodman: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
John K. Field: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre
Triantafillos Liloglou: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre
George Xinarianos: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre
Adrian Cassidy: Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre
John McLaughlin: Cancer Care Ontario, and the Samuel Lunenfeld Research Institute
Geoffrey Liu: Princess Margaret Hospital, Ontario Cancer Institute
Steven Narod: Women’s College Research Institute
Hans E. Krokan: Norwegian University of Science and Technology
Frank Skorpen: Norwegian University of Science and Technology
Maiken Bratt Elvestad: Norwegian University of Science and Technology
Kristian Hveem: Norwegian University of Science and Technology
Lars Vatten: Norwegian University of Science and Technology
Jakob Linseisen: German Cancer Research Centre (DKFZ), Heidelberg 69120, Germany
Françoise Clavel-Chapelon: INSERM ERI20, Institut Gustave Roussy
Paolo Vineis: Imperial College
H. Bas Bueno- de-Mesquita: Centre for Nutrition and Health, National Institute of Public Health and the Environment
Eiliv Lund: Institute of Community Medicine, University of Tromsö
Carmen Martinez: Andalusian school of Public Health and Ciber Epidemiology y Salud Publica
Sheila Bingham: MRC Centre for Nutrition and Cancer, University of Cambridge
Torgny Rasmuson: Oncology, Umea University
Pierre Hainaut: International Agency for Research on Cancer (IARC)
Elio Riboli: Imperial College
Wolfgang Ahrens: Epidemiological Methods and Etiologic Research, Bremen Institute for Prevention Research and Social Medicine
Simone Benhamou: INSERM U794, Fondation Jean Dausset-CEPH, Paris 75010, France
Pagona Lagiou: University of Athens School of Medicine, Athens 11527, Greece, Harvard School of Public Health, Boston, Massachusetts 02115, USA
Dimitrios Trichopoulos: University of Athens School of Medicine, Athens 11527, Greece, Harvard School of Public Health, Boston, Massachusetts 02115, USA
Ivana Holcátová: Institute of Hygiene and Epidemiology
Franco Merletti: University of Turin
Kristina Kjaerheim: Cancer registry of Norway
Antonio Agudo: Institut Català d’Oncologia
Gary Macfarlane: University of Aberdeen School of Medicine
Renato Talamini: Aviano cancer center
Lorenzo Simonato: University of Padua
Ray Lowry: University of Newcastle Dental School
David I. Conway: University of Glasgow Dental School
Ariana Znaor: Croatian National Cancer Registry, National Institute of Public Health
Claire Healy: Trinity College School of Dental Science
Diana Zelenika: Centre National de Genotypage, Institut Genomique, Commissariat à l’énergie Atomique, Evry 91000, France
Anne Boland: Centre National de Genotypage, Institut Genomique, Commissariat à l’énergie Atomique, Evry 91000, France
Marc Delepine: Centre National de Genotypage, Institut Genomique, Commissariat à l’énergie Atomique, Evry 91000, France
Mario Foglio: Centre National de Genotypage, Institut Genomique, Commissariat à l’énergie Atomique, Evry 91000, France
Doris Lechner: Centre National de Genotypage, Institut Genomique, Commissariat à l’énergie Atomique, Evry 91000, France
Fumihiko Matsuda: Centre National de Genotypage, Institut Genomique, Commissariat à l’énergie Atomique, Evry 91000, France
Helene Blanche: Fondation Jean Dausset-CEPH
Ivo Gut: Centre National de Genotypage, Institut Genomique, Commissariat à l’énergie Atomique, Evry 91000, France
Simon Heath: Fondation Jean Dausset-CEPH
Mark Lathrop: Centre National de Genotypage, Institut Genomique, Commissariat à l’énergie Atomique, Evry 91000, France
Paul Brennan: International Agency for Research on Cancer (IARC)

Nature, 2008, vol. 452, issue 7187, 633-637

Abstract: Where there's smoke... With the advent of large genomic data sets, geneticists can examine at a new level the influence of genes on behaviour. Two groups have conducted genome-wide association studies involving lung cancer, and both find that sequences in the nicotinic acetylcholine receptor subunit gene cluster contribute susceptibility, although the groups took different paths to this result. Hung et al. suggest that this susceptibility is not related to smoking status or frequency, and show association with a specific amino acid change. Thorgeirsson et al. find that alleles present in a cluster of nicotinic acid receptor genes do not influence whether or not a person smokes, but do affect the number of cigarettes smoked per day, and are therefore also associated with risk of lung cancer and peripheral arterial disease. Either way, the possible potential of nicotinic acetylcholine receptors as drug targets is underlined.

Date: 2008
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DOI: 10.1038/nature06885

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