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Lung cancer susceptibility locus at 5p15.33

Nature Genetics volume 40, pages 1404–1406 (2008)Cite this article

Abstract

We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 × 10−7 and P = 4 × 10−6) and replicated by the independent study series (P = 7 × 10−5 and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology.

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Figure 1: Forest plot representing lung cancer risk and the two variants in the 5p region (rs402710 and rs2736100).

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Acknowledgements

The authors thank all of the participants who took part in this research and the funders and support and technical staff who made this study possible. Support for the central Europe, HUNT2/Tromsø and CARET genome-wide studies and follow-up genotyping was provided by Institut National du Cancer, France. Support for the HUNT2/Tromsø genome-wide study was also provided by the European Community (Integrated Project DNA repair, grant no. LSHG-CT-2005-512113), the Norwegian Cancer Association and the Functional Genomics Programme of Research Council of Norway. Funding for the Toronto genome-wide study was provided by the Ontario Institute of Cancer Research. Funding for the Szczecin/Poland replication study was provided by European Community program “Marie-Curie Host Fellowships for the Transfer of Knowledge,” grant no. MTKD-CT-2004-510114. Additional funding for study coordination, genotyping of replication studies and statistical analysis was provided by the US National Cancer Institute (R01 CA092039).

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Author notes

  1. James D McKay, Rayjean J Hung, Valerie Gaborieau and Anne Tjønneland: These authors contributed equally to this work.

Authors and Affiliations

  1. International Agency for Research on Cancer (IARC), Lyon, 69008, France

    James D McKay, Rayjean J Hung, Valerie Gaborieau, Paolo Boffetta, Amelie Chabrier, Graham Byrnes, Jan Lubiñski & Paul Brennan

  2. Samuel Lunenfeld Research Institute, Toronto, M5T 3L9, Canada

    Rayjean J Hung & John McLaughlin

  3. Institute of Carcinogenesis, Cancer Research Centre, Moscow, 115478, Russia

    David Zaridze & Anush Mukeria

  4. Department of Epidemiology, Institute of Occupational Medicine, Lodz, 90950, Poland

    Neonilia Szeszenia-Dabrowska

  5. The M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, 02781, Poland

    Jolanta Lissowska

  6. National Institute of Environmental Health, Budapest, 1097, Hungary

    Peter Rudnai

  7. Specialized Institute of Hygiene and Epidemiology, Banska Bystrica, 97556, Slovakia

    Eleonora Fabianova

  8. Institute of Public Health, Bucharest, 050463, Romania

    Dana Mates

  9. Charles University in Prague, First Faculty of Medicine, Institute of Hygiene and Epidemiology, Prague, 2 12800, Czech Republic

    Vladimir Bencko

  10. Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, 65653, Czech Republic

    Lenka Foretova

  11. Palacky University, Olomouc, 77515, Czech Republic.

    Vladimir Janout

  12. Cancer Care Ontario, Toronto, M5G 2L7, Canada

    John McLaughlin

  13. Princess Margaret Hospital, Ontario Cancer Institute, Toronto, M5G 2M9, Canada

    Frances Shepherd

  14. McGill University and Genome Quebec Innovation Centre, Montreal, H3A 1A4, Canada

    Alexandre Montpetit

  15. Women's College Research Institute, Toronto, M5G 1N8, Canada

    Steven Narod

  16. Norwegian University of Science and Technology, Trondheim, 7489, Norway

    Hans E Krokan, Frank Skorpen, Maiken Bratt Elvestad & Lars Vatten

  17. Institute of Community Medicine, University of Tromsø, Tromsø, 9037, Norway

    Inger Njølstad

  18. Department of Medical Sciences, Uppsala University, SNP Technology Platform, Academic Hospital, Uppsala, 751 85, Sweden

    Tomas Axelsson

  19. Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, USA

    Chu Chen, Gary Goodman, Matt Barnett & Melissa M Loomis

  20. Department of Genetics and Pathology, Pomeranian Medical University, International Hereditary Cancer Center, Szczecin, 70 115, Poland

    Joanna Matyjasik, Marcin Lener & Dorota Oszutowska

  21. Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK

    John Field, Triantafillos Liloglou, George Xinarianos & Adrian Cassidy

  22. Commissariat à l'énergie Atomique, Institut Genomique, Centre National de Genotypage, Evry, 91000, France

    Diana Zelenika, Anne Boland, Marc Delepine, Mario Foglio, Doris Lechner, Fumihiko Matsuda, Ivo Gut, Simon Heath & Mark Lathrop

  23. Fondation Jean Dausset-CEPH, Paris, 75010, France

    Helene Blanche & Mark Lathrop

  24. Servizio di Epidemiologia dei Tumori, Università di Torino and CPO-Piemonte, Turin, 10126, Italy

    Paolo Vineis

  25. Department of Epidemiology and Public Health, Imperial College, London, SW7, UK

    Paolo Vineis & Elio Riboli

  26. INSERM, E3N-EPIC Group Institut Gustave Roussy, Villejuif, 94805, France

    Francoise Clavel-Chapelon

  27. Molecular and Nutrional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, 50139, Italy

    Domenico Palli

  28. Cancer Registry and Histopathology Unit, Azienda Ospedaliera “Civile M.P. Arezzo,”, Ragusa, 97100, Italy

    Rosario Tumino

  29. Istituto Nazionale dei Tumori, Milan, 20133, Italy

    Vittorio Krogh

  30. Dipartimento di Medicina Clinica e Sperimentale, Universita di Napoli, Federico II, Naples, 80131, Italy

    Salvatore Panico

  31. Servicio de Epidemiología y registro del Cáncer, Instituto Catalán de Oncología, Barcelona, 08907, Spain

    Carlos A González

  32. Jefe Sección Información Sanitaria, Consejería de Servicios Sociales, Principado de Asturias, Oviedo, 33001, Spain

    José Ramón Quirós

  33. Escuela Andaluza de Salud Pública, Granada, 18011, Spain

    Carmen Martínez

  34. Epidemiology Department, Murcia Health Council, Murcia, 18011, Spain

    Carmen Navarro

  35. CIBER Epidemiologia y Salud Publica (CIBERESP), Barcelona, 8003, Spain

    Carmen Navarro

  36. Registro de Cáncer de Navarra, Instituto de Salud Pública, Gobierno de Navarra, Pamplona, 31003, Spain

    Eva Ardanaz

  37. Subdirección de Salud Pública de Gipuzkoa, Gobierno Vasco, San Sebastian, 20113, Spain

    Nerea Larrañaga

  38. MRC Dunn Human Nutrition Unit, Cambridge, CB2 0XY, UK

    Kay Tee Kham

  39. Cancer Research UK, University of Oxford, Oxford, 0X3 7XP, UK

    Timothy Key

  40. Centre for Food and Health, National Institute of Public Health and the Environment (RIVM), Bilthoven, 3720 BA, The Netherlands

    H Bas Bueno-de-Mesquita

  41. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University of Utrecht, Utrecht, 3508 GA, The Netherlands

    Petra HM Peeters

  42. Department of Hygiene and Epidemiology, University of Athens, Athens, 11527, Greece

    Antonia Trichopoulou

  43. Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, 69120, Germany

    Jakob Linseisen

  44. Department of Epidemiology, Deutsches Institut für Ernährungsforschung, Potsdam-Rehbrücke, 14558, Germany

    Heiner Boeing

  45. Department of Public Health and Clinical Medicine, University of Umeå, Umeå, 90187, Sweden

    Göran Hallmans

  46. Department of Epidemiology and Social Medicine, Aarhus University, Aarhus, 8000, Denmark

    Kim Overvad

  47. The Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, 2100, Denmark

    Anne Tjønneland

  48. Institute of Community Medicine, University of Tromsø, Tromsø, 9037, Norway

    Merethe Kumle

Authors
  1. James D McKay
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  2. Rayjean J Hung
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  3. Valerie Gaborieau
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  4. Paolo Boffetta
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  5. Amelie Chabrier
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  6. Graham Byrnes
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  7. David Zaridze
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  8. Anush Mukeria
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  9. Neonilia Szeszenia-Dabrowska
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  10. Jolanta Lissowska
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  11. Peter Rudnai
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  12. Eleonora Fabianova
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  13. Dana Mates
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  14. Vladimir Bencko
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  16. Vladimir Janout
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  17. John McLaughlin
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  18. Frances Shepherd
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  19. Alexandre Montpetit
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  20. Steven Narod
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  21. Hans E Krokan
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  22. Frank Skorpen
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  40. Anne Boland
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  41. Marc Delepine
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  42. Mario Foglio
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  43. Doris Lechner
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  44. Fumihiko Matsuda
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Consortia

EPIC Study

  • Paolo Vineis
  • , Francoise Clavel-Chapelon
  • , Domenico Palli
  • , Rosario Tumino
  • , Vittorio Krogh
  • , Salvatore Panico
  • , Carlos A González
  • , José Ramón Quirós
  • , Carmen Martínez
  • , Carmen Navarro
  • , Eva Ardanaz
  • , Nerea Larrañaga
  • , Kay Tee Kham
  • , Timothy Key
  • , H Bas Bueno-de-Mesquita
  • , Petra HM Peeters
  • , Antonia Trichopoulou
  • , Jakob Linseisen
  • , Heiner Boeing
  • , Göran Hallmans
  • , Kim Overvad
  • , Anne Tjønneland
  • , Merethe Kumle
  •  & Elio Riboli

Contributions

P. Brennan and M. Lathrop designed the study. J.D.M., R.J.H., V.G., M.B.E., A.B. and H. Blanche coordinated the preparation and inclusion of all biological samples. J.D.M., S.H. and V.G. undertook the statistical analysis. Bioinformatics analysis was undertaken by F.M., M.F. and S.H. D.Z., D.L. and I.G. coordinated the genotyping of the central Europe samples. A.M. and R.J.H. coordinated the genotyping of the Toronto samples. J.D.M., D.Z., M.D., A.C., T.A. and H.E.K. coordinated the genotyping of the other studies. All other coauthors coordinated the initial recruitment and management of the studies. M. Lathrop obtained financial support for genotyping of the central Europe study; P. Brennan, R.J.H. and H.E.K. obtained financial support for genotyping of the other studies. P. Brennan and J.D.M. drafted the manuscript with substantial contributions from R.J.H. and M. Lathrop. All authors contributed to the final paper.

Corresponding author

Correspondence to Paul Brennan.

Additional information

A full list of authors appears at the end of this paper.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3, Supplementary Tables 1–4 and Supplementary Methods (PDF 1068 kb)

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McKay, J., Hung, R., Gaborieau, V. et al. Lung cancer susceptibility locus at 5p15.33. Nat Genet 40, 1404–1406 (2008). https://doi.org/10.1038/ng.254

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