Letter abstract

Nature Genetics 41, 1116 - 1121 (2009)
Published online: 20 September 2009 | doi:10.1038/ng.450

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study

Rosalind A Eeles1,2, Zsofia Kote-Jarai1, Ali Amin Al Olama3,52, Graham G Giles4,5,52, Michelle Guy1,52, Gianluca Severi4,5,52, Kenneth Muir6,52, John L Hopper5,52, Brian E Henderson7,52, Christopher A Haiman7,52, Johanna Schleutker8,52, Freddie C Hamdy9,52, David E Neal10,52, Jenny L Donovan11,52, Janet L Stanford12,13,52, Elaine A Ostrander14,52, Sue A Ingles15,52, Esther M John16,52, Stephen N Thibodeau17,52, Daniel Schaid17,52, Jong Y Park18,52, Amanda Spurdle19,52, Judith Clements20,52, Joanne L Dickinson21,52, Christiane Maier22,52, Walther Vogel22,52, Thilo Dörk23,52, Timothy R Rebbeck24,52, Kathleen A Cooney25,52, Lisa Cannon-Albright26,52, Pierre O Chappuis27,52, Pierre Hutter28,52, Maurice Zeegers29,30,52, Radka Kaneva31,52, Hong-Wei Zhang32,52, Yong-Jie Lu33,52, William D Foulkes34,52, Dallas R English5,52, Daniel A Leongamornlert1, Malgorzata Tymrakiewicz1, Jonathan Morrison3, Audrey T Ardern-Jones2, Amanda L Hall1,2, Lynne T O'Brien1, Rosemary A Wilkinson1, Edward J Saunders1, Elizabeth C Page1,2, Emma J Sawyer1, Stephen M Edwards1,51, David P Dearnaley1,2, Alan Horwich1,2, Robert A Huddart1,2, Vincent S Khoo1,2, Christopher C Parker1,2, Nicholas Van As2, Christopher J Woodhouse2, Alan Thompson2, Tim Christmas2, Chris Ogden2, Colin S Cooper1, Melissa C Southey35, Artitaya Lophatananon6,36, Jo-Fen Liu6, Laurence N Kolonel37, Loic Le Marchand37, Tiina Wahlfors8, Teuvo L Tammela38, Anssi Auvinen39, Sarah J Lewis11, Angela Cox40, Liesel M FitzGerald12,21, Joseph S Koopmeiners12,41, Danielle M Karyadi14, Erika M Kwon14, Mariana C Stern15, Roman Corral15, Amit D Joshi15, Ahva Shahabi15, Shannon K McDonnell17, Thomas A Sellers18, Julio Pow-Sang18, Suzanne Chambers42, Joanne Aitken42,43, R A (Frank) Gardiner44, Jyotsna Batra20, Mary Anne Kedda20, Felicity Lose19,20, Andrea Polanowski21, Briony Patterson21, Jürgen Serth45, Andreas Meyer46, Manuel Luedeke22, Klara Stefflova24, Anna M Ray25, Ethan M Lange47, Jim Farnham26, Humera Khan29, Chavdar Slavov48, Atanaska Mitkova31, Guangwen Cao32, The UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology49, The UK ProtecT Study Collaborators50, The PRACTICAL Consortium51 & Douglas F Easton3

Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 times 10-8 to P = 2.7 times 10-33).

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  1. The Institute of Cancer Research, Sutton, Surrey, UK.
  2. The Royal Marsden National Health Service Foundation Trust, Sutton, Surrey and London, UK.
  3. Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Cambridge, UK.
  4. Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria, Australia.
  5. Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Carlton, Victoria, Australia.
  6. University of Nottingham Medical School, Queens Medical Centre, Nottingham, UK.
  7. Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA.
  8. Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
  9. Nuffield Department of Surgery, University of Oxford, Oxford, UK.
  10. Surgical Oncology (Uro-Oncology), University of Cambridge, Cambridge, UK and Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
  11. Department of Social Medicine, University of Bristol, Canynge Hall, Bristol, UK.
  12. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  13. Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington, USA.
  14. National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
  15. Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
  16. Northern California Cancer Center, Fremont, California, USA and Stanford University School of Medicine, Stanford, California, USA.
  17. Mayo Clinic, Rochester, Minnesota, USA.
  18. Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
  19. Molecular Cancer Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
  20. Australian Prostate Cancer Research Centre-Queensland , Institute of Health and Biomedical Innovation and Schools of Life Science and Public Health, Queensland University of Technology, Brisbane, Australia.
  21. Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
  22. Institut für Humangenetik, Ulm, Germany.
  23. Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
  24. Center for Clinical Epidemiology and Biostatistics and Abramson Cancer Center, University of Pennsylvania, Philadelphia, Philadelphia, USA.
  25. Departments of Internal Medicine and Urology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  26. Genetic Epidemiology, Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
  27. Division of Genetic Medicine and Division of Oncology, University Hospitals of Geneva, Geneva, Switzerland.
  28. Division of Medical Genetics, Institut Central des Hôpitaux Valaisans, Sion, Switzerland.
  29. Unit of Genetic Epidemiology, Department of Public Health, Epidemiology and Biostatistics, School of Medicine, University of Birmingham, UK.
  30. Department of Complex Genetics, Cluster of Genetics and Cell Biology, Nutrition and Toxicology Research Institute, Maastricht University Medical Centre, The Netherlands.
  31. Molecular Medicine Center and Department of Chemistry and Biochemistry, Medical University of Sofia, Sofia, Bulgaria.
  32. Epidemiology Department, Second Military Medical University, Shanghai, China.
  33. Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London, UK.
  34. Program in Cancer Genetics, McGill University, Montreal, Quebec, Canada.
  35. Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
  36. Chulabhorn Cancer Research Centre, Bangkok, Thailand.
  37. Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii, USA.
  38. Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
  39. Tampere School of Public Health, University of Tampere, Tampere, Finland.
  40. Institute for Cancer Studies, University of Sheffield, Sheffield, UK.
  41. Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, Washington, USA.
  42. Viertel Centre for Research in Cancer Control, Cancer Council Queensland, Brisbane, Australia.
  43. School of Population Health, University of Queensland, Brisbane, Australia.
  44. University of Queensland, Department of Surgery, Royal Brisbane and Women's Hospital, Brisbane, Australia.
  45. Clinics of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany.
  46. Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.
  47. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
  48. Department of Urology, Alexandrovska University Hospital, Medical University of Sofia, Sofia, Bulgaria.
  49. UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology; membership list provided in the Supplementary Note.
  50. UK ProtecT Study Collaborators; membership list provided in the Supplementary Note.
  51. Full list of participants of The PRACTICAL Consortium is provided in the Supplementary Note.
  52. These authors contributed equally to this work.

Correspondence to: Rosalind A Eeles1,2 e-mail: rosalind.eeles@icr.ac.uk



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