Letter abstract
Nature Genetics 41, 920 - 925 (2009)
Published online: 5 July 2009 | doi:10.1038/ng.411
Genome-wide association study identifies three loci associated with melanoma risk
D Timothy Bishop1,
Florence Demenais2,
Mark M Iles1,
Mark Harland1,
John C Taylor1,
Eve Corda2,3,
Juliette Randerson-Moor1,
Joanne F Aitken4,
Marie-Francoise Avril5,
Esther Azizi6,
Bert Bakker7,
Giovanna Bianchi-Scarrà8,
Brigitte Bressac-de Paillerets9,
Donato Calista10,
Lisa A Cannon-Albright11,
Thomas Chin-A-Woeng12,
Tadeusz D
bniak13,
Gilli Galore-Haskel6,
Paola Ghiorzo8,
Ivo Gut14,
Johan Hansson15,
Marko Ho
evar16,
Veronica Höiom15,
John L Hopper17,
Christian Ingvar18,
Peter A Kanetsky19,
Richard F Kefford20,
Maria Teresa Landi21,
Julie Lang22,
Jan Lubi
ski13,
Rona Mackie23,
Josep Malvehy24,
Graham J Mann20,
Nicholas G Martin25,
Grant W Montgomery25,
Frans A van Nieuwpoort26,
Srdjan Novakovic16,
Håkan Olsson18,
Susana Puig24,
Marjan Weiss7,
Wilbert van Workum12,
Diana Zelenika14,
Kevin M Brown27,
Alisa M Goldstein21,
Elizabeth M Gillanders28,
Anne Boland14,
Pilar Galan29,
David E Elder30,
Nelleke A Gruis26,
Nicholas K Hayward25,
G Mark Lathrop3,14,
Jennifer H Barrett1
&
Julia A Newton Bishop1
We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 
10-7. Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 10-27 for rs258322), 11q14-q21 encompassing TYR (P = 2.41 10-14 for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 10-7 for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.
- Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK.
- INSERM, U946, Fondation Jean-Dausset–CEPH, 75010 Paris, France.
- Fondation Jean Dausset-CEPH, 75010, Paris, France.
- Viertel Centre for Research in Cancer Control, The Cancer Council, Queensland, Spring Hill, Brisbane, Australia.
- AP-HP, Hôpital Cochin, Service de Dermatologie, Faculté Paris 5, Paris, France.
- Department of Dermatology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel.
- Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
- Department of Oncology, Biology and Genetics, University of Genoa, Genova, Italy.
- Service de Génétique et FRE 2939 CNRS, Institut de Cancérologie Gustave Roussy, Villejuif, France.
- Dermatology Unit, Maurizio Bufalini Hospital, Cesena, Italy.
- Genetic Epidemiology, Biomedical Informatics, University of Utah, Salt Lake City, Utah, USA.
- ServiceXS, Plesmanlaan 1d, 2333 BZ Leiden, The Netherlands.
- International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
- Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France.
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
- Institute of Oncology Ljubljana, Zaloska 2, Ljubljana, Slovenia.
- Centre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, School of Population Health, University of Melbourne, Melbourne, Australia.
- Department of Oncology, University Hospital Lund, Barngatan 2B, Lund, Sweden.
- Centre for Clinical Epidemiology & Biostatistics and Department of Biostatistics & Epidemiology, University of Pennsylvania, Philadephia, Pennsylvania, USA.
- Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, Australia.
- Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
- Department of Medical Genetics, University of Glasgow, UK.
- Departments of Medical Genetics and of Public Health & Health Policy, 1 Lilybank Gardens, University of Glasgow, UK.
- Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain and CIBER de Enfermedades Raras, Barcelona, Spain.
- Queensland Institute of Medical Research, Herston, QLD, Australia.
- Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands.
- Melanoma Genomics Laboratory, The Translational Genomics Research Institute (TGen), Phoenix, Arizona, USA.
- Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, USA.
- UMR U557 Inserm, U1125 Inra, Cnam, Paris 13, CRNH Idf, Bobigny, France.
- Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Correspondence to: D Timothy Bishop1 e-mail: d.t.bishop@leeds.ac.uk
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