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Genome-wide association study identifies three loci associated with melanoma risk

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Genome-wide association study identifies three loci associated with melanoma risk

Auteurs : D Timothy Bishop [Royaume-Uni] ; Florence Demenais [France] ; Mark M. Iles [Royaume-Uni] ; Mark Harland [Royaume-Uni] ; John C. Taylor [Royaume-Uni] ; Eve Corda [France] ; Juliette Randerson-Moor [Royaume-Uni] ; Joanne F. Aitken [Australie] ; Marie-Francoise Avril [France] ; Esther Azizi [Israël] ; Bert Bakker [Pays-Bas] ; Giovanna Bianchi-Scarrà [Italie] ; Brigitte Bressac-De Paillerets [France] ; Donato Calista [Italie] ; Lisa A. Cannon-Albright [États-Unis] ; Thomas Chin-A-Woeng [Pays-Bas] ; Tadeusz D Bniak [Pologne] ; Gilli Galore-Haskel [Israël] ; Paola Ghiorzo [Italie] ; Ivo Gut [France] ; Johan Hansson [Suède] ; Marko Hocevar [Slovénie] ; Veronica Höiom [Suède] ; John L. Hopper [Australie] ; Christian Ingvar [Suède] ; Peter A. Kanetsky [États-Unis] ; Richard F. Kefford [Australie] ; Maria Teresa Landi [États-Unis] ; Julie Lang [Royaume-Uni] ; Jan Lubi Ski [Pologne] ; Rona Mackie [Royaume-Uni] ; Josep Malvehy [Espagne] ; Graham J. Mann [Australie] ; Nicholas G. Martin [Australie] ; Grant W. Montgomery [Australie] ; Frans A. Van Nieuwpoort [Pays-Bas] ; Srdjan Novakovic [Slovénie] ; H Kan Olsson [Suède] ; Susana Puig [Espagne] ; Marjan Weiss [Pays-Bas] ; Wilbert Van Workum [Pays-Bas] ; Diana Zelenika [France] ; Kevin M. Brown [États-Unis] ; Alisa M. Goldstein [États-Unis] ; Elizabeth M. Gillanders [États-Unis] ; Anne Boland [France] ; Pilar Galan ; David E. Elder [États-Unis] ; Nelleke A. Gruis [Pays-Bas] ; Nicholas K. Hayward [Australie] ; G. Mark Lathrop [France] ; Jennifer H. Barrett [Royaume-Uni] ; Julia A. Newton Bishop [Royaume-Uni]

Source :

Nature genetics [ 1061-4036 ] ; 2009.

RBID : PMC:2741419

Abstract

We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317k tagging SNPs for 1650 genetically-enriched cases (from Europe and Australia) and 4336 controls and subsequent replication in 1149 genetically-enriched cases and 964 controls and a population-based case-control study of 1163 cases and 903 controls. The genome-wide screen identified five regions with genotyped or imputed SNPs reaching p < 5×10⁻⁷; three regions were replicated: 16q24 encompassing MC1R (overall 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-recognised melanoma risk factors, while the 9p21 locus is novel for common variants 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 contribute independently to melanoma risk.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2741419

DOI: 10.1038/ng.411
PubMed: 19578364
PubMed Central: 2741419

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Pilar Galan

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<wicri:noCountry code="subfield">74 rue Marcel Cachin F-93017 Bobigny</wicri:noCountry>
</affiliation>

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<author><name sortKey="Landi, Maria Teresa" sort="Landi, Maria Teresa" uniqKey="Landi M" first="Maria Teresa" last="Landi">Maria Teresa Landi</name>
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<author><name sortKey="Lang, Julie" sort="Lang, Julie" uniqKey="Lang J" first="Julie" last="Lang">Julie Lang</name>
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<author><name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W." last="Montgomery">Grant W. Montgomery</name>
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<author><name sortKey="Van Nieuwpoort, Frans A" sort="Van Nieuwpoort, Frans A" uniqKey="Van Nieuwpoort F" first="Frans A" last="Van Nieuwpoort">Frans A. Van Nieuwpoort</name>
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<wicri:regionArea>Department of Dermatology, Leiden University Medical Centre, Leiden</wicri:regionArea>
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<author><name sortKey="Novakovic, Srdjan" sort="Novakovic, Srdjan" uniqKey="Novakovic S" first="Srdjan" last="Novakovic">Srdjan Novakovic</name>
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<country xml:lang="fr">Slovénie</country>
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<author><name sortKey="Olsson, H Kan" sort="Olsson, H Kan" uniqKey="Olsson H" first="H Kan" last="Olsson">H Kan Olsson</name>
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<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Oncology, University Hospital Lund, Barngatan 2B, 221 85 Lund</wicri:regionArea>
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<author><name sortKey="Puig, Susana" sort="Puig, Susana" uniqKey="Puig S" first="Susana" last="Puig">Susana Puig</name>
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</affiliation>
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<author><name sortKey="Weiss, Marjan" sort="Weiss, Marjan" uniqKey="Weiss M" first="Marjan" last="Weiss">Marjan Weiss</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van Workum, Wilbert" sort="Van Workum, Wilbert" uniqKey="Van Workum W" first="Wilbert" last="Van Workum">Wilbert Van Workum</name>
<affiliation wicri:level="1"><nlm:aff id="A12">ServiceXS, Plesmanlaan Id, 2333 BZ Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>ServiceXS, Plesmanlaan Id, 2333 BZ Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zelenika, Diana" sort="Zelenika, Diana" uniqKey="Zelenika D" first="Diana" last="Zelenika">Diana Zelenika</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Brown, Kevin M" sort="Brown, Kevin M" uniqKey="Brown K" first="Kevin M" last="Brown">Kevin M. Brown</name>
<affiliation wicri:level="1"><nlm:aff id="A27">Melanoma Genomics Laboratory, The Translational Genomics Research Institute (TGen), 445 N. Fifth Street, Phoenix, AZ 85004, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Melanoma Genomics Laboratory, The Translational Genomics Research Institute (TGen), 445 N. Fifth Street, Phoenix, AZ 85004</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Goldstein, Alisa M" sort="Goldstein, Alisa M" uniqKey="Goldstein A" first="Alisa M." last="Goldstein">Alisa M. Goldstein</name>
<affiliation wicri:level="1"><nlm:aff id="A21">Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute. NIH, Bethesda, MD 20892-7236, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute. NIH, Bethesda, MD 20892-7236</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gillanders, Elizabeth M" sort="Gillanders, Elizabeth M" uniqKey="Gillanders E" first="Elizabeth M." last="Gillanders">Elizabeth M. Gillanders</name>
<affiliation wicri:level="1"><nlm:aff id="A28">Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland 21224, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland 21224</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Boland, Anne" sort="Boland, Anne" uniqKey="Boland A" first="Anne" last="Boland">Anne Boland</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Galan, Pilar" sort="Galan, Pilar" uniqKey="Galan P" first="Pilar" last="Galan">Pilar Galan</name>
<affiliation><nlm:aff id="A29">UMR U557 Inserm ; U1125 Inra; Cnam; Paris 13, CRNH Idf, 74 rue Marcel Cachin F-93017 Bobigny</nlm:aff>
<wicri:noCountry code="subfield">74 rue Marcel Cachin F-93017 Bobigny</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Elder, David E" sort="Elder, David E" uniqKey="Elder D" first="David E." last="Elder">David E. Elder</name>
<affiliation wicri:level="1"><nlm:aff id="A30">Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gruis, Nelleke A" sort="Gruis, Nelleke A" uniqKey="Gruis N" first="Nelleke A" last="Gruis">Nelleke A. Gruis</name>
<affiliation wicri:level="1"><nlm:aff id="A26">Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Dermatology, Leiden University Medical Centre, Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hayward, Nicholas K" sort="Hayward, Nicholas K" uniqKey="Hayward N" first="Nicholas K." last="Hayward">Nicholas K. Hayward</name>
<affiliation wicri:level="1"><nlm:aff id="A25">Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lathrop, G Mark" sort="Lathrop, G Mark" uniqKey="Lathrop G" first="G. Mark" last="Lathrop">G. Mark Lathrop</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Fondation Jean Dausset-CEPH, 75010, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Fondation Jean Dausset-CEPH, 75010, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Barrett, Jennifer H" sort="Barrett, Jennifer H" uniqKey="Barrett J" first="Jennifer H" last="Barrett">Jennifer H. Barrett</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Newton Bishop, Julia A" sort="Newton Bishop, Julia A" uniqKey="Newton Bishop J" first="Julia A" last="Newton Bishop">Julia A. Newton Bishop</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
</titleStmt>
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<idno type="doi">10.1038/ng.411</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genome-wide association study identifies three loci associated with melanoma risk</title>
<author><name sortKey="Bishop, D Timothy" sort="Bishop, D Timothy" uniqKey="Bishop D" first="D Timothy" last="Bishop">D Timothy Bishop</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Demenais, Florence" sort="Demenais, Florence" uniqKey="Demenais F" first="Florence" last="Demenais">Florence Demenais</name>
<affiliation wicri:level="1"><nlm:aff id="A2">INSERM, U946, Fondation Jean-Dausset-CEPH, 75010 Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, U946, Fondation Jean-Dausset-CEPH, 75010 Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Iles, Mark M" sort="Iles, Mark M" uniqKey="Iles M" first="Mark M" last="Iles">Mark M. Iles</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Harland, Mark" sort="Harland, Mark" uniqKey="Harland M" first="Mark" last="Harland">Mark Harland</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Taylor, John C" sort="Taylor, John C" uniqKey="Taylor J" first="John C." last="Taylor">John C. Taylor</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Corda, Eve" sort="Corda, Eve" uniqKey="Corda E" first="Eve" last="Corda">Eve Corda</name>
<affiliation wicri:level="1"><nlm:aff id="A2">INSERM, U946, Fondation Jean-Dausset-CEPH, 75010 Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, U946, Fondation Jean-Dausset-CEPH, 75010 Paris</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Fondation Jean Dausset-CEPH, 75010, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Fondation Jean Dausset-CEPH, 75010, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Randerson Moor, Juliette" sort="Randerson Moor, Juliette" uniqKey="Randerson Moor J" first="Juliette" last="Randerson-Moor">Juliette Randerson-Moor</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Aitken, Joanne F" sort="Aitken, Joanne F" uniqKey="Aitken J" first="Joanne F." last="Aitken">Joanne F. Aitken</name>
<affiliation wicri:level="1"><nlm:aff id="A4">Viertel Centre for Research in Cancer Control, The Cancer Council, Queensland, Spring Hill, Brisbane, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Viertel Centre for Research in Cancer Control, The Cancer Council, Queensland, Spring Hill, Brisbane</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Avril, Marie Francoise" sort="Avril, Marie Francoise" uniqKey="Avril M" first="Marie-Francoise" last="Avril">Marie-Francoise Avril</name>
<affiliation wicri:level="1"><nlm:aff id="A5">AP-HP, Hôpital Cochin, Service de Dermatologie, Faculté Paris 5, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>AP-HP, Hôpital Cochin, Service de Dermatologie, Faculté Paris 5, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Azizi, Esther" sort="Azizi, Esther" uniqKey="Azizi E" first="Esther" last="Azizi">Esther Azizi</name>
<affiliation wicri:level="1"><nlm:aff id="A6">Department of Dermatology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea>Department of Dermatology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bakker, Bert" sort="Bakker, Bert" uniqKey="Bakker B" first="Bert" last="Bakker">Bert Bakker</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bianchi Scarra, Giovanna" sort="Bianchi Scarra, Giovanna" uniqKey="Bianchi Scarra G" first="Giovanna" last="Bianchi-Scarrà">Giovanna Bianchi-Scarrà</name>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Oncology, Biology and Genetics, University of Genoa, V. le Benedetto XV 6,16132 Genova, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Oncology, Biology and Genetics, University of Genoa, V. le Benedetto XV 6,16132 Genova</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bressac De Paillerets, Brigitte" sort="Bressac De Paillerets, Brigitte" uniqKey="Bressac De Paillerets B" first="Brigitte" last="Bressac-De Paillerets">Brigitte Bressac-De Paillerets</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Service de Génétique et FRE 2939 CNRS, Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Service de Génétique et FRE 2939 CNRS, Institut de Cancérologie Gustave Roussy, 94805 Villejuif</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Calista, Donato" sort="Calista, Donato" uniqKey="Calista D" first="Donato" last="Calista">Donato Calista</name>
<affiliation wicri:level="1"><nlm:aff id="A10">Dermatology Unit, Maurizio Bufalini Hospital, 47023 Cesena, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Dermatology Unit, Maurizio Bufalini Hospital, 47023 Cesena</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Cannon Albright, Lisa A" sort="Cannon Albright, Lisa A" uniqKey="Cannon Albright L" first="Lisa A." last="Cannon-Albright">Lisa A. Cannon-Albright</name>
<affiliation wicri:level="1"><nlm:aff id="A11">Genetic Epidemiology, Biomedical Informatics, 391 Chipeta Way, Suite D, University of Utah, Salt Lake City, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Genetic Epidemiology, Biomedical Informatics, 391 Chipeta Way, Suite D, University of Utah, Salt Lake City</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chin A Woeng, Thomas" sort="Chin A Woeng, Thomas" uniqKey="Chin A Woeng T" first="Thomas" last="Chin-A-Woeng">Thomas Chin-A-Woeng</name>
<affiliation wicri:level="1"><nlm:aff id="A12">ServiceXS, Plesmanlaan Id, 2333 BZ Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>ServiceXS, Plesmanlaan Id, 2333 BZ Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="D Bniak, Tadeusz" sort="D Bniak, Tadeusz" uniqKey="D Bniak T" first="Tadeusz" last="D Bniak">Tadeusz D Bniak</name>
<affiliation wicri:level="1"><nlm:aff id="A13">International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea>International Hereditary Cancer Center, Pomeranian Medical University, Szczecin</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Galore Haskel, Gilli" sort="Galore Haskel, Gilli" uniqKey="Galore Haskel G" first="Gilli" last="Galore-Haskel">Gilli Galore-Haskel</name>
<affiliation wicri:level="1"><nlm:aff id="A6">Department of Dermatology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel</nlm:aff>
<country xml:lang="fr">Israël</country>
<wicri:regionArea>Department of Dermatology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ghiorzo, Paola" sort="Ghiorzo, Paola" uniqKey="Ghiorzo P" first="Paola" last="Ghiorzo">Paola Ghiorzo</name>
<affiliation wicri:level="1"><nlm:aff id="A8">Department of Oncology, Biology and Genetics, University of Genoa, V. le Benedetto XV 6,16132 Genova, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Department of Oncology, Biology and Genetics, University of Genoa, V. le Benedetto XV 6,16132 Genova</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gut, Ivo" sort="Gut, Ivo" uniqKey="Gut I" first="Ivo" last="Gut">Ivo Gut</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hansson, Johan" sort="Hansson, Johan" uniqKey="Hansson J" first="Johan" last="Hansson">Johan Hansson</name>
<affiliation wicri:level="1"><nlm:aff id="A15">Department of Oncology-Pathology, Karolinska Institutet, SE-171 77 Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Oncology-Pathology, Karolinska Institutet, SE-171 77 Stockholm</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hocevar, Marko" sort="Hocevar, Marko" uniqKey="Hocevar M" first="Marko" last="Hocevar">Marko Hocevar</name>
<affiliation wicri:level="1"><nlm:aff id="A16">Institute of Oncology Ljubljana, Zaloska 2,1000 Ljubljana, Slovenia</nlm:aff>
<country xml:lang="fr">Slovénie</country>
<wicri:regionArea>Institute of Oncology Ljubljana, Zaloska 2,1000 Ljubljana</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hoiom, Veronica" sort="Hoiom, Veronica" uniqKey="Hoiom V" first="Veronica" last="Höiom">Veronica Höiom</name>
<affiliation wicri:level="1"><nlm:aff id="A15">Department of Oncology-Pathology, Karolinska Institutet, SE-171 77 Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Oncology-Pathology, Karolinska Institutet, SE-171 77 Stockholm</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hopper, John L" sort="Hopper, John L" uniqKey="Hopper J" first="John L." last="Hopper">John L. Hopper</name>
<affiliation wicri:level="1"><nlm:aff id="A17">Centre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, School of Population Health, University of Melbourne, Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, School of Population Health, University of Melbourne, Melbourne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ingvar, Christian" sort="Ingvar, Christian" uniqKey="Ingvar C" first="Christian" last="Ingvar">Christian Ingvar</name>
<affiliation wicri:level="1"><nlm:aff id="A18">Department of Oncology, University Hospital Lund, Barngatan 2B, 221 85 Lund, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Oncology, University Hospital Lund, Barngatan 2B, 221 85 Lund</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kanetsky, Peter A" sort="Kanetsky, Peter A" uniqKey="Kanetsky P" first="Peter A." last="Kanetsky">Peter A. Kanetsky</name>
<affiliation wicri:level="1"><nlm:aff id="A19">Centre for Clinical Epidemiology & Biostatistics and Department of Biostatistics & Epidemiology, 219 Blockley Hall, University of Pennsylvania, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Centre for Clinical Epidemiology & Biostatistics and Department of Biostatistics & Epidemiology, 219 Blockley Hall, University of Pennsylvania</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kefford, Richard F" sort="Kefford, Richard F" uniqKey="Kefford R" first="Richard F." last="Kefford">Richard F. Kefford</name>
<affiliation wicri:level="1"><nlm:aff id="A20">Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, NSW 2145, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, NSW 2145</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Landi, Maria Teresa" sort="Landi, Maria Teresa" uniqKey="Landi M" first="Maria Teresa" last="Landi">Maria Teresa Landi</name>
<affiliation wicri:level="1"><nlm:aff id="A21">Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute. NIH, Bethesda, MD 20892-7236, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute. NIH, Bethesda, MD 20892-7236</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lang, Julie" sort="Lang, Julie" uniqKey="Lang J" first="Julie" last="Lang">Julie Lang</name>
<affiliation wicri:level="1"><nlm:aff id="A22">Department of Medical Genetics, University of Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Medical Genetics, University of Glasgow</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lubi Ski, Jan" sort="Lubi Ski, Jan" uniqKey="Lubi Ski J" first="Jan" last="Lubi Ski">Jan Lubi Ski</name>
<affiliation wicri:level="1"><nlm:aff id="A13">International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea>International Hereditary Cancer Center, Pomeranian Medical University, Szczecin</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mackie, Rona" sort="Mackie, Rona" uniqKey="Mackie R" first="Rona" last="Mackie">Rona Mackie</name>
<affiliation wicri:level="1"><nlm:aff id="A23">Section of Public Health & Health Policy, 1 Lilybank Gardens, University of Glasgow, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Public Health & Health Policy, 1 Lilybank Gardens, University of Glasgow</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Malvehy, Josep" sort="Malvehy, Josep" uniqKey="Malvehy J" first="Josep" last="Malvehy">Josep Malvehy</name>
<affiliation wicri:level="1"><nlm:aff id="A24">Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain and CIBER de Enfermedades Raras, Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain and CIBER de Enfermedades Raras, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Mann, Graham J" sort="Mann, Graham J" uniqKey="Mann G" first="Graham J." last="Mann">Graham J. Mann</name>
<affiliation wicri:level="1"><nlm:aff id="A20">Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, NSW 2145, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, NSW 2145</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Martin, Nicholas G" sort="Martin, Nicholas G" uniqKey="Martin N" first="Nicholas G." last="Martin">Nicholas G. Martin</name>
<affiliation wicri:level="1"><nlm:aff id="A25">Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Montgomery, Grant W" sort="Montgomery, Grant W" uniqKey="Montgomery G" first="Grant W." last="Montgomery">Grant W. Montgomery</name>
<affiliation wicri:level="1"><nlm:aff id="A25">Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van Nieuwpoort, Frans A" sort="Van Nieuwpoort, Frans A" uniqKey="Van Nieuwpoort F" first="Frans A" last="Van Nieuwpoort">Frans A. Van Nieuwpoort</name>
<affiliation wicri:level="1"><nlm:aff id="A26">Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Dermatology, Leiden University Medical Centre, Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Novakovic, Srdjan" sort="Novakovic, Srdjan" uniqKey="Novakovic S" first="Srdjan" last="Novakovic">Srdjan Novakovic</name>
<affiliation wicri:level="1"><nlm:aff id="A16">Institute of Oncology Ljubljana, Zaloska 2,1000 Ljubljana, Slovenia</nlm:aff>
<country xml:lang="fr">Slovénie</country>
<wicri:regionArea>Institute of Oncology Ljubljana, Zaloska 2,1000 Ljubljana</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Olsson, H Kan" sort="Olsson, H Kan" uniqKey="Olsson H" first="H Kan" last="Olsson">H Kan Olsson</name>
<affiliation wicri:level="1"><nlm:aff id="A18">Department of Oncology, University Hospital Lund, Barngatan 2B, 221 85 Lund, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Oncology, University Hospital Lund, Barngatan 2B, 221 85 Lund</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Puig, Susana" sort="Puig, Susana" uniqKey="Puig S" first="Susana" last="Puig">Susana Puig</name>
<affiliation wicri:level="1"><nlm:aff id="A24">Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain and CIBER de Enfermedades Raras, Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain and CIBER de Enfermedades Raras, Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Weiss, Marjan" sort="Weiss, Marjan" uniqKey="Weiss M" first="Marjan" last="Weiss">Marjan Weiss</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Van Workum, Wilbert" sort="Van Workum, Wilbert" uniqKey="Van Workum W" first="Wilbert" last="Van Workum">Wilbert Van Workum</name>
<affiliation wicri:level="1"><nlm:aff id="A12">ServiceXS, Plesmanlaan Id, 2333 BZ Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>ServiceXS, Plesmanlaan Id, 2333 BZ Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zelenika, Diana" sort="Zelenika, Diana" uniqKey="Zelenika D" first="Diana" last="Zelenika">Diana Zelenika</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Brown, Kevin M" sort="Brown, Kevin M" uniqKey="Brown K" first="Kevin M" last="Brown">Kevin M. Brown</name>
<affiliation wicri:level="1"><nlm:aff id="A27">Melanoma Genomics Laboratory, The Translational Genomics Research Institute (TGen), 445 N. Fifth Street, Phoenix, AZ 85004, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Melanoma Genomics Laboratory, The Translational Genomics Research Institute (TGen), 445 N. Fifth Street, Phoenix, AZ 85004</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Goldstein, Alisa M" sort="Goldstein, Alisa M" uniqKey="Goldstein A" first="Alisa M." last="Goldstein">Alisa M. Goldstein</name>
<affiliation wicri:level="1"><nlm:aff id="A21">Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute. NIH, Bethesda, MD 20892-7236, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute. NIH, Bethesda, MD 20892-7236</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gillanders, Elizabeth M" sort="Gillanders, Elizabeth M" uniqKey="Gillanders E" first="Elizabeth M." last="Gillanders">Elizabeth M. Gillanders</name>
<affiliation wicri:level="1"><nlm:aff id="A28">Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland 21224, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland 21224</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Boland, Anne" sort="Boland, Anne" uniqKey="Boland A" first="Anne" last="Boland">Anne Boland</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Galan, Pilar" sort="Galan, Pilar" uniqKey="Galan P" first="Pilar" last="Galan">Pilar Galan</name>
<affiliation><nlm:aff id="A29">UMR U557 Inserm ; U1125 Inra; Cnam; Paris 13, CRNH Idf, 74 rue Marcel Cachin F-93017 Bobigny</nlm:aff>
<wicri:noCountry code="subfield">74 rue Marcel Cachin F-93017 Bobigny</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Elder, David E" sort="Elder, David E" uniqKey="Elder D" first="David E." last="Elder">David E. Elder</name>
<affiliation wicri:level="1"><nlm:aff id="A30">Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gruis, Nelleke A" sort="Gruis, Nelleke A" uniqKey="Gruis N" first="Nelleke A" last="Gruis">Nelleke A. Gruis</name>
<affiliation wicri:level="1"><nlm:aff id="A26">Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Dermatology, Leiden University Medical Centre, Leiden</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Hayward, Nicholas K" sort="Hayward, Nicholas K" uniqKey="Hayward N" first="Nicholas K." last="Hayward">Nicholas K. Hayward</name>
<affiliation wicri:level="1"><nlm:aff id="A25">Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lathrop, G Mark" sort="Lathrop, G Mark" uniqKey="Lathrop G" first="G. Mark" last="Lathrop">G. Mark Lathrop</name>
<affiliation wicri:level="1"><nlm:aff id="A14">Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Fondation Jean Dausset-CEPH, 75010, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Fondation Jean Dausset-CEPH, 75010, Paris</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Barrett, Jennifer H" sort="Barrett, Jennifer H" uniqKey="Barrett J" first="Jennifer H" last="Barrett">Jennifer H. Barrett</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Newton Bishop, Julia A" sort="Newton Bishop, Julia A" uniqKey="Newton Bishop J" first="Julia A" last="Newton Bishop">Julia A. Newton Bishop</name>
<affiliation wicri:level="1"><nlm:aff id="A1">Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature genetics</title>
<idno type="ISSN">1061-4036</idno>
<idno type="eISSN">1546-1718</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P3">We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317k tagging SNPs for 1650 genetically-enriched cases (from Europe and Australia) and 4336 controls and subsequent replication in 1149 genetically-enriched cases and 964 controls and a population-based case-control study of 1163 cases and 903 controls. The genome-wide screen identified five regions with genotyped or imputed SNPs reaching p < 5×10<sup>−7</sup>
; three regions were replicated: 16q24 encompassing <italic>MC1R</italic>
 (overall p=2.54×10<sup>−27</sup>
 for rs258322), 11q14-q21 encompassing <italic>TYR</italic>
 (p=2.41×10<sup>−14</sup>
 for rs1393350) and 9p21 adjacent to <italic>MTAP</italic>
 and flanking <italic>CDKN2A</italic>
 (p=4.03×10<sup>−7</sup>
 for rs7023329). <italic>MC1R</italic>
 and <italic>TYR</italic>
 are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognised melanoma risk factors, while the 9p21 locus is novel for common variants 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 contribute independently to melanoma risk.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <pmc-dir>properties manuscript</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-journal-id">9216904</journal-id>
<journal-id journal-id-type="pubmed-jr-id">2419</journal-id>
<journal-id journal-id-type="nlm-ta">Nat Genet</journal-id>
<journal-title>Nature genetics</journal-title>
<issn pub-type="ppub">1061-4036</issn>
<issn pub-type="epub">1546-1718</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">19578364</article-id>
<article-id pub-id-type="pmc">2741419</article-id>
<article-id pub-id-type="doi">10.1038/ng.411</article-id>
<article-id pub-id-type="manuscript">NIHMS130600</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Genome-wide association study identifies three loci associated with melanoma risk</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Bishop</surname>
<given-names>D Timothy</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Demenais</surname>
<given-names>Florence</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Iles</surname>
<given-names>Mark M</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harland</surname>
<given-names>Mark</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Taylor</surname>
<given-names>John C.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Corda</surname>
<given-names>Eve</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Randerson-Moor</surname>
<given-names>Juliette</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Aitken</surname>
<given-names>Joanne F.</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Avril</surname>
<given-names>Marie-Francoise</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Azizi</surname>
<given-names>Esther</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bakker</surname>
<given-names>Bert</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bianchi-Scarrà</surname>
<given-names>Giovanna</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bressac-de Paillerets</surname>
<given-names>Brigitte</given-names>
</name>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Calista</surname>
<given-names>Donato</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cannon-Albright</surname>
<given-names>Lisa A.</given-names>
</name>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chin-a-Woeng</surname>
<given-names>Thomas</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dębniak</surname>
<given-names>Tadeusz</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Galore-Haskel</surname>
<given-names>Gilli</given-names>
</name>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ghiorzo</surname>
<given-names>Paola</given-names>
</name>
<xref ref-type="aff" rid="A8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gut</surname>
<given-names>Ivo</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hansson</surname>
<given-names>Johan</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hocevar</surname>
<given-names>Marko</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Höiom</surname>
<given-names>Veronica</given-names>
</name>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hopper</surname>
<given-names>John L.</given-names>
</name>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ingvar</surname>
<given-names>Christian</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kanetsky</surname>
<given-names>Peter A.</given-names>
</name>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kefford</surname>
<given-names>Richard F.</given-names>
</name>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Landi</surname>
<given-names>Maria Teresa</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lang</surname>
<given-names>Julie</given-names>
</name>
<xref ref-type="aff" rid="A22">22</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lubiński</surname>
<given-names>Jan</given-names>
</name>
<xref ref-type="aff" rid="A13">13</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mackie</surname>
<given-names>Rona</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Malvehy</surname>
<given-names>Josep</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mann</surname>
<given-names>Graham J.</given-names>
</name>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Martin</surname>
<given-names>Nicholas G.</given-names>
</name>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Montgomery</surname>
<given-names>Grant W.</given-names>
</name>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Nieuwpoort</surname>
<given-names>Frans A</given-names>
</name>
<xref ref-type="aff" rid="A26">26</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Novakovic</surname>
<given-names>Srdjan</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Olsson</surname>
<given-names>Håkan</given-names>
</name>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Puig</surname>
<given-names>Susana</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Weiss</surname>
<given-names>Marjan</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Workum</surname>
<given-names>Wilbert</given-names>
</name>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zelenika</surname>
<given-names>Diana</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brown</surname>
<given-names>Kevin M</given-names>
</name>
<xref ref-type="aff" rid="A27">27</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Goldstein</surname>
<given-names>Alisa M.</given-names>
</name>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gillanders</surname>
<given-names>Elizabeth M.</given-names>
</name>
<xref ref-type="aff" rid="A28">28</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Boland</surname>
<given-names>Anne</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Galan</surname>
<given-names>Pilar</given-names>
</name>
<xref ref-type="aff" rid="A29">29</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Elder</surname>
<given-names>David E.</given-names>
</name>
<xref ref-type="aff" rid="A30">30</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gruis</surname>
<given-names>Nelleke A</given-names>
</name>
<xref ref-type="aff" rid="A26">26</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hayward</surname>
<given-names>Nicholas K.</given-names>
</name>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lathrop</surname>
<given-names>G. Mark</given-names>
</name>
<xref ref-type="aff" rid="A14">14</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Barrett</surname>
<given-names>Jennifer H</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Newton Bishop</surname>
<given-names>Julia A</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James's University Hospital, Leeds, UK</aff>
<aff id="A2"><label>2</label>
INSERM, U946, Fondation Jean-Dausset-CEPH, 75010 Paris, France</aff>
<aff id="A3"><label>3</label>
Fondation Jean Dausset-CEPH, 75010, Paris, France</aff>
<aff id="A4"><label>4</label>
Viertel Centre for Research in Cancer Control, The Cancer Council, Queensland, Spring Hill, Brisbane, Australia</aff>
<aff id="A5"><label>5</label>
AP-HP, Hôpital Cochin, Service de Dermatologie, Faculté Paris 5, Paris, France</aff>
<aff id="A6"><label>6</label>
Department of Dermatology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Israel</aff>
<aff id="A7"><label>7</label>
Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</aff>
<aff id="A8"><label>8</label>
Department of Oncology, Biology and Genetics, University of Genoa, V. le Benedetto XV 6,16132 Genova, Italy</aff>
<aff id="A9"><label>9</label>
Service de Génétique et FRE 2939 CNRS, Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France</aff>
<aff id="A10"><label>10</label>
Dermatology Unit, Maurizio Bufalini Hospital, 47023 Cesena, Italy</aff>
<aff id="A11"><label>11</label>
Genetic Epidemiology, Biomedical Informatics, 391 Chipeta Way, Suite D, University of Utah, Salt Lake City, USA</aff>
<aff id="A12"><label>12</label>
ServiceXS, Plesmanlaan Id, 2333 BZ Leiden, The Netherlands</aff>
<aff id="A13"><label>13</label>
International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland</aff>
<aff id="A14"><label>14</label>
Commissariat à l'énergie Atomique, Institut de Génomique, Centre National de Génotypage, Evry, France</aff>
<aff id="A15"><label>15</label>
Department of Oncology-Pathology, Karolinska Institutet, SE-171 77 Stockholm, Sweden</aff>
<aff id="A16"><label>16</label>
Institute of Oncology Ljubljana, Zaloska 2,1000 Ljubljana, Slovenia</aff>
<aff id="A17"><label>17</label>
Centre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology, School of Population Health, University of Melbourne, Melbourne, Australia</aff>
<aff id="A18"><label>18</label>
Department of Oncology, University Hospital Lund, Barngatan 2B, 221 85 Lund, Sweden</aff>
<aff id="A19"><label>19</label>
Centre for Clinical Epidemiology & Biostatistics and Department of Biostatistics & Epidemiology, 219 Blockley Hall, University of Pennsylvania, USA</aff>
<aff id="A20"><label>20</label>
Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, NSW 2145, Australia</aff>
<aff id="A21"><label>21</label>
Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute. NIH, Bethesda, MD 20892-7236, USA</aff>
<aff id="A22"><label>22</label>
Department of Medical Genetics, University of Glasgow, UK</aff>
<aff id="A23"><label>23</label>
Section of Public Health & Health Policy, 1 Lilybank Gardens, University of Glasgow, UK</aff>
<aff id="A24"><label>24</label>
Melanoma Unit, Dermatology Department, Hospital Clinic, IDIBAPS, Barcelona, Spain and CIBER de Enfermedades Raras, Barcelona, Spain</aff>
<aff id="A25"><label>25</label>
Queensland Institute of Medical Research. 300 Herston Rd, Herston, QLD 4029, Australia</aff>
<aff id="A26"><label>26</label>
Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands</aff>
<aff id="A27"><label>27</label>
Melanoma Genomics Laboratory, The Translational Genomics Research Institute (TGen), 445 N. Fifth Street, Phoenix, AZ 85004, USA</aff>
<aff id="A28"><label>28</label>
Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland 21224, USA</aff>
<aff id="A29"><label>29</label>
UMR U557 Inserm ; U1125 Inra; Cnam; Paris 13, CRNH Idf, 74 rue Marcel Cachin F-93017 Bobigny</aff>
<aff id="A30"><label>30</label>
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA</aff>
<author-notes><fn id="FN1"><p id="P1"><bold>Author Contributions</bold>
</p>
<p id="P2">D.T.B. led the analysis group, contributed to the design of the study and was a member of the writing team; F.D. advised on analysis, contributed to the design of the study and was a member of the writing team; M.M.I, and J.H.B. advised on and carried out analyses, contributed to the design of the study and were members of the writing team; M.H. contributed to the design of the study and contributed genotyping information; J.C.T. and E.C. carried out analyses and were members of the writing team; J.R.-M., T.C-a-W. and D.Z.contributed to the interpretation of genotyping data; J.F.A., M.-F.A., D.C., G.G.-FL, V.H., C.I., J.Lang, J.M., N.G.M., G.W.M. and S.N. contributed to the identification of suitable samples for the study; E.A., P.G., M.T.L. and R.M. contributed to the design of the study and contributed to the identification of suitable samples for the study; B.B. contributed to the design of the study and supervised the initial processing of samples; G.B.-S., B.B-deP., L.A.C.-A., T.D., I.G., J.H., M.H., J.L.H., R.F.K., I Lubiński, G.J.M., F.A. vanN., H.O., S.P., W. vanW., K.M.B., P.G. and D.E.E. contributed to the design of the study; P.A.K, N. K. H. contributed to the design of the study, contributed to the interpretation of genotyping data and advised the analysis group; M.W. contributed to the design of the sample handling process; A.M.G. and E.M.G. advised on statistical analysis; A.B. contributed genotyping information; N.A.G. contributed to the design of the study and was project deputy lead; G.M.L. contributed to the design of the study and the interpretation of genotyping data; J.A.N.B. led the study design group and was overall project lead.</p>
</fn>
<corresp id="cor1"><bold>Corresponding Author:</bold>
, Prof D Timothy Bishop FMedSci, Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, University of Leeds, Cancer Genetics Building, St James's Hospital, Beckett Street, LEEDS LS9 7TF, UK, Email: <email>d.t.bishop@leeds.ac.uk</email>
, Tel: +44-113-206-4573, FAX: +44-113-234-0183, Mobile: +44-7788415474</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>10</day>
<month>7</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="epub"><day>5</day>
<month>7</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="ppub"><month>8</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>2</month>
<year>2010</year>
</pub-date>
<volume>41</volume>
<issue>8</issue>
<fpage>920</fpage>
<lpage>925</lpage>
<abstract><p id="P3">We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317k tagging SNPs for 1650 genetically-enriched cases (from Europe and Australia) and 4336 controls and subsequent replication in 1149 genetically-enriched cases and 964 controls and a population-based case-control study of 1163 cases and 903 controls. The genome-wide screen identified five regions with genotyped or imputed SNPs reaching p < 5×10<sup>−7</sup>
; three regions were replicated: 16q24 encompassing <italic>MC1R</italic>
 (overall p=2.54×10<sup>−27</sup>
 for rs258322), 11q14-q21 encompassing <italic>TYR</italic>
 (p=2.41×10<sup>−14</sup>
 for rs1393350) and 9p21 adjacent to <italic>MTAP</italic>
 and flanking <italic>CDKN2A</italic>
 (p=4.03×10<sup>−7</sup>
 for rs7023329). <italic>MC1R</italic>
 and <italic>TYR</italic>
 are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognised melanoma risk factors, while the 9p21 locus is novel for common variants 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 contribute independently to melanoma risk.</p>
</abstract>
<contract-num rid="CA1">R01 CA083115-08</contract-num>
<contract-sponsor id="CA1">National Cancer Institute : NCI</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>

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Genome-wide association study identifies three loci associated with melanoma risk

Genome-wide association study identifies three loci associated with melanoma risk

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