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Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.
Duffy, David L; Zhu, Gu; Li, Xin; Sanna, Marianna; Iles, Mark M; Jacobs, Leonie C; Evans, David M; Yazar, Seyhan; Beesley, Jonathan; Law, Matthew H; Kraft, Peter; Visconti, Alessia; Taylor, John C; Liu, Fan; Wright, Margaret J; Henders, Anjali K; Bowdler, Lisa; Glass, Dan; Ikram, M Arfan; Uitterlinden, André G; Madden, Pamela A; Heath, Andrew C; Nelson, Elliot C; Green, Adele C; Chanock, Stephen; Barrett, Jennifer H; Brown, Matthew A; Hayward, Nicholas K; MacGregor, Stuart; Sturm, Richard A; Hewitt, Alex W; Kayser, Manfred; Hunter, David J; Newton Bishop, Julia A; Spector, Timothy D; Montgomery, Grant W; Mackey, David A; Smith, George Davey; Nijsten, Tamar E; Bishop, D Timothy; Bataille, Veronique; Falchi, Mario; Han, Jiali; Martin, Nicholas G.
Afiliação
  • Duffy DL; QIMR Berghofer Medical Research Institute, Brisbane, Australia. David.Duffy@qimrberghofer.edu.au.
  • Zhu G; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Li X; Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, 63110, USA.
  • Sanna M; Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
  • Iles MM; Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Jacobs LC; Department of Dermatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
  • Evans DM; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Yazar S; University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
  • Beesley J; Centre for Ophthalmology and Vision Science, University of Western Australia and the Lions Eye Institute, Perth, Australia.
  • Law MH; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Kraft P; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Visconti A; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USA.
  • Taylor JC; Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
  • Liu F; Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Wright MJ; Department of Genetic Identification, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
  • Henders AK; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Bowdler L; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Glass D; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Ikram MA; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Uitterlinden AG; Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
  • Madden PA; Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
  • Heath AC; Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
  • Nelson EC; Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands.
  • Green AC; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Chanock S; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Barrett JH; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Brown MA; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Hayward NK; Molecular Oncology Group, CRUK Manchester Institute, University of Manchester, Manchester, UK.
  • MacGregor S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Sturm RA; Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Hewitt AW; University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
  • Kayser M; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Hunter DJ; Dermatology Research Centre, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
  • Newton Bishop JA; Centre for Ophthalmology and Vision Science, University of Western Australia and the Lions Eye Institute, Perth, Australia.
  • Montgomery GW; Department of Genetic Identification, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
  • Mackey DA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 02115, MA, USA.
  • Smith GD; Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Nijsten TE; Department of Twin Research & Genetic Epidemiology, St Thomas Hospital Campus, Kings College, London, UK.
  • Bishop DT; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Bataille V; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  • Falchi M; Centre for Ophthalmology and Vision Science, University of Western Australia and the Lions Eye Institute, Perth, Australia.
  • Han J; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Martin NG; Department of Dermatology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Nat Commun ; 9(1): 4774, 2018 11 14.
Article em En | MEDLINE | ID: mdl-30429480
The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / População Branca / Pleiotropia Genética / Melanoma / Nevo Pigmentado Tipo de estudo: Etiology_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Commun Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cutâneas / População Branca / Pleiotropia Genética / Melanoma / Nevo Pigmentado Tipo de estudo: Etiology_studies / Risk_factors_studies / Systematic_reviews Limite: Humans Idioma: En Revista: Nat Commun Ano de publicação: 2018 Tipo de documento: Article