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Five endometrial cancer risk loci identified through genome-wide association analysis.
Cheng, Timothy Ht; Thompson, Deborah J; O'Mara, Tracy A; Painter, Jodie N; Glubb, Dylan M; Flach, Susanne; Lewis, Annabelle; French, Juliet D; Freeman-Mills, Luke; Church, David; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Webb, Penelope M; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Henders, Anjali K; Martin, Nicholas G; Montgomery, Grant W; Nyholt, Dale R; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Dennis, Joe; Fasching, Peter A; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Amant, Frederic; Schrauwen, Stefanie; Zhao, Hui; Lambrechts, Diether; Depreeuw, Jeroen; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone.
Afiliação
  • Cheng TH; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Thompson DJ; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • O'Mara TA; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Painter JN; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Glubb DM; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Flach S; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Lewis A; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • French JD; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Freeman-Mills L; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Church D; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Gorman M; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Martin L; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Hodgson S; Department of Clinical Genetics, St George's, University of London, London, UK.
  • Webb PM; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Attia J; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia.
  • Holliday EG; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, NSW, Australia.
  • McEvoy M; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia.
  • Scott RJ; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, NSW, Australia.
  • Henders AK; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, NSW, Australia.
  • Martin NG; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia.
  • Montgomery GW; Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia.
  • Nyholt DR; Centre for Information Based Medicine, University of Newcastle, NSW, Australia.
  • Ahmed S; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
  • Healey CS; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Shah M; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Dennis J; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Fasching PA; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Beckmann MW; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
  • Hein A; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Ekici AB; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Hall P; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Czene K; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Darabi H; University of California at Los Angeles, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, Los Angeles, CA, USA.
  • Li J; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Dörk T; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Dürst M; Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Hillemanns P; Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
  • Runnebaum I; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Amant F; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Schrauwen S; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Zhao H; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Lambrechts D; Hannover Medical School, Gynaecology Research Unit, Hannover, Germany.
  • Depreeuw J; Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany.
  • Dowdy SC; Hannover Medical School, Clinics of Gynaecology and Obstetrics, Hannover, Germany.
  • Goode EL; Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany.
  • Fridley BL; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals, KU Leuven - University of Leuven, Belgium.
  • Winham SJ; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals, KU Leuven - University of Leuven, Belgium.
  • Njølstad TS; Vesalius Research Center, VIB, Leuven, Belgium.
  • Salvesen HB; Laboratory for Translational Genetics, Department of Oncology, University Hospitals Leuven, Leuven, Belgium.
  • Trovik J; Vesalius Research Center, VIB, Leuven, Belgium.
Nat Genet ; 48(6): 667-674, 2016 06.
Article em En | MEDLINE | ID: mdl-27135401
ABSTRACT
We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias do Endométrio / Predisposição Genética para Doença / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias do Endométrio / Predisposição Genética para Doença / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Female / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article