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Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.
Painter, Jodie N; O'Mara, Tracy A; Morris, Andrew P; Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Hodson, Shirley; Jones, Angela; Martin, Nicholas G; Gordon, Scott; Henders, Anjali K; Attia, John; McEvoy, Mark; Holliday, Elizabeth G; Scott, Rodney J; Webb, Penelope M; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Rübner, Matthias; Hall, Per; Czene, Kamila; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Lambrechts, Diether; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Vanderstichele, Adriaan; Goode, Ellen L; Cunningham, Julie M; Dowdy, Sean C; Winham, Stacey J; Trovik, Jone; Hoivik, Erling; Werner, Henrica M J; Krakstad, Camilla; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Tham, Emma; Mints, Miriam; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Pharoah, Paul D P; Dunning, Alison M.
Afiliação
  • Painter JN; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • O'Mara TA; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Morris AP; Wellcome Trust for Human Genetics, University of Oxford, Oxford, UK.
  • Cheng THT; Department of Biostatistics, University of Liverpool, Liverpool, UK.
  • Gorman M; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Martin L; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Hodson S; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Jones A; Department of Clinical Genetics, St George's, University of London, London, UK.
  • Martin NG; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
  • Gordon S; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Henders AK; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Attia J; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • McEvoy M; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.
  • Holliday EG; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
  • Scott RJ; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
  • Webb PM; Hunter Medical Research Institute, John Hunter Hospital, Newcastle, New South Wales, Australia.
  • Fasching PA; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
  • Beckmann MW; Division of Molecular Medicine, Pathology North, John Hunter Hospital, Newcastle, New South Wales, Australia.
  • Ekici AB; Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Callaghan, New South Wales, Australia.
  • Hein A; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
  • Rübner M; Department of Gynaecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Hall P; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, California.
  • Czene K; Department of Gynaecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Dörk T; Institute of Human Genetics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Dürst M; Department of Gynaecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Hillemanns P; Department of Gynaecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
  • Runnebaum I; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Lambrechts D; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Amant F; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Annibali D; Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany.
  • Depreeuw J; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Vanderstichele A; Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany.
  • Goode EL; VIB Center for Cancer Biology, VIB, Leuven, Belgium.
  • Cunningham JM; Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium.
  • Dowdy SC; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals KU Leuven, University of Leuven, Leuven, Belgium.
  • Winham SJ; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals KU Leuven, University of Leuven, Leuven, Belgium.
  • Trovik J; Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium.
  • Hoivik E; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals KU Leuven, University of Leuven, Leuven, Belgium.
  • Werner HMJ; Vesalius Research Center, VIB, Leuven, Belgium.
  • Krakstad C; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals KU Leuven, University of Leuven, Leuven, Belgium.
  • Ashton K; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
  • Otton G; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
  • Proietto T; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, Minnesota.
  • Tham E; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
  • Mints M; Centre for Cancerbiomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Ahmed S; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
  • Healey CS; Centre for Cancerbiomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Shah M; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
  • Pharoah PDP; Centre for Cancerbiomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Dunning AM; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
Cancer Med ; 7(5): 1978-1987, 2018 05.
Article em En | MEDLINE | ID: mdl-29608257
ABSTRACT
Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg  = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3 ) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias do Endométrio / Predisposição Genética para Doença / Endometriose / Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Female / Humans País/Região como assunto: Oceania Idioma: En Revista: Cancer Med Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias do Endométrio / Predisposição Genética para Doença / Endometriose / Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores Tipo de estudo: Prognostic_studies / Systematic_reviews Limite: Female / Humans País/Região como assunto: Oceania Idioma: En Revista: Cancer Med Ano de publicação: 2018 Tipo de documento: Article