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Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.
Ramachandran, Dhanya; Tyrer, Jonathan P; Kommoss, Stefan; DeFazio, Anna; Riggan, Marjorie J; Webb, Penelope M; Fasching, Peter A; Lambrechts, Diether; García, María J; Rodríguez-Antona, Cristina; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten B; Karlan, Beth Y; Lester, Jenny; Kjaer, Susanne K; Jensen, Allan; Høgdall, Estrid; Goode, Ellen L; Cliby, William A; Kumar, Amanika; Wang, Chen; Cunningham, Julie M; Winham, Stacey J; Monteiro, Alvaro N; Schildkraut, Joellen M; Cramer, Daniel W; Terry, Kathryn L; Titus, Linda; Bjorge, Line; Thomsen, Liv Cecilie Vestrheim; Pejovic, Tanja; Høgdall, Claus K; McNeish, Iain A; May, Taymaa; Huntsman, David G; Pfisterer, Jacobus; Canzler, Ulrich; Park-Simon, Tjoung-Won; Schröder, Willibald; Belau, Antje; Hanker, Lars; Harter, Philipp; Sehouli, Jalid; Kimmig, Rainer; de Gregorio, Nikolaus; Schmalfeldt, Barbara; Baumann, Klaus; Hilpert, Felix; Burges, Alexander.
Affiliation
  • Ramachandran D; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Tyrer JP; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
  • Kommoss S; Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany.
  • DeFazio A; Centre for Cancer Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia.
  • Riggan MJ; Discipline of Obstetrics and Gynaecology, The University of Sydney, Sydney, NSW, Australia.
  • Webb PM; The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia.
  • Fasching PA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA.
  • García MJ; Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
  • Rodríguez-Antona C; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Goodman MT; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Modugno F; VIB Center for Cancer Biology, VIB, Leuven, Belgium.
  • Moysich KB; Biochemistry and Molecular Biology area, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain.
  • Karlan BY; Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
  • Lester J; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
  • Kjaer SK; Cancer Prevention and Control Program, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Jensen A; Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.
  • Høgdall E; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Goode EL; Women's Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, PA, USA.
  • Cliby WA; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
  • Kumar A; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, USA.
  • Wang C; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, USA.
  • Cunningham JM; Department of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark.
  • Winham SJ; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • Monteiro AN; Department of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark.
  • Schildkraut JM; Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
  • Cramer DW; Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA.
  • Terry KL; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, USA.
  • Titus L; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, USA.
  • Bjorge L; Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA.
  • Thomsen LCV; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
  • Pejovic T; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
  • Høgdall CK; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
  • McNeish IA; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gyneclogy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • May T; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Huntsman DG; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gyneclogy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Pfisterer J; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Canzler U; Norris Cotton Cancer Center, Lebanon, NH, USA.
  • Park-Simon TW; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
  • Schröder W; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Belau A; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.
  • Hanker L; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Sehouli J; Department of ObGyn, Providence Medical Center, Medford, OR, USA.
  • Kimmig R; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • de Gregorio N; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • Schmalfeldt B; Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, Imperial College London, London, UK.
  • Baumann K; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Hilpert F; Division of Gynecologic Oncology, University Health Network, Princess Margaret Hospital, Toronto, ON, Canada.
  • Burges A; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.
NPJ Genom Med ; 9(1): 19, 2024 Mar 05.
Article de En | MEDLINE | ID: mdl-38443389
ABSTRACT
Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Langue: En Journal: NPJ Genom Med Année: 2024 Type de document: Article Pays d'affiliation: Allemagne Pays de publication: Royaume-Uni
Texte intégral
Ajouter à My VHL
Imprimer
XML
PubMed Links
Recherche sur Google

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Langue: En Journal: NPJ Genom Med Année: 2024 Type de document: Article Pays d'affiliation: Allemagne Pays de publication: Royaume-Uni