Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.

Autor: 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.; Discipline of Obstetrics and Gynaecology, The University of Sydney, Sydney, NSW, Australia.; Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia.; The Daffodil Centre, The University of Sydney, a joint venture with Cancer Council NSW, Sydney, NSW, Australia., Riggan MJ; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA., Webb PM; Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Fasching PA; Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany., Lambrechts D; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.; VIB Center for Cancer Biology, VIB, Leuven, Belgium., García MJ; Biochemistry and Molecular Biology area, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain., Rodríguez-Antona C; Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain., Goodman MT; Cancer Prevention and Control Program, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Modugno F; Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Women's Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, PA, USA., Moysich KB; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA., Karlan BY; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, USA., Lester J; David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, CA, USA., Kjaer SK; Department of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark.; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Jensen A; Department of Virus, Lifestyle and Genes, Danish Cancer Institute, Copenhagen, Denmark., Høgdall E; Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark., Goode EL; Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, USA., Cliby WA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, USA., Kumar A; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, USA., Wang C; Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA., Cunningham JM; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Winham SJ; Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN, USA., Monteiro AN; Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA., Schildkraut JM; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Cramer DW; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gyneclogy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Terry KL; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gyneclogy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Titus L; Norris Cotton Cancer Center, Lebanon, NH, USA., Bjorge L; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway., Thomsen LCV; Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway.; Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway., Pejovic T; Department of ObGyn, Providence Medical Center, Medford, OR, USA.; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Høgdall CK; Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., McNeish IA; Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, Imperial College London, London, UK.; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK., May T; Division of Gynecologic Oncology, University Health Network, Princess Margaret Hospital, Toronto, ON, Canada., Huntsman DG; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada.; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada., Pfisterer J; Gynecologic Oncology Center, Kiel, Germany., Canzler U; University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany., Park-Simon TW; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Schröder W; Klinikum Bremen-Mitte, Bremen, Germany.; Gynaekologicum Bremen, Bremen, Germany., Belau A; University Hospital Greifswald, Greifswald, Germany.; Frauenarztpraxis Belau, Greifswald, Germany., Hanker L; University Hospital Frankfurt, Frankfurt, Germany.; University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Harter P; Department of Gynecology and Gynecologic Oncology, Evangelische Kliniken Essen-Mitte (KEM), Essen, Germany., Sehouli J; Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany., Kimmig R; University Hospital Essen, University of Duisburg-Essen, Essen, Germany., de Gregorio N; University Hospital Ulm, Ulm, Germany.; SLK-Kliniken Heilbronn, Klinikum am Gesundbrunnen, Heilbronn, Germany., Schmalfeldt B; University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Baumann K; University Hospital Gießen and Marburg, Site Marburg, Marburg, Germany.; Klinikum Ludwigshafen, Ludwigshafen, Germany., Hilpert F; University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.; Krankenhaus Jerusalem, Mammazentrum Hamburg, Hamburg, Germany., Burges A; University Hospital LMU Munich, Munich, Germany., Winterhoff B; Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, University of Minnesota, Minneapolis, MN, USA., Schürmann P; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Speith LM; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Hillemanns P; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Berchuck A; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC, USA., Johnatty SE; Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Ramus SJ; School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney, Sydney, NSW, Australia.; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, NSW, Australia., Chenevix-Trench G; Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Pharoah PDP; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.; Department of Computational Biomedicine, Cedars-Sinai Medical Center, West Hollywood, CA, USA.; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Dörk T; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany. doerk.thilo@mh-hannover.de., Heitz F; Department of Gynecology and Gynecologic Oncology, Evangelische Kliniken Essen-Mitte (KEM), Essen, Germany. F.Heitz@kem-med.com.; Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. F.Heitz@kem-med.com.; Department of Gynecology and Gynecological Oncology, HSK, Dr. Horst-Schmidt Klinik, Wiesbaden, Wiesbaden, Germany. F.Heitz@kem-med.com.
Jazyk: angličtina
Zdroj: NPJ genomic medicine [NPJ Genom Med] 2024 Mar 05; Vol. 9 (1), pp. 19. Date of Electronic Publication: 2024 Mar 05.
DOI: 10.1038/s41525-024-00395-y
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: