npj Genomic Medicine (Mar 2024)
Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease
- Dhanya Ramachandran,
- Jonathan P. Tyrer,
- Stefan Kommoss,
- Anna DeFazio,
- Marjorie J. Riggan,
- AOCS Group,
- Penelope M. Webb,
- Peter A. Fasching,
- Diether Lambrechts,
- María J. García,
- Cristina Rodríguez-Antona,
- Marc T. Goodman,
- Francesmary Modugno,
- Kirsten B. Moysich,
- Beth Y. Karlan,
- Jenny Lester,
- Susanne K. Kjaer,
- Allan Jensen,
- Estrid Høgdall,
- Ellen L. Goode,
- William A. Cliby,
- Amanika Kumar,
- Chen Wang,
- Julie M. Cunningham,
- Stacey J. Winham,
- Alvaro N. Monteiro,
- Joellen M. Schildkraut,
- Daniel W. Cramer,
- Kathryn L. Terry,
- Linda Titus,
- Line Bjorge,
- Liv Cecilie Vestrheim Thomsen,
- OPAL Study Group,
- Tanja Pejovic,
- Claus K. Høgdall,
- Iain A. McNeish,
- Taymaa May,
- David G. Huntsman,
- Jacobus Pfisterer,
- Ulrich Canzler,
- Tjoung-Won Park-Simon,
- Willibald Schröder,
- Antje Belau,
- Lars Hanker,
- Philipp Harter,
- Jalid Sehouli,
- Rainer Kimmig,
- Nikolaus de Gregorio,
- Barbara Schmalfeldt,
- Klaus Baumann,
- Felix Hilpert,
- Alexander Burges,
- Boris Winterhoff,
- Peter Schürmann,
- Lisa-Marie Speith,
- Peter Hillemanns,
- Andrew Berchuck,
- Sharon E. Johnatty,
- Susan J. Ramus,
- Georgia Chenevix-Trench,
- Paul D. P. Pharoah,
- Thilo Dörk,
- Florian Heitz
Affiliations
- Dhanya Ramachandran
- Gynaecology Research Unit, Hannover Medical School
- Jonathan P. Tyrer
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge
- Stefan Kommoss
- Department of Women’s Health, Tuebingen University Hospital
- Anna DeFazio
- Centre for Cancer Research, The Westmead Institute for Medical Research, University of Sydney
- Marjorie J. Riggan
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center
- AOCS Group
- Penelope M. Webb
- Population Health Program, QIMR Berghofer Medical Research Institute
- Peter A. Fasching
- Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen
- Diether Lambrechts
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
- María J. García
- Biochemistry and Molecular Biology area, Department of Basic Health Sciences, Faculty of Health Sciences, Rey Juan Carlos University
- Cristina Rodríguez-Antona
- Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO)
- Marc T. Goodman
- Cancer Prevention and Control Program, Cedars-Sinai Cancer, Cedars-Sinai Medical Center
- Francesmary Modugno
- Department of Epidemiology, University of Pittsburgh School of Public Health
- Kirsten B. Moysich
- Department of Cancer Prevention and Control, Roswell Park Cancer Institute
- Beth Y. Karlan
- David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles
- Jenny Lester
- David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles
- Susanne K. Kjaer
- Department of Virus, Lifestyle and Genes, Danish Cancer Institute
- Allan Jensen
- Department of Virus, Lifestyle and Genes, Danish Cancer Institute
- Estrid Høgdall
- Department of Pathology, Herlev Hospital, University of Copenhagen
- Ellen L. Goode
- Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic
- William A. Cliby
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic
- Amanika Kumar
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic
- Chen Wang
- Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic
- Julie M. Cunningham
- Department of Laboratory Medicine and Pathology, Mayo Clinic
- Stacey J. Winham
- Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic
- Alvaro N. Monteiro
- Department of Cancer Epidemiology, Moffitt Cancer Center
- Joellen M. Schildkraut
- Department of Epidemiology, Rollins School of Public Health, Emory University
- Daniel W. Cramer
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gyneclogy, Brigham and Women’s Hospital and Harvard Medical School
- Kathryn L. Terry
- Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gyneclogy, Brigham and Women’s Hospital and Harvard Medical School
- Linda Titus
- Norris Cotton Cancer Center
- Line Bjorge
- Department of Obstetrics and Gynecology, Haukeland University Hospital
- Liv Cecilie Vestrheim Thomsen
- Department of Obstetrics and Gynecology, Haukeland University Hospital
- OPAL Study Group
- Tanja Pejovic
- Department of ObGyn, Providence Medical Center
- Claus K. Høgdall
- Department of Gynaecology, Rigshospitalet, University of Copenhagen
- Iain A. McNeish
- Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, Imperial College London
- Taymaa May
- Division of Gynecologic Oncology, University Health Network, Princess Margaret Hospital
- David G. Huntsman
- Department of Obstetrics and Gynecology, University of British Columbia
- Jacobus Pfisterer
- Gynecologic Oncology Center
- Ulrich Canzler
- University Hospital Carl Gustav Carus, Technische Universität Dresden
- Tjoung-Won Park-Simon
- Gynaecology Research Unit, Hannover Medical School
- Willibald Schröder
- Klinikum Bremen-Mitte
- Antje Belau
- University Hospital Greifswald
- Lars Hanker
- University Hospital Frankfurt
- Philipp Harter
- Department of Gynecology and Gynecologic Oncology, Evangelische Kliniken Essen-Mitte (KEM)
- Jalid Sehouli
- Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
- Rainer Kimmig
- University Hospital Essen, University of Duisburg-Essen
- Nikolaus de Gregorio
- University Hospital Ulm
- Barbara Schmalfeldt
- University Medical Center Hamburg-Eppendorf
- Klaus Baumann
- University Hospital Gießen and Marburg, Site Marburg
- Felix Hilpert
- University Hospital Schleswig-Holstein
- Alexander Burges
- University Hospital LMU Munich
- Boris Winterhoff
- Department of Obstetrics, Gynecology and Women’s Health, Division of Gynecologic Oncology, University of Minnesota
- Peter Schürmann
- Gynaecology Research Unit, Hannover Medical School
- Lisa-Marie Speith
- Gynaecology Research Unit, Hannover Medical School
- Peter Hillemanns
- Gynaecology Research Unit, Hannover Medical School
- Andrew Berchuck
- Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center
- Sharon E. Johnatty
- Cancer Division, QIMR Berghofer Medical Research Institute
- Susan J. Ramus
- School of Clinical Medicine, UNSW Medicine and Health, University of NSW Sydney
- Georgia Chenevix-Trench
- Cancer Division, QIMR Berghofer Medical Research Institute
- Paul D. P. Pharoah
- Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge
- Thilo Dörk
- Gynaecology Research Unit, Hannover Medical School
- Florian Heitz
- Department of Gynecology and Gynecologic Oncology, Evangelische Kliniken Essen-Mitte (KEM)
- DOI
- https://doi.org/10.1038/s41525-024-00395-y
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 12
Abstract
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.
