Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Department of Gynecology and Obstetrics
- National Center for Tumor Diseases Dresden
- Hannover Medical School (MHH)
- University of Cambridge
- University Hospital Tübingen
- University of Sydney
- Westmead Hospital
- Duke University
- Queensland Institute of Medical Research
- Friedrich-Alexander University Erlangen-Nürnberg
- KU Leuven
- Flanders Institute for Biotechnology (VIB)
- Universidad Rey Juan Carlos
- Spanish National Cancer Centre (CNIO)
- CIBER - Center for Biomedical Research Network
- Cedars-Sinai Medical Center
- University of Pittsburgh
- Roswell Park Cancer Institute
- University of California at Los Angeles
- Danish Cancer Society
- Righospitalet
- University of Copenhagen
- Mayo Clinic Rochester, MN
- H. Lee Moffitt Cancer Center & Research Institute
- Emory University
- Harvard University
- Dartmouth-Hitchcock Clinic
- Haukeland universitetssjukehus
- University of Bergen
- Providence Portland Medical Center
- Oregon Health and Science University
- Imperial College London
- University of Glasgow
- University of Toronto
- University of British Columbia
- Gynecologic Oncology Center
- University Hospital Carl Gustav Carus Dresden
- Department of Gynecology and Obstetrics
- Klinikum Bremen-Mitte
- Gynaekologicum Bremen
- University of Greifswald
- Frauenarztpraxis Belau Greifswald
- University Hospital Frankfurt
- Universitätsklinikum Schleswig-Holstein - Campus Lübeck
- University of Duisburg-Essen
- Charité – Universitätsmedizin Berlin
- Ulm University
- SLK-Kliniken Heilbronn GmbH
- University of Hamburg
- University Hospital Gießen and Marburg
- Klinikum Ludwigshafen
- University Hospital Schleswig-Holstein Campus Kiel
- Jerusalem Hospital
- Ludwig Maximilian University of Munich
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.
Details
| Original language | English |
|---|---|
| Article number | 19 |
| Number of pages | 12 |
| Journal | npj Genomic Medicine |
| Volume | 9 |
| Issue number | 1 |
| Publication status | Published - 5 Mar 2024 |
| Peer-reviewed | Yes |