Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease
- PMID: 38443389
- PMCID: PMC10915171
- DOI: 10.1038/s41525-024-00395-y
Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease
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.
© 2024. The Author(s).
Conflict of interest statement
U.C. received honoraria for lectures from Lilly and AstraZeneca and is on the advisory board of AstraZeneca. J.P. received honoraria from Roche Pharma AG, AstraZeneca, Amgen, Clovis Oncology, MSD Oncology, GSK, Chugai Pharma, Teva, Medupdate, SAI MedPartners, Decision Resources, Simon-Kucher and partners, Juniper, Bionest partners, Vox Bio, Axiom healthcare strategies, Prosapient, iMed Institut, Lilly, and is a consultant/advisor for AstraZeneca, Roche, Pharma AG, Tesaro, Clovis Oncology, MSD Oncology. P.A.F. conducts research funded by Amgen, Novartis and Pfizer and received Honoraria from Roche, Novartis and Pfizer. None of these sponsors had any role in the design, data acquisition or interpretation of results in the present study.
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