Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.
Document Type
Article
Publication Date
3-5-2024
Publication Title
NPJ Genom Med
Keywords
oregon; medford; genomics
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.
Clinical Institute
Women & Children
Clinical Institute
Cancer
Department
Obstetrics & Gynecology
Department
Oncology
Department
Epidemiology
Recommended Citation
Ramachandran, Dhanya; Tyrer, Jonathan P; Kommoss, Stefan; DeFazio, Anna; Riggan, Marjorie J; Group, AOCS; 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; Study Group, OPAL; 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; Winterhoff, Boris; Schürmann, Peter; Speith, Lisa-Marie; Hillemanns, Peter; Berchuck, Andrew; Johnatty, Sharon E; Ramus, Susan J; Chenevix-Trench, Georgia; Pharoah, Paul D P; Dörk, Thilo; and Heitz, Florian, "Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease." (2024). Articles, Abstracts, and Reports. 8635.
https://digitalcommons.providence.org/publications/8635
