Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease
- Author(s)
- Ramachandran, D; Tyrer, JP; Kommoss, S; DeFazio, A; Riggan, MJ; AOCS Group; Webb, PM; Fasching, PA; Lambrechts, D; Garcia, MJ; Rodriguez-Antona, C; Goodman, MT; Modugno, F; Moysich, KB; Karlan, BY; Lester, J; Kjaer, SK; Jensen, A; Hogdall, E; Goode, EL; Cliby, WA; Kumar, A; Wang, C; Cunningham, JM; Winham, SJ; Monteiro, AN; Schildkraut, JM; Cramer, DW; Terry, KL; Titus, L; Bjorge, L; Thomsen, LCV; OPAL Study Group; Pejovic, T; Hogdall, CK; McNeish, IA; May, T; Huntsman, DG; Pfisterer, J; Canzler, U; Park-Simon, TW; Schroder, W; Belau, A; Hanker, L; Harter, P; Sehouli, J; Kimmig, R; de Gregorio, N; Schmalfeldt, B; Baumann, K; Hilpert, F; Burges, A; Winterhoff, B; Schurmann, P; Speith, LM; Hillemanns, P; Berchuck, A; Johnatty, SE; Ramus, SJ; Chenevix-Trench, G; Pharoah, PDP; Dork, T; Heitz, F;
- Journal Title
- NPJ Genomic Medicine
- Publication Type
- Research article
- 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 x 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 B56gamma subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.
- Department(s)
- Laboratory Research
- PubMed ID
- 38443389
- Publisher's Version
- https://doi.org/10.1038/s41525-024-00395-y
- Open Access at Publisher's Site
https://doi.org/10.1038/s41525-024-00395-y- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-20 06:17:49
Last Modified: 2024-08-20 06:56:39