| Title: |
Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease |
| Authors: |
Ramachandran, D; Tyrer, JP; Kommoss, S; DeFazio, A; Riggan, MJ; Webb, PM; Fasching, PA; Lambrechts, D; García, MJ; Rodríguez-Antona, C; Goodman, MT; Modugno, F; Moysich, KB; Karlan, BY; Lester, J; Kjaer, SK; Jensen, A; Høgdall, 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; Pejovic, T; Høgdall, CK; McNeish, IA; May, T; Huntsman, DG; Pfisterer, J; Canzler, U; Park-Simon, TW; Schröder, W; Belau, A; Hanker, L; Harter, P; Sehouli, J; Kimmig, R; de Gregorio, N; Schmalfeldt, B; Baumann, K; Hilpert, F; Burges, A; Winterhoff, B; Schürmann, P; Speith, LM; Hillemanns, P; Berchuck, A; Johnatty, SE; Ramus, SJ; Chenevix-Trench, G; Pharoah, PDP; Dörk, T; Heitz, F; Bowtell, D; Fereday, S; Traficante, N; Hung, J; Friedlander, M; Obermair, A; Grant, P; Beesley, V; Blomfield, P; Brand, A; Davis, A; Leung, Y; Nicklin, J; Quinn, M; Livingstone, K; O’Neill, H; Williams, M |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2024 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2056-7944 |
| Relation: |
NHMRC/310670; NHMRC/400281; NHMRC/628903; NHMRC/400413; https://hdl.handle.net/11343/352679 |
| Availability: |
https://hdl.handle.net/11343/352679 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.F5C5C1C6 |
| Database: |
BASE |