Dataset Information

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.

SUBMITTER: Ramachandran D

PROVIDER: S-EPMC10915171 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.

Ramachandran Dhanya D Tyrer Jonathan P JP Kommoss Stefan S DeFazio Anna A Riggan Marjorie J MJ Webb Penelope M PM Fasching Peter A PA Lambrechts Diether D García María J MJ Rodríguez-Antona Cristina C Goodman Marc T MT Modugno Francesmary F Moysich Kirsten B KB Karlan Beth Y BY Lester Jenny J Kjaer Susanne K SK Jensen Allan A Høgdall Estrid E Goode Ellen L EL Cliby William A WA Kumar Amanika A Wang Chen C Cunningham Julie M JM Winham Stacey J SJ Monteiro Alvaro N AN Schildkraut Joellen M JM Cramer Daniel W DW Terry Kathryn L KL Titus Linda L Bjorge Line L Thomsen Liv Cecilie Vestrheim LCV Pejovic Tanja T Høgdall Claus K CK McNeish Iain A IA May Taymaa T Huntsman David G DG Pfisterer Jacobus J Canzler Ulrich U Park-Simon Tjoung-Won TW Schröder Willibald W Belau Antje A Hanker Lars L Harter Philipp P Sehouli Jalid J Kimmig Rainer R de Gregorio Nikolaus N Schmalfeldt Barbara B Baumann Klaus K Hilpert Felix F Burges Alexander A Winterhoff Boris B Schürmann Peter P Speith Lisa-Marie LM Hillemanns Peter P Berchuck Andrew A Johnatty Sharon E SE Ramus Susan J SJ Chenevix-Trench Georgia G Pharoah Paul D P PDP Dörk Thilo T Heitz Florian F

NPJ genomic medicine 20240305 1

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<sup>-8</sup>). In gene-based analyses, PPP2R5C was the most strongly associated ...[more]

PMID: 38443389

Similar Datasets

Project description:ObjectiveTo describe oncologic outcomes after using acute normovolemic hemodilution (ANH) to reduce requirement for allogenic red blood cell transfusions (ABT) in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer.MethodsWe performed a post-hoc analysis of a recent prospective trial investigating the safety and feasibility of ANH during PDS for advanced ovarian cancer. We report long-term survival outcomes. We compared demographics, clinicopathological characteristics, survival outcomes in this cohort of Stage IIIB-IVB high-grade serous ovarian cancer patients undergoing ANH (ANH group), with a retrospective cohort of all other patients (standard group) undergoing PDS during the same time period (01/2012-04/2017). Standard statistical tests were used.ResultsThere were no demographic or clinicopathological differences between ANH (n = 33) and standard groups (n = 360), except for higher median age at diagnosis (57 vs. 62 years, respectively; p = 0.044) and shorter operative time (357 vs. 446 min, respectively; p < 0.001) in the standard group. Cytoreductive outcomes (ANH vs. standard): 0 mm, 69.7 vs. 63.9%; gross residual disease (RD) ≤1 cm, 21.2 vs. 26.9%; >1 cm, 9.1 vs. 9.2% (p = 0.78). RD after PDS was the only independent factor associated with worse progression-free survival (PFS) on multivariable analysis (p < 0.001). Patients with BRCA mutations trended towards improved PFS (p = 0.057). Significant factors for overall survival (OS) on multivariable analysis: preoperative CA125 (p = 0.004), ascites (p = 0.018), RD after PDS (p = 0.04), BRCA mutation status (p < 0.001). After adjustment for potential confounders, ANH was not independently associated with PFS or OS [PFS: HR 0.928 (0.618-1.395); p = 0.721; OS: HR 0.588 (95%CI: 0.317-1.092); p = 0.093].ConclusionsANH is an innovative approach in intraoperative management. It was previously proven to decrease need for ABT while maintaining the ability to achieve complete gross resection and associated benefits.

Dataset Information

Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.

Publications

Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets