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

OPAL Study Group; AOCS Group

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

OPAL Study Group
, AOCS Group

Department of Epidemiology and Environmental Health

Netherlands Cancer Institute
Hannover Medical School
University of Cambridge
University of Tübingen
The University of Sydney
Westmead Hospital
Duke University
Queensland Institute of Medical Research
Friedrich-Alexander University Erlangen-Nürnberg
KU Leuven
Flanders Institute for Biotechnology
Universidad Rey Juan Carlos
Spanish National Cancer Research Centre (CNIO)
AvMonforte de Lemos
Cedars-Sinai Medical Center
University of Pittsburgh
University of California at Los Angeles
Danish Cancer Institute
University of Copenhagen
Mayo Clinic Rochester, MN
Moffitt Cancer Center
Emory University
Brigham and Women’s Hospital
Harvard University
Dartmouth Medical School Norris Cotton Cancer Center
University of Bergen
Providence Medical Center
Oregon Health and Science University
Imperial College London
University of Glasgow
Toronto Hospital
University of British Columbia
Provincial Health Services Authority
Gynecologic Oncology Center
Technische Universität Dresden
Partner Site Dresden
Klinikum Bremen-Mitte
Gynaekologicum Bremen
University of Greifswald
Frauenarztpraxis Belau
Goethe University Frankfurt
Universitätsklinikum Schleswig-Holstein Campus Lübeck
Kliniken Essen-Mitte
Charité – Universitätsmedizin Berlin
University of Duisburg-Essen
Ulm University
SLK-Kliniken
University of Hamburg
University of Marburg
Klinikum Ludwigshafen
Universitätsklinikum Kiel
Krankenhaus Jerusalem
Ludwig Maximilian University of Munich

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English
Article number	19
Journal	npj Genomic Medicine
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41525-024-00395-y
State	Published - Dec 2024

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10.1038/s41525-024-00395-y

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@article{01c88db0dfa7461f94a849bfed90af94,

title = "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.",

author = "\{OPAL Study Group\} and \{AOCS Group\} and Dhanya Ramachandran and Tyrer, \{Jonathan P.\} and Stefan Kommoss and Anna DeFazio and Riggan, \{Marjorie J.\} and Webb, \{Penelope M.\} and Fasching, \{Peter A.\} and Diether Lambrechts and Garc{\'i}a, \{Mar{\'i}a J.\} and Cristina Rodr{\'i}guez-Antona and Goodman, \{Marc T.\} and Francesmary Modugno and Moysich, \{Kirsten B.\} and Karlan, \{Beth Y.\} and Jenny Lester and Kjaer, \{Susanne K.\} and Allan Jensen and Estrid H{\o}gdall and Goode, \{Ellen L.\} and Cliby, \{William A.\} and Amanika Kumar and Chen Wang and Cunningham, \{Julie M.\} and Winham, \{Stacey J.\} and Monteiro, \{Alvaro N.\} and Schildkraut, \{Joellen M.\} and Cramer, \{Daniel W.\} and Terry, \{Kathryn L.\} and Linda Titus and Line Bjorge and Thomsen, \{Liv Cecilie Vestrheim\} and Tanja Pejovic and H{\o}gdall, \{Claus K.\} and McNeish, \{Iain A.\} and Taymaa May and Huntsman, \{David G.\} and Jacobus Pfisterer and Ulrich Canzler and Park-Simon, \{Tjoung Won\} and Willibald Schr{\"o}der and Antje Belau and Lars Hanker and Philipp Harter and Jalid Sehouli and Rainer Kimmig and \{de Gregorio\}, Nikolaus and Barbara Schmalfeldt and Klaus Baumann and Felix Hilpert and Alexander Burges",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41525-024-00395-y",

language = "English",

volume = "9",

journal = "npj Genomic Medicine",

issn = "2056-7944",

publisher = "Nature Research",

number = "1",

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TY - JOUR

T1 - Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease

AU - OPAL Study Group

AU - AOCS Group

AU - Ramachandran, Dhanya

AU - Tyrer, Jonathan P.

AU - Kommoss, Stefan

AU - DeFazio, Anna

AU - Riggan, Marjorie J.

AU - Webb, Penelope M.

AU - Fasching, Peter A.

AU - Lambrechts, Diether

AU - García, María J.

AU - Rodríguez-Antona, Cristina

AU - Goodman, Marc T.

AU - Modugno, Francesmary

AU - Moysich, Kirsten B.

AU - Karlan, Beth Y.

AU - Lester, Jenny

AU - Kjaer, Susanne K.

AU - Jensen, Allan

AU - Høgdall, Estrid

AU - Goode, Ellen L.

AU - Cliby, William A.

AU - Kumar, Amanika

AU - Wang, Chen

AU - Cunningham, Julie M.

AU - Winham, Stacey J.

AU - Monteiro, Alvaro N.

AU - Schildkraut, Joellen M.

AU - Cramer, Daniel W.

AU - Terry, Kathryn L.

AU - Titus, Linda

AU - Bjorge, Line

AU - Thomsen, Liv Cecilie Vestrheim

AU - Pejovic, Tanja

AU - Høgdall, Claus K.

AU - McNeish, Iain A.

AU - May, Taymaa

AU - Huntsman, David G.

AU - Pfisterer, Jacobus

AU - Canzler, Ulrich

AU - Park-Simon, Tjoung Won

AU - Schröder, Willibald

AU - Belau, Antje

AU - Hanker, Lars

AU - Harter, Philipp

AU - Sehouli, Jalid

AU - Kimmig, Rainer

AU - de Gregorio, Nikolaus

AU - Schmalfeldt, Barbara

AU - Baumann, Klaus

AU - Hilpert, Felix

AU - Burges, Alexander

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85195145771

U2 - 10.1038/s41525-024-00395-y

DO - 10.1038/s41525-024-00395-y

M3 - Article

AN - SCOPUS:85195145771

SN - 2056-7944

VL - 9

JO - npj Genomic Medicine

JF - npj Genomic Medicine

IS - 1

M1 - 19

ER -

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

Abstract

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