| Title: |
Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk |
| Authors: |
Barnes, Daniel; Tyrer, Jonathan; Dennis, Joe; Leslie, Goska; Bolla, Manjeet; Lush, Michael; Aeilts, Amber; Aittomäki, Kristiina; Andrieu, Nadine; Andrulis, Irene; Anton-Culver, Hoda; Arason, Adalgeir; Arun, Banu; Balmaña, Judith; Bandera, Elisa; Barkardottir, Rosa; Berger, Lieke P.V.; Berrington de Gonzalez, Amy; Berthet, Pascaline; Białkowska, Katarzyna; Bjørge, Line; Blanco, Amie; Blok, Marinus; Bobolis, Kristie; Bogdanova, Natalia; Brenton, James; Butz, Henriett; Buys, Saundra; Caligo, Maria; Campbell, Ian; Castillo, Carmen; Claes, Kathleen B.M.; Colonna, Sarah; Cook, Linda; Daly, Mary; Dansonka-Mieszkowska, Agnieszka; de la Hoya, Miguel; Defazio, Anna; Depersia, Allison; Ding, Yuan Chun; Domchek, Susan; Dörk, Thilo; Einbeigi, Zakaria; Engel, Christoph; Evans, D. Gareth; Foretova, Lenka; Fortner, Renée; Fostira, Florentia; Foti, Maria Cristina; Friedman, Eitan; Frone, Megan; Ganz, Patricia; Gentry-Maharaj, Aleksandra; Glendon, Gord; Godwin, Andrew; González-Neira, Anna; Greene, Mark; Gronwald, Jacek; Guerrieri-Gonzaga, Aliana; Hamann, Ute; Hansen, Thomas V.O.; Harris, Holly; Hauke, Jan; Heitz, Florian; Hogervorst, Frans B.L.; Hooning, Maartje; Hopper, John; Huff, Chad; Huntsman, David; Imyanitov, Evgeny; Izatt, Louise; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; John, Esther; Kar, Siddhartha; Karlan, Beth; Kennedy, Catherine; Kiemeney, Lambertus A.L.M.; Konstantopoulou, Irene; Kupryjanczyk, Jolanta; Laitman, Yael; Lavie, Ofer; Lawrenson, Kate; Lester, Jenny; Lesueur, Fabienne; Lopez-Pleguezuelos, Carlos; Mai, Phuong; Manoukian, Siranoush; May, Taymaa; Mcneish, Iain; Menon, Usha; Milne, Roger; Modugno, Francesmary; Mongiovi, Jennifer; Montagna, Marco; Moysich, Kirsten; Neuhausen, Susan; Nielsen, Finn; Noguès, Catherine; Oláh, Edit; Olopade, Olufunmilayo; Osorio, Ana; Papi, Laura; Pathak, Harsh; Pearce, Celeste; Pedersen, Inge; Peixoto, Ana; Pejovic, Tanja; Peng, Pei-Chen; Peshkin, Beth; Peterlongo, Paolo; Powell, C. Bethan; Prokofyeva, Darya; Pujana, Miquel Angel; Radice, Paolo; Rashid, Muhammad; Rennert, Gad; Richenberg, George; Sandler, Dale; Sasamoto, Naoko; Setiawan, Veronica; Sharma, Priyanka; Sieh, Weiva; Singer, Christian; Snape, Katie; Sokolenko, Anna; Soucy, Penny; Southey, Melissa; Stoppa-Lyonnet, Dominique; Sutphen, Rebecca; Sutter, Christian; Teixeira, Manuel; Terry, Kathryn; Thomsen, Liv Cecilie V.; Tischkowitz, Marc; Toland, Amanda; van Gorp, Toon; Vega, Ana; Velez Edwards, Digna; Webb, Penelope; Weitzel, Jeffrey; Wentzensen, Nicolas; Whittemore, Alice; Winham, Stacey; Wu, Anna; Yadav, Siddhartha; Yu, Yao; Ziogas, Argyrios; Berchuck, Andrew; Couch, Fergus; Goode, Ellen; Goodman, Marc; Monteiro, Alvaro; Offit, Kenneth; Ramus, Susan; Risch, Harvey; Schildkraut, Joellen; Thomassen, Mads; Simard, Jacques; Easton, Douglas; Jones, Michelle; Chenevix-Trench, Georgia; Gayther, Simon; Antoniou, Antonis; Pharoah, Paul D.P. |
| Contributors: |
University of Cambridge Cambridge, UK (CAM); National Institutes of Health Bethesda, MD, USA (NIH); National Cancer Institute Bethesda (NCI-NIH); European Bioinformatics Institute Hinxton (EMBL-EBI); EMBL Heidelberg; The Ohio State University Columbus (OSU); Helsingin yliopisto = Helsingfors universitet = University of Helsinki; Innovation et Développement dans l'Agriculture et l'Alimentation (UMR Innovation); Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier; Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro); Département Environnements et Sociétés (Cirad-ES); Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad); Departments of Molecular Genetics and Laboratory Medicine and Pathobiology; University of Toronto-Cancer Care Ontario; University of California Irvine (UC Irvine); University of California (UC); Reykjavík University; MD Anderson Cancer Center Houston; The University of Texas Health Science Center at Houston (UTHealth); Unitat d'Alt Risc i Prevenció del Càncer; Vall d'Hebron University Hospital Barcelona; Rutgers cancer institute of New Jersey Newark, NJ; Landspitali National University Hospital of Iceland; University of Iceland Reykjavik; University of Groningen Groningen; Centre Régional de Lutte contre le Cancer François Baclesse Caen (UNICANCER/CRLC); Normandie Université (NU)-UNICANCER; Pomeranian Medical University Szczecin (PUM); University of Bergen (UiB); Haukeland University Hospital; Maastricht University Medical Center+ (Maastricht UMC+); Maastricht University Maastricht; Department of Obstetrics and Gynaecology (MHH); Medizinische Hochschule Hannover = Hannover Medical School (MHH); National Institute of Oncology Budapest, Hungary; Huntsman Cancer Institute Salt Lake City; University of Utah; Section of Genetic Oncology; University of Pisa Italy = Università di Pisa Italia = Université de Pise Italie (UniPi); Harvard Medical School Boston (HMS); Département de Chimie Moléculaire - Electrochimie Moléculaire et Photochimie Rédox (DCM - EmPRE); Département de Chimie Moléculaire (DCM); Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA); Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 ); Center for Medical Genetics Ghent; Ghent University Hospital; Princeton University; Division of Population Science; Fox Chase Cancer Center; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC); Instituto de Investigación Sanitaria del Hospital Clínico San Carlos Madrid, Spain (IdISSC); Westmead Hospital Sydney; NorthShore University HealthSystem; Beckman Research Institute of the City of Hope; Abramson Cancer Center; University of Pennsylvania Philadelphia; Department of Oncology, Division of Selected Clinical Specialities; Sahlgrenska University Hospital Gothenburg; Universität Regensburg = University of Regensburg = Université de Ratisbonne Allemagne (UR); St Mary's Hospital London; Manchester Academic Health Science Centre (MAHSC); University of Manchester Manchester; Masaryk Memorial Cancer Institute (MMCI); German Cancer Research Center - Deutsches Krebsforschungszentrum Heidelberg (DKFZ); Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES); National Center for Scientific Research "Demokritos" (NCSR); Università degli studi di Palermo - University of Palermo (UNIPA); City University of New York New York (CUNY); Graduate Center of the City University New York, NY, USA; National Library of Medicine Bethesda, MD (NLM); National Center for Biotechnology Information (NCBI); National Institutes of Health Bethesda, MD, USA (NIH)-National Institutes of Health Bethesda, MD, USA (NIH); Jonsson Comprehensive Cancer Center; University of California Los Angeles (UCLA); University of California (UC)-University of California (UC); Institute for Women's Health London; University College London Hospitals (UCLH); Mount Sinai Hospital Toronto, Canada (MSH); University of Kansas Kansas City; Spanish National Cancer Research Center (CNIO); West Pomeranian University of Technology Szczecin; European Institute of Oncology Milan (ESMO); Copenhagen University Hospital Denmark = Københavns Universitetshospital Danmark (KUH); Karolinska Institutet = Karolinska Institute Stockholm; University Hospital of Cologne Cologne; Kliniken Essen-Mitte; DNA diagnostic laboratory of the Family Cancer Clinic; The Netherlands Cancer Institute; Department of Medical Oncology, Family Cancer Clinic; Erasmus University Medical Center Rotterdam (Erasmus MC); Geological Survey of Denmark and Greenland (GEUS); British Columbia Cancer Agency, Vancouver |
| Source: |
https://inserm.hal.science/inserm-05441696 ; 2026. |
| Publisher Information: |
CCSD |
| Publication Year: |
2026 |
| Collection: |
Université Grenoble Alpes: HAL |
| Subject Terms: |
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| Description: |
International audience ; ABSTRACT Background Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1 / BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). Methods We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan Results Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3’-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76×10 -9 ). The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95%CI:1.37-1.54) per standard deviation in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62). Conclusions This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC. |
| Document Type: |
report |
| Language: |
English |
| Relation: |
MEDRXIV: 2024.02.29.24303243 |
| DOI: |
10.1101/2024.02.29.24303243 |
| Availability: |
https://inserm.hal.science/inserm-05441696; https://inserm.hal.science/inserm-05441696v1/document; https://inserm.hal.science/inserm-05441696v1/file/2024.02.29.24303243v1.full.pdf; https://doi.org/10.1101/2024.02.29.24303243 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.1EF17C0D |
| Database: |
BASE |