| Title: |
Genome-wide association study of 398,238 women unveils seven loci associated with high-grade serous ovarian cancer. |
| Authors: |
Barnes, Daniel R; Tyrer, Jonathan P; Dennis, Joe; Leslie, Goska; Bolla, Manjeet K; Lush, Michael; Aeilts, Amber M; Aittomäki, Kristiina; Andrieu, Nadine; Andrulis, Irene L; Anton-Culver, Hoda; Arason, Adalgeir; Arun, Banu K; Balmaña, Judith; Bandera, Elisa V; Barkardottir, Rosa B; Berger, Lieke PV; Berrington de Gonzalez, Amy; Berthet, Pascaline; Białkowska, Katarzyna; Bjørge, Line; Blanco, Amie M; Blok, Marinus J; Bobolis, Kristie A; Bogdanova, Natalia V; Brenton, James D; Butz, Henriett; Buys, Saundra S; Caligo, Maria A; Campbell, Ian; Castillo, Carmen; Claes, Kathleen BM; Colonna, Sarah V; Cook, Linda S; Daly, Mary B; Dansonka-Mieszkowska, Agnieszka; de la Hoya, Miguel; deFazio, Anna; DePersia, Allison; Ding, Yuan Chun; Doherty, Jennifer A; Domchek, Susan M; Dörk, Thilo; Einbeigi, Zakaria; Engel, Christoph; Evans, D Gareth; Foretova, Lenka; Fortner, Renée T; Fostira, Florentia; Foti, Maria Cristina; Friedman, Eitan; Frone, Megan N; Ganz, Patricia A; Gentry-Maharaj, Aleksandra; Glendon, Gord; Godwin, Andrew K; González-Neira, Anna; Greene, Mark H; Gronwald, Jacek; Guerrieri-Gonzaga, Aliana; Hamann, Ute; Hansen, Thomas VO; Harris, Holly R; Hauke, Jan; Heitz, Florian; Hogervorst, Frans BL; Hooning, Maartje J; Hopper, John L; Huff, Chad D; Huntsman, David G; Imyanitov, Evgeny N; Izatt, Louise; Jakubowska, Anna; James, Paul A; Janavicius, Ramunas; John, Esther M; Kar, Siddhartha; Karlan, Beth Y; Kennedy, Catherine J; Kiemeney, Lambertus ALM; Konstantopoulou, Irene; Kupryjanczyk, Jolanta; Laitman, Yael; Lavie, Ofer; Lawrenson, Kate; Lester, Jenny; Lesueur, Fabienne; Lopez-Pleguezuelos, Carlos; Mai, Phuong L; Manoukian, Siranoush; May, Taymaa; McNeish, Iain A; Menon, Usha; Milne, Roger L; Modugno, Francesmary; Mongiovi, Jennifer M; Montagna, Marco; Moysich, Kirsten B; Neuhausen, Susan L; Nielsen, Finn C; Noguès, Catherine; Oláh, Edit; Olopade, Olufunmilayo I; Osorio, Ana; Papi, Laura; Pathak, Harsh; Pearce, Celeste L; Pedersen, Inge S; Peixoto, Ana; Pejovic, Tanja; Peng, Pei-Chen; Peshkin, Beth N; Peterlongo, Paolo; Powell, C Bethan; Prokofyeva, Darya; Pujana, Miquel Angel; Radice, Paolo; Rashid, Muhammad U; Rennert, Gad; Richenberg, George; Sandler, Dale P; Sasamoto, Naoko; Setiawan, Veronica W; Sharma, Priyanka; Sieh, Weiva; Singer, Christian F; Snape, Katie; Sokolenko, Anna P; Soucy, Penny; Southey, Melissa C; Stoppa-Lyonnet, Dominique; Sutphen, Rebecca; Sutter, Christian; Tan, Yen Y; Teixeira, Manuel R; Terry, Kathryn L; Thomsen, Liv Cecilie V; Tischkowitz, Marc; Toland, Amanda E; Van Gorp, Toon; Vega, Ana; Velez Edwards, Digna R; Webb, Penelope M; Weitzel, Jeffrey N; Wentzensen, Nicolas; Whittemore, Alice S; Winham, Stacey J; Wu, Anna H; Yadav, Siddhartha; Yu, Yao; Ziogas, Argyrios; Berchuck, Andrew; Couch, Fergus J; Goode, Ellen L; Goodman, Marc T; Monteiro, Alvaro N; Offit, Kenneth; Ramus, Susan J; Risch, Harvey A; Schildkraut, Joellen M; Thomassen, Mads; Simard, Jacques; Easton, Douglas F; Jones, Michelle R; Chenevix-Trench, Georgia; Gayther, Simon A; Antoniou, Antonis C; Pharoah, Paul DP |
| Publisher Information: |
Springer Nature; Department of Public Health and Primary Care, Cancer Genetic Epidemiology |
| Publication Year: |
2025 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
31 Biological Sciences; 32 Biomedical and Clinical Sciences; 3211 Oncology and Carcinogenesis; 3105 Genetics; Women's Health; Cancer; Ovarian Cancer; Human Genome; Genetics; Prevention; Rare Diseases; 2.1 Biological and endogenous factors; 3 Good Health and Well Being |
| Description: |
Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We meta-analyzed >22 million variants for 398,238 women from the Ovarian Cancer Association Consortium (OCAC), UK Biobank (UKBB) and Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA) to identify novel HGSOC susceptibility loci. Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was TP53 3'-UTR SNP rs78378222-T's association with HGSOC (per-T-allele relative risk (RR) = 1.44, 95% CI:1.28-1.62, P = 1.76 × 10-9). Polygenic scores (PGS) were developed using OCAC and CIMBA data and trained on FinnGen data. 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 when validated in the UKBB. This study represents the largest HGSOC GWAS to date - demonstrating that improvements in imputation reference panels and increased sample sizes help to identify HGSOC associated variants that previously went undetected, ultimately improving PGS which can improve personalized HGSOC risk prediction. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/391574; https://doi.org/10.17863/CAM.122662 |
| DOI: |
10.17863/CAM.122662 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/391574; https://doi.org/10.17863/CAM.122662 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.20722C48 |
| Database: |
BASE |