Kuchenbaecker, Karoline B., Ramus, Susan J. and Tyrer, Jonathan et al. (2015) Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nature Genetics, 47 (2), 164-171. (doi:10.1038/ng.3185). (PMID:25581431)
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Abstract
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
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Accepted/In Press date: 5 December 2014
Published date: February 2015
Organisations:
Cancer Sciences
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Local EPrints ID: 376383
URI: http://eprints.soton.ac.uk/id/eprint/376383
DOI: doi:10.1038/ng.3185
ISSN: 1061-4036
PURE UUID: 4b8e243f-e766-4082-b88f-317fc242c571
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Date deposited: 27 Apr 2015 13:54
Last modified: 15 Mar 2024 02:40
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Author:
Karoline B. Kuchenbaecker
Author:
Susan J. Ramus
Author:
Jonathan Tyrer
Author:
Andrew Lee
Author:
Howard C. Shen
Author:
Jonathan Beesley
Author:
Kate Lawrenson
Author:
Lesley McGuffog
Author:
Sue Healey
Author:
Janet M. Lee
Author:
Tassja J. Spindler
Author:
Yvonne G. Lin
Author:
Tanja Pejovic
Author:
Yukie Bean
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Qiyuan Li
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Simon Coetzee
Author:
Dennis Hazelett
Author:
Alexander Miron
Author:
Melissa Southey
Author:
Mary Beth Terry
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David E. Goldgar
Author:
Saundra S. Buys
Author:
Ramunas Janavicius
Author:
Cecilia M. Dorfling
Author:
Elizabeth J. van Rensburg
Author:
Susan L. Neuhausen
Author:
Yuan Chun Ding
Author:
Thomas V.O. Hansen
Author:
Lars Jønson
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Anne-Marie Gerdes
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Bent Ejlertsen
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Daniel Barrowdale
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Joe Dennis
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Javier Benitez
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Ana Osorio
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Maria Jose Garcia
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Ian Komenaka
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Jeffrey N. Weitzel
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Pamela Ganschow
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Paolo Peterlongo
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Loris Bernard
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Alessandra Viel
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Bernardo Bonanni
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Bernard Peissel
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Siranoush Manoukian
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Paolo Radice
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Laura Ottini
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Florentia Fostira
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Radka Platte
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Miguel de la Hoya
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Trinidad Caldes
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Heli Nevanlinna
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J. Margriet Collée
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Matti A. Rookus
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Jan C. Oosterwijk
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Laima Tihomirova
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Nadine Tung
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Ute Hamann
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Claudine Isaccs
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Marc Tischkowitz
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Evgeny N. Imyanitov
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Maria A. Caligo
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Ian G. Campbell
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Frans B.L. Hogervorst
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Edith Olah
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Ignacio Blanco
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Joan Brunet
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