Identification of six new susceptibility loci for invasive epithelial ovarian cancer

EMBRACE; GEMO Study Collaborators; Breast cancer Family Registry; HeBon; KConFab Investigators; Australian cancer study (ovarian cancer Investigators); Australian Ovarian Cancer Study Group; consortium of Investigators of modifiers of BRCA1 and BRCA2

doi:10.1038/ng.3185

Identification of six new susceptibility loci for invasive epithelial ovarian cancer

EMBRACE
, GEMO Study Collaborators
, Breast cancer Family Registry
, HeBon
, KConFab Investigators
, Australian cancer study (ovarian cancer Investigators)
, Australian Ovarian Cancer Study Group
, consortium of Investigators of modifiers of BRCA1 and BRCA2

Department of Epidemiology and Environmental Health

Netherlands Cancer Institute
University of Cambridge
University of Southern California
Queensland Institute of Medical Research
Oregon Health and Science University
Dana-Farber Cancer Institute
Universidade de São Paulo
Center for Cell-Based Therapy (CEPID/FAPESP)
Center for Integrative Systems Biology - CISBi
Case Western Reserve University
University of Melbourne
Columbia University
University of Utah
Vilnius University
State Research Institute Centre for Innovative Medicine
University of Pretoria
City of Hope National Med Center
University of Copenhagen
Spanish National Cancer Research Centre (CNIO)
AvMonforte de Lemos
FIRC Institute of Molecular Oncology
IRCCS Istituto Europeo di Oncologia - Milano
Cogentech Cancer Genetic Test Laboratory
IRCCS Centro di Riferimento Oncologico - Aviano PN
Unit of Medical Genetics
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
University of Florence
University of Rome La Sapienza
Demokritos National Centre for Scientific Research

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

212 Scopus citations

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 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

Original language	English
Pages (from-to)	164-171
Number of pages	8
Journal	Nature Genetics
Volume	47
Issue number	2
DOIs	https://doi.org/10.1038/ng.3185
State	Published - Jan 1 2015

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EMBRACE, GEMO Study Collaborators, Breast cancer Family Registry, HeBon, KConFab Investigators, Australian cancer study (ovarian cancer Investigators), Australian Ovarian Cancer Study Group, & consortium of Investigators of modifiers of BRCA1 and BRCA2 (2015). Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nature Genetics, 47(2), 164-171. https://doi.org/10.1038/ng.3185

@article{9e66c46020ac46afa3e88ddea0c82d8b,

title = "Identification of six new susceptibility loci for invasive epithelial ovarian cancer",

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 {\^a}+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.",

author = "EMBRACE and \{GEMO Study Collaborators\} and \{Breast cancer Family Registry\} and HeBon and \{KConFab Investigators\} and \{Australian cancer study (ovarian cancer Investigators)\} and \{Australian Ovarian Cancer Study Group\} and \{consortium of Investigators of modifiers of BRCA1 and BRCA2\} and Kuchenbaecker, \{Karoline B.\} and Ramus, \{Susan J.\} and Jonathan Tyrer and Andrew Lee and Shen, \{Howard C.\} and Jonathan Beesley and Kate Lawrenson and Lesley McGuffog and Sue Healey and Lee, \{Janet M.\} and Spindler, \{Tassja J.\} and Lin, \{Yvonne G.\} and Tanja Pejovic and Yukie Bean and Qiyuan Li and Simon Coetzee and Dennis Hazelett and Alexander Miron and Melissa Southey and Terry, \{Mary Beth\} and Goldgar, \{David E.\} and Buys, \{Saundra S.\} and Ramunas Janavicius and Dorfling, \{Cecilia M.\} and \{Van Rensburg\}, \{Elizabeth J.\} and Neuhausen, \{Susan L.\} and Ding, \{Yuan Chun\} and Hansen, \{Thomas V.O.\} and Lars J{\o}nson and Gerdes, \{Anne Marie\} and Bent Ejlertsen and Daniel Barrowdale and Joe Dennis and Javier Benitez and Ana Osorio and Garcia, \{Maria Jose\} and Ian Komenaka and Weitzel, \{Jeffrey N.\} and Pamela Ganschow and Paolo Peterlongo and Loris Bernard and Alessandra Viel and Bernardo Bonanni and Bernard Peissel and Siranoush Manoukian and Paolo Radice and Laura Papi and Laura Ottini and Florentia Fostira and Moysich, \{Kirsten B.\}",

year = "2015",

month = jan,

day = "1",

doi = "10.1038/ng.3185",

language = "English",

volume = "47",

pages = "164--171",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "2",

}

EMBRACE, GEMO Study Collaborators, Breast cancer Family Registry, HeBon, KConFab Investigators, Australian cancer study (ovarian cancer Investigators), Australian Ovarian Cancer Study Group & consortium of Investigators of modifiers of BRCA1 and BRCA2 2015, 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer', Nature Genetics, vol. 47, no. 2, pp. 164-171. https://doi.org/10.1038/ng.3185

TY - JOUR

T1 - Identification of six new susceptibility loci for invasive epithelial ovarian cancer

AU - EMBRACE

AU - GEMO Study Collaborators

AU - Breast cancer Family Registry

AU - HeBon

AU - KConFab Investigators

AU - Australian cancer study (ovarian cancer Investigators)

AU - Australian Ovarian Cancer Study Group

AU - consortium of Investigators of modifiers of BRCA1 and BRCA2

AU - Kuchenbaecker, Karoline B.

AU - Ramus, Susan J.

AU - Tyrer, Jonathan

AU - Lee, Andrew

AU - Shen, Howard C.

AU - Beesley, Jonathan

AU - Lawrenson, Kate

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Lee, Janet M.

AU - Spindler, Tassja J.

AU - Lin, Yvonne G.

AU - Pejovic, Tanja

AU - Bean, Yukie

AU - Li, Qiyuan

AU - Coetzee, Simon

AU - Hazelett, Dennis

AU - Miron, Alexander

AU - Southey, Melissa

AU - Terry, Mary Beth

AU - Goldgar, David E.

AU - Buys, Saundra S.

AU - Janavicius, Ramunas

AU - Dorfling, Cecilia M.

AU - Van Rensburg, Elizabeth J.

AU - Neuhausen, Susan L.

AU - Ding, Yuan Chun

AU - Hansen, Thomas V.O.

AU - Jønson, Lars

AU - Gerdes, Anne Marie

AU - Ejlertsen, Bent

AU - Barrowdale, Daniel

AU - Dennis, Joe

AU - Benitez, Javier

AU - Osorio, Ana

AU - Garcia, Maria Jose

AU - Komenaka, Ian

AU - Weitzel, Jeffrey N.

AU - Ganschow, Pamela

AU - Peterlongo, Paolo

AU - Bernard, Loris

AU - Viel, Alessandra

AU - Bonanni, Bernardo

AU - Peissel, Bernard

AU - Manoukian, Siranoush

AU - Radice, Paolo

AU - Papi, Laura

AU - Ottini, Laura

AU - Fostira, Florentia

AU - Moysich, Kirsten B.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

AB - 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 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

UR - https://www.scopus.com/pages/publications/84929171835

U2 - 10.1038/ng.3185

DO - 10.1038/ng.3185

M3 - Article

C2 - 25581431

AN - SCOPUS:84929171835

SN - 1061-4036

VL - 47

SP - 164

EP - 171

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

Identification of six new susceptibility loci for invasive epithelial ovarian cancer

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