Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

AOCS study group; EMBRACE Study; OPAL Study Group; KConFab Investigators; GEMO Study Collaborators; HEBON Study

doi:10.1038/ng.3826

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

AOCS study group
, EMBRACE Study
, OPAL Study Group
, KConFab Investigators
, GEMO Study Collaborators
, HEBON Study

Department of Epidemiology and Environmental Health

Netherlands Cancer Institute
Moffitt Cancer Center
Wellcome Trust Sanger Institute
University of Cambridge
Cedars-Sinai Medical Center
Mayo Clinic Rochester, MN
Duke University
Queensland Institute of Medical Research
Université Laval
Amsterdam University Medical Center
Radboud University Nijmegen
Netherlands Comprehensive Cancer Organisation
Johns Hopkins University
Leeds Teaching Hospitals NHS Trust
University of Toronto
University of California at Irvine
N.N. Alexandrov National Cancer Centre of Belarus
‘Agii Anargiri’ Cancer Hospital
Universitätsklinikum Kiel
University of Texas MD Anderson Cancer Center
Karolinska Institutet
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
University Hospital
Royal Marsden NHS Foundation Trust
Centre Léon Bérard
Landspitali University Hospital
University of Iceland
Oregon Health and Science University
Friedrich-Alexander University Erlangen-Nürnberg
Vanderbilt University
Spanish National Cancer Research Centre (CNIO)
AvMonforte de Lemos
Russian Academy of Sciences
University Health Network
Massachusetts General Hospital
University of Bergen
National Institutes of Health
City of Hope National Med Center
Maastricht University

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

389 Scopus citations

Abstract

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

Original language	English
Pages (from-to)	680-691
Number of pages	12
Journal	Nature Genetics
Volume	49
Issue number	5
DOIs	https://doi.org/10.1038/ng.3826
State	Published - May 1 2017

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10.1038/ng.3826

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@article{1467d5bdbdd3453697c43bd6d62538db,

title = "Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer",

abstract = "To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.",

author = "\{AOCS study group\} and \{EMBRACE Study\} and \{OPAL Study Group\} and \{KConFab Investigators\} and \{GEMO Study Collaborators\} and \{HEBON Study\} and Phelan, \{Catherine M.\} and Kuchenbaecker, \{Karoline B.\} and Tyrer, \{Jonathan P.\} and Kar, \{Siddhartha P.\} and Kate Lawrenson and Winham, \{Stacey J.\} and Joe Dennis and Ailith Pirie and Riggan, \{Marjorie J.\} and Ganna Chornokur and Earp, \{Madalene A.\} and Lyra, \{Paulo C.\} and Lee, \{Janet M.\} and Simon Coetzee and Jonathan Beesley and Lesley McGuffog and Penny Soucy and Ed Dicks and Andrew Lee and Daniel Barrowdale and Julie Lecarpentier and Goska Leslie and Aalfs, \{Cora M.\} and Aben, \{Katja K.H.\} and Marcia Adams and Julian Adlard and Andrulis, \{Irene L.\} and Hoda Anton-Culver and Natalia Antonenkova and Gerasimos Aravantinos and Norbert Arnold and Arun, \{Banu K.\} and Brita Arver and Jacopo Azzollini and Judith Balma{\~n}a and Banerjee, \{Susana N.\} and Laure Barjhoux and Barkardottir, \{Rosa B.\} and Yukie Bean and Beckmann, \{Matthias W.\} and Alicia Beeghly-Fadiel and Javier Benitez and Marina Bermisheva and Bernardini, \{Marcus Q.\} and Birrer, \{Michael J.\} and Line Bjorge and Amanda Black and Kenneth Blankstein and Blok, \{Marinus J.\} and Moysich, \{Kirsten B.\}",

year = "2017",

month = may,

day = "1",

doi = "10.1038/ng.3826",

language = "English",

volume = "49",

pages = "680--691",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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T1 - Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

AU - AOCS study group

AU - EMBRACE Study

AU - OPAL Study Group

AU - KConFab Investigators

AU - GEMO Study Collaborators

AU - HEBON Study

AU - Phelan, Catherine M.

AU - Kuchenbaecker, Karoline B.

AU - Tyrer, Jonathan P.

AU - Kar, Siddhartha P.

AU - Lawrenson, Kate

AU - Winham, Stacey J.

AU - Dennis, Joe

AU - Pirie, Ailith

AU - Riggan, Marjorie J.

AU - Chornokur, Ganna

AU - Earp, Madalene A.

AU - Lyra, Paulo C.

AU - Lee, Janet M.

AU - Coetzee, Simon

AU - Beesley, Jonathan

AU - McGuffog, Lesley

AU - Soucy, Penny

AU - Dicks, Ed

AU - Lee, Andrew

AU - Barrowdale, Daniel

AU - Lecarpentier, Julie

AU - Leslie, Goska

AU - Aalfs, Cora M.

AU - Aben, Katja K.H.

AU - Adams, Marcia

AU - Adlard, Julian

AU - Andrulis, Irene L.

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia

AU - Aravantinos, Gerasimos

AU - Arnold, Norbert

AU - Arun, Banu K.

AU - Arver, Brita

AU - Azzollini, Jacopo

AU - Balmaña, Judith

AU - Banerjee, Susana N.

AU - Barjhoux, Laure

AU - Barkardottir, Rosa B.

AU - Bean, Yukie

AU - Beckmann, Matthias W.

AU - Beeghly-Fadiel, Alicia

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Bernardini, Marcus Q.

AU - Birrer, Michael J.

AU - Bjorge, Line

AU - Black, Amanda

AU - Blankstein, Kenneth

AU - Blok, Marinus J.

AU - Moysich, Kirsten B.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

AB - To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

UR - https://www.scopus.com/pages/publications/85016117389

U2 - 10.1038/ng.3826

DO - 10.1038/ng.3826

M3 - Article

C2 - 28346442

AN - SCOPUS:85016117389

SN - 1061-4036

VL - 49

SP - 680

EP - 691

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Abstract

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