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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Catherine M. Phelan
  • Karoline B. Kuchenbaecker
  • Jonathan P. Tyrer
  • Siddhartha P. Kar
  • Kate Lawrenson
  • Stacey J. Winham
  • Joe Dennis
  • Ailith Pirie
  • Marjorie J. Riggan
  • Ganna Chornokur
  • Madalene A. Earp
  • Paulo C. Lyra
  • Janet M. Lee
  • Simon Coetzee
  • Jonathan Beesley
  • Lesley McGuffog
  • Penny Soucy
  • Ed Dicks
  • Andrew Lee
  • Daniel Barrowdale
  • Julie Lecarpentier
  • Goska Leslie
  • Cora M. Aalfs
  • Katja K.H. Aben
  • Marcia Adams
  • Julian Adlard
  • Irene L. Andrulis
  • Hoda Anton-Culver
  • Natalia Antonenkova
  • Gerasimos Aravantinos
  • Norbert Arnold
  • Banu K. Arun
  • Brita Arver
  • Jacopo Azzollini
  • Judith Balmaña
  • Susana N. Banerjee
  • Laure Barjhoux
  • Rosa B. Barkardottir
  • Yukie Bean
  • Matthias W. Beckmann
  • Alicia Beeghly-Fadiel
  • Javier Benitez
  • Marina Bermisheva
  • Marcus Q. Bernardini
  • Michael J. Birrer
  • Åke Borg
  • Per Broberg
  • Mats Jernetz
  • Päivi Kannisto
  • Håkan Olsson
  • HEBON Study
  • AOCS study group
  • EMBRACE Study
  • OPAL study group
  • KConFab Investigators
  • GEMO Study Collaborators
Organisations
External organisations
  • Wellcome Trust Sanger Institute
  • Academic Medical Center
  • Chapel Allerton Hospital
  • University Medical Center Schleswig-Holstein Campus Kiel
  • University of Iceland
  • Massachusetts General Hospital
  • Skåne University Hospital
  • H. Lee Moffitt Cancer Center & Research Institute
  • University of Cambridge
  • Cedars-Sinai Medical Center
  • Mayo Clinic Minnesota
  • Duke University
  • QIMR Berghofer Medical Research Institute
  • Centre hospitalier universitaire de Québec
  • Radboud University Nijmegen
  • Johns Hopkins University School of Medicine
  • University of Toronto
  • University of California, Irvine
  • University of Texas
  • Karolinska University Hospital
  • Istituto Nazionale dei Tumori
  • Royal Marsden Hospital
  • Centre Léon Bérard
  • Oregon Health & Science University
  • Friedrich-Alexander University Erlangen-Nürnberg
  • Vanderbilt University School of Medicine
  • Vanderbilt University
  • Spanish National Cancer Research Center (CNIO)
  • Biomedical Network on Rare Diseases (CIBERER)
  • Princess Margaret Hospital University of Toronto
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)680-691
Number of pages12
JournalNature Genetics
Volume49
Issue number5
Publication statusPublished - 2017 May 1
Publication categoryResearch
Peer-reviewedYes