Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10-8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.

Detaljer

Författare
  • Fergus J Couch
  • Karoline B. Kuchenbaecker
  • Kyriaki Michailidou
  • Gustavo A. Mendoza-Fandino
  • Silje Nord
  • Janna Lilyquist
  • Curtis Olswold
  • Emily Hallberg
  • Simona Agata
  • Habibul Ahsan
  • Kristiina Aittomäki
  • Christine Ambrosone
  • Irene L Andrulis
  • Hoda Anton-Culver
  • Volker Arndt
  • Banu K. Arun
  • Brita Arver
  • Monica Barile
  • Rosa B. Barkardottir
  • Daniel Barrowdale
  • Lars Beckmann
  • Matthias W Beckmann
  • Javier Benitez
  • Stephanie V. Blank
  • Carl Blomqvist
  • Natalia V Bogdanova
  • Stig E Bojesen
  • Manjeet K Bolla
  • Bernardo Bonanni
  • Hiltrud Brauch
  • Hermann Brenner
  • Barbara Burwinkel
  • Saundra Buys
  • Trinidad Caldes
  • Maria A. Caligo
  • Federico Canzian
  • Jane Carpenter
  • Jenny Chang-Claude
  • Stephen J Chanock
  • Wendy K. Chung
  • Kathleen B M Claes
  • Angela Cox
  • Simon S Cross
  • Julie M. Cunningham
  • Kamila Czene
  • Mary B. Daly
  • Francesca Damiola
  • Hatef Darabi
  • Miguel de la Hoya
  • Peter Devilee
  • Orland Diez
  • Yuan C. Ding
  • Riccardo Dolcetti
  • Susan M Domchek
  • Cecilia M. Dorfling
  • Isabel Dos Santos Silva
  • Martine Dumont
  • Alison M. Dunning
  • Diana M. Eccles
  • Arif B Ekici
  • A Heather Eliassen
  • Steve Ellis
  • Peter A Fasching
  • Jonine Figueroa
  • Dieter Flesch-Janys
  • Florentia Fostira
  • William D Foulkes
  • Tara Friebel
  • Eitan Friedman
  • Debra Frost
  • Marike Gabrielson
  • Marilie D. Gammon
  • Patricia A. Ganz
  • Susan M Gapstur
  • Judy Garber
  • Mia Gaudet
  • Simon A. Gayther
  • Anne-Marie Gerdes
  • Maya Ghoussaini
  • Graham G Giles
  • Gord Glendon
  • Andrew K Godwin
  • Mark S Goldberg
  • David E. Goldgar
  • Anna González-Neira
  • Mark H Greene
  • Jacek Gronwald
  • Pascal Guénel
  • Marc Gunter
  • Lothar Haeberle
  • Christopher A. Haiman
  • Ute Hamann
  • Thomas V. O. Hansen
  • Steven Hart
  • Sue Healey
  • Tuomas Heikkinen
  • Brian E. Henderson
  • Josef Herzog
  • Frans B. L. Hogervorst
  • Antoinette Hollestelle
  • Maartje J. Hooning
  • Robert N. Hoover
  • John L Hopper
  • Keith Humphreys
  • David J Hunter
  • Tomasz Huzarski
  • Evgeny N Imyanitov
  • Claudine Isaacs
  • Anna Jakubowska
  • Paul James
  • Ramunas Janavicius
  • Uffe Birk Jensen
  • Esther M. John
  • Michael Jones
  • Maria Kabisch
  • Siddhartha Kar
  • Beth Y. Karlan
  • Sofia Khan
  • Kay Tee Khaw
  • Muhammad G Kibriya
  • Julia A Knight
  • Yon-Dschun Ko
  • Irene Konstantopoulou
  • Veli-Matti Kosma
  • Vessela Kristensen
  • Ava Kwong
  • Yael Laitman
  • Diether Lambrechts
  • Conxi Lazaro
  • Eunjung Lee
  • Loic Le Marchand
  • Jenny Lester
  • Annika Lindblom
  • Noralane Lindor
  • Sara Lindstrom
  • Jianjun Liu
  • Jirong Long
  • Jan Lubinski
  • Phuong L Mai
  • Enes Makalic
  • Kathleen E Malone
  • Arto Mannermaa
  • Siranoush Manoukian
  • Sara Margolin
  • Frederik Marme
  • John W M Martens
  • Lesley McGuffog
  • Alfons Meindl
  • Austin Miller
  • Roger L. Milne
  • Penelope Miron
  • Marco Montagna
  • Sylvie Mazoyer
  • Anna Marie Mulligan
  • Taru A. Muranen
  • Katherine L Nathanson
  • Susan L. Neuhausen
  • Heli Nevanlinna
  • Børge G Nordestgaard
  • Robert L Nussbaum
  • Kenneth Offit
  • Edith Olah
  • Olufunmilayo I. Olopade
  • Janet E Olson
  • Ana Osorio
  • Sue K. Park
  • Petra H. Peeters
  • Bernard Peissel
  • Paolo Peterlongo
  • Julian Peto
  • Catherine M. Phelan
  • Robert Pilarski
  • Bruce Poppe
  • Katri Pylkäs
  • Paolo Radice
  • Nazneen Rahman
  • Johanna Rantala
  • Christine Rappaport
  • Gad Rennert
  • Andrea L. Richardson
  • Mark Robson
  • Isabelle Romieu
  • Anja Rudolph
  • Emiel J. Rutgers
  • Maria-Jose Sanchez
  • Regina M. Santella
  • Elinor J Sawyer
  • Daniel F. Schmidt
  • Marjanka K Schmidt
  • Rita K Schmutzler
  • Fredrick Schumacher
  • Rodney Scott
  • Leigha Senter
  • Priyanka Sharma
  • Jacques Simard
  • Christian F. Singer
  • Olga M Sinilnikova
  • Penny Soucy
  • Melissa Southey
  • Doris Steinemann
  • Marie Stenmark-Askmalm
  • Dominique Stoppa-Lyonnet
  • Anthony Swerdlow
  • Csilla I Szabo
  • Rulla Tamimi
  • William Tapper
  • Manuel R Teixeira
  • Soo-Hwang Teo
  • Mary B. Terry
  • Mads Thomassen
  • Deborah Thompson
  • Laima Tihomirova
  • Amanda E Toland
  • Robert A E M Tollenaar
  • Ian Tomlinson
  • Thérèse Truong
  • Helen Tsimiklis
  • Alex Teulé
  • Rosario Tumino
  • Nadine Tung
  • Clare Turnbull
  • Giski Ursin
  • Carolien H. M. van Deurzen
  • Elizabeth J. van Rensburg
  • Raymonda Varon-Mateeva
  • Zhaoming Wang
  • Shan Wang-Gohrke
  • Elisabete Weiderpass
  • Jeffrey N. Weitzel
  • Alice S. Whittemore
  • Hans Wildiers
  • Robert Winqvist
  • Xiaohong R Yang
  • Drakoulis Yannoukakos
  • Song Yao
  • M Pilar Zamora
  • Wei Zheng
  • Per Hall
  • Peter Kraft
  • Celine Vachon
  • Susan Slager
  • Georgia Chenevix-Trench
  • Paul P. D. Pharoah
  • Alvaro N Monteiro
  • Montserrat García-Closas
  • Douglas F Easton
  • Antonis C Antoniou
Enheter & grupper
Externa organisationer
  • Mayo Clinic Minnesota
  • University of Cambridge
  • German Cancer Research Centre
  • Hannover Medical School
  • University of Tübingen
  • Heidelberg University
  • University of Sydney
  • Karolinska Institute
  • Leiden University Medical Centre
  • University of Pennsylvania
  • University of Southampton
  • Uppsala universitet
  • University Medical Center Hamburg-Eppendorf
  • Cedars-Sinai Medical Center
  • McGill University
  • Copenhagen University Hospital
  • INSERM U1018
  • Imperial College London
  • Erasmus University Medical Center
  • Memorial Sloan-Kettering Cancer Center
  • University of Hong Kong
  • Vanderbilt University
  • Technical University of Munich
  • University of Toronto
  • Seoul National University
  • University Medical Center Utrecht
  • University of Oulu
  • King's College London
  • University of Cologne
  • Linköping University
  • Paris Descartes University
  • National Human Genome Research Institute
  • Odense University Hospital
  • Beth Israel Deaconess Medical Center
  • Cancer Registry of Norway Institute of Population-Based Cancer Research
  • Folkhälsans forskningscentrum
  • University Hospitals Leuven
  • Karolinska University Hospital
  • Ghent University Hospital
  • Skåne University Hospital
  • Ohio State University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi
Originalspråkengelska
Artikelnummer11375
TidskriftNature Communications
Volym7
StatusPublished - 2016 apr 27
PublikationskategoriForskning
Peer review utfördJa