Association analysis identifies 65 new breast cancer risk loci

NBCS Collaborators; ABCTB Investigators; kConFab/AOCS Investigators

doi:10.1038/nature24284

Association analysis identifies 65 new breast cancer risk loci

NBCS Collaborators
, ABCTB Investigators
, kConFab/AOCS Investigators

Institute of Human Genetics

Australian Breast Cancer Tissue Bank
University of Cambridge
Cyprus Institute of Neurology and Genetics
University of Washington
Harvard T.H. Chan School of Public Health
Queensland Institute of Medical Research
University of Toronto
Research Center
St. Jude Children Research Hospital
National Cancer Institute (NCI)
Antoni van Leeuwenhoek Hospital
German Cancer Research Center
UQ Centre for Clinical Research
Cancer Research UK Cambridge Institute
Massachusetts Institute of Technology
Johns Hopkins University
VU University Medical Center Amsterdam
The University of Chicago
Helsinki University Hospital
University of California, Irvine
The N.N. Alexandrov Research Institute of Oncology and Medical Radiology
Queen's University
MD Anderson Cancer Center
Fred Hutchinson Cancer Research Center
University of Wisconsin-Milwaukee
McGill University
Friedrich-Alexander University Erlangen-Nürnberg
Centro de Investigación en Red de Enfermedades Raras
Centre for Biomedical Research on Rare Diseases (CIBERER)
Russian Academy of Sciences
Beckman Research Institute of City of Hope
Hannover Medical School
Copenhagen University Hospital – Herlev and Gentofte
University of Copenhagen
European Institute of Oncology
Oslo University Hospital-Radiumhospitalet
Karolinska Institutet
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
University of Tübingen
International Agency for Research on Cancer
Lund University
University of Sheffield
Provincial Health Services Authority
Simon Fraser University
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA)
Heidelberg University
Vanderbilt University
Hospital Clinico San Carlos
Complejo Hospitalario Universitario de Santiago
University of Santiago de Compostela
American Cancer Society
Xerencia de Xestion Integrada de Vigo-SERGAS
Hong Kong Hereditary Breast Cancer Family Registry
Hong Kong Sanatorium & Hospital
Roswell Park Cancer Institute
National University of Singapore
Seoul National University
Seoul National University Cancer Research Institute
University of Sydney
Erasmus University Rotterdam
Institut national de la santé et de la recherche médicale
Imperial College London
Centre de Recherche en Cancérologie de Lyon
Mayo Clinic Rochester, MN
Fox Chase Cancer Center
Leiden University
London School of Hygiene and Tropical Medicine
University of Southampton, Faculty of Medicine
University of Westminster
Channing Division of Network Medicine
Bashkir State University
Leipzig University
University of California at Los Angeles
University of Edinburgh
University of Hamburg
Institute of Cancer Research
Curtin University
Moores Cancer Center
Shanghai Cancer Institute
Heraklion University Hospital
Cancer Council Victoria
Centre for Epidemiology and Biostatistics
McGill University Health Centre, Royal Victoria Hospital
Huntsman Cancer Institute
Oulu University Hospital
Pomeranian Medical University in Szczecin
Montreal Diabetes Research Center and University of Montreal Hospital Research Centre (CRCHUM)
University of Cologne
Center for Integrated Oncology
Universität zu Köln
Keck School of Medicine of USC
University of Massachusetts
University of Eastern Finland
National University Health System
University of Western Australia
Erasmus MC Cancer Institute
Kaohsiung Medical University
Academia Sinica - Institute of Biomedical Sciences
Aichi Cancer Center Hospital and Research Institute
Nagoya University
National Cancer Center Japan
Ulm University
Cancer Prevention Institute of California
Stanford University School of Medicine
Stanford University
Nagano Matsushiro General Hospital
University of Galway
The Catholic University of Korea
University of Oslo
Oslo University Hospital
The University of Hong Kong
Flanders Institute for Biotechnology
KU Leuven
University of Hawaii Cancer Center
Soonchunhyang University
University of Ulsan
Carmel Medical Center and Technion Faculty of Medicine
Maria Sklodowska-Curie Institute of Oncology
German Breast Group GmbH
University of Warwick
University of Manchester
Macedonian Academy of Sciences and Arts
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
Harvard University
Cancer Research Malaysia
University of California at San Diego
Alfred Health
Technical University of Munich
Hospital Monte Naranco
University College London
University of Malaya
University Health Network
Université Paris Sorbonne Cité
University of New Mexico
The Curtin UWA Centre for Genetic Origins of Health and Disease Curtin University and University of Western Australia
FIRC Institute of Molecular Oncology
Peter Maccallum Cancer Centre
University of Melbourne
University of Oulu
Northern Finland Laboratory Centre Oulu
Ludwig Maximilian University of Munich
Hospital Puerta de Hierro
Städtischen Klinikum Karlsruhe
National Institute of Environmental Health Sciences (NIEHS)
The National Cancer Institute
Guy’s Hospital
Case Western Reserve University
Hunter New England Health
University of Newcastle
University of Kansas
China Medical University Taichung
University of British Columbia
Saarland Cancer Registry
Columbia University
Ministry of Public Health
University of Oxford
Baden-Baden
Cancer Registry of Norway Institute of Population-Based Cancer Research
Helios Clinics Berlin-Buch
Utrecht University
Sime Darby Berhad
Armed Forces Capital Hospital
Tri-Service General Hospital
Shanghai Municipal Center for Disease Control and Prevention
University of California at San Francisco
Royal Brisbane and Women's Hospital
Dartmouth College
Stockholm County Council

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

1113 Scopus citations

Abstract

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10^-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

Original language	English
Pages (from-to)	92-94
Number of pages	3
Journal	Nature
Volume	551
Issue number	7678
DOIs	https://doi.org/10.1038/nature24284
State	Published - 02 Nov 2017

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/nature24284

Cite this

@article{82b105a6b50645a6b5b0fbe8d7dd3614,

title = "Association analysis identifies 65 new breast cancer risk loci",

abstract = "Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.",

author = "\{NBCS Collaborators\} and \{ABCTB Investigators\} and \{kConFab/AOCS Investigators\} and Kyriaki Michailidou and Sara Lindstr{\"o}m and Joe Dennis and Jonathan Beesley and Shirley Hui and Siddhartha Kar and Audrey Lema{\c c}on and Penny Soucy and Dylan Glubb and Asha Rostamianfar and Bolla, \{Manjeet K.\} and Qin Wang and Jonathan Tyrer and Ed Dicks and Andrew Lee and Zhaoming Wang and Jamie Allen and Renske Keeman and Ursula Eilber and French, \{Juliet D.\} and Chen, \{Xiao Qing\} and Laura Fachal and Karen McCue and Reed, \{Amy E.Mc Cart\} and Maya Ghoussaini and Carroll, \{Jason S.\} and Xia Jiang and Hilary Finucane and Marcia Adams and Adank, \{Muriel A.\} and Habibul Ahsan and Kristiina Aittom{\"a}ki and Hoda Anton-Culver and Antonenkova, \{Natalia N.\} and Volker Arndt and Aronson, \{Kristan J.\} and Banu Arun and Auer, \{Paul L.\} and Fran{\c c}ois Bacot and Myrto Barrdahl and Caroline Baynes and Beckmann, \{Matthias W.\} and Sabine Behrens and Javier Benitez and Marina Bermisheva and Leslie Bernstein and Carl Blomqvist and Bogdanova, \{Natalia V.\} and Bojesen, \{Stig E.\} and Diana Torres",

year = "2017",

month = nov,

day = "2",

doi = "10.1038/nature24284",

language = "English",

volume = "551",

pages = "92--94",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7678",

}

TY - JOUR

T1 - Association analysis identifies 65 new breast cancer risk loci

AU - NBCS Collaborators

AU - ABCTB Investigators

AU - kConFab/AOCS Investigators

AU - Michailidou, Kyriaki

AU - Lindström, Sara

AU - Dennis, Joe

AU - Beesley, Jonathan

AU - Hui, Shirley

AU - Kar, Siddhartha

AU - Lemaçon, Audrey

AU - Soucy, Penny

AU - Glubb, Dylan

AU - Rostamianfar, Asha

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Tyrer, Jonathan

AU - Dicks, Ed

AU - Lee, Andrew

AU - Wang, Zhaoming

AU - Allen, Jamie

AU - Keeman, Renske

AU - Eilber, Ursula

AU - French, Juliet D.

AU - Chen, Xiao Qing

AU - Fachal, Laura

AU - McCue, Karen

AU - Reed, Amy E.Mc Cart

AU - Ghoussaini, Maya

AU - Carroll, Jason S.

AU - Jiang, Xia

AU - Finucane, Hilary

AU - Adams, Marcia

AU - Adank, Muriel A.

AU - Ahsan, Habibul

AU - Aittomäki, Kristiina

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N.

AU - Arndt, Volker

AU - Aronson, Kristan J.

AU - Arun, Banu

AU - Auer, Paul L.

AU - Bacot, François

AU - Barrdahl, Myrto

AU - Baynes, Caroline

AU - Beckmann, Matthias W.

AU - Behrens, Sabine

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Bernstein, Leslie

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V.

AU - Bojesen, Stig E.

AU - Torres, Diana

PY - 2017/11/2

Y1 - 2017/11/2

N2 - Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

AB - Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

UR - https://www.scopus.com/pages/publications/85033379332

U2 - 10.1038/nature24284

DO - 10.1038/nature24284

M3 - Article

C2 - 29059683

AN - SCOPUS:85033379332

SN - 0028-0836

VL - 551

SP - 92

EP - 94

JO - Nature

JF - Nature

IS - 7678

ER -

Association analysis identifies 65 new breast cancer risk loci

Abstract

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