Authors

Kate Lawrenson, University of Southern California, Los Angeles
Siddhartha Kar, University of Cambridge
Karen McCue, QIMR Berghofer Medical Research Institute
Karoline Kuchenbaeker, University of Cambridge
Kyriaki Michailidou, University of Cambridge
Jonathan Tyrer, University of Cambridge
Jonathan Beesley, QIMR Berghofer Medical Research Institute
Susan J. Ramus, University of Southern California, Los Angeles
Qiyuan Li, Xiamen University
Melissa K. Delgado, University of Southern California, Los Angeles
Janet M. Lee, University of Southern California, Los Angeles
Kristiina Aittomäki, University of Helsinki
Irene L. Andrulis, University of Toronto, Ontario
Hoda Anton-Culver, University of California Irvine
Volker Arndt, German Cancer Research Center (DKFZ), Heidelberg, Germany
Banu K. Arun, University of Texas MD
Brita Arver, Karolinska University Hospital, Stockholm, Sweden.
Elisa V. Bandera, Rutgers Cancer Institute of New Jersey
Monica Barile, Istituto Europeo di Oncologia, Milan
Rosa B. Barkardottir, University of Iceland
Daniel Barrowdale, University of Cambridge
Matthias W. Beckmann, University Hospital Erlangen
Javier Benitez, Spanish National Cancer Research Centre, Madrid
Andrew Berchuck, Duke University Medical Center
Maria Bisogna, Memorial Sloan-Kettering Cancer Center, New York
Line Bjorge, Haukeland University Hospital
Carl Blomqvist, University of Helsinki
William Blot, Vanderbilt University
Natalie Bogdanova, Hannover Medical School, Germany
Anders Bojesen, Vejle Hospital, Denmark
Stig E. Bojesen, University of Copenhagen
Manjeet K. Bolla, University of Cambridge
Bernardo Bonanni, Istituto Europeo di Oncologia, Milan
Anne-Lise Børresen-Dale, University of Oslo
Hiltrud Brauch, Dr Margarete Fischer- Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
Paul Brennan, International Agency for Research on Cancer, Lyon, France
Hermann Brenner, German Cancer Research Center (DKFZ), Heidelberg, Germany
Fionna Bruinsma, Cancer Council Victoria, Victoria, Australia
Joan Brunet, IDIBGI (Institut d’Investigacio Biomedica de Girona), Catalan Institute of Oncology, Girona, Spain
Shaik Ahmad Buhari, National University Health System, Singapore
Barbara Burwinkel, German Cancer Research Center (DKFZ), Heidelberg, Germany
Ralf Butzow, University of Helsinki
Sandra S. Buys, University of Utah School of Medicine
Qiuyin Cai, Vanderbilt University
Trinidad Caldes, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigacion Sanitaria del Hospital Clınico San Carlos), Madrid
Ian Campbell, MacCallum Cancer Centre, Melbourne, Victoria, Australia
Rikki Canniotto, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York
Jenny Chang-Claude, German Cancer Research Center (DKFZ), Heidelberg, Germany
Jocelyne Chiquette, Centre de recherche FRSQ du Centre hospitalier affilie universitaire de Quebec
Ji-Yeob Choi, Seoul National University
Kathleen B.M Claes, Ghent University
GEMO Study Collaborators
Linda S. Cook, University of New Mexico, Albuquerque
Angela Cox, University of Sheffield
Daniel W. Cramer, Harvard HT Chan School of Public Health
Simon S. Cross, University of Sheffield
Cezary Cybulski, Pomeranian Medical University
Kamila Czene, Karolinska Institutet
Mary B. Daly, Fox Chase Cancer Center, Philadelphia, Pennsylvania
Francesca Damiola, Universite Lyon, France
Agnieszka Dansonka-Mieszkowska, Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology, Poland.
Hatef Darabi, Karolinska Institutet
Joe Dennis, University of Cambridge
Peter Devilee, Leiden University Medical Center
Orland Diaz, Universitat Autonoma de Barcelona
Jennifer A. Doherty, Dartmouth College

Document Type

Article

Publication Date

2016

Publication Title

Nature Communications

Abstract

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 X 10-20), ER-negative BC (P = 1.1 X 10-13), BRCA1 -associated BC (P = 7.7 X 10-16) and triple negative BC (P-diff = 2 X 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 X 10-3) and ABHD8 (P < 2 X 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8 , and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

DOI

10.1038/ncomms12675

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