Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

Journal article

Publication Details

Author(s): Darabi H, Beesley J, Droit A, Kar S, Nord S, Marjaneh MM, Soucy P, Michailidou K, Ghoussaini M, Wahl HF, Bolla MK, Wang Q, Dennis J, Alonso MR, Andrulis IL, Anton-Culver H, Arndt V, Beckmann M, Benitez J, Bogdanova NV, Bojesen SE, Brauch H, Brenner H, Broeks A, Bruening T, Burwinkel B, Chang-Claude J, Choi JY, Conroy DM, Couch FJ, Cox A, Cross SS, Czene K, Devilee P, Doerk T, Easton DF, Fasching P, Figueroa J, Fletcher O, Flyger H, Galle E, Garcia-Closas M, Giles GG, Goldberg MS, Gonzalez-Neira A, Guenel P, Haiman CA, Hallberg E, Hamann U, Hartman M, Hollestelle A, Hopper JL, Ito H, Jakubowska A, Johnson N, Kang D, Khan S, Kosma VM, Kriege M, Kristensen V, Lambrechts D, Le Marchand L, Lee SC, Lindblom A, Lophatananon A, Lubinski J, Mannermaa A, Manoukian S, Margolin S, Matsuo K, Mayes R, Mckay J, Meindl A, Milne RL, Muir K, Neuhausen SL, Nevanlinna H, Olswold C, Orr N, Peterlongo P, Pita G, Pylkaes K, Rudolph A, Sangrajrang S, Sawyer EJ, Schmidt MK, Schmutzler RK, Seynaeve C, Shah M, Shen CY, Shu XO, Southey MC, Stram DO, Surowy H, Swerdlow A, Teo SH, Tessier DC, Tomlinson I, Torres D, Truong T, Vachon CM, Vincent D, Winqvist R, Wu AH, Wu PE, Yip CH, Zheng W, Pharoah PDP, Hall P, Edwards SL, Simard J, French JD, Chenevix-Trench G, Dunning AM
Journal: Scientific Reports
Publication year: 2016
Volume: 6
ISSN: 2045-2322


Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe

External institutions with authors

Academia Sinica / 中央研究院
Aichi Cancer Center Research Institute
Antoni van Leeuwenhoek
Beckman Research Institute of City of Hope (BRI)
Cancer Council Victoria
Cancer Research Initiatives Foundation (CARIF)
Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC))
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
École Polytechnique - Université Paris-Saclay
Erasmus University Medical Center
Helsingin yliopisto / University of Helsinki
IFOM - FIRC Institute of Molecular Oncology
International Agency for Research on Cancer (IARC)
Istituto Nazionale dei Tumori
Karolinska Institute
King’s College London
Leiden University
Mayo Clinic
McGill University
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National University Health System (NUHS)
National University of Singapore (NUS)
Oslo universitetssykehus Rikshospitalet
Oulun Yliopisto / University of Oulo
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Ruhr-Universität Bochum (RUB)
Ruprecht-Karls-Universität Heidelberg
Seoul National University (SNU) / 서울대학교
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Technische Universität München (TUM)
The Institute of Cancer Research (ICR)
The University of Melbourne
Universitätsklinikum Köln
Université Laval (UL)
University of California Irvine
University of Cambridge
University of Eastern Finland
University of Edinburgh
University of Hawaii (U.H.)
University of Malaya (UM) / Universiti Malaya
University of Sheffield
University of Southern California (USC)
University of Warwick
Vanderbilt University
Wellcome Trust Sanger Institute - Genome Research Limited

How to cite

Darabi, H., Beesley, J., Droit, A., Kar, S., Nord, S., Marjaneh, M.M.,... Dunning, A.M. (2016). Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs). Scientific Reports, 6.

Darabi, Hatef, et al. "Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)." Scientific Reports 6 (2016).


Last updated on 2019-28-02 at 06:24