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

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 (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 6

DOI: 10.1038/srep32512

Abstract

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.

Authors with CRIS profile

Involved external institutions

Karolinska Institute Sweden (SE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Université Laval (UL) Canada (CA) University of Cambridge United Kingdom (GB) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Mount Sinai Hospital (MSH) Canada (CA) University of California Irvine United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Copenhagen University Hospital Denmark (DK) Robert-Bosch-Krankenhaus Germany (DE) Antoni van Leeuwenhoek Netherlands (NL) Ruhr-Universität Bochum (RUB) Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Mayo Clinic United States (USA) (US) University of Sheffield United Kingdom (GB) Leiden University Netherlands (NL) University of Edinburgh United Kingdom (GB) The Institute of Cancer Research (ICR) United Kingdom (GB) Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC)) Belgium (BE) National Cancer Institute (NCI) United States (USA) (US) Cancer Council Victoria Australia (AU) McGill University Canada (CA) École Polytechnique - Université Paris-Saclay France (FR) University of Southern California (USC) United States (USA) (US) National University of Singapore (NUS) Singapore (SG) Erasmus University Medical Center (MC) Netherlands (NL) The University of Melbourne Australia (AU) Aichi Cancer Center Research Institute Japan (JP) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Helsingin yliopisto / University of Helsinki Finland (FI) University of Eastern Finland Finland (FI) University of Hawaii (U.H.) United States (USA) (US) National University Health System (NUHS) Singapore (SG) University of Warwick United Kingdom (GB) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Beckman Research Institute of City of Hope (BRI) United States (USA) (US) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Oulun Yliopisto / University of Oulo Finland (FI) King’s College London United Kingdom (GB) Universitätsklinikum Köln Germany (DE) Academia Sinica / 中央研究院 Taiwan (TW) Vanderbilt University United States (USA) (US) Cancer Research Initiatives Foundation (CARIF) / Cancer Research Malaysia (CRM) Malaysia (MY) Wellcome Trust Sanger Institute - Genome Research Limited United Kingdom (GB) University of Malaya (UM) / Universiti Malaya Malaysia (MY) International Agency for Research on Cancer (IARC) France (FR) Technische Universität München (TUM) Germany (DE)

How to cite

APA:

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. https://dx.doi.org/10.1038/srep32512

MLA:

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).

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