Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

Journal article

Publication Details

Author(s): Horne HN, Chung CC, Zhang H, Yu K, Prokunina-Olsson L, Michailidou K, Bolla MK, Wang Q, Dennis J, Hopper JL, Southey MC, Schmidt MK, Broeks A, Muir K, Lophatananon A, Fasching P, Beckmann M, Fletcher O, Johnson N, Sawyer EJ, Tomlinson I, Burwinkel B, Marme F, Guenel P, Truong T, Bojesen SE, Flyger H, Benitez J, Gonzalez-Neira A, Anton-Culver H, Neuhausen SL, Brenner H, Arndt V, Meindl A, Schmutzler RK, Brauch H, Hamann U, Nevanlinna H, Khan S, Matsuo K, Iwata H, Dork T, Bogdanova NV, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Chenevix-Trench G, Wu AH, Den Berg DV, Smeets A, Zhao H, Chang-Claude J, Rudolph A, Radice P, Barile M, Couch FJ, Vachon C, Giles GG, Milne RL, Haiman CA, Le Marchand L, Goldberg MS, Teo SH, Taib NAM, Kristensen V, Borresen-Dale AL, Zheng W, Shrubsole M, Winqvist R, Jukkola-Vuorinen A, Andrulis IL, Knight JA, Devilee P, Seynaeve C, Garcia-Closas M, Czene K, Darabi H, Hollestelle A, Martens JWM, Li J, Lu W, Shu XO, Cox A, Cross SS, Blot W, Cai Q, Shah M, Luccarini C, Baynes C, Harrington P, Kang D, Choi JY, Hartman M, Chia KS, Kabisch M, Torres D, Jakubowska A, Lubinski J, Sangrajrang S, Brennan P, Slager S, Yannoukakos D, Shen CY, Hou MF, Swerdlow A, Orr N, Simard J, Hall P, Pharoah PDP, Easton DF, Chanock SJ, Dunning AM, Figueroa JD
Journal: PLoS ONE
Publication year: 2016
Volume: 11
Journal issue: 8
ISSN: 1932-6203


The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

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

Aichi Cancer Center Research Institute
Antoni van Leeuwenhoek
Beckman Research Institute of City of Hope (BRI)
Cancer Research Initiatives Foundation (CARIF)
Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC))
China Medical University (CMU) / 中國醫藥大學
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Fondazione IRCCS: Istituto Nazionale dei Tumori
Helsingin yliopisto / University of Helsinki
International Agency for Research on Cancer (IARC)
Kaohsiung Medical University (KMU) / 高雄醫學大學
Karolinska Institute
King’s College London
Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri
Kyushu University / 九州大学
Leiden University
Mayo Clinic
McGill University
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National Centre for Scientific Research (NCSR) "Demokritos"
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
National University of Singapore (NUS)
Oslo University Hospital / Oslo Universitetssykehus
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)
Ruprecht-Karls-Universität Heidelberg
Seoul National University (SNU) / 서울대학교
Shanghai Center For Disease Control And Prevention (SCDC)
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 Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of California Irvine
University of Cambridge
University of Hawaii (U.H.)
University of Malaya (UM) / Universiti Malaya
University of Oxford
University of Sheffield
University of Southern California (USC)
University of Warwick
Vanderbilt University

How to cite

Horne, H.N., Chung, C.C., Zhang, H., Yu, K., Prokunina-Olsson, L., Michailidou, K.,... Figueroa, J.D. (2016). Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus. PLoS ONE, 11(8).

Horne, Hisani N., et al. "Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus." PLoS ONE 11.8 (2016).


Last updated on 2019-21-07 at 07:56