Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk

Journal article


Publication Details

Author(s): Guo X, Long J, Zeng C, Michailidou K, Ghoussaini M, Bolla MK, Wang Q, Milne RL, Shu XO, Cai Q, Beesley J, Kar SP, Andrulis IL, Anton-Culver H, Arndt V, Beckmann M, Beeghly-Fadiel A, Benitez J, Blot W, Bogdanova N, Bojesen SE, Brauch H, Brenner H, Brinton L, Broeks A, Bruening T, Burwinkel B, Cai H, Canisius S, Chang-Claude J, Choi JY, Couch FJ, Cox A, Cross SS, Czene K, Darabi H, Devilee P, Droit A, Doerk T, Fasching P, Fletcher O, Flyger H, Fostira F, Gaborieau V, Garcia-Closas M, Giles GG, Grip M, Guenel P, Haiman CA, Hamann U, Hartman M, Hollestelle A, Hopper JL, Hsiung CN, Ito H, Jakubowska A, Johnson N, Kabisch M, Kang D, Khan S, Knight JA, Kosma VM, Lambrechts D, Le Marchand L, Li J, Lindblom A, Lophatananon A, Lubinski J, Mannermaa A, Manoukian S, Margolin S, Marme F, Matsuo K, Mclean CA, Meindl A, Muir K, Neuhausen SL, Nevanlinna H, Nord S, Olson JE, Orr N, Peterlongo P, Putti TC, Rudolph A, Sangrajrang S, Sawyer EJ, Schmidt MK, Schmutzler RK, Shen CY, Shi J, Shrubsole MJ, Southey MC, Swerdlow A, Teo SH, Thienpont B, Toland AE, Tollenaar RAEM, Tomlinson IPM, Truong T, Tseng CC, Van Den Ouweland A, Wen W, Winqvist R, Wu A, Yip CH, Zamora MP, Zheng Y, Hall P, Pharoah PDP, Simard J, Chenevix-Trench G, Dunning AM, Easton DF, Zheng W
Journal: Cancer Epidemiology Biomarkers & Prevention
Publication year: 2015
Volume: 24
Journal issue: 11
Pages range: 1680-91
ISSN: 1055-9965


Abstract

A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored.We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10(-4); OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P = 1.86 × 10(-4); OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r(2) >= 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.


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))
China Medical University (CMU) / 中國醫藥大學
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
Fondazione IRCCS: Istituto Nazionale dei Tumori
Helsingin yliopisto / University of Helsinki
Herlev Hospital
Hospital Universitario La Paz
IFOM - FIRC Institute of Molecular Oncology
Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA)
International Agency for Research on Cancer (IARC)
Karolinska Institute
King’s College London
Kyushu University / 九州大学
Leiden University
Mayo Clinic
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 Health System (NUHS)
National University of Singapore (NUS)
Ohio State University
Oslo University Hospital / Oslo Universitetssykehus
Oulun Yliopisto / University of Oulo
Oulu University Hospital
Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU)
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Robert-Bosch-Krankenhaus
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 Alfred Hospital
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 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

APA:
Guo, X., Long, J., Zeng, C., Michailidou, K., Ghoussaini, M., Bolla, M.K.,... Zheng, W. (2015). Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk. Cancer Epidemiology Biomarkers & Prevention, 24(11), 1680-91. https://dx.doi.org/10.1158/1055-9965.EPI-15-0363

MLA:
Guo, Xingyi, et al. "Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk." Cancer Epidemiology Biomarkers & Prevention 24.11 (2015): 1680-91.

BibTeX: 

Last updated on 2019-21-07 at 08:03