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

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 (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 24

Pages Range: 1680-91

Journal Issue: 11

DOI: 10.1158/1055-9965.EPI-15-0363

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.

Authors with CRIS profile

Involved external institutions

Center for Cancer Biology (CCB) (formerly Vesalius Research Center (VRC)) Belgium (BE) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) IFOM - FIRC Institute of Molecular Oncology Italy (IT) China Medical University (CMU) / 中國醫藥大學 Taiwan (TW) University of Southern California (USC) United States (USA) (US) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) University of Oxford United Kingdom (GB) Leiden University Netherlands (NL) Ohio State University United States (USA) (US) Cancer Research Initiatives Foundation (CARIF) / Cancer Research Malaysia (CRM) Malaysia (MY) The Institute of Cancer Research (ICR) United Kingdom (GB) The University of Melbourne Australia (AU) Vanderbilt University United States (USA) (US) Universitätsklinikum Köln Germany (DE) Antoni van Leeuwenhoek Netherlands (NL) King’s College London United Kingdom (GB) National Cancer Institute (NCI) United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) National University Health System (NUHS) Singapore (SG) Mayo Clinic United States (USA) (US) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Helsingin yliopisto / University of Helsinki Finland (FI) Beckman Research Institute of City of Hope (BRI) United States (USA) (US) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Technische Universität München (TUM) Germany (DE) University of Eastern Finland Finland (FI) The Alfred Hospital Australia (AU) Kyushu University / 九州大学 Japan (JP) Ruprecht-Karls-Universität Heidelberg Germany (DE) Karolinska Institute Sweden (SE) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University of Warwick United Kingdom (GB) University of Hawaii (U.H.) United States (USA) (US) Mount Sinai Hospital (MSH) Canada (CA) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Academia Sinica / 中央研究院 Taiwan (TW) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) National University of Singapore (NUS) Singapore (SG) Oulu University Hospital Finland (FI) Cancer Council Victoria Australia (AU) International Agency for Research on Cancer (IARC) France (FR) Copenhagen University Hospital Denmark (DK) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Université Laval (UL) Canada (CA) University of Sheffield United Kingdom (GB) Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA) Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Herlev Hospital Denmark (DK) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) University of California Irvine United States (USA) (US) University of Cambridge United Kingdom (GB) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Shanghai Center For Disease Control And Prevention (SCDC) China (CN) Hospital Universitario La Paz Spain (ES) University of Malaya (UM) / Universiti Malaya Malaysia (MY) Oulun Yliopisto / University of Oulo Finland (FI)

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://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: Download