Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

Journal article


Publication Details

Author(s): Milne RL, Burwinkel B, Michailidou K, Arias-Perez JI, Pilar Zamora M, Menendez-Rodriguez P, Hardisson D, Mendiola M, Gonzalez-Neira A, Pita G, Rosario Alonso M, Dennis J, Wang Q, Bolla MK, Swerdlow A, Ashworth A, Orr N, Schoemaker M, Ko YD, Brauch H, Hamann U, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Matsuo K, Ito H, Iwata H, Tajima K, Li J, Brand JS, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Lambrechts D, Peuteman G, Christiaens MR, Smeets A, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Hartman M, Hui M, Lim WY, Chan CW, Marme F, Yang R, Bugert P, Lindblom A, Margolin S, Garcia-Closas M, Chanock SJ, Lissowska J, Figueroa JD, Bojesen SE, Nordestgaard BG, Flyger H, Hooning MJ, Kriege M, Van Den Ouweland AMW, Koppert LB, Fletcher O, Johnson N, Dos-Santos-Silva I, Peto J, Zheng W, Deming-Halverson S, Shrubsole MJ, Long J, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Cox A, Cross SS, Reed MWR, Schmidt MK, Broeks A, Cornelissen S, Braaf L, Kang D, Choi JY, Park SK, Noh DY, Simard J, Dumont M, Goldberg MS, Labreche F, Fasching P, Hein A, Ekici AB, Beckmann M, Radice P, Peterlongo P, Azzollini J, Barile M, Sawyer E, Tomlinson I, Kerin M, Miller N, Hopper JL, Schmidt DF, Makalic E, Southey MC, Teo SH, Yip CH, Sivanandan K, Tay WT, Shen CY, Hsiung CN, Yu JC, Hou MF, Guenel P, Therese Truong , Sanchez M, Mulot C, Blot W, Cai Q, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Bogdanova N, Doerk T, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Shu XO, Lu W, Gao YT, Zhang B, Couch FJ, Toland AE, Yannoukakos D, Sangrajrang S, Mckay J, Wang X, Olson JE, Vachon C, Purrington K, Severi G, Baglietto L, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Devilee P, Tollenaar RAEM, Seynaeve C, Czene K, Eriksson M, Humphreys K, Darabi H, Ahmed S, Shah M, Pharoah PDP, Hall P, Giles GG, Benitez J, Dunning AM, Chenevix-Trench G, Easton DF
Journal: Human Molecular Genetics
Publication year: 2014
Volume: 23
Journal issue: 22
Pages range: 6096-111
ISSN: 0964-6906


Abstract


Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.



FAU Authors / FAU Editors

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe
Hein, Alexander PD Dr.
Frauenklinik


External institutions with authors

Academia Sinica / 中央研究院
Aichi Cancer Center Research Institute
Antoni van Leeuwenhoek
Cancer Council Victoria
Centre hospitalier universitaire de Québec
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
Eberhard Karls Universität Tübingen
Erasmus University Medical Center
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Evangelische Kliniken Bonn gGmbH
Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB)
Fondazione IRCCS: Istituto Nazionale dei Tumori
Genome Institute of Singapore
Helsingin yliopisto / University of Helsinki
Herlev Hospital
Hospital Monte Naranco
Hospital Universitario La Paz
IFOM - FIRC Institute of Molecular Oncology
International Agency for Research on Cancer (IARC)
Kaohsiung Medical University (KMU) / 高雄醫學大學
Karolinska Institute
King’s College London
Krebsregister Saarland / Saarland Cancer Registry
Kyushu University / 九州大学
Leiden University
London School of Hygiene and Tropical Medicine
Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie
Mayo Clinic
McGill University
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
Mie University / 三重大学
Ministry of Public Health (MOPH) / กระทรวงสาธารณสุข
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
National Cancer Institute of Thailand
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 Ireland (NUI), Galway
National University of Singapore (NUS)
Ohio State University
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)
Ramsay Sime Darby Health Care (RSDHC)
Robert-Bosch-Krankenhaus
Ruprecht-Karls-Universität Heidelberg
Seoul National University (SNU) / 서울대학교
Shanghai Cancer Institute / 上海市肿瘤研究所
Shanghai Center For Disease Control And Prevention (SCDC)
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
The University of Melbourne
Tri-Service General Hospital (TSGH) / 三軍總醫院
Universidad Autónoma de Madrid (UAM)
Universitätsklinikum Hamburg-Eppendorf (UKE)
Université de Montréal
University College London (UCL)
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of Cambridge
University of Eastern Finland
University of Hawaii (U.H.)
University of Malaya (UM) / Universiti Malaya
University of Manchester
University of Oxford
University of Sheffield
University of Southern California (USC)
University of Toronto
University of Warwick
Vanderbilt University


How to cite

APA:
Milne, R.L., Burwinkel, B., Michailidou, K., Arias-Perez, J.-I., Pilar Zamora, M., Menendez-Rodriguez, P.,... Easton, D.F. (2014). Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium. Human Molecular Genetics, 23(22), 6096-111. https://dx.doi.org/10.1093/hmg/ddu311

MLA:
Milne, Roger L., et al. "Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium." Human Molecular Genetics 23.22 (2014): 6096-111.

BibTeX: 

Last updated on 2019-21-07 at 07:53