Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer

Kabisch M, Bermejo JL, Duennebier T, Ying S, Michailidou K, Bolla MK, Wang Q, Dennis J, Shah M, Perkins BJ, Czene K, Darabi H, Eriksson M, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Lambrechts D, Neven P, Peeters S, Weltens C, Couch FJ, Olson JE, Wang X, Purrington K, Chang-Claude J, Rudolph A, Seibold P, Flesch-Janys D, Peto J, Dos-Santos-Silva I, Johnson N, Fletcher O, Nevanlinna H, Muranen TA, Aittomaki K, Blomqvist C, Schmidt MK, Broeks A, Cornelissen S, Hogervorst FBL, Li J, Brand JS, Humphreys K, Guenel P, Truong T, Menegaux F, Sanchez M, Burwinkel B, Marme F, Yang R, Bugert P, Gonzalez-Neira A, Benitez J, Pilar Zamora M, Arias Perez JI, Cox A, Cross SS, Reed MWR, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Haiman CA, Schumacher F, Henderson BE, Le Marchand L, Lindblom A, Margolin S, Hooning MJ, Hollestelle A, Kriege M, Koppert LB, Hopper JL, Southey MC, Tsimiklis H, Apicella C, Slettedahl S, Toland AE, Vachon C, Yannoukakos D, Giles GG, Milne RL, Mclean C, Fasching P, Rübner M, Ekici AB, Beckmann M, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Ashworth A, Orr N, Schoemaker MJ, Swerdlow A, Garcia-Closas M, Figueroa J, Chanock SJ, Lissowska J, Goldberg MS, Labreche F, Dumont M, Winqvist R, Pylkas K, Jukkola-Vuorinen A, Grip M, Brauch H, Bruening T, Ko YD, Radice P, Peterlongo P, Scuvera G, Fortuzzi S, Bogdanova N, Doerk T, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Devilee P, Tollenaar RAEM, Seynaeve C, Van Asperen CJ, Jakubowska A, Lubinski J, Jaworska-Bieniek K, Durda K, Zheng W, Shrubsole MJ, Cai Q, Torres D, Anton-Culver H, Kristensen V, Bacot F, Tessier DC, Vincent D, Luccarini C, Baynes C, Ahmed S, Maranian M, Simard J, Chenevix-Trench G, Hall P, Pharoah PDP, Dunning AM, Easton DF, Hamann U (2015)


Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 36

Pages Range: 256-71

Journal Issue: 2

DOI: 10.1093/carcin/bgu326

Abstract

The chromosomal passenger complex (CPC) plays a pivotal role in the regulation of cell division. Therefore, inherited CPC variability could influence tumor development. The present candidate gene approach investigates the relationship between single nucleotide polymorphisms (SNPs) in genes encoding key CPC components and breast cancer risk. Fifteen SNPs in four CPC genes (INCENP, AURKB, BIRC5 and CDCA8) were genotyped in 88 911 European women from 39 case-control studies of the Breast Cancer Association Consortium. Possible associations were investigated in fixed-effects meta-analyses. The synonymous SNP rs1675126 in exon 7 of INCENP was associated with overall breast cancer risk [per A allele odds ratio (OR) 0.95, 95% confidence interval (CI) 0.92-0.98, P = 0.007] and particularly with estrogen receptor (ER)-negative breast tumors (per A allele OR 0.89, 95% CI 0.83-0.95, P = 0.0005). SNPs not directly genotyped were imputed based on 1000 Genomes. The SNPs rs1047739 in the 3' untranslated region and rs144045115 downstream of INCENP showed the strongest association signals for overall (per T allele OR 1.03, 95% CI 1.00-1.06, P = 0.0009) and ER-negative breast cancer risk (per A allele OR 1.06, 95% CI 1.02-1.10, P = 0.0002). Two genotyped SNPs in BIRC5 were associated with familial breast cancer risk (top SNP rs2071214: per G allele OR 1.12, 95% CI 1.04-1.21, P = 0.002). The data suggest that INCENP in the CPC pathway contributes to ER-negative breast cancer susceptibility in the European population. In spite of a modest contribution of CPC-inherited variants to the total burden of sporadic and familial breast cancer, their potential as novel targets for breast cancer treatment should be further investigated.

Authors with CRIS profile

Involved external institutions

The Institute of Cancer Research (ICR) GB United Kingdom (GB) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Hospital Monte Naranco ES Spain (ES) University of Cambridge GB United Kingdom (GB) Karolinska Institute SE Sweden (SE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) AU Australia (AU) Centre hospitalier universitaire de Québec CA Canada (CA) Krebsregister Saarland / Saarland Cancer Registry DE Germany (DE) The Alfred Hospital AU Australia (AU) The University of Melbourne AU Australia (AU) National Centre for Scientific Research (NCSR) "Demokritos" GR Greece (GR) Mayo Clinic US United States (USA) (US) Ohio State University US United States (USA) (US) Erasmus University Medical Center (MC) NL Netherlands (NL) University of Hawaii (U.H.) US United States (USA) (US) University of Southern California (USC) US United States (USA) (US) University Hospital Galway IE Ireland (IE) University of Oxford GB United Kingdom (GB) King’s College London GB United Kingdom (GB) Mount Sinai Hospital (MSH) CA Canada (CA) University of Sheffield GB United Kingdom (GB) Hospital Universitario La Paz ES Spain (ES) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) ES Spain (ES) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) Genome Institute of Singapore SG Singapore (SG) Antoni van Leeuwenhoek NL Netherlands (NL) Helsingin yliopisto / University of Helsinki FI Finland (FI) University College London (UCL) GB United Kingdom (GB) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Wayne State University (WSU) US United States (USA) (US) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) BE Belgium (BE) Copenhagen University Hospital DK Denmark (DK) Universitätsklinikum Heidelberg DE Germany (DE) McGill University CA Canada (CA) University of California Irvine US United States (USA) (US) Vanderbilt University US United States (USA) (US) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet NO Norway (NO) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) PL Poland (PL) Leiden University NL Netherlands (NL) University of Eastern Finland FI Finland (FI) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) IFOM - FIRC Institute of Molecular Oncology IT Italy (IT) Fondazione IRCCS: Istituto Nazionale dei Tumori IT Italy (IT) Evangelische Kliniken Bonn gGmbH DE Germany (DE) Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA) DE Germany (DE) Robert-Bosch-Krankenhaus DE Germany (DE) Oulun Yliopisto / University of Oulo FI Finland (FI) Université de Montréal CA Canada (CA) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie PL Poland (PL) National Cancer Institute (NCI) US United States (USA) (US)

How to cite

APA:

Kabisch, M., Bermejo, J.L., Duennebier, T., Ying, S., Michailidou, K., Bolla, M.K.,... Hamann, U. (2015). Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer. Carcinogenesis, 36(2), 256-71. https://dx.doi.org/10.1093/carcin/bgu326

MLA:

Kabisch, Maria, et al. "Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer." Carcinogenesis 36.2 (2015): 256-71.

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