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

Authors:
Maria Kabisch Justo Lorenzo Bermejo Thomas Dünnebier Shibo Ying Kyriaki Michailidou Manjeet K Bolla Qin Wang Joe Dennis Mitul Shah Barbara J Perkins Kamila Czene Hatef Darabi Mikael Eriksson Stig E Bojesen Børge G Nordestgaard Sune F Nielsen Henrik Flyger Diether Lambrechts Patrick Neven Stephanie Peeters Caroline Weltens Fergus J Couch Janet E Olson Xianshu Wang Kristen Purrington Jenny Chang-Claude Anja Rudolph Petra Seibold Dieter Flesch-Janys Julian Peto Isabel dos-Santos-Silva Nichola Johnson Olivia Fletcher Heli Nevanlinna Taru A Muranen Kristiina Aittomäki Carl Blomqvist Marjanka K Schmidt Annegien Broeks Sten Cornelissen Frans B L Hogervorst Jingmei Li Judith S Brand Keith Humphreys Pascal Guénel Thérèse Truong Florence Menegaux Marie Sanchez Barbara Burwinkel Frederik Marmé Rongxi Yang Peter Bugert Anna González-Neira Javier Benitez M Pilar Zamora Jose I Arias Perez Angela Cox Simon S Cross Malcolm W R Reed Irene L Andrulis Julia A Knight Gord Glendon Sandrine Tchatchou Elinor J Sawyer Ian Tomlinson Michael J Kerin Nicola Miller Christopher A Haiman Fredrick Schumacher Brian E Henderson Loic Le Marchand Annika Lindblom Sara Margolin Maartje J Hooning Antoinette Hollestelle Mieke Kriege Linetta B Koppert John L Hopper Melissa C Southey Helen Tsimiklis Carmel Apicella Seth Slettedahl Amanda E Toland Celine Vachon Drakoulis Yannoukakos Graham G Giles Roger L Milne Catriona McLean Peter A Fasching Matthias Ruebner Arif B Ekici Matthias W Beckmann Hermann Brenner Aida K Dieffenbach Volker Arndt Christa Stegmaier Alan Ashworth Nicholas Orr Minouk J Schoemaker Anthony Swerdlow Montserrat García-Closas Jonine Figueroa Stephen J Chanock Jolanta Lissowska Mark S Goldberg France Labrèche Martine Dumont Robert Winqvist Katri Pylkäs Arja Jukkola-Vuorinen Mervi Grip Hiltrud Brauch Thomas Brüning Yon-Dschun Ko Paolo Radice Paolo Peterlongo Giulietta Scuvera Stefano Fortuzzi Natalia Bogdanova Thilo Dörk Arto Mannermaa Vesa Kataja Veli-Matti Kosma Jaana M Hartikainen Peter Devilee Robert A E M Tollenaar Caroline Seynaeve Christi J Van Asperen Anna Jakubowska Jan Lubinski Katarzyna Jaworska-Bieniek Katarzyna Durda Wei Zheng Martha J Shrubsole Qiuyin Cai Diana Torres Hoda Anton-Culver Vessela Kristensen François Bacot Daniel C Tessier Daniel Vincent Craig Luccarini Caroline Baynes Shahana Ahmed Mel Maranian Jacques Simard Georgia Chenevix-Trench Per Hall Paul D P Pharoah Alison M Dunning Douglas F Easton Ute Hamann

Carcinogenesis 2015 Feb 13;36(2):256-71. Epub 2015 Jan 13.

Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany,

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.

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Source
http://dx.doi.org/10.1093/carcin/bgu326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335262PMC
February 2015
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