Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

Purrington KS, Slettedahl S, Bolla MK, Michailidou K, Czene K, Nevanlinna H, Bojesen SE, Andrulis IL, Cox A, Hall P, Carpenter J, Yannoukakos D, Haiman CA, Fasching P, Mannermaa A, Winqvist R, Brenner H, Lindblom A, Chenevix-Trench G, Benitez J, Swerdlow A, Kristensen V, Guenel P, Meindl A, Darabi H, Eriksson M, Fagerholm R, Aittomaki K, Blomqvist C, Nordestgaard BG, Nielsen SF, Flyger H, Wang X, Olswold C, Olson JE, Mulligan AM, Knight JA, Tchatchou S, Reed MWR, Cross SS, Liu J, Li J, Humphreys K, Clarke C, Scott R, Fostira F, Fountzilas G, Konstantopoulou I, Henderson BE, Schumacher F, Le Marchand L, Ekici AB, Hartmann A, Beckmann M, Hartikainen JM, Kosma VM, Kataja V, Jukkola-Vuorinen A, Pylkas K, Kauppila S, Dieffenbach AK, Stegmaier C, Arndt V, Margolin S, Balleine R, Arias Perez JI, Pilar Zamora M, Menendez P, Ashworth A, Jones M, Orr N, Arveux P, Kerbrat P, Therese Truong , Bugert P, Toland AE, Ambrosone CB, Labreche F, Goldberg MS, Dumont M, Ziogas A, Lee E, Dite GS, Apicella C, Southey MC, Long J, Shrubsole M, Deming-Halverson S, Ficarazzi F, Barile M, Peterlongo P, Durda K, Jaworska-Bieniek K, Tollenaar RAEM, Seynaeve C, Bruening T, Ko YD, Van Deurzen CHM, Martens JWM, Kriege M, Figueroa JD, Chanock SJ, Lissowska J, Tomlinson I, Kerin MJ, Miller N, Schneeweiss A, Tapper WJ, Gerty SM, Durcan L, Mclean C, Milne RL, Baglietto L, Silva IDS, Fletcher O, Johnson N, Van'T Veer LJ, Cornelissen S, Foersti A, Torres D, Ruediger T, Rudolph A, Flesch-Janys D, Nickels S, Weltens C, Floris G, Moisse M, Dennis J, Wang Q, Dunning AM, Shah M, Brown J, Simard J, Anton-Culver H, Neuhausen SL, Hopper JL, Bogdanova N, Doerk T, Zheng W, Radice P, Jakubowska A, Lubinski J, Devillee P, Brauch H, Hooning M, Garcia-Closas M, Sawyer E, Burwinkel B, Marmee F, Eccles DM, Giles GG, Peto J, Schmidt M, Broeks A, Hamann U, Chang-Claude J, Lambrechts D, Pharoah PDP, Easton D, Pankratz VS, Slager S, Vachon CM, Couch FJ (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 23

Pages Range: 6034-46

Journal Issue: 22

DOI: 10.1093/hmg/ddu300

Abstract

Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16-1.33, P = 4.2 × 10(-10)) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04-1.11, P = 8.7 × 10(-6)) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07-1.23, P = 7.9 × 10(-5)) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.

Authors with CRIS profile

Involved external institutions

Centre Eugène Marquis France (FR) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) DRK-Blutspendedienst Baden-Württemberg - Hessen / German Red Cross Blood Donor Service Baden-Wuerttemberg – Hessen Germany (DE) Ohio State University United States (USA) (US) Roswell Park Cancer Institute United States (USA) (US) Université de Montréal Canada (CA) McGill University Canada (CA) Australian Breast Cancer Tissue Bank Australia (AU) National Centre for Scientific Research (NCSR) "Demokritos" Greece (GR) Mayo Clinic United States (USA) (US) University of Cambridge United Kingdom (GB) Karolinska Institute Sweden (SE) Helsingin yliopisto / University of Helsinki Finland (FI) University of Copenhagen Denmark (DK) Mount Sinai Hospital (MSH) Canada (CA) University of Sheffield United Kingdom (GB) University of Southern California (USC) United States (USA) (US) University of Eastern Finland Finland (FI) Oulun Yliopisto / University of Oulo Finland (FI) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Technische Universität München (TUM) Germany (DE) Copenhagen University Hospital Denmark (DK) University of Toronto Canada (CA) Genome Institute of Singapore Singapore (SG) University of Sydney (USYD) Australia (AU) Hunter Area Pathology Service Australia (AU) Aristotle University of Thessaloniki Greece (GR) University of Hawaii (U.H.) United States (USA) (US) Hospital Monte Naranco Spain (ES) Hospital Universitario La Paz Spain (ES) Centre Georges François Leclerc (UNICANCER) France (FR) Centre hospitalier universitaire de Québec Canada (CA) University of California Irvine United States (USA) (US) The University of Melbourne Australia (AU) Vanderbilt University United States (USA) (US) Cogentech Italy (IT) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) Italy (IT) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Leiden University Netherlands (NL) Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA) Germany (DE) Evangelische Kliniken Bonn gGmbH Germany (DE) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam Netherlands (NL) Erasmus University Medical Center (MC) Netherlands (NL) National Cancer Institute (NCI) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) University of Oxford United Kingdom (GB) University Hospital Galway Ireland (IE) Ruprecht-Karls-Universität Heidelberg Germany (DE) University of Southampton United Kingdom (GB) The Alfred Hospital Australia (AU) London School of Hygiene and Tropical Medicine United Kingdom (GB) Antoni van Leeuwenhoek Netherlands (NL) Städtisches Klinikum Karlsruhe Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) City of Hope Medical Center United States (USA) (US) Krebsregister Saarland / Saarland Cancer Registry Germany (DE) Westmead Institute for Medical Research Australia (AU) IFOM - FIRC Institute of Molecular Oncology Italy (IT) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Robert-Bosch-Krankenhaus Germany (DE) King’s College London United Kingdom (GB)

How to cite

APA:

Purrington, K.S., Slettedahl, S., Bolla, M.K., Michailidou, K., Czene, K., Nevanlinna, H.,... Couch, F.J. (2014). Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade. Human Molecular Genetics, 23(22), 6034-46. https://doi.org/10.1093/hmg/ddu300

MLA:

Purrington, Kristen S., et al. "Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade." Human Molecular Genetics 23.22 (2014): 6034-46.

BibTeX: Download