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

Journal article


Publication Details

Author(s): 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
Journal: Human Molecular Genetics
Publication year: 2014
Volume: 23
Journal issue: 22
Pages range: 6034-46
ISSN: 0964-6906


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.



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
Hartmann, Arndt Prof. Dr. med.
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie


External institutions with authors

Antoni van Leeuwenhoek
Aristotle University of Thessaloniki
Australian Breast Cancer Tissue Bank
Centre Eugène Marquis
Centre Georges François Leclerc (UNICANCER)
Centre hospitalier universitaire de Québec
City of Hope Medical Center
Cogentech
Copenhagen University Hospital
Deutsches Krebsforschungszentrum (DKFZ)
DRK-Blutspendedienst Baden-Württemberg - Hessen / German Red Cross Blood Donor Service Baden-Wuerttemberg – Hessen
Erasmus University Medical Center
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
European Institute of Oncology / Istituto Europeo di Oncologia (IEO)
Evangelische Kliniken Bonn gGmbH
Fondazione IRCCS: Istituto Nazionale dei Tumori
Genome Institute of Singapore
Helsingin yliopisto / University of Helsinki
Hospital Monte Naranco
Hospital Universitario La Paz
Hunter Area Pathology Service
IFOM - FIRC Institute of Molecular Oncology
Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA)
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
King’s College London
Krebsregister Saarland / Saarland Cancer Registry
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
Mount Sinai Hospital (MSH)
National Cancer Institute (NCI)
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)
Ohio State University
Oslo University Hospital / Oslo Universitetssykehus
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)
Robert-Bosch-Krankenhaus
Roswell Park Cancer Institute
Ruprecht-Karls-Universität Heidelberg
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
Städtisches Klinikum Karlsruhe
Technische Universität München (TUM)
The Alfred Hospital
The University of Melbourne
Universitätsklinikum Hamburg-Eppendorf (UKE)
Université de Montréal
University Hospital Galway
University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven
University of California Irvine
University of Cambridge
University of Copenhagen
University of Eastern Finland
University of Hawaii (U.H.)
University of Oxford
University of Sheffield
University of Southampton
University of Southern California (USC)
University of Sydney
University of Toronto
Vanderbilt University
Westmead Institute for Medical Research


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://dx.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: 

Last updated on 2019-20-07 at 07:18