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

The GENICA Network; The GENICA Network; The GENICA Network; The GENICA Network; ABCTB Investigators; kConFab Investigators; The GENICA Network; The GENICA Network; The GENICA Network

doi:10.1093/hmg/ddu300

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

The GENICA Network
, The GENICA Network
, The GENICA Network
, The GENICA Network
, ABCTB Investigators
, kConFab Investigators
, The GENICA Network
, The GENICA Network
, The GENICA Network

Instituto de Genética Humana

Institute of Pathology
University of Bonn
Institute of Occupational Medicine and Maritime Medicine
University of Hamburg
University of Tübingen
Westmead Millennium Institute for Medical Research
Peter Maccallum Cancer Centre
Molecular Genetics of Breast Cancer
German Cancer Research Center
Ruhr University Bochum
Department of Internal Medicine
Evangelical Clinics of Bonn
Mayo Clinic Rochester, MN
Wayne State University
Centre for Cancer Genetic Epidemiology
Department of Medical Epidemiology and Biostatistics
University of Helsinki
Copenhagen University Hospital – Herlev and Gentofte
Cancer Care Ontario
University of Toronto
University of Sheffield
Heidelberg University
University of California, Irvine
Demokritos National Centre for Scientific Research
Keck School of Medicine of USC
Friedrich-Alexander University Erlangen-Nürnberg
University of California at Los Angeles
University of Eastern Finland
Imaging Center
University of Oulu
Division of Clinical Epidemiology and Aging Research
Department of Molecular Medicine and Surgery
Queensland Institute of Medical Research
Centro de Investigación en Red de Enfermedades Raras
Centre for Biomedical Research on Rare Diseases (CIBERER)
Institute of Cancer Research
University of Oslo
National Institute of Health Bogotá
Occupational and Social Determinants of Health
Technical University of Munich
University Health Network
Prosserman Centre for Population Health Research
Genome Institute of Singapore
Hunter Area Pathology Service
Hospital Universitario La Paz
Aristotle University of Thessaloniki
University of Hawaii Cancer Center
Oulu University Hospital
Saarland Cancer Registry
Karolinska Institutet
National Breast Cancer Foundation Cancer
Research Center
McGill University Health Centre, Royal Victoria Hospital
McGill University
Hospital Monte Naranco
Centre Georges-François Leclerc
Centre Eugène Marquis Rennes
German Red Cross Blood Service of Baden-Wurttemberg-Hessen
Ohio State University
Roswell Park Cancer Institute
University of Montreal
Université Laval Research Center
Melbourne School of Population and Global Health
University of Melbourne
Vanderbilt University
Cogentech Cancer Genetic Test Laboratory
FIRC Institute of Molecular Oncology
European Institute of Oncology
University of Szczecin
Leiden University
Erasmus University Rotterdam
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA)
University Hospital Galway
University of Southampton, Faculty of Medicine
Alfred Health
Cancer Council Victoria
London School of Hygiene and Tropical Medicine
Antoni van Leeuwenhoek Hospital
Division of Molecular Genetic Epidemiology
Lund University
Städtischen Klinikum Karlsruhe
Division of Cancer Epidemiology
University Hospitals Leuven
KU Leuven
Flanders Institute for Biotechnology
University of Cambridge
Beckman Research Institute of City of Hope
Hannover Medical School
IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
Guy’s Hospital

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12 Citas (Scopus)

Resumen

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 = 39067 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% C11.041.11, P = 8.7 × 10^-6) were significantly associated with risk of low-grade breast cancer. The TACC2signal was retained (rs17550038: OR = 1.15, 95% C11.07-1.23, P = 7.9 × 10^-5) after adjustment for breast cancer risk SNPs in the nearby FGFR2gene, 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.

Idioma original	Inglés
Páginas (desde-hasta)	6034-6046
Número de páginas	13
Publicación	Human Molecular Genetics
Volumen	23
N.º	22
DOI	https://doi.org/10.1093/hmg/ddu300
Estado	Publicada - 15 nov. 2014

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@article{5951c68f3a8e4368a2b1898d1b84f44b,

title = "Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade",

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 = 39067 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\% C11.041.11, P = 8.7 × 10-6) were significantly associated with risk of low-grade breast cancer. The TACC2signal was retained (rs17550038: OR = 1.15, 95\% C11.07-1.23, P = 7.9 × 10-5) after adjustment for breast cancer risk SNPs in the nearby FGFR2gene, 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.",

author = "\{The GENICA Network\} and \{The GENICA Network\} and \{The GENICA Network\} and \{The GENICA Network\} and \{ABCTB Investigators\} and \{kConFab Investigators\} and \{The GENICA Network\} and \{The GENICA Network\} and \{The GENICA Network\} and Purrington, \{Kristen S.\} and Seth Slettedahl and Bolla, \{Manjeet K.\} and Kyriaki Michailidou and Kamila Czene and Heli Nevanlinna and Bojesen, \{Stig E.\} and Andrulis, \{Irene L.\} and Angela Cox and Per Hall and Jane Carpenter and Drakoulis Yannoukakos and \{A. Haiman\}, Christopher and Fasching, \{Peter A.\} and Arto Mannermaa and Robert Winqvist and Hermann Brenner and Annika Lindblom and Georgia Chenevix-Trench and Javier Benitez and Anthony Swerdlow and Vessela Kristensen and Pascal Gu{\'e}nel and Alfons Meindl and Hatef Darabi and Mikael Eriksson and Rainer Fagerholm and Kristiina Aittomaki and Carl Blomqvist and Nordestgaard, \{B{\o}rge G.\} and Nielsen, \{Sune F.\} and Henrik Flyger and Xianshu Wang and Curtis Olswold and Olson, \{Janet E.\} and Mulligan, \{Anna Marie\} and Knight, \{Julia A.\} and Sandrine Tchatchou and Reed, \{Malcolm W.R.\} and Cross, \{Simon S.\} and Jianjun Liu and Jingmei Li and Keith Humphreys and Christine Clarke and Rodney Scott and Rosemary Balleine and Robert Baxter and Stephen Braye and Jane Dahlstrom and Diana Torres",

note = "Publisher Copyright: {\textcopyright} Published by Oxford University Press 2014.",

year = "2014",

month = nov,

day = "15",

doi = "10.1093/hmg/ddu300",

language = "English",

volume = "23",

pages = "6034--6046",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "22",

}

The GENICA Network, The GENICA Network, The GENICA Network, The GENICA Network, ABCTB Investigators, kConFab Investigators, The GENICA Network, The GENICA Network & The GENICA Network 2014, 'Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade', Human Molecular Genetics, vol. 23, n.º 22, pp. 6034-6046. https://doi.org/10.1093/hmg/ddu300

TY - JOUR

T1 - Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

AU - The GENICA Network

AU - ABCTB Investigators

AU - kConFab Investigators

AU - The GENICA Network

AU - Purrington, Kristen S.

AU - Slettedahl, Seth

AU - Bolla, Manjeet K.

AU - Michailidou, Kyriaki

AU - Czene, Kamila

AU - Nevanlinna, Heli

AU - Bojesen, Stig E.

AU - Andrulis, Irene L.

AU - Cox, Angela

AU - Hall, Per

AU - Carpenter, Jane

AU - Yannoukakos, Drakoulis

AU - A. Haiman, Christopher

AU - Fasching, Peter A.

AU - Mannermaa, Arto

AU - Winqvist, Robert

AU - Brenner, Hermann

AU - Lindblom, Annika

AU - Chenevix-Trench, Georgia

AU - Benitez, Javier

AU - Swerdlow, Anthony

AU - Kristensen, Vessela

AU - Guénel, Pascal

AU - Meindl, Alfons

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Fagerholm, Rainer

AU - Aittomaki, Kristiina

AU - Blomqvist, Carl

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F.

AU - Flyger, Henrik

AU - Wang, Xianshu

AU - Olswold, Curtis

AU - Olson, Janet E.

AU - Mulligan, Anna Marie

AU - Knight, Julia A.

AU - Tchatchou, Sandrine

AU - Reed, Malcolm W.R.

AU - Cross, Simon S.

AU - Liu, Jianjun

AU - Li, Jingmei

AU - Humphreys, Keith

AU - Clarke, Christine

AU - Scott, Rodney

AU - Balleine, Rosemary

AU - Baxter, Robert

AU - Braye, Stephen

AU - Dahlstrom, Jane

AU - Torres, Diana

PY - 2014/11/15

Y1 - 2014/11/15

N2 - 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 = 39067 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% C11.041.11, P = 8.7 × 10-6) were significantly associated with risk of low-grade breast cancer. The TACC2signal was retained (rs17550038: OR = 1.15, 95% C11.07-1.23, P = 7.9 × 10-5) after adjustment for breast cancer risk SNPs in the nearby FGFR2gene, 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.

AB - 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 = 39067 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% C11.041.11, P = 8.7 × 10-6) were significantly associated with risk of low-grade breast cancer. The TACC2signal was retained (rs17550038: OR = 1.15, 95% C11.07-1.23, P = 7.9 × 10-5) after adjustment for breast cancer risk SNPs in the nearby FGFR2gene, 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.

UR - https://www.scopus.com/pages/publications/84911431178

U2 - 10.1093/hmg/ddu300

DO - 10.1093/hmg/ddu300

M3 - Article

C2 - 24927736

AN - SCOPUS:84911431178

SN - 0964-6906

VL - 23

SP - 6034

EP - 6046

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 22

ER -

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

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