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

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	6034-6046
Number of pages	13
Journal	Human Molecular Genetics
Volume	23
Issue number	22
DOIs	https://doi.org/10.1093/hmg/ddu300
Publication status	Published - 15 Nov 2014
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/hmg/ddu300

Cite this

@article{f94c71605b384dbabaab7d58d9a21447,

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 John Forbes and Soon Lee and Debbie Marsh and Adrienne Morey and Nirmala Pathmanathan and Allan Spigelman and Nicholas Wilcken and Desmond Yip and Silke Landrith and Sonja Oeser and Matthias R{\"u}bner and Eileen Williams and Elaine Ryder-Mills and Kara Sargus and Gabrielle Colleran and Andrew Rowan and Angela Jones and Andersen, {Dorthe Uldall} and Arnadottir, {Maria Birna} and Anne Bank and Dorthe Kjeldg{\aa}rd and Hansenguillermo Pita and Charo Alonso and Daniel Herrero and Nuria {\'A}lvarez and Zamora, {M. Pilar} and Primitiva Menendez and James Lacey and Sophia Wang and Huiyan Ma and Yani Lu and Jessica Clague and Dennis Deapen and Rich Pinder and Eunjung Lee and Fred Schumacher and Pam Horn-Ross and Peggy Reynolds and David Nelson and Hartwig Ziegler and Sonja Wolf and Volker Hermann and Heide Hellebrand and Stefanie Engert and Florentia Fostira and George Fountzilas and Irene Konstantopoulou and Henderson, {Brian E.} and {Le Marchand}, Loic and Kerin, {Michael J.} and Nicola Miller",

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, no. 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 - Forbes, John

AU - Lee, Soon

AU - Marsh, Debbie

AU - Morey, Adrienne

AU - Pathmanathan, Nirmala

AU - Spigelman, Allan

AU - Wilcken, Nicholas

AU - Yip, Desmond

AU - Landrith, Silke

AU - Oeser, Sonja

AU - Rübner, Matthias

AU - Williams, Eileen

AU - Ryder-Mills, Elaine

AU - Sargus, Kara

AU - Colleran, Gabrielle

AU - Rowan, Andrew

AU - Jones, Angela

AU - Andersen, Dorthe Uldall

AU - Arnadottir, Maria Birna

AU - Bank, Anne

AU - Kjeldgård, Dorthe

AU - Pita, Hansenguillermo

AU - Alonso, Charo

AU - Herrero, Daniel

AU - Álvarez, Nuria

AU - Zamora, M. Pilar

AU - Menendez, Primitiva

AU - Lacey, James

AU - Wang, Sophia

AU - Ma, Huiyan

AU - Lu, Yani

AU - Clague, Jessica

AU - Deapen, Dennis

AU - Pinder, Rich

AU - Lee, Eunjung

AU - Schumacher, Fred

AU - Horn-Ross, Pam

AU - Reynolds, Peggy

AU - Nelson, David

AU - Ziegler, Hartwig

AU - Wolf, Sonja

AU - Hermann, Volker

AU - Hellebrand, Heide

AU - Engert, Stefanie

AU - Fostira, Florentia

AU - Fountzilas, George

AU - Konstantopoulou, Irene

AU - Henderson, Brian E.

AU - Le Marchand, Loic

AU - Kerin, Michael J.

AU - Miller, Nicola

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 - http://www.scopus.com/inward/record.url?scp=84911431178&partnerID=8YFLogxK

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

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this