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

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 & 132 others 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. 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. 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 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. Pharoah, Alison M. Dunning, Douglas F. Easton, Ute Hamann

Research output: Contribution to journalArticle

Abstract

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 fixedeffects 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.

Original languageEnglish (US)
Pages (from-to)256-271
Number of pages16
JournalCarcinogenesis
Volume36
Issue number2
DOIs
StatePublished - Aug 20 2014
Externally publishedYes

Fingerprint

Centromere
Estrogen Receptors
Single Nucleotide Polymorphism
Breast Neoplasms
Alleles
Odds Ratio
Confidence Intervals
Proteins
Genes
3' Untranslated Regions
Cell Division
Meta-Analysis
Case-Control Studies
Exons
Genome
Population
Neoplasms

ASJC Scopus subject areas

  • Cancer Research

Cite this

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

In: Carcinogenesis, Vol. 36, No. 2, 20.08.2014, p. 256-271.

Research output: Contribution to journalArticle

Kabisch, M, Bermejo, JL, Dünnebier, T, Ying, S, Michailidou, K, Bolla, MK, Wang, Q, Dennis, J, Shah, M, Perkins, BJ, Czene, K, Darabi, H, Eriksson, M, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Lambrechts, D, Neven, P, Peeters, S, Weltens, C, Couch, FJ, Olson, JE, Wang, X, Purrington, K, Chang-Claude, J, Rudolph, A, Seibold, P, Flesch-Janys, D, Peto, J, dos-Santos-Silva, I, Johnson, N, Fletcher, O, Nevanlinna, H, Muranen, TA, Aittomäki, K, Blomqvist, C, Schmidt, MK, Broeks, A, Cornelissen, S, Hogervorst, FB, Li, J, Brand, JS, Humphreys, K, Guénel, P, Truong, T, Menegaux, F, Sanchez, M, Burwinkel, B, Marmé, F, Yang, R, Bugert, P, González-Neira, A, Benitez, J, Pilar Zamora, M, Arias Perez, JI, Cox, A, Cross, SS, Reed, MW, Andrulis, IL, Knight, JA, Glendon, G, Tchatchou, S, Sawyer, EJ, Tomlinson, I, Kerin, MJ, Miller, N, Haiman, CA, Schumacher, F, Henderson, BE, Marchand, LL, Lindblom, A, Margolin, S, Hooning, MJ, Hollestelle, A, Kriege, M, Koppert, LB, Hopper, JL, Southey, MC, Tsimiklis, H, Apicella, C, Slettedahl, S, Toland, AE, Vachon, C, Yannoukakos, D, Giles, GG, Milne, RL, McLean, C, Fasching, PA, Ruebner, M, Ekici, AB, Beckmann, MW, Brenner, H, Dieffenbach, AK, Arndt, V, Stegmaier, C, Ashworth, A, Orr, N, Schoemaker, MJ, Swerdlow, A, García-Closas, M, Figueroa, J, Chanock, SJ, Lissowska, J, Goldberg, MS, Labrèche, F, Dumont, M, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Brauch, H, Brüning, T, Ko, YD, Radice, P, Peterlongo, P, Scuvera, G, Fortuzzi, S, Bogdanova, N, Dörk, T, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Devilee, P, Tollenaar, RAM, Seynaeve, C, Van Asperen, CJ, Jakubowska, A, Lubinski, J, Jaworska-Bieniek, K, Durda, K, Zheng, W, Shrubsole, MJ, Cai, Q, Torres, D, Anton-Culver, H, Kristensen, V, Bacot, F, Tessier, DC, Vincent, D, Luccarini, C, Baynes, C, Ahmed, S, Maranian, M, Simard, J, Chenevix-Trench, G, Hall, P, Pharoah, PD, Dunning, AM, Easton, DF & Hamann, U 2014, 'Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer', Carcinogenesis, vol. 36, no. 2, pp. 256-271. https://doi.org/10.1093/carcin/bgu326
Kabisch, Maria ; Bermejo, Justo Lorenzo ; Dünnebier, Thomas ; Ying, Shibo ; Michailidou, Kyriaki ; Bolla, Manjeet K. ; Wang, Qin ; Dennis, Joe ; Shah, Mitul ; Perkins, Barbara J. ; Czene, Kamila ; Darabi, Hatef ; Eriksson, Mikael ; Bojesen, Stig E. ; Nordestgaard, Børge G. ; Nielsen, Sune F. ; Flyger, Henrik ; Lambrechts, Diether ; Neven, Patrick ; Peeters, Stephanie ; Weltens, Caroline ; Couch, Fergus J. ; Olson, Janet E. ; Wang, Xianshu ; Purrington, Kristen ; Chang-Claude, Jenny ; Rudolph, Anja ; Seibold, Petra ; Flesch-Janys, Dieter ; Peto, Julian ; dos-Santos-Silva, Isabel ; Johnson, Nichola ; Fletcher, Olivia ; Nevanlinna, Heli ; Muranen, Taru A. ; Aittomäki, Kristiina ; Blomqvist, Carl ; Schmidt, Marjanka K. ; Broeks, Annegien ; Cornelissen, Sten ; Hogervorst, Frans B. ; Li, Jingmei ; Brand, Judith S. ; Humphreys, Keith ; Guénel, Pascal ; Truong, Thérèse ; Menegaux, Florence ; Sanchez, Marie ; Burwinkel, Barbara ; Marmé, Frederik ; Yang, Rongxi ; Bugert, Peter ; González-Neira, Anna ; Benitez, Javier ; Pilar Zamora, M. ; Arias Perez, Jose I. ; Cox, Angela ; Cross, Simon S. ; Reed, Malcolm W. ; Andrulis, Irene L. ; Knight, Julia A. ; Glendon, Gord ; Tchatchou, Sandrine ; Sawyer, Elinor J. ; Tomlinson, Ian ; Kerin, Michael J. ; Miller, Nicola ; Haiman, Christopher A. ; Schumacher, Fredrick ; Henderson, Brian E. ; Marchand, Loic Le ; Lindblom, Annika ; Margolin, Sara ; Hooning, Maartje J. ; Hollestelle, Antoinette ; Kriege, Mieke ; Koppert, Linetta B. ; Hopper, John L. ; Southey, Melissa C. ; Tsimiklis, Helen ; Apicella, Carmel ; Slettedahl, Seth ; Toland, Amanda E. ; Vachon, Celine ; Yannoukakos, Drakoulis ; Giles, Graham G. ; Milne, Roger L. ; McLean, Catriona ; Fasching, Peter A. ; Ruebner, Matthias ; Ekici, Arif B. ; Beckmann, Matthias W. ; Brenner, Hermann ; Dieffenbach, Aida K. ; Arndt, Volker ; Stegmaier, Christa ; Ashworth, Alan ; Orr, Nicholas ; Schoemaker, Minouk J. ; Swerdlow, Anthony ; García-Closas, Montserrat ; Figueroa, Jonine ; Chanock, Stephen J. ; Lissowska, Jolanta ; Goldberg, Mark S. ; Labrèche, France ; Dumont, Martine ; Winqvist, Robert ; Pylkäs, Katri ; Jukkola-Vuorinen, Arja ; Grip, Mervi ; Brauch, Hiltrud ; Brüning, Thomas ; Ko, Yon Dschun ; Radice, Paolo ; Peterlongo, Paolo ; Scuvera, Giulietta ; Fortuzzi, Stefano ; Bogdanova, Natalia ; Dörk, Thilo ; Mannermaa, Arto ; Kataja, Vesa ; Kosma, Veli Matti ; Hartikainen, Jaana M. ; Devilee, Peter ; Tollenaar, Robert A M ; Seynaeve, Caroline ; Van Asperen, Christi J. ; Jakubowska, Anna ; Lubinski, Jan ; Jaworska-Bieniek, Katarzyna ; Durda, Katarzyna ; Zheng, Wei ; Shrubsole, Martha J. ; Cai, Qiuyin ; Torres, Diana ; Anton-Culver, Hoda ; Kristensen, Vessela ; Bacot, François ; Tessier, Daniel C. ; Vincent, Daniel ; Luccarini, Craig ; Baynes, Caroline ; Ahmed, Shahana ; Maranian, Mel ; Simard, Jacques ; Chenevix-Trench, Georgia ; Hall, Per ; Pharoah, Paul D. ; Dunning, Alison M. ; Easton, Douglas F. ; Hamann, Ute. / Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer. In: Carcinogenesis. 2014 ; Vol. 36, No. 2. pp. 256-271.
@article{2292dde89d004e1d9779b063515544f8,
title = "Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer",
abstract = "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 fixedeffects 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.",
author = "Maria Kabisch and Bermejo, {Justo Lorenzo} and Thomas D{\"u}nnebier and Shibo Ying and Kyriaki Michailidou and Bolla, {Manjeet K.} and Qin Wang and Joe Dennis and Mitul Shah and Perkins, {Barbara J.} and Kamila Czene and Hatef Darabi and Mikael Eriksson and Bojesen, {Stig E.} and Nordestgaard, {B{\o}rge G.} and Nielsen, {Sune F.} and Henrik Flyger and Diether Lambrechts and Patrick Neven and Stephanie Peeters and Caroline Weltens and Couch, {Fergus J.} and Olson, {Janet E.} and Xianshu Wang and Kristen Purrington and Jenny Chang-Claude and Anja Rudolph and Petra Seibold and Dieter Flesch-Janys and Julian Peto and Isabel dos-Santos-Silva and Nichola Johnson and Olivia Fletcher and Heli Nevanlinna and Muranen, {Taru A.} and Kristiina Aittom{\"a}ki and Carl Blomqvist and Schmidt, {Marjanka K.} and Annegien Broeks and Sten Cornelissen and Hogervorst, {Frans B.} and Jingmei Li and Brand, {Judith S.} and Keith Humphreys and Pascal Gu{\'e}nel and Th{\'e}r{\`e}se Truong and Florence Menegaux and Marie Sanchez and Barbara Burwinkel and Frederik Marm{\'e} and Rongxi Yang and Peter Bugert and Anna Gonz{\'a}lez-Neira and Javier Benitez and {Pilar Zamora}, M. and {Arias Perez}, {Jose I.} and Angela Cox and Cross, {Simon S.} and Reed, {Malcolm W.} and Andrulis, {Irene L.} and Knight, {Julia A.} and Gord Glendon and Sandrine Tchatchou and Sawyer, {Elinor J.} and Ian Tomlinson and Kerin, {Michael J.} and Nicola Miller and Haiman, {Christopher A.} and Fredrick Schumacher and Henderson, {Brian E.} and Marchand, {Loic Le} and Annika Lindblom and Sara Margolin and Hooning, {Maartje J.} and Antoinette Hollestelle and Mieke Kriege and Koppert, {Linetta B.} and Hopper, {John L.} and Southey, {Melissa C.} and Helen Tsimiklis and Carmel Apicella and Seth Slettedahl and Toland, {Amanda E.} and Celine Vachon and Drakoulis Yannoukakos and Giles, {Graham G.} and Milne, {Roger L.} and Catriona McLean and Fasching, {Peter A.} and Matthias Ruebner and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Hermann Brenner and Dieffenbach, {Aida K.} and Volker Arndt and Christa Stegmaier and Alan Ashworth and Nicholas Orr and Schoemaker, {Minouk J.} and Anthony Swerdlow and Montserrat Garc{\'i}a-Closas and Jonine Figueroa and Chanock, {Stephen J.} and Jolanta Lissowska and Goldberg, {Mark S.} and France Labr{\`e}che and Martine Dumont and Robert Winqvist and Katri Pylk{\"a}s and Arja Jukkola-Vuorinen and Mervi Grip and Hiltrud Brauch and Thomas Br{\"u}ning and Ko, {Yon Dschun} and Paolo Radice and Paolo Peterlongo and Giulietta Scuvera and Stefano Fortuzzi and Natalia Bogdanova and Thilo D{\"o}rk and Arto Mannermaa and Vesa Kataja and Kosma, {Veli Matti} and Hartikainen, {Jaana M.} and Peter Devilee and Tollenaar, {Robert A M} and Caroline Seynaeve and {Van Asperen}, {Christi J.} and Anna Jakubowska and Jan Lubinski and Katarzyna Jaworska-Bieniek and Katarzyna Durda and Wei Zheng and Shrubsole, {Martha J.} and Qiuyin Cai and Diana Torres and Hoda Anton-Culver and Vessela Kristensen and Fran{\cc}ois Bacot and Tessier, {Daniel C.} and Daniel Vincent and Craig Luccarini and Caroline Baynes and Shahana Ahmed and Mel Maranian and Jacques Simard and Georgia Chenevix-Trench and Per Hall and Pharoah, {Paul D.} and Dunning, {Alison M.} and Easton, {Douglas F.} and Ute Hamann",
year = "2014",
month = "8",
day = "20",
doi = "10.1093/carcin/bgu326",
language = "English (US)",
volume = "36",
pages = "256--271",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer

AU - Kabisch, Maria

AU - Bermejo, Justo Lorenzo

AU - Dünnebier, Thomas

AU - Ying, Shibo

AU - Michailidou, Kyriaki

AU - Bolla, Manjeet K.

AU - Wang, Qin

AU - Dennis, Joe

AU - Shah, Mitul

AU - Perkins, Barbara J.

AU - Czene, Kamila

AU - Darabi, Hatef

AU - Eriksson, Mikael

AU - Bojesen, Stig E.

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F.

AU - Flyger, Henrik

AU - Lambrechts, Diether

AU - Neven, Patrick

AU - Peeters, Stephanie

AU - Weltens, Caroline

AU - Couch, Fergus J.

AU - Olson, Janet E.

AU - Wang, Xianshu

AU - Purrington, Kristen

AU - Chang-Claude, Jenny

AU - Rudolph, Anja

AU - Seibold, Petra

AU - Flesch-Janys, Dieter

AU - Peto, Julian

AU - dos-Santos-Silva, Isabel

AU - Johnson, Nichola

AU - Fletcher, Olivia

AU - Nevanlinna, Heli

AU - Muranen, Taru A.

AU - Aittomäki, Kristiina

AU - Blomqvist, Carl

AU - Schmidt, Marjanka K.

AU - Broeks, Annegien

AU - Cornelissen, Sten

AU - Hogervorst, Frans B.

AU - Li, Jingmei

AU - Brand, Judith S.

AU - Humphreys, Keith

AU - Guénel, Pascal

AU - Truong, Thérèse

AU - Menegaux, Florence

AU - Sanchez, Marie

AU - Burwinkel, Barbara

AU - Marmé, Frederik

AU - Yang, Rongxi

AU - Bugert, Peter

AU - González-Neira, Anna

AU - Benitez, Javier

AU - Pilar Zamora, M.

AU - Arias Perez, Jose I.

AU - Cox, Angela

AU - Cross, Simon S.

AU - Reed, Malcolm W.

AU - Andrulis, Irene L.

AU - Knight, Julia A.

AU - Glendon, Gord

AU - Tchatchou, Sandrine

AU - Sawyer, Elinor J.

AU - Tomlinson, Ian

AU - Kerin, Michael J.

AU - Miller, Nicola

AU - Haiman, Christopher A.

AU - Schumacher, Fredrick

AU - Henderson, Brian E.

AU - Marchand, Loic Le

AU - Lindblom, Annika

AU - Margolin, Sara

AU - Hooning, Maartje J.

AU - Hollestelle, Antoinette

AU - Kriege, Mieke

AU - Koppert, Linetta B.

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Tsimiklis, Helen

AU - Apicella, Carmel

AU - Slettedahl, Seth

AU - Toland, Amanda E.

AU - Vachon, Celine

AU - Yannoukakos, Drakoulis

AU - Giles, Graham G.

AU - Milne, Roger L.

AU - McLean, Catriona

AU - Fasching, Peter A.

AU - Ruebner, Matthias

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Brenner, Hermann

AU - Dieffenbach, Aida K.

AU - Arndt, Volker

AU - Stegmaier, Christa

AU - Ashworth, Alan

AU - Orr, Nicholas

AU - Schoemaker, Minouk J.

AU - Swerdlow, Anthony

AU - García-Closas, Montserrat

AU - Figueroa, Jonine

AU - Chanock, Stephen J.

AU - Lissowska, Jolanta

AU - Goldberg, Mark S.

AU - Labrèche, France

AU - Dumont, Martine

AU - Winqvist, Robert

AU - Pylkäs, Katri

AU - Jukkola-Vuorinen, Arja

AU - Grip, Mervi

AU - Brauch, Hiltrud

AU - Brüning, Thomas

AU - Ko, Yon Dschun

AU - Radice, Paolo

AU - Peterlongo, Paolo

AU - Scuvera, Giulietta

AU - Fortuzzi, Stefano

AU - Bogdanova, Natalia

AU - Dörk, Thilo

AU - Mannermaa, Arto

AU - Kataja, Vesa

AU - Kosma, Veli Matti

AU - Hartikainen, Jaana M.

AU - Devilee, Peter

AU - Tollenaar, Robert A M

AU - Seynaeve, Caroline

AU - Van Asperen, Christi J.

AU - Jakubowska, Anna

AU - Lubinski, Jan

AU - Jaworska-Bieniek, Katarzyna

AU - Durda, Katarzyna

AU - Zheng, Wei

AU - Shrubsole, Martha J.

AU - Cai, Qiuyin

AU - Torres, Diana

AU - Anton-Culver, Hoda

AU - Kristensen, Vessela

AU - Bacot, François

AU - Tessier, Daniel C.

AU - Vincent, Daniel

AU - Luccarini, Craig

AU - Baynes, Caroline

AU - Ahmed, Shahana

AU - Maranian, Mel

AU - Simard, Jacques

AU - Chenevix-Trench, Georgia

AU - Hall, Per

AU - Pharoah, Paul D.

AU - Dunning, Alison M.

AU - Easton, Douglas F.

AU - Hamann, Ute

PY - 2014/8/20

Y1 - 2014/8/20

N2 - 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 fixedeffects 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.

AB - 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 fixedeffects 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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U2 - 10.1093/carcin/bgu326

DO - 10.1093/carcin/bgu326

M3 - Article

VL - 36

SP - 256

EP - 271

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 2

ER -