Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer
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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; Lorenzo Bermejo, Justo; 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 L; 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 R; 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; Le Marchand, Loic; 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 E 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 P; Dunning, Alison M; Easton, Douglas F; Hamann, Ute; KConFab Investigators.
in: CARCINOGENESIS, Jahrgang 36, Nr. 2, 13.01.2015, S. 256-71.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 - Lorenzo Bermejo, Justo
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 L
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 R
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 - Le Marchand, Loic
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 E 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 P
AU - Dunning, Alison M
AU - Easton, Douglas F
AU - Hamann, Ute
AU - KConFab Investigators
AU - Harth, Volker
N1 - © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
PY - 2015/1/13
Y1 - 2015/1/13
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 fixed-effects 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 fixed-effects 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.
KW - 3' Untranslated Regions
KW - Aurora Kinase B
KW - Breast Neoplasms
KW - Case-Control Studies
KW - Cell Cycle Proteins
KW - Chromosomal Proteins, Non-Histone
KW - European Continental Ancestry Group
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Inhibitor of Apoptosis Proteins
KW - Polymorphism, Single Nucleotide
KW - Receptors, Estrogen
KW - Risk
U2 - 10.1093/carcin/bgu326
DO - 10.1093/carcin/bgu326
M3 - SCORING: Journal article
C2 - 25586992
VL - 36
SP - 256
EP - 271
JO - CARCINOGENESIS
JF - CARCINOGENESIS
SN - 0143-3334
IS - 2
ER -