Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade
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Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade. / Purrington, Kristen S; Slettedahl, Seth; Bolla, Manjeet K; Michailidou, Kyriaki; Czene, Kamila; Nevanlinna, Heli; Bojesen, Stig E; Andrulis, Irene L; Cox, Angela; Hall, Per; Carpenter, Jane; Yannoukakos, Drakoulis; Haiman, Christopher A; Fasching, Peter A; Mannermaa, Arto; Winqvist, Robert; Brenner, Hermann; Lindblom, Annika; Chenevix-Trench, Georgia; Benitez, Javier; Swerdlow, Anthony; Kristensen, Vessela; Guénel, Pascal; Meindl, Alfons; Darabi, Hatef; Eriksson, Mikael; Fagerholm, Rainer; Aittomäki, Kristiina; Blomqvist, Carl; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Wang, Xianshu; Olswold, Curtis; Olson, Janet E; Mulligan, Anna Marie; Knight, Julia A; Tchatchou, Sandrine; Reed, Malcolm W R; Cross, Simon S; Liu, Jianjun; Li, Jingmei; Humphreys, Keith; Clarke, Christine; Scott, Rodney; Fostira, Florentia; Fountzilas, George; Konstantopoulou, Irene; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Ekici, Arif B; Hartmann, Arndt; Beckmann, Matthias W; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Jukkola-Vuorinen, Arja; Pylkäs, Katri; Kauppila, Saila; Dieffenbach, Aida Karina; Stegmaier, Christa; Arndt, Volker; Margolin, Sara; Balleine, Rosemary; Arias Perez, Jose Ignacio; Pilar Zamora, M; Menéndez, Primitiva; Ashworth, Alan; Jones, Michael; Orr, Nick; Arveux, Patrick; Kerbrat, Pierre; Truong, Thérèse; Bugert, Peter; Toland, Amanda E; Ambrosone, Christine B; Labrèche, France; Goldberg, Mark S; Dumont, Martine; Ziogas, Argyrios; Lee, Eunjung; Dite, Gillian S; Apicella, Carmel; Southey, Melissa C; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Ficarazzi, Filomena; Barile, Monica; Peterlongo, Paolo; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Tollenaar, Robert A E M; Seynaeve, Caroline; Brüning, Thomas; Ko, Yon-Dschun; Van Deurzen, Carolien H M; Martens, John W M; Kriege, Mieke; Figueroa, Jonine D; Chanock, Stephen J; Lissowska, Jolanta; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Schneeweiss, Andreas; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Mclean, Catriona; Milne, Roger L; Baglietto, Laura; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Van'T Veer, Laura J; Cornelissen, Sten; Försti, Asta; Torres, Diana; Rüdiger, Thomas; Rudolph, Anja; Flesch-Janys, Dieter; Nickels, Stefan; Weltens, Caroline; Floris, Giuseppe; Moisse, Matthieu; Dennis, Joe; Wang, Qin; Dunning, Alison M; Shah, Mitul; Brown, Judith; Simard, Jacques; Anton-Culver, Hoda; Neuhausen, Susan L; Hopper, John L; Bogdanova, Natalia; Dörk, Thilo; Zheng, Wei; Radice, Paolo; Jakubowska, Anna; Lubinski, Jan; Devillee, Peter; Brauch, Hiltrud; Hooning, Maartje; García-Closas, Montserrat; Sawyer, Elinor; Burwinkel, Barbara; Marmee, Frederick; Eccles, Diana M; Giles, Graham G; Peto, Julian; Schmidt, Marjanka; Broeks, Annegien; Hamann, Ute; Chang-Claude, Jenny; Lambrechts, Diether; Pharoah, Paul D P; Easton, Douglas; Pankratz, V Shane; Slager, Susan; Vachon, Celine M; Couch, Fergus J; ABCTB Investigators.
in: HUM MOL GENET, Jahrgang 23, Nr. 22, 15.11.2014, S. 6034-46.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade
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 - Haiman, Christopher A
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 - Aittomäki, 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 - Fostira, Florentia
AU - Fountzilas, George
AU - Konstantopoulou, Irene
AU - Henderson, Brian E
AU - Schumacher, Fredrick
AU - Le Marchand, Loic
AU - Ekici, Arif B
AU - Hartmann, Arndt
AU - Beckmann, Matthias W
AU - Hartikainen, Jaana M
AU - Kosma, Veli-Matti
AU - Kataja, Vesa
AU - Jukkola-Vuorinen, Arja
AU - Pylkäs, Katri
AU - Kauppila, Saila
AU - Dieffenbach, Aida Karina
AU - Stegmaier, Christa
AU - Arndt, Volker
AU - Margolin, Sara
AU - Balleine, Rosemary
AU - Arias Perez, Jose Ignacio
AU - Pilar Zamora, M
AU - Menéndez, Primitiva
AU - Ashworth, Alan
AU - Jones, Michael
AU - Orr, Nick
AU - Arveux, Patrick
AU - Kerbrat, Pierre
AU - Truong, Thérèse
AU - Bugert, Peter
AU - Toland, Amanda E
AU - Ambrosone, Christine B
AU - Labrèche, France
AU - Goldberg, Mark S
AU - Dumont, Martine
AU - Ziogas, Argyrios
AU - Lee, Eunjung
AU - Dite, Gillian S
AU - Apicella, Carmel
AU - Southey, Melissa C
AU - Long, Jirong
AU - Shrubsole, Martha
AU - Deming-Halverson, Sandra
AU - Ficarazzi, Filomena
AU - Barile, Monica
AU - Peterlongo, Paolo
AU - Durda, Katarzyna
AU - Jaworska-Bieniek, Katarzyna
AU - Tollenaar, Robert A E M
AU - Seynaeve, Caroline
AU - Brüning, Thomas
AU - Ko, Yon-Dschun
AU - Van Deurzen, Carolien H M
AU - Martens, John W M
AU - Kriege, Mieke
AU - Figueroa, Jonine D
AU - Chanock, Stephen J
AU - Lissowska, Jolanta
AU - Tomlinson, Ian
AU - Kerin, Michael J
AU - Miller, Nicola
AU - Schneeweiss, Andreas
AU - Tapper, William J
AU - Gerty, Susan M
AU - Durcan, Lorraine
AU - Mclean, Catriona
AU - Milne, Roger L
AU - Baglietto, Laura
AU - dos Santos Silva, Isabel
AU - Fletcher, Olivia
AU - Johnson, Nichola
AU - Van'T Veer, Laura J
AU - Cornelissen, Sten
AU - Försti, Asta
AU - Torres, Diana
AU - Rüdiger, Thomas
AU - Rudolph, Anja
AU - Flesch-Janys, Dieter
AU - Nickels, Stefan
AU - Weltens, Caroline
AU - Floris, Giuseppe
AU - Moisse, Matthieu
AU - Dennis, Joe
AU - Wang, Qin
AU - Dunning, Alison M
AU - Shah, Mitul
AU - Brown, Judith
AU - Simard, Jacques
AU - Anton-Culver, Hoda
AU - Neuhausen, Susan L
AU - Hopper, John L
AU - Bogdanova, Natalia
AU - Dörk, Thilo
AU - Zheng, Wei
AU - Radice, Paolo
AU - Jakubowska, Anna
AU - Lubinski, Jan
AU - Devillee, Peter
AU - Brauch, Hiltrud
AU - Hooning, Maartje
AU - García-Closas, Montserrat
AU - Sawyer, Elinor
AU - Burwinkel, Barbara
AU - Marmee, Frederick
AU - Eccles, Diana M
AU - Giles, Graham G
AU - Peto, Julian
AU - Schmidt, Marjanka
AU - Broeks, Annegien
AU - Hamann, Ute
AU - Chang-Claude, Jenny
AU - Lambrechts, Diether
AU - Pharoah, Paul D P
AU - Easton, Douglas
AU - Pankratz, V Shane
AU - Slager, Susan
AU - Vachon, Celine M
AU - Couch, Fergus J
AU - ABCTB Investigators
AU - Harth, Volker
N1 - Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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 = 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.
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 = 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.
U2 - 10.1093/hmg/ddu300
DO - 10.1093/hmg/ddu300
M3 - SCORING: Journal article
C2 - 24927736
VL - 23
SP - 6034
EP - 6046
JO - HUM MOL GENET
JF - HUM MOL GENET
SN - 0964-6906
IS - 22
ER -