Advanced

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 and Hall, Per, et al. (2014) In Human Molecular Genetics 23(22). p.6034-6046
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 2,156 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% CI 1.16-1.33, p=4.2x10(-10)) and EIF3H (rs799890: OR=1.07, 95% confidence interval (CI) 1.04-1.11, p=8.7x10(-6)) were significantly associated with risk of low grade breast cancer. The TACC2 signal was... (More)
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 2,156 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% CI 1.16-1.33, p=4.2x10(-10)) and EIF3H (rs799890: OR=1.07, 95% confidence interval (CI) 1.04-1.11, p=8.7x10(-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=7.9x10(-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=2.1x10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
23
issue
22
pages
6034 - 6046
publisher
Oxford University Press
external identifiers
  • pmid:24927736
  • wos:000344671900016
  • scopus:84911431178
ISSN
0964-6906
DOI
10.1093/hmg/ddu300
language
English
LU publication?
yes
id
1a531ab8-e901-4a6d-a683-da915f40f7bb (old id 4528506)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24927736?dopt=Abstract
date added to LUP
2014-07-05 21:27:35
date last changed
2017-09-24 03:25:32
@article{1a531ab8-e901-4a6d-a683-da915f40f7bb,
  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 2,156 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% CI 1.16-1.33, p=4.2x10(-10)) and EIF3H (rs799890: OR=1.07, 95% confidence interval (CI) 1.04-1.11, p=8.7x10(-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=7.9x10(-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=2.1x10(-3)). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer.},
  author       = {Purrington, Kristen S and Slettedahl, Seth and Bolla, Manjeet K and Michailidou, Kyriaki and Czene, Kamila and Nevanlinna, Heli and Bojesen, Stig E and Andrulis, Irene L and Cox, Angela and Hall, Per and Carpenter, Jane and Yannoukakos, Drakoulis and Haiman, Christopher A and Fasching, Peter A and Mannermaa, Arto and Winqvist, Robert and Brenner, Hermann and Lindblom, Annika and Chenevix-Trench, Georgia and Benitez, Javier and Swerdlow, Anthony and Kristensen, Vessela and Guénel, Pascal and Meindl, Alfons and Darabi, Hatef and Eriksson, Mikael and Fagerholm, Rainer and Aittomäki, Kristiina and Blomqvist, Carl and Nordestgaard, Børge G and Nielsen, Sune F and Flyger, Henrik and Wang, Xianshu and Olswold, Curtis and Olson, Janet E and Mulligan, Anna Marie and Knight, Julia A and Tchatchou, Sandrine and Reed, Malcolm W R and Cross, Simon S and Liu, Jianjun and Li, Jingmei and Humphreys, Keith and Clarke, Christine and Scott, Rodney and Fostira, Florentia and Fountzilas, George and Konstantopoulou, Irene and Henderson, Brian E and Schumacher, Fredrick and Le Marchand, Loic and Ekici, Arif B and Hartmann, Arndt and Beckmann, Matthias W and Hartikainen, Jaana M and Kosma, Veli-Matti and Kataja, Vesa and Jukkola-Vuorinen, Arja and Pylkäs, Katri and Kauppila, Saila and Dieffenbach, Aida Karina and Stegmaier, Christa and Arndt, Volker and Margolin, Sara and Balleine, Rosemary and Arias Perez, Jose Ignacio and Zamora, M Pilar and Menéndez, Primitiva and Ashworth, Alan and Jones, Michael and Orr, Nick and Arveux, Patrick and Kerbrat, Pierre and Truong, Thérèse and Bugert, Peter and Toland, Amanda E and Ambrosone, Christine B and Labrèche, France and Goldberg, Mark S and Dumont, Martine and Ziogas, Argyrios and Lee, Eunjung and Dite, Gillian S and Apicella, Carmel and Southey, Melissa C and Long, Jirong and Shrubsole, Martha and Deming-Halverson, Sandra and Ficarazzi, Filomena and Barile, Monica and Peterlongo, Paolo and Durda, Katarzyna and Jaworska-Bieniek, Katarzyna and Tollenaar, Robert A E M and Seynaeve, Caroline and Brüning, Thomas and Ko, Yon-Dschun and van Deurzen, Carolien H M and Martens, John W M and Kriege, Mieke and Figueroa, Jonine D and Chanock, Stephen J and Lissowska, Jolanta and Tomlinson, Ian and Kerin, Michael J and Miller, Nicola and Schneeweiss, Andreas and Tapper, William J and Gerty, Susan M and Durcan, Lorraine and McLean, Catriona and Milne, Roger L and Baglietto, Laura and Dos Santos Silva, Isabel and Fletcher, Olivia and Johnson, Nichola and Van't Veer, Laura J and Cornelissen, Sten and Försti, Asta and Torres, Diana and Rüdiger, Thomas and Rudolph, Anja and Flesch-Janys, Dieter and Nickels, Stefan and Weltens, Caroline and Floris, Giuseppe and Moisse, Matthieu and Dennis, Joe and Wang, Qin and Dunning, Alison M and Shah, Mitul and Brown, Judith and Simard, Jacques and Anton-Culver, Hoda and Neuhausen, Susan L and Hopper, John L and Bogdanova, Natalia and Dörk, Thilo and Zheng, Wei and Radice, Paolo and Jakubowska, Anna and Lubinski, Jan and Devillee, Peter and Brauch, Hiltrud and Hooning, Maartje and García-Closas, Montserrat and Sawyer, Elinor and Burwinkel, Barbara and Marmee, Frederick and Eccles, Diana M and Giles, Graham G and Peto, Julian and Schmidt, Marjanka and Broeks, Annegien and Hamann, Ute and Chang-Claude, Jenny and Lambrechts, Diether and Pharoah, Paul D P and Easton, Douglas and Pankratz, V Shane and Slager, Susan and Vachon, Celine M and Couch, Fergus J},
  issn         = {0964-6906},
  language     = {eng},
  number       = {22},
  pages        = {6034--6046},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade.},
  url          = {http://dx.doi.org/10.1093/hmg/ddu300},
  volume       = {23},
  year         = {2014},
}