| Literature DB >> 24927736 |
Kristen S Purrington1, Seth Slettedahl2, Manjeet K Bolla3, Kyriaki Michailidou3, Kamila Czene4, Heli Nevanlinna5, Stig E Bojesen6, Irene L Andrulis7, Angela Cox8, Per Hall4, Jane Carpenter9, Drakoulis Yannoukakos10, Christopher A Haiman11, Peter A Fasching12, Arto Mannermaa13, Robert Winqvist14, Hermann Brenner15, Annika Lindblom16, Georgia Chenevix-Trench17, Javier Benitez18, Anthony Swerdlow19, Vessela Kristensen20, Pascal Guénel21, Alfons Meindl22, Hatef Darabi4, Mikael Eriksson4, Rainer Fagerholm23, Kristiina Aittomäki24, Carl Blomqvist25, Børge G Nordestgaard26, Sune F Nielsen27, Henrik Flyger28, Xianshu Wang29, Curtis Olswold2, Janet E Olson2, Anna Marie Mulligan30, Julia A Knight31, Sandrine Tchatchou32, Malcolm W R Reed8, Simon S Cross33, Jianjun Liu34, Jingmei Li34, Keith Humphreys4, Christine Clarke35, Rodney Scott36, Florentia Fostira10, George Fountzilas37, Irene Konstantopoulou10, Brian E Henderson11, Fredrick Schumacher11, Loic Le Marchand38, Arif B Ekici39, Arndt Hartmann40, Matthias W Beckmann41, Jaana M Hartikainen13, Veli-Matti Kosma13, Vesa Kataja42, Arja Jukkola-Vuorinen43, Katri Pylkäs14, Saila Kauppila44, Aida Karina Dieffenbach15, Christa Stegmaier45, Volker Arndt46, Sara Margolin47, Rosemary Balleine48, Jose Ignacio Arias Perez49, M Pilar Zamora50, Primitiva Menéndez51, Alan Ashworth52, Michael Jones53, Nick Orr52, Patrick Arveux54, Pierre Kerbrat55, Thérèse Truong21, Peter Bugert56, Amanda E Toland57, Christine B Ambrosone58, France Labrèche59, Mark S Goldberg60, Martine Dumont61, Argyrios Ziogas62, Eunjung Lee11, Gillian S Dite63, Carmel Apicella63, Melissa C Southey64, Jirong Long65, Martha Shrubsole57, Sandra Deming-Halverson65, Filomena Ficarazzi66, Monica Barile67, Paolo Peterlongo68, Katarzyna Durda69, Katarzyna Jaworska-Bieniek69, Robert A E M Tollenaar70, Caroline Seynaeve71, Thomas Brüning72, Yon-Dschun Ko73, Carolien H M Van Deurzen74, John W M Martens75, Mieke Kriege75, Jonine D Figueroa76, Stephen J Chanock76, Jolanta Lissowska77, Ian Tomlinson78, Michael J Kerin79, Nicola Miller79, Andreas Schneeweiss80, William J Tapper81, Susan M Gerty81, Lorraine Durcan81, Catriona Mclean82, Roger L Milne83, Laura Baglietto83, Isabel dos Santos Silva84, Olivia Fletcher85, Nichola Johnson85, Laura J Van'T Veer86, Sten Cornelissen86, Asta Försti87, Diana Torres88, Thomas Rüdiger89, Anja Rudolph90, Dieter Flesch-Janys91, Stefan Nickels90, Caroline Weltens92, Giuseppe Floris92, Matthieu Moisse93, Joe Dennis3, Qin Wang3, Alison M Dunning94, Mitul Shah94, Judith Brown3, Jacques Simard61, Hoda Anton-Culver62, Susan L Neuhausen95, John L Hopper63, Natalia Bogdanova96, Thilo Dörk97, Wei Zheng65, Paolo Radice98, Anna Jakubowska69, Jan Lubinski69, Peter Devillee99, Hiltrud Brauch100, Maartje Hooning75, Montserrat García-Closas52, Elinor Sawyer101, Barbara Burwinkel102, Frederick Marmee80, Diana M Eccles81, Graham G Giles83, Julian Peto84, Marjanka Schmidt86, Annegien Broeks86, Ute Hamann103, Jenny Chang-Claude90, Diether Lambrechts93, Paul D P Pharoah104, Douglas Easton104, V Shane Pankratz2, Susan Slager2, Celine M Vachon2, Fergus J Couch105.
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 = 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. 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.Entities:
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Year: 2014 PMID： 24927736 PMCID： PMC4204763 DOI： 10.1093/hmg/ddu300
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150