| Autor: |
Qin Wang, Anna González-Neira, Betül T. Yesilyurt, Paolo Radice, Jenny Chang-Claude, Malcolm W.R. Reed, Graham G. Giles, Robert A.E.M. Tollenaar, Gianluca Severi, Gillian S. Dite, Fredrick R. Schumacher, J. Margriet Collée, Pascal Guénel, Fergus J. Couch, Núria Malats, Dieter Flesch-Janys, Ute Hamann, Michael J. Kerin, Asta Försti, Guillermo Pita, Christina A. Clarke, Heli Nevanlinna, Anja Rudolph, Jolanta Lissowska, Javier Benitez, Pilar Zamora, Brian E. Henderson, Elinor J. Sawyer, Arto Mannermaa, Hiltrud Brauch, Jesús Herranz, Henrik Flyger, Aida Karina Dieffenbach, Karin Leunen, Xianshu Wang, Angela Cox, Celine M. Vachon, Arif B. Ekici, Maartje J. Hooning, Antoinette Hollestelle, Volker Arndt, Hatef Darabi, Penny Soucy, Minouk J. Schoemaker, Thilo Dörk, Hoda Anton-Culver, Melissa C. Southey, Stig E. Bojesen, Yon-Dschun Ko, Natalia Bogdanova, Veli-Matti Kosma, Robert Winqvist, Argyrios Ziogas, Jingmei Li, Carmel Apicella, M. Rosario Alonso, Douglas F. Easton, Arja Jukkola-Vuorinen, Paolo Mariani, Hermann Brenner, Peter A. Fasching, Drakoulis Yannoukakos, Paolo Peterlongo, Annegien Broeks, Federik Marme, Caroline Seynaeve, Taru A. Muranen, Anna Jakubowska, Paul D.P. Pharoah, Joe Dennis, Vesa Kataja, Kamila Czene, Alison M. Dunning, Mikael Eriksson, Vessela N. Kristensen, Ian Tomlinson, Thérèse Truong, Jonathan Tyrer, Thomas Rüdiger, Montserrat Garcia-Closas, Manjeet K. Bolla, Amanda E. Toland, Thomas Brüning, John L. Hopper, kConFab Investigators, Carl Blomqvist, Lothar Häberle, Hans Ulrich Ulmer, Anna Marie Mulligan, Jan Lubinski, Diether Lambrechts, Ian W. Brock, Emiel J. Th. Rutgers, Anthony J. Swerdlow, Grethe I. Grenaker Alnæs, Stephen J. Chanock, Katarzyna Durda, Olivia Fletcher, Mervi Grip, Per Hall, Claire Mulot, Keith Humphreys, Jonine D. Figueroa, Julia A. Knight, Petra Seibold, Alan Ashworth, Laura Baglietto, Katarzyna Jaworska-Bieniek, José Ignacio Arias-Perez, Sara Margolin, Mitul Shah, Matthias W. Beckmann, Bernard Peissel, Kyriaki Michailidou, Peter Devilee, Anne Lise Børresen-Dale, Julian Peto, Georgia Chenevix-Trench, Børge G. Nordestgaard, Barbara Burwinkel, Kristiina Aittomäki, Nicola Miller, Isabel dos Santos Silva, Agnes Jager, Janet E. Olson, Roger L. Milne, Kristen S. Purrington, Jacques Simard, Irene L. Andrulis, Nick Orr, Martine Dumont, Annika Lindblom, Nichola Johnson, Marjanka K. Schmidt, Susan L. Neuhausen, Marie Sanchez, Christopher A. Haiman, Loic Le Marchand, Katri Pylkäs, Giuseppe Floris, Christa Stegmaier, Senno Verhoef, Jaana M. Hartikainen, Gord Glendon |
| Přispěvatelé: |
Cancer Center Amsterdam, Oncogenomics, Clinical Genetics, Medical Oncology |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
|
| Zdroj: |
Human Molecular Genetics; Vol 23
Human Molecular Genetics, 23(7), 1934-1946
Human molecular genetics, 23(7), 1934-1946. Oxford University Press
Human Molecular Genetics, 23(7), 1934-1946. Oxford University Press
Human Molecular Genetics |
| ISSN: |
1934-1946
0964-6906 |
| Popis: |
Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10−4) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10−8. Results from the second analytic approach were consistent with those from the first (P > 10−10). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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