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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
Nature Communications ( IF 11.878 ) Pub Date : 2020-01-16 , DOI: 10.1038/s41467-019-14100-6
Maria Escala-Garcia; Jean Abraham; Irene L. Andrulis; Hoda Anton-Culver; Volker Arndt; Alan Ashworth; Paul L. Auer; Päivi Auvinen; Matthias W. Beckmann; Jonathan Beesley; Sabine Behrens; Javier Benitez; Marina Bermisheva; Carl Blomqvist; William Blot; Natalia V. Bogdanova; Stig E. Bojesen; Manjeet K. Bolla; Anne-Lise Børresen-Dale; Hiltrud Brauch; Hermann Brenner; Sara Y. Brucker; Barbara Burwinkel; Carlos Caldas; Federico Canzian; Jenny Chang-Claude; Stephen J. Chanock; Suet-Feung Chin; Christine L. Clarke; Fergus J. Couch; Angela Cox; Simon S. Cross; Kamila Czene; Mary B. Daly; Joe Dennis; Peter Devilee; Janet A. Dunn; Alison M. Dunning; Miriam Dwek; Helena M. Earl; Diana M. Eccles; A. Heather Eliassen; Carolina Ellberg; D. Gareth Evans; Peter A. Fasching; Jonine Figueroa; Henrik Flyger; Manuela Gago-Dominguez; Susan M. Gapstur; Montserrat García-Closas; José A. García-Sáenz; Mia M. Gaudet; Angela George; Graham G. Giles; David E. Goldgar; Anna González-Neira; Mervi Grip; Pascal Guénel; Qi Guo; Christopher A. Haiman; Niclas Håkansson; Ute Hamann; Patricia A. Harrington; Louise Hiller; Maartje J. Hooning; John L. Hopper; Anthony Howell; Chiun-Sheng Huang; Guanmengqian Huang; David J. Hunter; Anna Jakubowska; Esther M. John; Rudolf Kaaks; Pooja Middha Kapoor; Renske Keeman; Cari M. Kitahara; Linetta B. Koppert; Peter Kraft; Vessela N. Kristensen; Diether Lambrechts; Loic Le Marchand; Flavio Lejbkowicz; Annika Lindblom; Jan Lubiński; Arto Mannermaa; Mehdi Manoochehri; Siranoush Manoukian; Sara Margolin; Maria Elena Martinez; Tabea Maurer; Dimitrios Mavroudis; Alfons Meindl; Roger L. Milne; Anna Marie Mulligan; Susan L. Neuhausen; Heli Nevanlinna; William G. Newman; Andrew F. Olshan; Janet E. Olson; Håkan Olsson; Nick Orr; Paolo Peterlongo; Christos Petridis; Ross L. Prentice; Nadege Presneau; Kevin Punie; Dhanya Ramachandran; Gad Rennert; Atocha Romero; Mythily Sachchithananthan; Emmanouil Saloustros; Elinor J. Sawyer; Rita K. Schmutzler; Lukas Schwentner; Christopher Scott; Jacques Simard; Christof Sohn; Melissa C. Southey; Anthony J. Swerdlow; Rulla M. Tamimi; William J. Tapper; Manuel R. Teixeira; Mary Beth Terry; Heather Thorne; Rob A. E. M. Tollenaar; Ian Tomlinson; Melissa A. Troester; Thérèse Truong; Clare Turnbull; Celine M. Vachon; Lizet E. van der Kolk; Qin Wang; Robert Winqvist; Alicja Wolk; Xiaohong R. Yang; Argyrios Ziogas; Paul D. P. Pharoah; Per Hall; Lodewyk F. A. Wessels; Georgia Chenevix-Trench; Gary D. Bader; Thilo Dörk; Douglas F. Easton; Sander Canisius; Marjanka K. Schmidt

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
更新日期:2020-01-16

 

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