A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
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Published:2020-01-16
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Escala-Garcia Maria, Abraham Jean, Andrulis Irene L.ORCID, Anton-Culver Hoda, Arndt VolkerORCID, Ashworth Alan, Auer Paul L., Auvinen Päivi, Beckmann Matthias W., Beesley Jonathan, Behrens Sabine, Benitez Javier, Bermisheva Marina, Blomqvist Carl, Blot William, Bogdanova Natalia V., Bojesen Stig E.ORCID, Bolla Manjeet K., Børresen-Dale Anne-Lise, Brauch HiltrudORCID, Brenner Hermann, Brucker Sara Y., Burwinkel Barbara, Caldas CarlosORCID, Canzian FedericoORCID, Chang-Claude Jenny, Chanock Stephen J.ORCID, Chin Suet-FeungORCID, Clarke Christine L., Couch Fergus J., Cox Angela, Cross Simon S., Czene Kamila, Daly Mary B., Dennis JoeORCID, Devilee PeterORCID, Dunn Janet A., Dunning Alison M.ORCID, Dwek MiriamORCID, Earl Helena M., Eccles Diana M., Eliassen A. Heather, Ellberg CarolinaORCID, Evans D. Gareth, Fasching Peter A.ORCID, Figueroa Jonine, Flyger Henrik, Gago-Dominguez Manuela, Gapstur Susan M., García-Closas MontserratORCID, García-Sáenz José A.ORCID, Gaudet Mia M., George Angela, Giles Graham G.ORCID, Goldgar David E., González-Neira Anna, Grip Mervi, Guénel PascalORCID, Guo Qi, Haiman Christopher A., Håkansson NiclasORCID, Hamann Ute, Harrington Patricia A., Hiller Louise, Hooning Maartje J., Hopper John L., Howell Anthony, Huang Chiun-Sheng, Huang Guanmengqian, Hunter David J., Jakubowska Anna, John Esther M., Kaaks Rudolf, Kapoor Pooja MiddhaORCID, Keeman RenskeORCID, Kitahara Cari M., Koppert Linetta B., Kraft PeterORCID, Kristensen Vessela N., Lambrechts DietherORCID, Le Marchand Loic, Lejbkowicz Flavio, Lindblom Annika, Lubiński Jan, Mannermaa Arto, Manoochehri Mehdi, Manoukian Siranoush, Margolin Sara, Martinez Maria Elena, Maurer Tabea, Mavroudis Dimitrios, Meindl Alfons, Milne Roger L.ORCID, Mulligan Anna Marie, Neuhausen Susan L., Nevanlinna HeliORCID, Newman William G.ORCID, Olshan Andrew F., Olson Janet E.ORCID, Olsson Håkan, Orr NickORCID, Peterlongo PaoloORCID, Petridis Christos, Prentice Ross L., Presneau Nadege, Punie KevinORCID, Ramachandran DhanyaORCID, Rennert GadORCID, Romero AtochaORCID, Sachchithananthan Mythily, Saloustros EmmanouilORCID, Sawyer Elinor J., Schmutzler Rita K., Schwentner Lukas, Scott ChristopherORCID, Simard JacquesORCID, Sohn Christof, Southey Melissa C., Swerdlow Anthony J., Tamimi Rulla M., Tapper William J., Teixeira Manuel R.ORCID, Terry Mary Beth, Thorne Heather, Tollenaar Rob A. E. M., Tomlinson IanORCID, Troester Melissa A., Truong ThérèseORCID, Turnbull Clare, Vachon Celine M., van der Kolk Lizet E., Wang Qin, Winqvist RobertORCID, Wolk AlicjaORCID, Yang Xiaohong R., Ziogas ArgyriosORCID, Pharoah Paul D. P.ORCID, Hall Per, Wessels Lodewyk F. A., Chenevix-Trench Georgia, Bader Gary D.ORCID, Dörk ThiloORCID, Easton Douglas F.ORCID, Canisius SanderORCID, Schmidt Marjanka K.ORCID
Abstract
AbstractIdentifying 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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