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

description: 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.