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A Network Analysis to Identify Mediators of Germline-Driven Differences in Breast Cancer Prognosis

Citation

Escala-Garcia, Maria; Abraham, Jean; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Ashworth, Alan; Auer, Paul L.; Auvinen, Päivi; Beckmann, Matthias W.; & Beesley, Jonathan, et al. (2020). A Network Analysis to Identify Mediators of Germline-Driven Differences in Breast Cancer Prognosis. Nature Communications, 11(1), 312. PMCID: PMC6965101

Abstract

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.

URL

http://dx.doi.org/10.1038/s41467-019-14100-6

Reference Type

Journal Article

Journal Title

Nature Communications

Author(s)

Escala-Garcia, Maria
Abraham, Jean
Andrulis, Irene L.
Anton-Culver, Hoda
Arndt, Volker
Ashworth, Alan
Auer, Paul L.
Auvinen, Päivi
Beckmann, Matthias W.
Beesley, Jonathan
Behrens, Sabine
Benitez, Javier
Bermisheva, Marina
Blomqvist, Carl
Blot, William J.
Bogdanova, Natalia V.
Bojesen, Stig Egil
Bolla, Manjeet K.
Børresen-Dale, Anne-Lise
Brauch, Hiltrud
Brenner, Hermann
Brucker, Sara Y.
Burwinkel, Barbara
Caldas, Carlos
Canzian, Federico
Chang-Claude, Jenny
Chanock, Stephen J.
Chin, Suet-Feung
Clarke, Christine L.
Couch, Fergus J.
Cox, Angela
Cross, Simon S.
Czene, Kamila
Daly, Mary B.
Dennis, Joe G.
Devilee, Peter
Dunn, Janet A.
Dunning, Alison M.
Dwek, Miriam
Earl, Helena M.
Eccles, Diana M.
Eliassen, A. Heather
Ellberg, Carolina
Evans, D. Gareth
Fasching, Peter A.
Figueroa, Jonine
Flyger, Henrik
Gago-Dominguez, Manuela
Gapstur, Susan M.
García-Closas, Montserrat
García-Sáenz, José A.
Gaudet, Mia M.
George, Angela
Giles, Graham G.
Goldgar, David E.
González-Neira, Anna
Grip, Mervi
Guénel, Pascal
Guo, Qi
Haiman, Christopher A.
Håkansson, Niclas
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 Middha
Keeman, Renske
Kitahara, Cari M.
Koppert, Linetta B.
Kraft, Peter
Kristensen, Vessela N.
Lambrechts, Diether
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.
Mulligan, Anna Marie
Neuhausen, Susan L.
Nevanlinna, Heli
Newman, William G.
Olshan, Andrew F.
Olson, Janet E.
Olsson, Håkan
Orr, Nick
Peterlongo, Paolo
Petridis, Christos
Prentice, Ross L.
Presneau, Nadege
Punie, Kevin
Ramachandran, Dhanya
Rennert, Gad
Romero, Atocha
Sachchithananthan, Mythily
Saloustros, Emmanouil
Sawyer, Elinor J.
Schmutzler, Rita K.
Schwentner, Lukas
Scott, Christopher
Simard, Jacques
Sohn, Christof
Southey, Melissa C.
Swerdlow, Anthony J.
Tamimi, Rulla M.
Tapper, William J.
Teixeira, Manuel R.
Terry, Mary Beth
Thorne, Heather
Tollenaar, Rob A. E. M.
Tomlinson, Ian
Troester, Melissa A.
Truong, Thérèse
Turnbull, Clare
Vachon, Celine M.
van der Kolk, Lizet E.
Wang, Qin
Winqvist, Robert
Wolk, Alicja
Yang, Xiaohong R.
Ziogas, Argyrios
Pharoah, Paul D. P.
Hall, Per
Wessels, Lodewyk F. A.
Chenevix-Trench, Georgia
Bader, Gary D.
Dörk, Thilo
Easton, Douglas F.
Canisius, Sander
Schmidt, Marjanka K.

Year Published

2020

Volume Number

11

Issue Number

1

Pages

312

PMCID

PMC6965101

Reference ID

13064