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.
| Original language | English (US) |
|---|---|
| Article number | 312 |
| Journal | Nature communications |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2020 |
ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis. / 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; Bogdanova, Natalia V.; Bojesen, Stig E.; 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; 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.
In: Nature communications, Vol. 11, No. 1, 312, 01.12.2020.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
AU - Escala-Garcia, Maria
AU - Abraham, Jean
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Ashworth, Alan
AU - Auer, Paul L.
AU - Auvinen, Päivi
AU - Beckmann, Matthias W.
AU - Beesley, Jonathan
AU - Behrens, Sabine
AU - Benitez, Javier
AU - Bermisheva, Marina
AU - Blomqvist, Carl
AU - Blot, William
AU - Bogdanova, Natalia V.
AU - Bojesen, Stig E.
AU - Bolla, Manjeet K.
AU - Børresen-Dale, Anne Lise
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Brucker, Sara Y.
AU - Burwinkel, Barbara
AU - Caldas, Carlos
AU - Canzian, Federico
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Chin, Suet Feung
AU - Clarke, Christine L.
AU - Couch, Fergus J.
AU - Cox, Angela
AU - Cross, Simon S.
AU - Czene, Kamila
AU - Daly, Mary B.
AU - Dennis, Joe
AU - Devilee, Peter
AU - Dunn, Janet A.
AU - Dunning, Alison M.
AU - Dwek, Miriam
AU - Earl, Helena M.
AU - Eccles, Diana M.
AU - Eliassen, A. Heather
AU - Ellberg, Carolina
AU - Evans, D. Gareth
AU - Fasching, Peter A.
AU - Figueroa, Jonine
AU - Flyger, Henrik
AU - Gago-Dominguez, Manuela
AU - Gapstur, Susan M.
AU - García-Closas, Montserrat
AU - García-Sáenz, José A.
AU - Gaudet, Mia M.
AU - George, Angela
AU - Giles, Graham G.
AU - Goldgar, David E.
AU - González-Neira, Anna
AU - Grip, Mervi
AU - Guénel, Pascal
AU - Guo, Qi
AU - Haiman, Christopher A.
AU - Håkansson, Niclas
AU - Hamann, Ute
AU - Harrington, Patricia A.
AU - Hiller, Louise
AU - Hooning, Maartje J.
AU - Hopper, John L.
AU - Howell, Anthony
AU - Huang, Chiun Sheng
AU - Huang, Guanmengqian
AU - Hunter, David J.
AU - Jakubowska, Anna
AU - John, Esther M.
AU - Kaaks, Rudolf
AU - Kapoor, Pooja Middha
AU - Keeman, Renske
AU - Kitahara, Cari M.
AU - Koppert, Linetta B.
AU - Kraft, Peter
AU - Kristensen, Vessela N.
AU - Lambrechts, Diether
AU - Le Marchand, Loic
AU - Lejbkowicz, Flavio
AU - Lindblom, Annika
AU - Lubiński, Jan
AU - Mannermaa, Arto
AU - Manoochehri, Mehdi
AU - Manoukian, Siranoush
AU - Margolin, Sara
AU - Martinez, Maria Elena
AU - Maurer, Tabea
AU - Mavroudis, Dimitrios
AU - Meindl, Alfons
AU - Milne, Roger L.
AU - Mulligan, Anna Marie
AU - Neuhausen, Susan L.
AU - Nevanlinna, Heli
AU - Newman, William G.
AU - Olshan, Andrew F.
AU - Olson, Janet E.
AU - Olsson, Håkan
AU - Orr, Nick
AU - Peterlongo, Paolo
AU - Petridis, Christos
AU - Prentice, Ross L.
AU - Presneau, Nadege
AU - Punie, Kevin
AU - Ramachandran, Dhanya
AU - Rennert, Gad
AU - Romero, Atocha
AU - Sachchithananthan, Mythily
AU - Saloustros, Emmanouil
AU - Sawyer, Elinor J.
AU - Schmutzler, Rita K.
AU - Schwentner, Lukas
AU - Scott, Christopher
AU - Simard, Jacques
AU - Sohn, Christof
AU - Southey, Melissa C.
AU - Swerdlow, Anthony J.
AU - Tamimi, Rulla M.
AU - Tapper, William J.
AU - Teixeira, Manuel R.
AU - Terry, Mary Beth
AU - Thorne, Heather
AU - Tollenaar, Rob A.E.M.
AU - Tomlinson, Ian
AU - Troester, Melissa A.
AU - Truong, Thérèse
AU - Turnbull, Clare
AU - Vachon, Celine M.
AU - van der Kolk, Lizet E.
AU - Wang, Qin
AU - Winqvist, Robert
AU - Wolk, Alicja
AU - Yang, Xiaohong R.
AU - Ziogas, Argyrios
AU - Pharoah, Paul D.P.
AU - Hall, Per
AU - Wessels, Lodewyk F.A.
AU - Chenevix-Trench, Georgia
AU - Bader, Gary D.
AU - Dörk, Thilo
AU - Easton, Douglas F.
AU - Canisius, Sander
AU - Schmidt, Marjanka K.
N1 - Publisher Copyright: © 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85077940819&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077940819&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-14100-6
DO - 10.1038/s41467-019-14100-6
M3 - Article
C2 - 31949161
AN - SCOPUS:85077940819
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 312
ER -