A network analysis to identify mediators of germline-driven differences in breast cancer prognosis

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Escala-Garcia , M , Abraham , J , Andrulis , I L , Anton-Culver , H , Arndt , V , Ashworth , A , Auer , P L , Auvinen , P , Beckmann , M W , Beesley , J , Behrens , S , Benitez , J , Bermisheva , M , Blomqvist , C , Blot , W , Bogdanova , N V , Bojesen , S E , Bolla , M K , Børresen-Dale , A-L , Brauch , H , Brenner , H , Brucker , S Y , Burwinkel , B , Caldas , C , Canzian , F , Chang-Claude , J , Chanock , S J , Chin , S-F , Clarke , C L , Couch , F J , Cox , A , Cross , S S , Czene , K , Daly , M B , Dennis , J , Devilee , P , Dunn , J A , Dunning , A M , Dwek , M , Earl , H M , Eccles , D M , Eliassen , A H , Ellberg , C , Evans , D G , Fasching , P A , Figueroa , J , Flyger , H , Gago-Dominguez , M , Gapstur , S M , García-Closas , M , García-Sáenz , J A , Gaudet , M M , George , A , Giles , G G , Goldgar , D E , González-Neira , A , Grip , M , Guénel , P , Guo , Q , Haiman , C A , Håkansson , N , Hamann , U , Harrington , P A , Hiller , L , Hooning , M J , Hopper , J L , Howell , A , Huang , C-S , Huang , G , Hunter , D J , Jakubowska , A , John , E M , Kaaks , R , Kapoor , P M , Keeman , R , Kitahara , C M , Koppert , L B , Kraft , P , Kristensen , V N , Lambrechts , D , Le Marchand , L , Lejbkowicz , F , Lindblom , A , Lubiński , J , Mannermaa , A , Manoochehri , M , Manoukian , S , Margolin , S , Martinez , M E , Maurer , T , Mavroudis , D , Meindl , A , Milne , R L , Mulligan , A M , Neuhausen , S L , Nevanlinna , H , Newman , W G , Olshan , A F , Olson , J E , Olsson , H , Orr , N , Peterlongo , P , Petridis , C , Prentice , R L , Presneau , N , Punie , K , Ramachandran , D , Rennert , G , Romero , A , Sachchithananthan , M , Saloustros , E , Sawyer , E J , Schmutzler , R K , Schwentner , L , Scott , C , Simard , J , Sohn , C , Southey , M C , Swerdlow , A J , Tamimi , R M , Tapper , W J , Teixeira , M R , Terry , M B , Thorne , H , Tollenaar , R A E M , Tomlinson , I , Troester , M A , Truong , T , Turnbull , C , Vachon , C M , van der Kolk , L E , Wang , Q , Winqvist , R , Wolk , A , Yang , X R , Ziogas , A , Pharoah , P D P , Hall , P , Wessels , L F A , Chenevix-Trench , G , Bader , G D , Dörk , T , Easton , D F , Canisius , S & Schmidt , M K 2020 , ' A network analysis to identify mediators of germline-driven differences in breast cancer prognosis ' , Nature Communications , vol. 11 , no. 1 , 312 . https://doi.org/10.1038/s41467-019-14100-6

Title: A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
Author: Escala-Garcia, M.; Abraham, J.; Andrulis, I.L.; Anton-Culver, H.; Arndt, V.; Ashworth, A.; Auer, P.L.; Auvinen, P.; Beckmann, M.W.; Beesley, J.; Behrens, S.; Benitez, J.; Bermisheva, M.; Blomqvist, C.; Blot, W.; Bogdanova, N.V.; Bojesen, S.E.; Bolla, M.K.; Børresen-Dale, A.-L.; Brauch, H.; Brenner, H.; Brucker, S.Y.; Burwinkel, B.; Caldas, C.; Canzian, F.; Chang-Claude, J.; Chanock, S.J.; Chin, S.-F.; Clarke, C.L.; Couch, F.J.; Cox, A.; Cross, S.S.; Czene, K.; Daly, M.B.; Dennis, J.; Devilee, P.; Dunn, J.A.; Dunning, A.M.; Dwek, M.; Earl, H.M.; Eccles, D.M.; Eliassen, A.H.; Ellberg, C.; Evans, D.G.; Fasching, P.A.; Figueroa, J.; Flyger, H.; Gago-Dominguez, M.; Gapstur, S.M.; García-Closas, M.; García-Sáenz, J.A.; Gaudet, M.M.; George, A.; Giles, G.G.; Goldgar, D.E.; González-Neira, A.; Grip, M.; Guénel, P.; Guo, Q.; Haiman, C.A.; Håkansson, N.; Hamann, U.; Harrington, P.A.; Hiller, L.; Hooning, M.J.; Hopper, J.L.; Howell, A.; Huang, C.-S.; Huang, G.; Hunter, D.J.; Jakubowska, A.; John, E.M.; Kaaks, R.; Kapoor, P.M.; Keeman, R.; Kitahara, C.M.; Koppert, L.B.; Kraft, P.; Kristensen, V.N.; Lambrechts, D.; Le Marchand, L.; Lejbkowicz, F.; Lindblom, A.; Lubiński, J.; Mannermaa, A.; Manoochehri, M.; Manoukian, S.; Margolin, S.; Martinez, M.E.; Maurer, T.; Mavroudis, D.; Meindl, A.; Milne, R.L.; Mulligan, A.M.; Neuhausen, S.L.; Nevanlinna, H.; Newman, W.G.; Olshan, A.F.; Olson, J.E.; Olsson, H.; Orr, N.; Peterlongo, P.; Petridis, C.; Prentice, R.L.; Presneau, N.; Punie, K.; Ramachandran, D.; Rennert, G.; Romero, A.; Sachchithananthan, M.; Saloustros, E.; Sawyer, E.J.; Schmutzler, R.K.; Schwentner, L.; Scott, C.; Simard, J.; Sohn, C.; Southey, M.C.; Swerdlow, A.J.; Tamimi, R.M.; Tapper, W.J.; Teixeira, M.R.; Terry, M.B.; Thorne, H.; Tollenaar, R.A.E.M.; Tomlinson, I.; Troester, M.A.; Truong, T.; Turnbull, C.; Vachon, C.M.; van der Kolk, L.E.; Wang, Q.; Winqvist, R.; Wolk, A.; Yang, X.R.; Ziogas, A.; Pharoah, P.D.P.; Hall, P.; Wessels, L.F.A.; Chenevix-Trench, G.; Bader, G.D.; Dörk, T.; Easton, D.F.; Canisius, S.; Schmidt, M.K.
Contributor: University of Helsinki, HUS Comprehensive Cancer Center
University of Helsinki, HUS Gynecology and Obstetrics
Date: 2020-01-16
Language: eng
Number of pages: 14
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/313373
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 similar to 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.
Subject: 3122 Cancers
3123 Gynaecology and paediatrics
GENOME-WIDE ASSOCIATION
PROTEIN-COUPLED RECEPTORS
CIRCADIAN CLOCK
TUMOR-GROWTH
CELL-GROWTH
GENE
PATHWAY
VARIANTS
PTEN
METASTASIS
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