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

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

doi:10.1038/s41467-019-14100-6

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

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

29 Citationer (Scopus)

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.

Originalsprog	Engelsk
Artikelnummer	312
Tidsskrift	Nature Communications
Vol/bind	11
Udgave nummer	1
Sider (fra-til)	312
ISSN	2041-1722
DOI	https://doi.org/10.1038/s41467-019-14100-6
Status	Udgivet - 16 jan. 2020

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10.1038/s41467-019-14100-6

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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., ... Schmidt, M. K. (2020). A network analysis to identify mediators of germline-driven differences in breast cancer prognosis. Nature Communications, 11(1), 312. Artikel 312. https://doi.org/10.1038/s41467-019-14100-6

Escala-Garcia, M, Abraham, J, Andrulis, IL, Anton-Culver, H, Arndt, V, Ashworth, A, Auer, PL, Auvinen, P, Beckmann, MW, Beesley, J, Behrens, S, Benitez, J, Bermisheva, M, Blomqvist, C, Blot, W, Bogdanova, NV, Bojesen, SE, Bolla, MK, Børresen-Dale, A-L, Brauch, H, Brenner, H, Brucker, SY, Burwinkel, B, Caldas, C, Canzian, F, Chang-Claude, J, Chanock, SJ, Chin, S-F, Clarke, CL, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Dunn, JA, Dunning, AM, Dwek, M, Earl, HM, Eccles, DM, Eliassen, AH, Ellberg, C, Evans, DG, Fasching, PA, Figueroa, J, Flyger, H, Gago-Dominguez, M, Gapstur, SM, García-Closas, M, García-Sáenz, JA, Gaudet, MM, George, A, Giles, GG, Goldgar, DE, González-Neira, A, Grip, M, Guénel, P, Guo, Q, Haiman, CA, Håkansson, N, Hamann, U, Harrington, PA, Hiller, L, Hooning, MJ, Hopper, JL, Howell, A, Huang, C-S, Huang, G, Hunter, DJ, Jakubowska, A, John, EM, Kaaks, R, Kapoor, PM, Keeman, R, Kitahara, CM, Koppert, LB, Kraft, P, Kristensen, VN, Lambrechts, D, Le Marchand, L, Lejbkowicz, F, Lindblom, A, Lubiński, J, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, ME, Maurer, T, Mavroudis, D, Meindl, A, Milne, RL, Mulligan, AM, Neuhausen, SL, Nevanlinna, H, Newman, WG, Olshan, AF, Olson, JE, Olsson, H, Orr, N, Peterlongo, P, Petridis, C, Prentice, RL, Presneau, N, Punie, K, Ramachandran, D, Rennert, G, Romero, A, Sachchithananthan, M, Saloustros, E, Sawyer, EJ, Schmutzler, RK, Schwentner, L, Scott, C, Simard, J, Sohn, C, Southey, MC, Swerdlow, AJ, Tamimi, RM, Tapper, WJ, Teixeira, MR, Terry, MB, Thorne, H, Tollenaar, RAEM, Tomlinson, I, Troester, MA, Truong, T, Turnbull, C, Vachon, CM, van der Kolk, LE, Wang, Q, Winqvist, R, Wolk, A, Yang, XR, Ziogas, A, Pharoah, PDP, Hall, P, Wessels, LFA, Chenevix-Trench, G, Bader, GD, Dörk, T, Easton, DF, Canisius, S & Schmidt, MK 2020, 'A network analysis to identify mediators of germline-driven differences in breast cancer prognosis', Nature Communications, bind 11, nr. 1, 312, s. 312. https://doi.org/10.1038/s41467-019-14100-6

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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

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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.

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DO - 10.1038/s41467-019-14100-6

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SN - 2041-1722

VL - 11

SP - 312

JO - Nature Communications

JF - Nature Communications

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ER -

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

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