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

Research output: Contribution to journal › Article › peer-review

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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	https://doi.org/10.1038/s41467-019-14100-6
State	Published - Dec 1 2020

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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), Article 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, AL, Brauch, H, Brenner, H, Brucker, SY, Burwinkel, B, Caldas, C, Canzian, F, Chang-Claude, J, Chanock, SJ, Chin, SF, 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, CS, 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, vol. 11, no. 1, 312. https://doi.org/10.1038/s41467-019-14100-6

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title = "A network analysis to identify mediators of germline-driven differences in breast cancer prognosis",

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.",

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

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month = dec,

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doi = "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.

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.

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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

SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 312

ER -

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

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