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

Escala-Garcia M, Abraham J, Andrulis IL, Anton-Culver H, Arndt V, Ashworth A, Auer PL, Auvinen P, Beckmann M, 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 P, 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 RA, 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 PD, Hall P, Wessels LF, Chenevix-Trench G, Bader GD, Dörk T, Easton DF, Canisius S, Schmidt MK (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 11

Pages Range: 312-

Journal Issue: 1

DOI: 10.1038/s41467-019-14100-6

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.

Authors with CRIS profile

Involved external institutions

Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI / NKI-AVL) Netherlands (NL) University of Cambridge United Kingdom (GB) Mount Sinai Hospital (MSH) Canada (CA) University of California Irvine United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) UCSF Helen Diller Family Comprehensive Cancer Center United States (USA) (US) Fred Hutchinson Cancer Research Center United States (USA) (US) Kuopio University Hospital / Pohjois-Savon sairaanhoitopiiri Finland (FI) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Melbourne School of Population and Global Health Australia (AU) University of Manchester United Kingdom (GB) National Taiwan University (NTU) Taiwan (TW) Harvard T.H. Chan School of Public Health United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) Stanford Cancer Institute United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) Erasmus University Medical Center (MC) Netherlands (NL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Flanders Institute for Biotechnology / Vlaams Instituut voor Biotechnologie (VIB) Belgium (BE) University of Hawaiʻi at Mānoa United States (USA) (US) Technion - Israel Institute of Technology Israel (IL) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS) Russian Federation (RU) Helsinki University Central Hospital (HUCH) / Helsingin seudun yliopistollinen keskussairaala (HYKS) Finland (FI) Vanderbilt University Medical Center United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Herlev Hospital Denmark (DK) Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie Germany (DE) Eberhard Karls Universität Tübingen Germany (DE) University of Sydney (USYD) Australia (AU) Mayo Clinic United States (USA) (US) University of Sheffield United Kingdom (GB) Karolinska Institute Sweden (SE) Fox Chase Cancer Center United States (USA) (US) Leiden University Medical Center Netherlands (NL) Warwick Medical School United Kingdom (GB) University of Westminster United Kingdom (GB) University of Southampton United Kingdom (GB) Veterans Affairs Healthcare System Boston and Harvard Medical School United States (USA) (US) Lund University / Lunds universitet Sweden (SE) Complejo Hospitalario Universitario de Santiago de Compostela Spain (ES) American Cancer Society United States (USA) (US) Hospital Clínico San Carlos Spain (ES) The Institute of Cancer Research (ICR) United Kingdom (GB) Cancer Council Victoria Australia (AU) University of Utah United States (USA) (US) Oulun Yliopisto / University of Oulo Finland (FI) Université Paris-Sud France (FR) Keck School of Medicine of USC United States (USA) (US) University of Eastern Finland Finland (FI) Fondazione IRCCS: Istituto Nazionale dei Tumori Italy (IT) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) Moores Cancer Center United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University General Hospital of Heraklion Greece (GR) Ludwig-Maximilians-Universität (LMU) Germany (DE) University of Toronto Canada (CA) City of Hope Medical Center United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) Queen's University United Kingdom (GB) IFOM - FIRC Institute of Molecular Oncology Italy (IT) King’s College London United Kingdom (GB) University Hospital Leuven (UZ) / Universitaire ziekenhuizen Leuven Belgium (BE) Hospital Universitario Puerta de Hierro - Majadahonda Spain (ES) General University Hospital of Larissa Greece (GR) Universitätsklinikum Köln Germany (DE) Universitätsklinikum Ulm Germany (DE) Centre hospitalier universitaire de Québec Canada (CA) Ruprecht-Karls-Universität Heidelberg Germany (DE) Monash University Australia (AU) Instituto Português de Oncologia do Porto FG, EPE (IPO-Porto) Portugal (PT) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) University of Birmingham United Kingdom (GB)

How to cite

APA:

Escala-Garcia, M., Abraham, J., Andrulis, I.L., Anton-Culver, H., Arndt, V., Ashworth, A.,... Schmidt, M.K. (2020). A network analysis to identify mediators of germline-driven differences in breast cancer prognosis. Nature Communications, 11(1), 312-. https://doi.org/10.1038/s41467-019-14100-6

MLA:

Escala-Garcia, Maria, et al. "A network analysis to identify mediators of germline-driven differences in breast cancer prognosis." Nature Communications 11.1 (2020): 312-.

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