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

Author

Listed:
  • Maria Escala-Garcia

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital)

  • Jean Abraham

    (University of Cambridge
    Cambridge Experimental Cancer Medicine Centre
    University of Cambridge NHS Foundation Hospitals)

  • Irene L. Andrulis

    (Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital
    University of Toronto)

  • Hoda Anton-Culver

    (University of California Irvine)

  • Volker Arndt

    (German Cancer Research Center (DKFZ))

  • Alan Ashworth

    (University of California San Francisco)

  • Paul L. Auer

    (Fred Hutchinson Cancer Research Center
    University of Wisconsin-Milwaukee)

  • Päivi Auvinen

    (Kuopio University Hospital
    University of Eastern Finland
    University of Eastern Finland)

  • Matthias W. Beckmann

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg)

  • Jonathan Beesley

    (QIMR Berghofer Medical Research Institute)

  • Sabine Behrens

    (German Cancer Research Center (DKFZ))

  • Javier Benitez

    (Spanish National Cancer Research Centre (CNIO)
    Biomedical Network on Rare Diseases (CIBERER))

  • Marina Bermisheva

    (Ufa Scientific Center of Russian Academy of Sciences)

  • Carl Blomqvist

    (Helsinki University Hospital, University of Helsinki
    Örebro University Hospital)

  • William Blot

    (Vanderbilt University School of Medicine
    International Epidemiology Institute)

  • Natalia V. Bogdanova

    (Hannover Medical School
    Hannover Medical School
    N.N. Alexandrov Research Institute of Oncology and Medical Radiology)

  • Stig E. Bojesen

    (Copenhagen University Hospital
    Copenhagen University Hospital
    University of Copenhagen)

  • Manjeet K. Bolla

    (University of Cambridge)

  • Anne-Lise Børresen-Dale

    (Oslo University Hospital-Radiumhospitalet
    University of Oslo)

  • Hiltrud Brauch

    (Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
    University of Tuebingen
    German Cancer Consortium (DKTK))

  • Hermann Brenner

    (German Cancer Research Center (DKFZ)
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT))

  • Sara Y. Brucker

    (University of Tübingen)

  • Barbara Burwinkel

    (German Cancer Research Center (DKFZ)
    University of Heidelberg)

  • Carlos Caldas

    (University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Federico Canzian

    (German Cancer Research Center (DKFZ))

  • Jenny Chang-Claude

    (German Cancer Research Center (DKFZ)
    University Medical Center Hamburg-Eppendorf)

  • Stephen J. Chanock

    (National Cancer Institute, National Institutes of Health)

  • Suet-Feung Chin

    (University of Cambridge)

  • Christine L. Clarke

    (University of Sydney)

  • Fergus J. Couch

    (Mayo Clinic)

  • Angela Cox

    (University of Sheffield)

  • Simon S. Cross

    (University of Sheffield)

  • Kamila Czene

    (Karolinska Institutet)

  • Mary B. Daly

    (Fox Chase Cancer Center)

  • Joe Dennis

    (University of Cambridge)

  • Peter Devilee

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Janet A. Dunn

    (University of Warwick)

  • Alison M. Dunning

    (University of Cambridge)

  • Miriam Dwek

    (University of Westminster)

  • Helena M. Earl

    (University of Cambridge NHS Foundation Hospitals
    University of Cambridge)

  • Diana M. Eccles

    (University of Southampton)

  • A. Heather Eliassen

    (Harvard Medical School
    Harvard T.H. Chan School of Public Health)

  • Carolina Ellberg

    (Lund University)

  • D. Gareth Evans

    (University of Manchester
    Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre
    Manchester University NHS Foundation Trust)

  • Peter A. Fasching

    (University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg
    University of California at Los Angeles)

  • Jonine Figueroa

    (National Cancer Institute, National Institutes of Health
    The University of Edinburgh Medical School
    Cancer Research UK Edinburgh Centre)

  • Henrik Flyger

    (Copenhagen University Hospital)

  • Manuela Gago-Dominguez

    (Complejo Hospitalario Universitario de Santiago, SERGAS
    University of California San Diego)

  • Susan M. Gapstur

    (American Cancer Society)

  • Montserrat García-Closas

    (National Cancer Institute, National Institutes of Health
    Institute of Cancer Research)

  • José A. García-Sáenz

    (Centro Investigación Biomédica en Red de Cáncer (CIBERONC))

  • Mia M. Gaudet

    (American Cancer Society)

  • Angela George

    (The Institute of Cancer Research)

  • Graham G. Giles

    (Cancer Council Victoria
    The University of Melbourne
    Monash University)

  • David E. Goldgar

    (University of Utah School of Medicine)

  • Anna González-Neira

    (Spanish National Cancer Research Centre (CNIO))

  • Mervi Grip

    (University of Oulu)

  • Pascal Guénel

    (University Paris-Saclay, INSERM, University Paris-Sud)

  • Qi Guo

    (University of Cambridge)

  • Christopher A. Haiman

    (University of Southern California)

  • Niclas Håkansson

    (Karolinska Institutet)

  • Ute Hamann

    (German Cancer Research Center (DKFZ))

  • Patricia A. Harrington

    (University of Cambridge)

  • Louise Hiller

    (University of Warwick)

  • Maartje J. Hooning

    (Erasmus MC Cancer Institute)

  • John L. Hopper

    (The University of Melbourne)

  • Anthony Howell

    (University of Manchester)

  • Chiun-Sheng Huang

    (National Taiwan University Hospital and National Taiwan University College of Medicine)

  • Guanmengqian Huang

    (German Cancer Research Center (DKFZ))

  • David J. Hunter

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health
    University of Oxford)

  • Anna Jakubowska

    (Pomeranian Medical University
    Pomeranian Medical University)

  • Esther M. John

    (Stanford Cancer Institute, Stanford University School of Medicine)

  • Rudolf Kaaks

    (German Cancer Research Center (DKFZ))

  • Pooja Middha Kapoor

    (German Cancer Research Center (DKFZ)
    University of Heidelberg)

  • Renske Keeman

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital)

  • Cari M. Kitahara

    (National Cancer Institute)

  • Linetta B. Koppert

    (Erasmus MC Cancer Institute)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Vessela N. Kristensen

    (Oslo University Hospital-Radiumhospitalet
    University of Oslo)

  • Diether Lambrechts

    (VIB, VIB Center for Cancer Biology
    University of Leuven)

  • Loic Le Marchand

    (University of Hawaii Cancer Center)

  • Flavio Lejbkowicz

    (Clalit National Cancer Control Center)

  • Annika Lindblom

    (Karolinska Institutet
    Karolinska University Hospital)

  • Jan Lubiński

    (Pomeranian Medical University)

  • Arto Mannermaa

    (University of Eastern Finland
    University of Eastern Finland
    Kuopio University Hospital)

  • Mehdi Manoochehri

    (German Cancer Research Center (DKFZ))

  • Siranoush Manoukian

    (Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT))

  • Sara Margolin

    (Sšdersjukhuset
    Karolinska Institutet)

  • Maria Elena Martinez

    (University of California San Diego
    University of California San Diego)

  • Tabea Maurer

    (University Medical Center Hamburg-Eppendorf)

  • Dimitrios Mavroudis

    (University Hospital of Heraklion)

  • Alfons Meindl

    (Ludwig Maximilian University of Munich)

  • Roger L. Milne

    (Cancer Council Victoria
    The University of Melbourne
    Monash University)

  • Anna Marie Mulligan

    (University of Toronto
    University Health Network)

  • Susan L. Neuhausen

    (Beckman Research Institute of City of Hope)

  • Heli Nevanlinna

    (University of Helsinki)

  • William G. Newman

    (University of Manchester
    Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre)

  • Andrew F. Olshan

    (University of North Carolina at Chapel Hill)

  • Janet E. Olson

    (Mayo Clinic)

  • Håkan Olsson

    (Lund University)

  • Nick Orr

    (Queen’s University Belfast)

  • Paolo Peterlongo

    (IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology)

  • Christos Petridis

    (King’s College London)

  • Ross L. Prentice

    (Fred Hutchinson Cancer Research Center)

  • Nadege Presneau

    (University of Westminster)

  • Kevin Punie

    (Leuven Cancer Institute, University Hospitals Leuven)

  • Dhanya Ramachandran

    (Hannover Medical School)

  • Gad Rennert

    (Clalit National Cancer Control Center)

  • Atocha Romero

    (Hospital Universitario Puerta de Hierro)

  • Mythily Sachchithananthan

    (University of Sydney)

  • Emmanouil Saloustros

    (University Hospital of Larissa)

  • Elinor J. Sawyer

    (King’s College London)

  • Rita K. Schmutzler

    (University Hospital of Cologne
    University of Cologne)

  • Lukas Schwentner

    (University Hospital Ulm)

  • Christopher Scott

    (Mayo Clinic)

  • Jacques Simard

    (Centre Hospitalier Universitaire de Québec - Université Laval)

  • Christof Sohn

    (University of Heidelberg)

  • Melissa C. Southey

    (Monash University
    The University of Melbourne)

  • Anthony J. Swerdlow

    (The Institute of Cancer Research
    The Institute of Cancer Research)

  • Rulla M. Tamimi

    (Harvard Medical School
    Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • William J. Tapper

    (University of Southampton)

  • Manuel R. Teixeira

    (Portuguese Oncology Institute
    University of Porto)

  • Mary Beth Terry

    (Columbia University)

  • Heather Thorne

    (Peter MacCallum Cancer Center
    The University of Melbourne)

  • Rob A. E. M. Tollenaar

    (Leiden University Medical Center)

  • Ian Tomlinson

    (University of Birmingham
    University of Oxford)

  • Melissa A. Troester

    (University of North Carolina at Chapel Hill)

  • Thérèse Truong

    (University Paris-Saclay, INSERM, University Paris-Sud)

  • Clare Turnbull

    (The Institute of Cancer Research)

  • Celine M. Vachon

    (Mayo Clinic)

  • Lizet E. Kolk

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital)

  • Qin Wang

    (University of Cambridge)

  • Robert Winqvist

    (University of Oulu
    Northern Finland Laboratory Centre Oulu)

  • Alicja Wolk

    (Karolinska Institutet
    Uppsala University)

  • Xiaohong R. Yang

    (National Cancer Institute, National Institutes of Health)

  • Argyrios Ziogas

    (University of California Irvine)

  • Paul D. P. Pharoah

    (University of Cambridge
    University of Cambridge)

  • Per Hall

    (Karolinska Institutet
    Sšdersjukhuset)

  • Lodewyk F. A. Wessels

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
    Delft University of Technology)

  • Georgia Chenevix-Trench

    (QIMR Berghofer Medical Research Institute)

  • Gary D. Bader

    (University of Toronto
    University of Toronto)

  • Thilo Dörk

    (Hannover Medical School)

  • Douglas F. Easton

    (University of Cambridge
    University of Cambridge)

  • Sander Canisius

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
    The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital)

  • Marjanka K. Schmidt

    (The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
    The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital)

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.

Suggested Citation

  • 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 & Ja, 2020. "A network analysis to identify mediators of germline-driven differences in breast cancer prognosis," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14100-6
    DOI: 10.1038/s41467-019-14100-6
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    Cited by:

    1. Mischan Vali-Pour & Solip Park & Jose Espinosa-Carrasco & Daniel Ortiz-Martínez & Ben Lehner & Fran Supek, 2022. "The impact of rare germline variants on human somatic mutation processes," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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