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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.
Nat Commun 2020; 11(1):312NC

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+Show Affiliations

Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. Cambridge Experimental Cancer Medicine Centre, Cambridge, UK. Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, University of Cambridge NHS Foundation Hospitals, Cambridge, UK.Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Canada.Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.Cancer Center, Kuopio University Hospital, Kuopio, Finland. Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland. Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland.Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia.Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. Department of Oncology, Örebro University Hospital, Örebro, Sweden.Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA. International Epidemiology Institute, Rockville, MD, USA.Department of Radiation Oncology, Hannover Medical School, Hannover, Germany. Gynaecology Research Unit, Hannover Medical School, Hannover, Germany. N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany. iFIT-Cluster of Excellence, University of Tuebingen, Tuebingen, Germany. German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.Department of Gynecology and Obstetrics, University of Tübingen, Tübingen, Germany.Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany. Molecular Biology of Breast Cancer, University Womens Clinic Heidelberg, University of Heidelberg, Heidelberg, Germany.Cancer Research UK Cambridge Institute, Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge, UK. Breast Cancer Programme, CRUK Cambridge Cancer Centre and NIHR Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia.Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.Department of Oncology and Metabolism, Sheffield Institute for Nucleic Acids (SInFoNiA), University of Sheffield, Sheffield, UK.Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK.Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, University of Cambridge NHS Foundation Hospitals, Cambridge, UK. Department of Oncology, University of Cambridge, Cambridge, UK.Cancer Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. Genomic Medicine, St Mary's Hospital, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany. Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK. Cancer Research UK Edinburgh Centre, Edinburgh, UK.Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS, Santiago de Compostela, Spain. Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.Department of Surgery, Oulu University Hospital, University of Oulu, Oulu, Finland.Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), University Paris-Saclay, INSERM, University Paris-Sud, Villejuif, France.Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.Warwick Clinical Trials Unit, University of Warwick, Coventry, UK.Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.Division of Cancer Sciences, University of Manchester, Manchester, UK.Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Nuffield Department of Population Health, University of Oxford, Oxford, UK.Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland. Independent Laboratory of Molecular Biology and Genetic Diagnostics, Pomeranian Medical University, Szczecin, Poland.Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.Department of Surgical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.VIB, VIB Center for Cancer Biology, Leuven, Belgium. Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium.Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.Carmel Medical Center and Technion Faculty of Medicine, Clalit National Cancer Control Center, Haifa, Israel.Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland. Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland. Department of Clinical Pathology, Imaging Center, Kuopio University Hospital, Kuopio, Finland.Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.Unit of Medical Genetics, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT), Milan, Italy.Department of Oncology, Sšdersjukhuset, Stockholm, Sweden. Department of Clinical Science and Education, Sšdersjukhuset, Karolinska Institutet, Stockholm, Sweden.Moores Cancer Center, University of California San Diego, La Jolla, CA, USA. Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Medical Oncology, University Hospital of Heraklion, Heraklion, Greece.Department of Gynecology and Obstetrics, Ludwig Maximilian University of Munich, Munich, Germany.Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.Division of Evolution and Genomic Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. Genomic Medicine, St Mary's Hospital, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.Department of Epidemiology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.Department of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Ireland, UK.Genome Diagnostics Program, IFOM - the FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy.Research Oncology, Guy's Hospital, King's College London, London, UK.Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK.Department of Oncology, Leuven Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.Carmel Medical Center and Technion Faculty of Medicine, Clalit National Cancer Control Center, Haifa, Israel.Medical Oncology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain.Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia.Department of Oncology, University Hospital of Larissa, Larissa, Greece.Research Oncology, Guy's Hospital, King's College London, London, UK.Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany. Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.Department of Gynaecology and Obstetrics, University Hospital Ulm, Ulm, Germany.Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.Genomics Center, Research Center, Centre Hospitalier Universitaire de Québec - Université Laval, Québec City, QC, Canada.National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia. Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, Australia.Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.Faculty of Medicine, University of Southampton, Southampton, UK.Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.Peter MacCallum Cancer Center, Melbourne, VIC, Australia. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia.Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.Department of Epidemiology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), University Paris-Saclay, INSERM, University Paris-Sud, Villejuif, France.Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.Biocenter Oulu, Cancer and Translational Medicine Research Unit, Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, Oulu, Finland. Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland.Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, CA, USA.Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Oncology, Sšdersjukhuset, Stockholm, Sweden.Division of Molecular Carcinogenesis, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Faculty of EEMCS, Delft University of Technology, Delft, The Netherlands.Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.Department of Molecular Genetics, University of Toronto, Toronto, Canada. The Donnelly Centre, University of Toronto, Toronto, ON, Canada.Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK. Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. s.canisius@nki.nl. Division of Molecular Carcinogenesis, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. s.canisius@nki.nl.Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. mk.schmidt@nki.nl. Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. mk.schmidt@nki.nl.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31949161

Citation

Escala-Garcia, Maria, et al. "A Network Analysis to Identify Mediators of Germline-driven Differences in Breast Cancer Prognosis." Nature Communications, vol. 11, no. 1, 2020, p. 312.
Escala-Garcia M, Abraham J, Andrulis IL, et al. A network analysis to identify mediators of germline-driven differences in breast cancer prognosis. Nat Commun. 2020;11(1):312.
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), p. 312. doi:10.1038/s41467-019-14100-6.
Escala-Garcia M, et al. A Network Analysis to Identify Mediators of Germline-driven Differences in Breast Cancer Prognosis. Nat Commun. 2020 Jan 16;11(1):312. PubMed PMID: 31949161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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, Y1 - 2020/01/16/ PY - 2019/01/31/received PY - 2019/12/17/accepted PY - 2020/1/18/entrez PY - 2020/1/18/pubmed PY - 2020/1/18/medline SP - 312 EP - 312 JF - Nature communications JO - Nat Commun VL - 11 IS - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/31949161/A_network_analysis_to_identify_mediators_of_germline-driven_differences_in_breast_cancer_prognosis L2 - http://dx.doi.org/10.1038/s41467-019-14100-6 DB - PRIME DP - Unbound Medicine ER -