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Shared heritability and functional enrichment across six solid cancers

  • Xia Jiang
  • , Hilary K. Finucane
  • , Fredrick R. Schumacher
  • , Stephanie L. Schmit
  • , Jonathan P. Tyrer
  • , Younghun Han
  • , Kyriaki Michailidou
  • , Corina Lesseur
  • , Karoline B. Kuchenbaecker
  • , Joe Dennis
  • , David V. Conti
  • , Graham Casey
  • , Mia M. Gaudet
  • , Jeroen R. Huyghe
  • , Demetrius Albanes
  • , Melinda C. Aldrich
  • , Angeline S. Andrew
  • , Irene L. Andrulis
  • , Hoda Anton-Culver
  • , Antonis C. Antoniou
  • Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L. Carvalho, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen B.M. Claes, Frank Claessens, Judith Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna deFazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L. Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Edlund, Digna R.Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J. Gallinger, Patricia A. Ganz, Judy Garber, José A. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary Goodman, Kjell Grankvist, Mark H. Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun Chul Hong, John L. Hopper, Richard Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay Tee Khaw, Elza Khusnutdinova, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B. Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejovic, Kathryn L. Penney, Wilbert H.M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, V. Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina Dalsgaard Sorensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloiza H. Tajara, Catherine M. Tangen, Adonina Tardon, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine M.L. West, Emily White, Alice S. Whittemore, H. Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A. Eeles, Georgia Chenevix-Trench, Paul J. Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D.P. Pharoah, Alkes L. Price, Bogdan Pasaniuc, Christopher I. Amos, Peter Kraft, Sara Lindström
  • Harvard University
  • Karolinska Institutet
  • Broad Institute
  • Case Western Reserve University
  • Case Western University Hospitals
  • H. Lee Moffitt Cancer Center & Research Institute
  • University of Cambridge
  • Dartmouth College
  • Cyprus Institute of Neurology and Genetics
  • International Agency for Research on Cancer
  • University College London
  • Keck School of Medicine of USC
  • University of Virginia
  • University of Virginia School of Medicine
  • American Cancer Society
  • Fred Hutchinson Cancer Research Center
  • National Cancer Institute (NCI)
  • Vanderbilt University Medical Center
  • Dartmouth Hitchcock Medical Center
  • Samuel Lunenfeld Research Institute
  • University of Toronto
  • University of California, Irvine
  • The N.N. Alexandrov Research Institute of Oncology and Medical Radiology
  • University of Kentucky
  • Queen's University
  • MD Anderson Cancer Center
  • Rutgers - The State University of New Jersey, New Brunswick
  • Landspitali University Hospital
  • Faculty of Medicine, University of Iceland
  • Translational Research Institute Australia
  • Queensland University of Technology
  • Friedrich-Alexander University Erlangen-Nürnberg
  • Centro de Investigación en Red de Enfermedades Raras
  • Centre for Biomedical Research on Rare Diseases (CIBERER)
  • Institute of Cancer Research
  • Duke University
  • University Medical Center Goettingen
  • University of Washington
  • Helsinki University Hospital
  • Örebro University
  • Fondazione Policlinico Universitario A. Gemelli IRCCS
  • Catholic University of the Sacred Heart
  • Hannover Medical School
  • Copenhagen University Hospital – Herlev and Gentofte
  • University of Copenhagen
  • Robert Bosch Foundation
  • University of Tübingen
  • German Cancer Research Center
  • Institute Catala Oncologia
  • Lund University
  • Division of Laboratory Medicine
  • University of Melbourne
  • Royal Melbourne Hospital
  • Heidelberg University 
  • University of Helsinki
  • Hospital Clínico San Carlos de Madrid
  • University Hospital of Pisa
  • Peter Maccallum Cancer Centre
  • Sorbonne Université
  • Tenon Hospital
  • University of Utah School of Medicine
  • VA Medical Center
  • University of Pisa
  • Barretos Cancer Hospital
  • Massachusetts General Hospital
  • University of Hamburg
  • Ghent University
  • KU Leuven
  • Erasmus University Rotterdam
  • University of Puerto Rico, Medical Sciences Campus
  • Mayo Clinic Rochester, MN
  • University of Sheffield
  • Pomeranian Medical University in Szczecin
  • Karolinska University Hospital
  • Fox Chase Cancer Center
  • The University of Sydney
  • Westmead Hospital
  • Leiden University
  • Vall d'Hebron University Hospital
  • Complejo Hospitalario Universitario de Santiago
  • Moores Cancer Center
  • University of Bristol
  • University of Westminster
  • University of Southampton, Faculty of Medicine
  • University of Manchester
  • University of California at Los Angeles
  • University of Pittsburgh
  • University of Liverpool
  • Cedars-Sinai Medical Center
  • Demokritos National Centre for Scientific Research
  • Sheba Medical Center at Tel Hashomer
  • Tel Aviv University
  • Mount Sinai Hospital of University of Toronto
  • University Health Network Toronto General Hospital
  • Dana-Farber Cancer Institute
  • Cancer Council Victoria
  • Melbourne School of Population and Global Health
  • Eastern Health Clinical School
  • University of Kansas
  • McGill University
  • McGill University Health Centre, Royal Victoria Hospital
  • University of Utah
  • Swedish Medical Center
  • Umeå University
  • Occupational and Social Determinants of Health
  • University of Oxford
  • Princess Margaret Hospital
  • Technische Universität Dresden
  • National Institute of Occupational Health
  • DrHorst Schmidt Kliniken Wiesbaden
  • Kliniken Essen-Mitte
  • Danish Cancer Society
  • University of Copenhagen
  • Seoul National University
  • NorthShore University HealthSystem
  • The University of Chicago
  • University of British Columbia
  • BC Cancer
  • University of British Columbia, Faculty of Medicine
  • Russian Ministry of Health
  • Georgetown University
  • Stanford University
  • Medical University Sofia
  • Medical University of South Carolina
  • Bashkir State University
  • Russian Academy of Sciences
  • Brigham and Women’s Hospital
  • Radboud University Nijmegen
  • Barcelona Institute for Global Health
  • IMIM (Hospital Del Mar Research Institute)
  • Universitat Pompeu Fabra Barcelona
  • Oslo University Hospital-Radiumhospitalet
  • University of Oslo
  • Oslo University Hospital
  • Maria Sklodowska-Curie Institute of Oncology
  • Maastricht University
  • VIB Department of Molecular Microbiology
  • Washington State University Spokane
  • Carmel Medical Center and Technion Faculty of Medicine
  • Memorial Sloan-Kettering Cancer Center
  • NYU Langone Medical Center
  • University of Santiago de Compostela
  • Mayo Clinic Scottsdale-Phoenix, Arizona
  • Istituto Oncologico Veneto – IRCCS
  • Ulm University
  • University of Eastern Finland
  • University of Hawai'i at Mānoa
  • Technical University of Munich
  • Roswell Park Cancer Institute
  • University of Pittsburgh Cancer Institute
  • University of Barcelona
  • University of Warwick
  • University Health Network
  • University of Pennsylvania Health System
  • Beckman Research Institute of City of Hope
  • Rigshospitalet
  • Latvian Biomedical Research and Study Centre
  • University of California at San Francisco
  • National Institute of Oncology
  • Department of Clinical Neurosciences
  • University of North Carolina at Chapel Hill
  • University of North Carolina
  • University of Surrey
  • Queensland Institute of Medical Research
  • Oregon Health and Science University
  • Macedonian Academy of Sciences and Arts
  • IRCCS Fondazione Istituto Nazionale per lo studio e la cura dei tumori - Milano
  • deCODE Genetics
  • University of New South Wales
  • Garvan Institute of Medical Research
  • Vanderbilt University
  • University of Pretoria
  • Yale University
  • University of Salzburg
  • Translational Lung Research Center Heidelberg (TLRC-H)
  • Icahn School of Medicine at Mount Sinai
  • Heraklion University Hospital
  • National Institute of Environmental Health Sciences (NIEHS)
  • Guy’s Hospital
  • University of Turku
  • Turku University Hospital
  • Tampere University
  • Antoni van Leeuwenhoek Hospital
  • Nanjing Medical University
  • Medical University of Vienna
  • Aarhus University Hospital
  • Aarhus University
  • Monash University
  • Ludwig Maximilian University of Munich
  • University of Western Australia
  • University of Gothenburg
  • University of South Florida
  • School of Medicine of São José do Rio Preto
  • Universidade de São Paulo
  • University of Oviedo
  • North Region Cancer Registry, Portuguese Oncology Institute
  • University of Porto
  • Mailman School of Public Health
  • Odense University Hospital
  • University of Bergen
  • Ohio State University
  • Beth Israel Deaconess Medical Center
  • University of Alberta
  • University Hospitals Leuven
  • University of North Carolina School of Medicine
  • Stanford University School of Medicine
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • University of Oulu
  • Northern Finland Laboratory Centre Oulu
  • Uppsala University
  • Memorial University of Newfoundland
  • Department of Breast Surgery
  • Université Laval
  • Univ. of California
  • Baylor College of Medicine

Producción: Contribución a una revistaArtículorevisión exhaustiva

87 Citas (Scopus)

Resumen

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10−8), breast and ovarian cancer (rg = 0.24, p = 7 × 10−5), breast and lung cancer (rg = 0.18, p =1.5 × 10−6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10−4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.

Idioma originalInglés
Número de artículo431
PublicaciónNature Communications
Volumen10
N.º1
DOI
EstadoPublicada - 01 dic 2019

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

  1. ODS 3: Salud y bienestar
    ODS 3: Salud y bienestar

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