Genome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions

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Lindström, SaraDepartment of Epidemiology, University of Washington, WA, Seattle, United States; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United States (författare)

Genome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions

Artikel/kapitelEngelska2023

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2023-03-17
Oxford University Press,2023
printrdacarrier

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LIBRIS-ID:oai:DiVA.org:umu-211988
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-211988URI
https://doi.org/10.1093/jnci/djad043DOI

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Språk:engelska
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BACKGROUND: The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from 12 cancer genome-wide association studies (GWAS) to quantify pairwise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.METHODS: We collected GWAS summary statistics for 12 solid cancers based on 376 759 participants with cancer and 532 864 participants without cancer of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci.RESULTS: We observed widespread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and transcriptome-wide association studies, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least 2 cancer types by testing for pleiotropy at known cancer susceptibility loci.CONCLUSIONS: Overall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer-specific and thus tissue-specific. The increase in statistical power associated with larger sample sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.

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Wang, LuDepartment of Environmental and Occupational Health Sciences, University of Washington, WA, Seattle, United States (författare)
Feng, HelianDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, MA, Boston, United States (författare)
Majumdar, ArunabhaDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, CA, Los Angeles, United States; Department of Mathematics, Indian Institute of Technology Hyderabad, Telangana, Kandi, India (författare)
Huo, SijiaDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, MA, Boston, United States (författare)
Macdonald, JamesDepartment of Environmental and Occupational Health Sciences, University of Washington, WA, Seattle, United States (författare)
Harrison, TabithaDepartment of Epidemiology, University of Washington, WA, Seattle, United States (författare)
Turman, ConstanceDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States (författare)
Chen, HongjieDepartment of Epidemiology, University of Washington, WA, Seattle, United States (författare)
Mancuso, NicholasDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, CA, Los Angeles, United States (författare)
Bammler, TheoDepartment of Environmental and Occupational Health Sciences, University of Washington, WA, Seattle, United States (författare)
Gallinger, SteveLunenfeld Tanenbaum Research Institute, University of Toronto, Mount Sinai Hospital, ON, Toronto, Canada (författare)
Gruber, Stephen B.Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA (författare)
Gunter, Marc J.International Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Le Marchand, LoicUniversity of Hawaii Cancer Center, HI, Honolulu, United States (författare)
Moreno, VictorOncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain; ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (författare)
Offit, KennethClinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA (författare)
De Vivo, ImmaculataDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, MA, Boston, United States (författare)
O'Mara, Tracy A.Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, QLD, Brisbane, Australia (författare)
Spurdle, Amanda B.Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, QLD, Brisbane, Australia (författare)
Tomlinson, IanCancer Research Centre, University of Edinburgh, Edinburgh, United Kingdom (författare)
Fitzgerald, RebeccaMRC Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, United Kingdom (författare)
Gharahkhani, PuyaStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia (författare)
Gockel, InesDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany (författare)
Jankowski, JanuszUniversity College London, United Kingdom; University of the South Pacific, Suva, Fiji (författare)
Macgregor, StuartStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia (författare)
Schumacher, JohannesCenter for Human Genetics, University Hospital of Marburg, Marburg, Germany (författare)
Barnholtz-Sloan, JillDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States; Trans-Divisional Research Program, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Bondy, Melissa L.Department of Epidemiology and Population Health, Stanford University, CA, Palo Alto, United States (författare)
Houlston, Richard S.Division of Genetics and Epidemiology, Institute of Cancer Research, London, United Kingdom (författare)
Jenkins, Robert B.Department of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, MN, Rochester, United States (författare)
Melin, Beatrice S.Umeå universitet,Institutionen för strålningsvetenskaper(Swepub:umu)bema0010 (författare)
Wrensch, MargaretDepartment of Neurological Surgery, University of California, CA, San Francisco, United States (författare)
Brennan, PaulInternational Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Christiani, David C.Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, MA, Boston, United States (författare)
Johansson, MattiasInternational Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Mckay, JamesInternational Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Aldrich, Melinda C.Department of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, TN, Nashville, United States (författare)
Amos, Christopher I.Institute for Clinical and Translational Research, Baylor College of Medicine, TX, Houston, United States (författare)
Landi, Maria TeresaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Tardon, AdoninaUniversity Institute of Oncology of the Principality of Asturias (IUOPA), University of Oviedo and Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Oviedo, Spain (författare)
Bishop, D TimothyLeeds Institute for Data Analytics, University of Leeds, Leeds, United Kingdom (författare)
Demenais, FlorenceInstitut National de la Santé et de la Recherche Médicale (INSERM), Paris, France (författare)
Goldstein, Alisa M.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Iles, Mark M.Leeds Institute for Data Analytics, University of Leeds, Leeds, United Kingdom (författare)
Kanetsky, Peter A.Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, FL, Tampa, United States (författare)
Law, Matthew H.Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia (författare)
Amundadottir, Laufey T.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Stolzenberg-Solomon, RachaelDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Wolpin, Brian M.Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, MA, Boston, United States (författare)
Klein, AlisonDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, MD, Baltimore, United States; Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, MD, Baltimore, United States (författare)
Petersen, GloriaDepartment of Quantitative Health Science, Mayo Clinic, MN, Rochester, United States (författare)
Risch, HarveyYale School of Public Health, Chronic Disease Epidemiology, CT, New Haven, United States (författare)
Chanock, Stephen J.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Purdue, Mark P.Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, MD, Bethesda, United States (författare)
Scelo, GhislaineInternational Agency for Research on Cancer, World Health Organization, Lyon, France (författare)
Pharoah, PaulCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (författare)
Kar, SiddharthaMedical Research Council Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom (författare)
Hung, Rayjean J.Prosserman Centre for Population Health Research, Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, ON, Toronto, Canada (författare)
Pasaniuc, BogdanDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, CA, Los Angeles, United States; Department of Human Genetics, David Geffen School of Medicine, University of California, CA, Los Angeles, United States; Department of Computational Medicine, David Geffen School of Medicine, University of California, CA, Los Angeles, United States (författare)
Kraft, PeterDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, MA, Boston, United States; Department of Epidemiology, Harvard T.H. Chan School of Public Health, MA, Boston, United States (författare)
Department of Epidemiology, University of Washington, WA, Seattle, United States; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, WA, Seattle, United StatesDepartment of Environmental and Occupational Health Sciences, University of Washington, WA, Seattle, United States (creator_code:org_t)

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Ingår i:Journal of the National Cancer Institute: Oxford University Press115:6, s. 712-7320027-88741460-2105

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Av författaren/redakt...: Lindström, Sara; Wang, Lu; Feng, Helian; Majumdar, Arunab ...; Huo, Sijia; Macdonald, James; visa fler...; Harrison, Tabith ...; Turman, Constanc ...; Chen, Hongjie; Mancuso, Nichola ...; Bammler, Theo; Gallinger, Steve; Gruber, Stephen ...; Gunter, Marc J.; Le Marchand, Loi ...; Moreno, Victor; Offit, Kenneth; De Vivo, Immacul ...; O'Mara, Tracy A.; Spurdle, Amanda ...; Tomlinson, Ian; Fitzgerald, Rebe ...; Gharahkhani, Puy ...; Gockel, Ines; Jankowski, Janus ...; Macgregor, Stuar ...; Schumacher, Joha ...; Barnholtz-Sloan, ...; Bondy, Melissa L ...; Houlston, Richar ...; Jenkins, Robert ...; Melin, Beatrice ...; Wrensch, Margare ...; Brennan, Paul; Christiani, Davi ...; Johansson, Matti ...; Mckay, James; Aldrich, Melinda ...; Amos, Christophe ...; Landi, Maria Ter ...; Tardon, Adonina; Bishop, D Timoth ...; Demenais, Floren ...; Goldstein, Alisa ...; Iles, Mark M.; Kanetsky, Peter ...; Law, Matthew H.; Amundadottir, La ...; Stolzenberg-Solo ...; Wolpin, Brian M.; Klein, Alison; Petersen, Gloria; Risch, Harvey; Chanock, Stephen ...; Purdue, Mark P.; Scelo, Ghislaine; Pharoah, Paul; Kar, Siddhartha; Hung, Rayjean J.; Pasaniuc, Bogdan; Kraft, Peter; visa färre...

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