ArticleJournal of the National Cancer Institute2023
Genome-wide analyses characterize shared heritability among cancers and identify novel cancer susceptibility regions.
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Article in Journal of the National Cancer Institute, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed.
- Identifying shared polygenic risk across cancers.PLoS genetics · 2026Article
- Genomic structural equation modelling of 12 cancers identifies a latent pan-cancer susceptibility factor and shared determinants of carcinogenesis.EBioMedicine · 2026Article
- Cell type-specific contextualisation of the human phenome: towards the systematic treatment of all rare diseases.Genome medicine · 2026Article
- Integrated Clinicogenomic Risk Modeling for Metachronous Second Primary Cancers.medRxiv : the preprint server for health sciences · 2026Article
- Article
- Isoform-level analyses of 6 cancers uncover extensive genetic risk mechanisms undetected at the gene-level.British journal of cancer · 2025Article
- Systematic decoding of functional enhancer connectomes and risk variants in human glioma.Nature cell biology · 2025Article
- Sleep patterns, genetic susceptibility, and gastrointestinal cancer mortality: a large-scale prospective cohort study.Sleep & breathing = Schlaf & Atmung · 2025Observational
- A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis.The Journal of clinical investigation · 2025Article
- Phenome-wide association study identifies multiple traits associated with a polygenic risk score for colorectal cancer.Human genomics · 2025Article
- Transcriptome-wide association study of alternative polyadenylation identifies susceptibility genes in non-small cell lung cancer.Oncogene · 2025Article
- Validation and Derivation of miRNA-Based Germline Signatures Predicting Radiation Toxicity in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Novel Shared Heritable Candidate Risk Loci of Breast and Endometrial Cancer-A Swedish Haplotype Genome-Wide Association Study.International journal of molecular sciences · 2025Article
- Mechanistic Insights into Tumorigenesis from Serum Proteins.medRxiv : the preprint server for health sciences · 2025Article
- Research trends and hotspots of single nucleotide polymorphisms in endometrial cancer: a bibliometric analysis.Discover oncology · 2025Article
- A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases.Nature communications · 2025Article
- Article
- Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank.PLoS medicine · 2025Article
- GWAS and 3D chromatin mapping identifies multicancer risk genes associated with hormone-dependent cancers.PLoS genetics · 2024Article
- Nonadditive Effects of Common Genetic Variants Have a Negligent Contribution to Cancer Heritability.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
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Authors and funding
68 authors.
Sara LindströmDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7137-7281
Lu WangDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
Helian FengDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Arunabha MajumdarDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Sijia HuoDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
James MacdonaldDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
Tabitha HarrisonDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Constance TurmanDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-7790-8311
Hongjie ChenDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-6438-108X
Nicholas MancusoDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Theo BammlerDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
Breast Cancer Association Consortium (BCAC)
Steve GallingerLunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Stephen B GruberDepartment of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.ORCID 0000-0001-8656-7822
Marc J GunterInternational Agency for Research on Cancer, World Health Organization, Lyon, France.
Loic Le MarchandUniversity of Hawaii Cancer Center, Honolulu, HI, USA.ORCID 0000-0001-5013-980X
Victor MorenoOncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID 0000-0002-2818-5487
Kenneth OffitClinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-2180-2032
Colorectal Transdisciplinary Study (CORECT), Colon Cancer Family Registry Study (CCFR), Genetics And Epidemiology Of Colorectal Cancer Consortium (GECCO)
Immaculata De VivoDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Tracy A O'MaraDepartment of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Amanda B SpurdleDepartment of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ian TomlinsonCancer Research Centre, The University of Edinburgh, Edinburgh, UK.
Endometrial Cancer Association Consortium (ECAC)
Rebecca FitzgeraldMRC Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, UK.
Puya GharahkhaniStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.ORCID 0000-0002-4203-5952
Ines GockelDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany.
Janusz JankowskiInstitute for Clinical Trials, University College London, Holborn, UK.
Stuart MacgregorStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.ORCID 0000-0001-6731-8142
Johannes SchumacherCenter for Human Genetics, University Hospital of Marburg, Marburg, Germany.ORCID 0000-0001-9217-6457
Jill Barnholtz-SloanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Melissa L BondyDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA.
Richard S HoulstonDivision of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.ORCID 0000-0002-5268-0242
Robert B JenkinsDepartment of Laboratory Medicine and Pathology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, MN, USA.
Beatrice MelinDepartment of Radiation Sciences, Umeå University, Umeå, Sweden.
Margaret WrenschDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Paul BrennanInternational Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID 0000-0002-0518-8714
David C ChristianiDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Mattias JohanssonInternational Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID 0000-0002-3116-5081
James MckayInternational Agency for Research on Cancer, World Health Organization, Lyon, France.
Melinda C AldrichDepartment of Thoracic Surgery, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA.
Christopher I AmosInstitute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA.
Maria Teresa LandiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Adonina TardonUniversity 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.
International Lung Cancer Consortium (ILCCO)
D Timothy BishopLeeds Institute for Data Analytics, University of Leeds, Leeds, UK.
Florence DemenaisUniversité Paris Cité, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR-1124, Paris, France.
Alisa M GoldsteinDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Mark M IlesLeeds Institute for Data Analytics, University of Leeds, Leeds, UK.ORCID 0000-0002-2603-6509
Peter A KanetskyDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Matthew H LawStatistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.ORCID 0000-0002-4303-8821
Ovarian Cancer Association Consortium (OCAC)
Laufey T AmundadottirDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-1859-8971
Rachael Stolzenberg-SolomonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Pancreatic Cancer Cohort Consortium (Panscan)
Alison KleinDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-2737-8399
Gloria PetersenDepartment of Quantitative Health Science, Mayo Clinic, Rochester, MN, USA.
Harvey RischYale School of Public Health, Chronic Disease Epidemiology, New Haven, CT, USA.
Pancreatic Cancer Case-Control Consortium (Panc4), The PRACTICAL Consortium
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-2324-3393
Mark P PurdueDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ghislaine SceloInternational Agency for Research on Cancer, World Health Organization, Lyon, France.
Paul PharoahCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Siddhartha KarMedical Research Council Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-2314-1426
Rayjean J HungProsserman Centre for Population Health Research, Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Bogdan PasaniucDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Peter KraftDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-4472-8103
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTranslational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4MUSC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3MStatistical Methods for Integrative Genomics in CancerP01CA196569 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Paul Marjoram · 2016 to 2026
$25.5MMolecular pathological epidemiology of colorectal cancerU01CA137088 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2009 to 2018
$21.8MTransdisciplinary Team Science in Colorectal Cancer Prognosis: the ColoCare StudyU01CA206110 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jane C. Figueiredo, Christopher I Li · 2016 to 2026
$18.6MData sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8MDetection of Colorectal Cancer Susceptibility Loci Using Genome-Wide SequencingU01CA164930 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2012 to 2015
$12.4MGenome-Wide Association Study of Nonsynonymous SNPs in Colon CancerR01CA059045 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 1994 to 2011
$11.5MTransdisciplinary Studies of Genetic Variation in Colorectal CancerU19CA148107 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GRUBER, STEPHEN B · 2010 to 2014
$11.1MStatistical Methods for Analysis of Massive Genetic and Genomic Data in Cancer ResearchR35CA197449 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI XIHONG LIN · 2015 to 2026
$10.9MCancer Research UK 25514Cancer Research UK 29017Cancer Research UK 4584Cancer Research UK C1287/A10118CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001ENCI NIH HHS P01 CA196569NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014089NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA059045NCI NIH HHS R01 CA081488NCI NIH HHS R01 CA143237NCI NIH HHS R01 CA189184NCI NIH HHS R01 CA194393NCI NIH HHS R01 CA197350NCI NIH HHS R01 CA201407NCI NIH HHS R01 CA242218NCI NIH HHS R21 CA191312NCI NIH HHS R35 CA197449NCI NIH HHS U01 CA122839NCI NIH HHS U01 CA137088NCI NIH HHS U01 CA164930NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA182883NCI NIH HHS U01 CA194393NCI NIH HHS U01 CA206110NCI NIH HHS U01 CA261339NCI NIH HHS U19 CA148065NCI NIH HHS U19 CA148107NHLBI NIH HHS HHSN268201000029CNHLBI NIH HHS HHSN268201200008CNHLBI NIH HHS HHSN268201200008INHLBI NIH HHS HHSN268201700006CNIA NIH HHS U01 AG018033NIA NIH HHS U01 AG18033NIDA NIH HHS R01 DA006227NIEHS NIH HHS T32 ES013678NIH HHS R01 CA189184NIH HHS S10 OD028685NIH HHS T32 ES013678NIH HHS U01 CA122839NIH HHS U01 CA167551NIH HHS U19 CA148065NIMH NIH HHS R01 MH090936NIMH NIH HHS R01 MH090937NIMH NIH HHS R01 MH090941NIMH NIH HHS R01 MH090948NIMH NIH HHS R01 MH090951NIMH NIH HHS R01 MH101782NIMH NIH HHS R01 MH101810NIMH NIH HHS R01 MH101814NIMH NIH HHS R01 MH101819NIMH NIH HHS R01 MH101820NIMH NIH HHS R01 MH101822NIMH NIH HHS R01 MH101825World Health Organization 001
Abstract
backgroundThe 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.
methodsWe 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.
resultsWe 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.
conclusionsOverall, 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.
Indexed as
Genome-Wide Association StudyNeoplasmsGenetic Predisposition to DiseaseHumansMalePolymorphism, Single NucleotideRisk FactorsTranscriptome
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