ArticleGenome medicine2021
A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.
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Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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20citing papers in PubMed, 1 pooled it
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20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Endoplasmic stress-inducing variants in CPB1 and CPA1 and risk of pancreatic cancer: A case-control study and meta-analysis.International journal of cancer · 2022Pooled it
- Pancreatic cancer.Nature reviews. Disease primers · 2026Review
- Association between immune cells and multiple cancers: Insights from Mendelian randomization and gene-based analysis.iScience · 2026Article
- Predictive prioritization of enhancers associated with pancreatic disease risk.Cell genomics · 2026Article
- Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis.Nature communications · 2025Article
- Development of a consensus molecular classifier for pancreatic ductal adenocarcinoma.Genome medicine · 2025Article
- Comprehensive assessment of disulfidptosis-related long non-coding RNA index as biomarkers for predicting clinical outcomes and immune microenvironment in pancreatic cancer.Translational cancer research · 2025Article
- SIAH3 is frequently epigenetically silenced in cancer and regulates mitochondrial metabolism.International journal of cancer · 2025Article
- Genetically predicted gut bacteria, circulating bacteria-associated metabolites and pancreatic ductal adenocarcinoma: a Mendelian randomisation study.Scientific reports · 2024Article
- Primary osteoarthritis chondrocyte map of chromatin conformation reveals novel candidate effector genes.Annals of the rheumatic diseases · 2024Article
- The relationship and clinical significance of lactylation modification in digestive system tumors.Cancer cell international · 2024Review
- PancanQTLv2.0: a comprehensive resource for expression quantitative trait loci across human cancers.Nucleic acids research · 2024Article
- The PENGUIN approach to reconstruct protein interactions at enhancer-promoter regions and its application to prostate cancer.Nature communications · 2023Article
- An Integrative Pancreatic Cancer Risk Prediction Model in the UK Biobank.Biomedicines · 2023Article
- Cuproptosis-related lncRNA scoring system to predict the clinical outcome and immune landscape in pancreatic adenocarcinoma.Scientific reports · 2023Article
- Enlightening the molecular mechanisms of type 2 diabetes with a novel pathway clustering and pathway subnetwork approach.Turkish journal of biology = Turk biyoloji dergisi · 2022Article
- A novel genomic instability-derived lncRNA signature to predict prognosis and immune characteristics of pancreatic ductal adenocarcinoma.Frontiers in immunology · 2022Article
- UEG position paper on pancreatic cancer. Bringing pancreatic cancer to the 21st century: Prevent, detect, and treat the disease earlier and better.United European gastroenterology journal · 2021Review
- A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer.Genome medicine · 2021Article
- Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk.Frontiers in genetics · 2021Article
Corrections and comments
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Authors and funding
77 authors at 20 institutions in 11 countries.
Evangelina López de Maturana *Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
Juan Antonio Rodríguez *CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Lola AlonsoGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
Oscar LaoCNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Esther Molina-MontesGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
Isabel Adoración Martín-AntonianoGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
Paulina Gómez-RubioGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
Rita LawlorARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Alfredo CarratoCIBERONC, Madrid, Spain.
Manuel HidalgoMadrid-Norte-Sanchinarro Hospital, Madrid, Spain.
Mar IglesiasCIBERONC, Madrid, Spain.
Xavier MoleroHospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Matthias LöhrGastrocentrum, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Christopher MichalskiDepartment of Surgery, Technical University of Munich, Munich, Germany.
José PereaDepartment of Surgery, Hospital 12 de Octubre, and Department of Surgery and Health Research Institute, Fundación Jiménez Díaz, Madrid, Spain.
Michael O'RorkeCentre for Public Health, Queen's University Belfast, Belfast, UK.
Victor Manuel BarberàMolecular Genetics Laboratory, General University Hospital of Elche, Elche, Spain.
Adonina TardónDepartment of Medicine, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain.
Antoni FarréDepartment of Gastroenterology and Clinical Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Luís Muñoz-BellvísCIBERONC, Madrid, Spain.
Tanja Crnogorac-JurcevicBarts Cancer Institute, Centre for Molecular Oncology, Queen Mary University of London, London, UK.
Enrique Domínguez-MuñozDepartment of Gastroenterology, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
Thomas GressDepartment of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany.
William GreenhalfDepartment of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Linda SharpNational Cancer Registry Ireland and HRB Clinical Research Facility, University College Cork, Cork, Ireland.
Luís ArnesCentre for Stem Cell Research and Developmental Biology, University of Copenhagen, Copenhagen, Denmark.
Lluís CecchiniCIBERONC, Madrid, Spain.
Joaquim BalsellsHospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
Eithne CostelloDepartment of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Lucas IlzarbeCIBERONC, Madrid, Spain.
Jörg KleeffDepartment of Surgery, Technical University of Munich, Munich, Germany.
Bo KongDepartment of Surgery, Technical University of Munich, Munich, Germany.
Mirari MárquezGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
Josefina MoraDepartment of Gastroenterology and Clinical Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Damian O'DriscollNational Cancer Registry Ireland and HRB Clinical Research Facility, University College Cork, Cork, Ireland.
Aldo ScarpaARC-Net Centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Weimin YeDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stokholm, Sweden.
Jingru YuDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stokholm, Sweden.
PanGenEU Investigators
Montserrat García-ClosasDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Manolis KogevinasCIBERESP, Madrid, Spain.
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Debra T SilvermanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
SBC/EPICURO Investigators
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Alan A ArslanDepartment of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Laura Beane-FreemanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Paige M BracciDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Paul BrennanInternational Agency for Research on Cancer (IARC), Lyon, France.
Bas Bueno-de-MesquitaDeparment for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Julie BuringDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ, Heidelberg, Germany.
Margaret DuDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Steve GallingerProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
J Michael GazianoDepartments of Medicine, Brigham and Women's Hospital, VA Boston and Harvard Medical School, Boston, MA, USA.
Phyllis J GoodmanSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Marc GunterInternational Agency for Research on Cancer (IARC), Lyon, France.
Loic LeMarchandCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Donghui LiUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rachael E NealePopulation Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ulrika PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Gloria M PetersenDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Maria José SánchezEscuela Andaluza de Salud Pública (EASP), Granada, Spain.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Mark D ThornquistDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Kala VisvanathanDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Douglas EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Brian M WolpinDepartment Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
Rachael Z Stolzenberg-SolomonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Alison P KleinDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Laufey T AmundadottirLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Marc A Marti-RenomNational Centre for Genomic Analysis (CNAG), Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Universitat Pompeu Fabra (UPF), ICREA, Baldiri Reixac 4, 08028, Barcelona, Spain. martirenom@cnag.crg.eu.
Francisco X RealCIBERONC, Madrid, Spain.
Núria MalatsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro 3, 28029, Madrid, Spain. nmalats@cnio.es.ORCID 0000-0003-2538-3784
National Institutes of Health · USSpanish National Cancer Research Centre · ESBrigham and Women's Hospital · USUniversitat Autònoma de Barcelona · ESHospital de Sant Pau · ESKarolinska Institutet · SEMayo Clinic · USUniversity of Liverpool · GBVanderbilt University · USBoston University · USGerman Cancer Research Center · DEKarolinska University Hospital · SEQueen Mary University of London · GBThe University of Texas MD Anderson Cancer Center · USUniversity College Cork · IEUniversity of California, San Francisco · USUniversity of Hawaiʻi at Mānoa · USCentre for Genomic Regulation · ESCentro de Investigación Biomédica en Red de Cáncer · ESCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública · ES
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MSWOG Foreign AccrualsU10CA037429 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI BLANKE, CHARLES D., MEYSKENS, FRANK L. · 1985 to 2014
$205.2MSWOG NCORP Research BaseUG1CA189974 · NCI · THE HOPE FOUNDATION · PI CHARLES D. BLANKE, DAWN HERSHMAN · 2014 to 2026
$80.6MViral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Jon C.D. Houtman · 2000 to 2026
$70.0MTumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI THOMPSON, ELIZABETH D · 1993 to 2022
$54.6MShanghai Womens Health StudyUM1CA182910 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ZHENG, WEI · 2014 to 2018
$5.9MValidation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci (Study)R01CA154823 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, ALISON P · 2011 to 2020
$5.7MPCPT and SELECT Cohorts: Core Infrastructure Support for Cancer ResearchU01CA182883 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI TANGEN, CATHERINE M., THOMPSON, IAN M. · 2019 to 2023
$5.4MMulti-Ancestry Mapping of Pancreatic Cancer Susceptibility LociU01CA247283 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, ALISON P · 2020 to 2025
$3.5MNCI NIH HHS HHSN261200800001ENCI NIH HHS P30 CA008748NCI NIH HHS P50 CA062924NCI NIH HHS R01 CA154823NCI NIH HHS U01 CA182883NCI NIH HHS U01 CA247283NCI NIH HHS U10 CA037429NCI NIH HHS UG1 CA189974NCI NIH HHS UM1 CA182910World Health Organization 001
Abstract
backgroundPancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance.
methodsWe complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants.
resultsWe identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E-06 in 1D approach and a Local Moran's Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8-a lncRNA associated with pancreatic carcinogenesis-with a lowest p value = 6.91E-05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1-a major regulator of the ER stress and unfolded protein responses in acinar cells-identified by 3D; all of them with a strong in silico functional support.
conclusionsThis multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.
Indexed as
Genetic Predisposition to DiseaseGenome-Wide Association StudyBiomarkers, TumorCell Line, TumorComputer SimulationGene Regulatory NetworksGenome, HumanHumansLinkage DisequilibriumPancreatic NeoplasmsReproducibility of ResultsSignal TransductionBiomarkers, Tumor3D genomic structureGenetic susceptibilityGenome-wide association analysisLocal indices of genome spatial autocorrelationPancreatic cancer risk
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