ArticleThe American journal of clinical nutrition2021
Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies.
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12 citing papers in PubMed, 38 citations in OpenAlex.
- Discovery of a Secretory Granule Lumen-Enriched Serum Protein Signature in Resectable Pancreatic Ductal Adenocarcinoma.Medicina (Kaunas, Lithuania) · 2026Article
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- SLC40A1 (iron transporter): mechanistic regulation, role in disease pathogenesis, and prospects for targeted therapy.Frontiers in cell and developmental biology · 2026Review
- Elevated expression of transferrin receptor-1 in pancreatic cancer: clinical implications and prognostic significance.Clinical and experimental medicine · 2025Article
- Review
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Genistein: a promising modulator of apoptosis and survival signaling in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- HIF2α, Hepcidin and their crosstalk as tumour-promoting signalling.British journal of cancer · 2023Review
- Relevant Membrane Transport Proteins as Possible Gatekeepers for Effective Pharmacological Ascorbate Treatment in Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma.Diagnostic pathology · 2022Article
- Development and validation of a prognostic prediction model for iron metabolism-related genes in patients with pancreatic adenocarcinoma.Frontiers in genetics · 2022Article
- Activation of the PPARγ Prevents Ferroptosis-Induced Neuronal Loss in Response to Intracerebral Hemorrhage Through Synergistic Actions With the Nrf2.Frontiers in pharmacology · 2022Article
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Authors and funding
79 authors at 20 institutions in 9 countries.
Sachelly Julián-SerranoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.ORCID 0000-0002-8912-8232
Fangcheng YuanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
William WheelerInformation Management Services, Silver Spring, MD, USA.
Beben BenyaminAustralian Centre for Precision Health, Allied Health and Human Performance, University of South Australia, Adelaide, Australia.
Mitchell J MachielaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Alan A ArslanDepartment of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Laura E Beane-FreemanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Paige M BracciDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Eric J DuellUnit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.
Mengmeng DuDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Steven GallingerLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
Graham G GilesCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.ORCID 0000-0003-4946-9099
Phyllis J GoodmanSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Loic Le MarchandDepartment of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, USA.
Rachel E NealePopulation Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia.ORCID 0000-0001-7162-0854
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Stephen K Van Den EedenDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.ORCID 0000-0002-5599-8387
Kala VisvanathanDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0002-0582-8005
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.ORCID 0000-0001-8330-4293
Gabriella AndreottiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Eva ArdanazNavarra Public Health Institute, Pamplona, Spain.
Ana BabicDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Lauren K BraisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Paul BrennanInternational Agency for Research on Cancer (IARC), Lyon, France.
Bas Bueno-de-MesquitaDepartment for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.ORCID 0000-0002-1834-1829
Julie E BuringDivision of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Erica J ChildsDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Charles C ChungDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Eleonora FabiánováSpecialized Institute of Hygiene and Epidemiology, Banska Bystrica, Slovakia.
Lenka ForetováDepartment of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Charles S FuchsYale Cancer Center and Smilow Cancer Hospital, New Haven, CT, USA.ORCID 0000-0003-1582-9842
J Michael GazianoDivision of Aging, Brigham and Women's Hospital, Boston, MA, USA.
Manuel GentiluomoDepartment of Biology, University of Pisa, Italy.
Edward L GiovannucciDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Michael G GogginsDepartment of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Thilo HackertDepartment of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.ORCID 0000-0002-7012-1196
Patricia HartgeDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Manal M HassanDepartment of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ivana HolcátováInstitute of Public Health and Preventive Medicine, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Elizabeth A HollyDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
Rayjean I HungLunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.
Vladimir JanoutFaculty of Health Sciences, University of Olomouc, Olomouc, Czech Republic.
Robert C KurtzDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
I-Min LeeDivision of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Núria MalatsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
David McKeanDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
Roger L MilneCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
Christina C NewtonDepartment of Population Science, American Cancer Society, Atlanta, GA, USA.
Ann L ObergDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.ORCID 0000-0003-2539-9807
Sandra PerdomoInternational Agency for Research on Cancer (IARC), Lyon, France.
Ulrike PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Miquel PortaHospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0003-1684-7428
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Matthias B SchulzeDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
Howard D SessoDivision of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Debra T SilvermanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Ian M ThompsonCHRISTUS Santa Rosa Hospital-Medical Center, San Antonio, TX, USA.
Jean Wactawski-WendeDepartment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.ORCID 0000-0003-3096-9595
Elisabete WeiderpassDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.ORCID 0000-0003-2237-0128
Nicolas WenstzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.ORCID 0000-0003-1251-0836
Emily WhiteDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lynne R WilkensDepartment of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, USA.
Herbert YuDepartment of Epidemiology, University of Hawaii Cancer Center, Honolulu, HI, USA.
Anne Zeleniuch-JacquotteDepartment of Population Health and Perlmutter Cancer Center, New York University School of Medicine, New York, NY, USA.
Jun ZhongDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Peter KraftDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-4472-8103
Dounghui LiDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID 0000-0002-7542-0662
Peter T CampbellDepartment of Population Science, American Cancer Society, Atlanta, GA, USA.
Gloria M PetersenDepartment of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.ORCID 0000-0001-5337-3941
Laufey T AmundadottirDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Alison P KleinDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.ORCID 0000-0003-2737-8399
Kai YuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Rachael Z Stolzenberg-SolomonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.ORCID 0000-0003-3698-7006
National Cancer Institute · USFred Hutch Cancer Center · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USJohns Hopkins University · USUniversity of Hawaiʻi at Mānoa · USAmerican Cancer Society · USCentre international de recherche sur le cancer · FRLunenfeld-Tanenbaum Research Institute · CAMayo Clinic · USMemorial Sloan Kettering Cancer Center · USNew York University · USSidney Kimmel Comprehensive Cancer Center · USThe University of Melbourne · AUThe University of Texas MD Anderson Cancer Center · USUniversity of California, San Francisco · USVanderbilt University · USBellvitge University Hospital · ESCharles University · CZChristus Santa Rosa Health System · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3MSWOG NCORP Research BaseUG1CA189974 · NCI · THE HOPE FOUNDATION · PI CHARLES D. BLANKE, DAWN HERSHMAN · 2014 to 2026
$80.6MTumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI JAFFEE, ELIZABETH M. · 1993 to 2022
$54.6MUnderstanding Population Differences in Cancer: The MEC StudyU01CA164973 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI HAIMAN, CHRISTOPHER ALAN, LE MARCHAND, LOIC · 2015 to 2025
$37.4MTissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI MUKHOPADHYAY, DEBABRATA · 2004 to 2018
$32.7MData sharing: the Colon Cancer Family Registry CohortU01CA167551 · NCI · UNIVERSITY OF MELBOURNE · PI Daniel David BUCHANAN, Steven Gallinger · 2018 to 2026
$16.8MONTARIO REGISTRY FOR STUDIES OF FAMILIAL COLON CANCERU01CA074783 · NCI · CANCER CARE ONTARIO · PI GALLINGER, STEVEN · 1997 to 2008
$12.5MBIOCHEMICAL MARKERS IN THE NURSES'HEALTH STUDY COHORTR01CA049449 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI HANKINSON, SUSAN E · 1989 to 2008
$11.3MWhole Genome Scan in the Pancreatic Cancer Cohort Consortium (PanScan)ZIACP010193 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI STOLZENBERG-SOLOMON, RACHAEL · 2009 to 2025
$9.5MValidation and Fine-Scale Mapping of Pancreatic Cancer Susceptibility Loci (Study)R01CA154823 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, ALISON P · 2011 to 2020
$5.7MMulti-Center Study of Pancreatic Cancer EtiologyR01CA102765 · NCI · KAISER FOUNDATION HEALTH PLAN OF WASHINGTON · PI MANDELSON, MARGARET · 2004 to 2009
$5.5MNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA062924NCI NIH HHS P50 CA102701NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA098380NCI NIH HHS R01 CA102765NCI NIH HHS R01 CA154823NCI NIH HHS R03 CA123546NCI NIH HHS U01 CA074783NCI NIH HHS U01CA164973NCI NIH HHS U01 CA167551NCI NIH HHS U01 CA182883NCI NIH HHS U01 CA182913NCI NIH HHS U01 CA182934NCI NIH HHS U01 CA247283NCI NIH HHS UG1 CA189974NCI NIH HHS UM1 CA182883NHLBI NIH HHS HHSN268201600001CNHLBI NIH HHS HHSN268201600002CNHLBI NIH HHS HHSN268201600003CNHLBI NIH HHS HHSN268201600004CNHLBI NIH HHS HHSN268201600018CNHLBI NIH HHS R01 HL034595NIH HHS RO1CA154823World Health Organization 001
Abstract
backgroundEpidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis.
objectivesThe objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC.
methodsWe conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs.
resultsThe hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association.
conclusionsOur results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.
Indexed as
AdenocarcinomaAgedCase-Control StudiesFemaleGene Expression Regulation, NeoplasticGenotypeHepcidinsHumansIronLinkage DisequilibriumMaleMiddle AgedPancreatic NeoplasmsPolymorphism, Single NucleotideHepcidinsIronepidemiologygenetic susceptibilityhepcidiniron metabolism pathwaypancreatic cancer
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