ArticleJournal of the National Cancer Institute2026
Different diabetes types and pancreatic ductal adenocarcinoma: a Mendelian randomization and pathway/gene-set analysis.
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Article in Journal of the National Cancer Institute, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2citing papers in PubMed
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Who cites it
2 citing papers in PubMed.
- Causal association of type 1 diabetes with pancreatic cancer: a multi-ancestry Mendelian randomization study.Archives of medical science : AMS · 2026Article
- Epidemiological Trends and Shared Molecular Signatures of Pancreatic Ductal Adenocarcinoma and Diabetes: An Integrative Analysis Based on Global Burden of Disease and Gene Expression Omnibus Datasets.Journal of Cancer · 2026Article
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Authors and funding
71 authors.
Ting ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-9862-9434
Xing HuaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.
Chirayu MohindrooMedical Oncology Service, Center of Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-5825-3356
Xiaoyu WangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0009-0005-5143-6909
Diptavo DuttaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-6634-9040
Jia LiuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-4885-7180
Shilpa KattaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.
Shengchao A LiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0001-9252-1492
Jiahui WangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.
Samuel O AntwiDepartment of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL, United States.ORCID 0000-0003-2372-9489
Alan A ArslanDepartment of Obstetrics and Gynecology, New York University Grossman School of Medicine, New York, NY, United States.ORCID 0000-0002-7775-8085
Laura E Beane FreemanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0003-1294-4124
Paige M BracciDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States.ORCID 0000-0001-9338-9307
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0002-4261-4583
Mengmeng DuDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.ORCID 0000-0001-6156-1491
Steven GallingerLunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada.
Phyllis J GoodmanSWOG Statistical Center, Fred Hutchinson Cancer Center, Seattle, WA, United States.ORCID 0000-0001-9660-7074
Verena KatzkeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0002-6509-6555
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, United States.ORCID 0000-0002-7986-8560
Loic Le MarchandCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States.ORCID 0000-0001-5013-980X
Rachel E NealePopulation Health Program, QIMR Berghofer, Brisbane, QLD, Australia.ORCID 0000-0001-7162-0854
Alpa V PatelDepartment of Population Science, American Cancer Society, Atlanta, GA, United States.
Sandra PerdomoGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.ORCID 0000-0001-7740-8141
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States.ORCID 0000-0002-0711-8314
Kala VisvanathanDepartment of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, United States.ORCID 0000-0002-0582-8005
Stephen K Van Den EedenDivision of Research, Kaiser Permanente Northern California, Pleasanton, CA, United States.ORCID 0000-0002-5599-8387
Emily WhiteCancer Prevention Program, Fred Hutchinson Cancer Center, Seattle, WA, United States.ORCID 0000-0002-8177-0829
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, United States.ORCID 0000-0003-1226-070X
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0001-8330-4293
Gabriella AndreottiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-1096-3324
William R BamletDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States.
Paul BrennanGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.ORCID 0000-0002-0518-8714
Julie E BuringDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.ORCID 0000-0003-2648-8692
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-2324-3393
Yu ChenDepartment of Population Health, New York University Grossman School of Medicine, New York, NY, United States.ORCID 0000-0002-1519-4894
Burcu DarstDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, United States.ORCID 0000-0002-6205-4632
Pietro FerrariNutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID 0000-0001-9358-7338
Edward L GiovannucciDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.ORCID 0000-0002-6123-0219
Michael GogginsDepartment of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, United States.ORCID 0000-0002-4286-2296
Christopher HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.ORCID 0000-0002-0097-9971
Manal HassanDepartment of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States.ORCID 0000-0002-8413-449X
Elizabeth A HollyDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States.
Rayjean J HungLunenfeld-Tanenbaum Research Institute, Sinai Health System and University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-4486-7496
Miranda R JonesDepartment of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, United States.ORCID 0000-0003-4863-104X
Peter KraftDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-4472-8103
Robert C KurtzGastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
Núria MalatsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.ORCID 0000-0003-2538-3784
Steven C MooreDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-8169-1661
Kimmie NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.ORCID 0000-0003-0631-1494
Ann L ObergDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States.ORCID 0000-0003-2539-9807
Irene OrlowDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.ORCID 0000-0001-6234-6961
Ulrike PetersDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, United States.ORCID 0000-0001-5666-9318
Miquel PortaCentro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.ORCID 0000-0003-1684-7428
Kari G RabeDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United States.ORCID 0000-0002-7313-1875
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.
Maria-José SánchezGranada Cancer Registry, Escuela Andaluza de Salud Pública (EASP), Granada, Spain.ORCID 0000-0003-4817-0757
Howard D SessoDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States.ORCID 0000-0002-9698-9954
Debra T SilvermanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.
Melissa C SoutheyPrecision Medicine, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, VIC, Australia.ORCID 0000-0002-6313-9005
Caroline Y UmDepartment of Population Science, American Cancer Society, Atlanta, GA, United States.ORCID 0000-0001-5449-6230
James YarmolinskyDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.ORCID 0000-0003-4371-0873
Herbert YuCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States.ORCID 0000-0003-3950-4815
Chen YuanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.ORCID 0000-0002-0708-9648
Jun ZhongDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-3700-9434
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.ORCID 0000-0002-0455-1032
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, United States.ORCID 0000-0001-5337-3941
Laufey T AmundadottirDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0003-1859-8971
Alison P KleinDepartment of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, United States.ORCID 0000-0003-2737-8399
Kai YuDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0002-5337-137X
Haoyu ZhangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0001-6423-0444
Rachael Z Stolzenberg-SolomonDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, United States.ORCID 0000-0003-3698-7006
Funding
The Patient-Reported Outcomes, Community-Engagement and Language (PRO-CEL) CoreP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · 1985 to 2025
$88.4MSToP Cancer SPORE: Developmental Research ProgramP50CA257911 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 to 2025
$6.4MWhole Genome Scan in the Pancreatic Cancer Cohort Consortium (PanScan)ZIACP010193 · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · 2025 to 2025
$681kHHSIntramural NIH HHS Z01 CP010193Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA CP010193NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA257911NIH HHSNIH HHS 75N910D00024World Health Organization 001
Abstract
backgroundThe associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood.
methodsWe investigated associations of genetic susceptibility to type 2 diabetes (T2D), 8 T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242 283 cases, 1 569 734 controls), T1D (18 942 cases, 501 638 controls), and PDAC (10 244 cases and 360 535 controls) in individuals of European ancestry.
resultsTwo-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI = 1.05 to 1.15), particularly the T2D obesity (OR = 1.28; 95% CI = 1.15 to 1.42) and lipodystrophy (OR = 1.25; 95% CI = 1.03 to 1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI = 0.99 to 1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10-8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10-4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions.
conclusionsOur results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.
Indexed as
Carcinoma, Pancreatic DuctalDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2Pancreatic NeoplasmsCase-Control StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideRisk Factors
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