ArticlemedRxiv : the preprint server for health sciences2026
Novel Genetic Risk Loci for Pancreatic Ductal Adenocarcinoma Identified in a Genome-wide Study of African Ancestry Individuals.
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87 authors.
Candelaria VergaraDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Zhanmo NiDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Jun ZhongLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0002-3700-9434
David McKeanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Katelyn E ConnellyLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Samuel O AntwiDepartment of Quantitative Health Sciences, Mayo Clinic College of Medicine, Jacksonville, FL, USA.
Alan A ArslanDepartments of Obstetrics and Gynecology and Population Health, NYU Grossman School of Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, NY, USA.
Paige M BracciDepartment of Epidemiology and Biostatistics,, University of California San Francisco, San Francisco, CA, USA.
Mengmeng DuDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center,, New York, NY, USA.
Steven GallingerLunenfeld-Tanenbaum Research Institute,, Sinai Health System and University of Toronto,, Toronto, Ontario, Canada.
Jeanine GenkingerDepartment of Epidemiology, Columbia University, New York, NY, USA.
Christopher A HaimanDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Manal HassanDepartment of Gastrointestinal Medical Oncology, Houston, TX, USA.
Rayjean J HungLunenfeld-Tanenbaum Research Institute,, Sinai Health System and University of Toronto,, Toronto, Ontario, Canada.
Chad HuffDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Fay KastrinosDivision of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, NY, USA.
Loic LeMarchandCancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
WooHyung LeeDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Shannon M LynchCancer Prevention and Control,, Fox Chase Cancer Center, Philadelphia, PA, USA.
Stephen C MooreMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ann L ObergDepartment of Quantitative Health Sciences, Rochester, MN, USA.
Margaret A ParkDepartment of GI Oncology and Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Jennifer B PermuthDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Harvey A RischDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
Paul ScheetDept of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ann SchwartzDepartment of Oncology, Wayne State University School of Medicine, Detroit, MI, Detriot, MI, USA.
Xiao-Ou ShuDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Rachael Z 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, Harvard Medical School, Harvard University, Boston, MA, USA.
Wei ZhengDivision of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.ORCID 0000-0003-1226-070X
Demetrius AlbanesMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Gabriella AndreottiOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
William R BamletDepartment of Quantitative Health Sciences, Mayo Clinic College of Medicine, Rochester, MN, USA.
Laura Beane-FreemanOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Sonja I BerndtOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Paul BrennanInternational Agency for Research on Cancer, Lyon, France.
Julie E BuringDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Natalia Cabrera-CastroDepartment of Epidemiology, Murcia Regional Health Council, Murcia, Spain.
Daniele CampaUnit of Genetics., Department of Biology, University of Pisa, Pisa, Italy.
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0002-4261-4583
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Yu ChenDepartment of Population Health, NYU Grossman School of Medicine, NYU Perlmutter Comprehensive Cancer Center, New York, NY, USA.
Charles C ChungCancer Genomics Research Laboratory, Frederick National Lab for Cancer Research, Frederick, MD, USA.
A Heather EliassenDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
J Michael GazianoDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Graham G GilesCancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
Edward L GiovannucciDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Michael GogginsDepartment of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Phyllis J GoodmanSWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Belynda HicksCancer Genomics Research Laboratory, Frederick National Lab for Cancer Research, Frederick, MD, USA.
Amy HutchinsonCancer Genomics Research Laboratory, Frederick National Lab for Cancer Research, Frederick, MD, USA.
Miranda R JonesDepartment of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA.
Verena KatzkeDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Manolis KogevinasISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Robert C KurtzGastroenterology, Hepatology, and Nutrition Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Daniel LaheruDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
I-Min LeeDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Núria MalatsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.ORCID 0000-0003-2538-3784
Roger MilneCancer Epidemiology Division, Cancer Council Victoria, East Melbourne, VIC, Australia.
Lorelei MucciDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Rachel E NealeDepartment of Population Health, QIMR Berghofer Medical Research Institute, Queensland, Australia.
Irene OrlowDepartment of Epidemiology and Biostatistics,, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Alpa V PatelEpidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
Laia PeruchetImperial College, London, Unitied Kingdom.
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.
Kari G RabeDepartment of Quantitative Health Sciences, Mayo Clinic College of Medicine, Rochester, MN, USA.
Francisco X RealEpithelial Carcinogenesis Group, Tumor Biology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Fulvio RicceriCentre for Biostatistics, Epidemiology, and Public Health (C-BEPH), Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Howard D SessoDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Veronica W SetiawanDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Debra SilvermanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Melissa C SoutheyPrecision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
Meir J StampferDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Geoffrey S TobiasDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Caroline UmDepartment of Population Science, American Cancer Society, Atlanta, GA, USA.
Kala VisvanathanDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Jean Wactawski-WendeDepartment of Epidemiology and Environmental Health, University of Buffalo, Buffalo, NY, USA.
Nicolas WentzensenDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Walter C WillettDepartment of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Herbert YuEpidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Peter KraftTrans-Divisional Research Program (TDRP), Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Priya DuggalDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.ORCID 0000-0001-5809-2081
Laufey T AmundadottirLaboratory of Translational Genomics, Division 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.ORCID 0000-0003-2737-8399
Funding
Multi-Ancestry Mapping of Pancreatic Cancer Susceptibility LociU01CA247283 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, ALISON P · 2020 to 2025
$3.5MCCR NIH HHS HHSN261200800001CNCI NIH HHS U01 CA247283NIH HHS HHSN261200800001E
Abstract
Pancreatic cancer disproportionately affects Black individuals in the United States, but they have limited representation in genetic studies of pancreatic ductal adenocarcinoma (PDAC). To address this gap, we performed admixture mapping and genome-wide association analysis (GWAS) in genetically inferred African ancestry individuals (1,030 cases and 889 controls). Admixture mapping identified three regions with a significantly higher proportion of African ancestry in cases compared to controls (5q33.3, 10p1, 22q12.3). GWAS identified a genome-wide significant association at 5p15.33 ( Statement of Significance: To understand how genetic variation contributes to PDAC risk in Black people in North American, we studied individuals of genetically-inferred African ancestry. We identified novel risk loci and differences in the contribution of known loci. This demonstrates that ancestry-informed genetic analyses improve our understanding of PDAC risk and enhances discovery.
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