ArticleBiological research2023
Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.
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- The 12-Year Experience of the Hungarian Pancreatic Study Group.Journal of clinical medicine · 2025Review
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73 authors at 20 institutions in 12 countries.
Margherita Piccardi *Department of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy.
Manuel Gentiluomo *Department of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy.
Stefania BertonciniDepartment of Biology, Unit of Zoology and Anthropology, University of Pisa, Pisa, Italy.
Raffaele PezzilliPotenza County Medical Association, Potenza, Italy.
Bálint ErőssInstitute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Stefania BunducInstitute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Faik G UzunogluDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Renata Talar-WojnarowskaDepartment of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
Tomas VanagasDepartment of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Cosimo SpertiDepartment DISCOG, Chirurgia Generale 1, University of Padova, Padua, Italy.
Martin OliveriusDepartment of Surgery, Third Faculty of Medicine, University Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic.
Mateus Nóbrega AokiLaboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Curitiba, Brazil.
Stefano ErminiBlood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Children's Hospital, Florence, Italy.
Tamás HusseinInstitute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Ugo BoggiDivision of General and Transplantation Surgery, University of Pisa, Pisa, Italy.
Krzysztof JamroziakDepartment of Hematology, Transplantation and Internal Medicine, University of Warsaw, Warsaw, Poland.
Evaristo MaielloDepartment of Oncology, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.
Luca MorelliDepartment of Translational Research and New Technologies in Medicine and Surgery, General Surgery Unit, University of Pisa, Pisa, Italy.
Ludmila VodickovaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
Gregorio Di FrancoDepartment of Translational Research and New Technologies in Medicine and Surgery, General Surgery Unit, University of Pisa, Pisa, Italy.
Stefano LandiDepartment of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy.
Andrea SzentesiInstitute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Martin LovecekDepartment of Surgery I, University Hospital Olomouc, Olomouc, Czech Republic.
Marta PuzzonoGastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Francesca TavanoDivision of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.
Hanneke W M van LaarhovenDepartment of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
Alessandro ZerbiPancreatic Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
Beatrice Mohelnikova-DuchonovaDepartment of Oncology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
Hannah StockerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Eithne CostelloDepartment of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Gabriele CapursoDigestive and Liver Disease Unit, S Andrea Hospital, Rome, Italy.
Laura GinocchiOncological Department, Oncology of Massa Carrara, ASL Toscana Nord Ovest, Massa Carrara, Italy.
Rita T LawlorARC-NET Research Centre and Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy.
Giuseppe VanellaDigestive and Liver Disease Unit, S Andrea Hospital, Rome, Italy.
Francesca BazzocchiDepartment of Surgery, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.
Jakob R IzbickiDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anna LatianoDivision of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.
Bas Bueno-de-MesquitaCentre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Ruggero Ponz de Leon PisaniPancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy.
Ben SchöttkerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Pavel SoucekBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Péter HegyiInstitute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Maria GazouliLaboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Thilo HackertDepartment of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Juozas KupcinskasDepartment of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Lina PoskieneDepartment of Pathology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Matteo TacelliPancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy.
Susanne RothDepartment of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Silvia CarraraDepartment of Gastroenterology, Endoscopic Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
Francesco PerriDivision of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.
Viktor HlavacBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
George E TheodoropoulosFirst Department of Propaedeutic Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Olivier R BuschDepartment of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands.
Andrea MambriniOncological Department, Oncology of Massa Carrara, ASL Toscana Nord Ovest, Massa Carrara, Italy.
Casper H J van EijckDepartment of Surgery, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Paolo ArcidiaconoPancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy.
Aldo ScarpaARC-NET Research Centre and Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy.
Claudio PasqualiDepartment DISCOG, Chirurgia Generale 3, University of Padova, Padua, Italy.
Daniela BassoDepartment DIMED, Laboratory Medicine, University of Padova, Padua, Italy.
Maurizio LucchesiOncological Department, Oncology of Massa Carrara, ASL Toscana Nord Ovest, Massa Carrara, Italy.
Anna Caterina MilanettoDepartment DISCOG, Chirurgia Generale 3, University of Padova, Padua, Italy.
John P NeoptolemosDepartment of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Giulia Martina CavestroGastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Dainius JanciauskasDepartment of Pathology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Xuechen ChenDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Roger ChammasDepartment of Radiology and Oncology, Institute of Cancer of São Paulo (ICESP) São Paulo, Sao Paulo, Brazil.
Mara GoetzDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hermann BrennerDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Livia ArchibugiDigestive and Liver Disease Unit, S Andrea Hospital, Rome, Italy.
Michael DannemannEstonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Sergio TofanelliDepartment of Biology, Unit of Zoology and Anthropology, University of Pisa, Pisa, Italy.
Daniele CampaDepartment of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy. daniele.campa@unipi.it.
University of Pisa · ITCasa Sollievo della Sofferenza · ITCharles University · CZGerman Cancer Research Center · DEHeidelberg University · DEIstituti di Ricovero e Cura a Carattere Scientifico · ITLithuanian University of Health Sciences · LTUniversity of Padua · ITVita-Salute San Raffaele University · ITUniversity of Pecs · HUIRCCS Humanitas Research Hospital · ITUniversity Medical Center Hamburg-Eppendorf · DEUniversity of Verona · ITAmsterdam University Medical Centers · NLCarol Davila University of Medicine and Pharmacy · ROErasmus MC · NLFundação Carlos Chagas · BRHippocration General Hospital · GRMedical University of Lodz · PLMeyer Children's Hospital · IT
Funding
Cancer Research UK 26881Cancer Research UK C7690/A26881
Abstract
backgroundThe genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations.
resultsThe high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10
conclusionsOur results show only a minimal contribution of Neandertal SNPs to PDAC risk.
Indexed as
Carcinoma, Pancreatic DuctalDiabetes Mellitus, Type 2NeanderthalsPancreatic NeoplasmsAnimalsHumansPolymorphism, Single NucleotideAdmixtureAssociation studyEurasiansIntrogressionNeandertalPancreatic cancer
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