Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

Biological Research

Research Article

Aldo Scarpa¹  Rita T. Lawlor¹  Pavel Soucek²  Viktor Hlavac²  Stefano Ermini³  Bas Bueno-de-Mesquita⁴  Daniela Basso⁵  Cosimo Sperti⁶  Claudio Pasquali⁷  Anna Caterina Milanetto⁷  Daniele Campa⁸  Stefano Landi⁸  Manuel Gentiluomo⁸  Margherita Piccardi⁸  Sergio Tofanelli⁹  Stefania Bertoncini⁹  Renata Talar-Wojnarowska^1,10  Juozas Kupcinskas^1,11  Silvia Carrara^1,12  Mara Goetz^1,13  Faik G. Uzunoglu^1,13  Jakob R. Izbicki^1,13  Thilo Hackert^1,14  Susanne Roth^1,14  John P. Neoptolemos^1,14  Krzysztof Jamroziak^1,15  Hanneke W. M. van Laarhoven^1,16  Eithne Costello^1,17  Ludmila Vodickova^1,18  Beatrice Mohelnikova-Duchonova^1,19  Evaristo Maiello^2,20  Dainius Janciauskas^2,21  Lina Poskiene^2,21  Roger Chammas^2,22  Martin Lovecek^2,23  Olivier R. Busch^2,24  Casper H. J. van Eijck^2,25  Francesca Bazzocchi^2,26  Tomas Vanagas^2,27  Martin Oliverius^2,28  Gregorio Di Franco^2,29  Luca Morelli^2,29  Giuseppe Vanella^3,30  Gabriele Capurso^3,30  Livia Archibugi^3,30  Hermann Brenner^3,31  Xuechen Chen^3,32  Ben Schöttker^3,33  Hannah Stocker^3,33  Francesco Perri^3,34  Francesca Tavano^3,34  Anna Latiano^3,34  Ugo Boggi^3,35  Michael Dannemann^3,36  George E. Theodoropoulos^3,37  Giulia Martina Cavestro^3,38  Marta Puzzono^3,38  Federico Canzian^3,39  Tamás Hussein^4,40  Bálint Erőss^4,40  Stefania Bunduc^4,41  Andrea Szentesi^4,42  Péter Hegyi^4,43  Mateus Nóbrega Aoki^4,44  Maria Gazouli^4,45  Maurizio Lucchesi^4,46  Andrea Mambrini^4,46  Laura Ginocchi^4,46  Alessandro Zerbi^4,47  Paolo Arcidiacono^4,48  Ruggero Ponz de Leon Pisani^4,48  Matteo Tacelli^4,48  Raffaele Pezzilli^4,49 

[1] ARC-NET Research Centre and Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy;Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic;Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Children’s Hospital, Florence, Italy;Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands;Department DIMED, Laboratory Medicine, University of Padova, Padua, Italy;Department DISCOG, Chirurgia Generale 1, University of Padova, Padua, Italy;Department DISCOG, Chirurgia Generale 3, University of Padova, Padua, Italy;Department of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy;Department of Biology, Unit of Zoology and Anthropology, University of Pisa, Pisa, Italy;Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland;Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania;Department of Gastroenterology, Endoscopic Unit, IRCCS Humanitas Research Hospital, Milan, Italy;Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany;Department of Hematology, Transplantation and Internal Medicine, University of Warsaw, Warsaw, Poland;Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands;Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK;Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic;Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic;Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic;Department of Oncology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic;Department of Oncology, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital, San Giovanni Rotondo, Foggia, Italy;Department of Pathology, Lithuanian University of Health Sciences, Kaunas, Lithuania;Department of Radiology and Oncology, Institute of Cancer of São Paulo (ICESP) São Paulo, Sao Paulo, Brazil;Faculty of Medicine, University of São Paulo, São Paulo, Brazil;Department of Surgery I, University Hospital Olomouc, Olomouc, Czech Republic;Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands;Department of Surgery, Erasmus MC University Medical Center, Rotterdam, the Netherlands;Department of Surgery, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital, San Giovanni Rotondo, Foggia, Italy;Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania;Department of Surgery, Third Faculty of Medicine, University Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic;Department of Translational Research and New Technologies in Medicine and Surgery, General Surgery Unit, University of Pisa, Pisa, Italy;Digestive and Liver Disease Unit, S Andrea Hospital, Rome, Italy;Pancreas Translational and Clinical Research Center, Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, San Raffaele Scientific Institute IRCCS, Milan, Italy;Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany;Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany;German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany;Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany;Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany;Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany;Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany;Division of Gastroenterology and Research Laboratory, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital, San Giovanni Rotondo, Foggia, Italy;Division of General and Transplantation Surgery, University of Pisa, Pisa, Italy;Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia;First Department of Propaedeutic Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece;Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy;Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany;Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary;Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary;Center for Translational Medicine, Semmelweis University, Budapest, Hungary;Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary;Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary;János Szentágothai Research Center, University of Pécs, Pécs, Hungary;Center for Translational Medicine, Semmelweis University, Budapest, Hungary;Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary;János Szentágothai Research Center, University of Pécs, Pécs, Hungary;Center for Translational Medicine, Semmelweis University, Budapest, Hungary;Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary;Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Curitiba, Brazil;Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece;Oncological Department, Oncology of Massa Carrara, ASL Toscana Nord Ovest, Massa Carrara, Italy;Pancreatic Unit, IRCCS Humanitas Research Hospital, Milan, Italy;Department of Biomedical Sciences, Humanitas University, Milan, Italy;Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy;Potenza County Medical Association, Potenza, Italy;

关键词: Neandertal;    Pancreatic cancer;    Association study;    Introgression;    Eurasians;    Admixture;   

DOI  :  10.1186/s40659-023-00457-y

 received in 2022-06-30, accepted in 2023-07-20,  发布年份 2023

来源: Springer

【 摘 要 】

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 × 10–6), with a P-value close to a threshold that takes into account multiple testing.ConclusionsOur results show only a minimal contribution of Neandertal SNPs to PDAC risk.

【 授权许可】

CC BY   
© Sociedad de Biologia de Chile 2023

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