Biological Research (Aug 2023)
Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians
- Margherita Piccardi,
- Manuel Gentiluomo,
- Stefania Bertoncini,
- Raffaele Pezzilli,
- Bálint Erőss,
- Stefania Bunduc,
- Faik G. Uzunoglu,
- Renata Talar-Wojnarowska,
- Tomas Vanagas,
- Cosimo Sperti,
- Martin Oliverius,
- Mateus Nóbrega Aoki,
- Stefano Ermini,
- Tamás Hussein,
- Ugo Boggi,
- Krzysztof Jamroziak,
- Evaristo Maiello,
- Luca Morelli,
- Ludmila Vodickova,
- Gregorio Di Franco,
- Stefano Landi,
- Andrea Szentesi,
- Martin Lovecek,
- Marta Puzzono,
- Francesca Tavano,
- Hanneke W. M. van Laarhoven,
- Alessandro Zerbi,
- Beatrice Mohelnikova-Duchonova,
- Hannah Stocker,
- Eithne Costello,
- Gabriele Capurso,
- Laura Ginocchi,
- Rita T. Lawlor,
- Giuseppe Vanella,
- Francesca Bazzocchi,
- Jakob R. Izbicki,
- Anna Latiano,
- Bas Bueno-de-Mesquita,
- Ruggero Ponz de Leon Pisani,
- Ben Schöttker,
- Pavel Soucek,
- Péter Hegyi,
- Maria Gazouli,
- Thilo Hackert,
- Juozas Kupcinskas,
- Lina Poskiene,
- Matteo Tacelli,
- Susanne Roth,
- Silvia Carrara,
- Francesco Perri,
- Viktor Hlavac,
- George E. Theodoropoulos,
- Olivier R. Busch,
- Andrea Mambrini,
- Casper H. J. van Eijck,
- Paolo Arcidiacono,
- Aldo Scarpa,
- Claudio Pasquali,
- Daniela Basso,
- Maurizio Lucchesi,
- Anna Caterina Milanetto,
- John P. Neoptolemos,
- Giulia Martina Cavestro,
- Dainius Janciauskas,
- Xuechen Chen,
- Roger Chammas,
- Mara Goetz,
- Hermann Brenner,
- Livia Archibugi,
- Michael Dannemann,
- Federico Canzian,
- Sergio Tofanelli,
- Daniele Campa
Affiliations
- Margherita Piccardi
- Department of Biology, Unit of Genetics, University of Pisa
- Manuel Gentiluomo
- Department of Biology, Unit of Genetics, University of Pisa
- Stefania Bertoncini
- Department of Biology, Unit of Zoology and Anthropology, University of Pisa
- Raffaele Pezzilli
- Potenza County Medical Association
- Bálint Erőss
- Institute for Translational Medicine, Medical School, University of Pécs
- Stefania Bunduc
- Institute for Translational Medicine, Medical School, University of Pécs
- Faik G. Uzunoglu
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf
- Renata Talar-Wojnarowska
- Department of Digestive Tract Diseases, Medical University of Lodz
- Tomas Vanagas
- Department of Surgery, Lithuanian University of Health Sciences
- Cosimo Sperti
- Department DISCOG, Chirurgia Generale 1, University of Padova
- Martin Oliverius
- Department of Surgery, Third Faculty of Medicine, University Hospital Kralovske Vinohrady, Charles University
- Mateus Nóbrega Aoki
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute
- Stefano Ermini
- Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Children’s Hospital
- Tamás Hussein
- Institute for Translational Medicine, Medical School, University of Pécs
- Ugo Boggi
- Division of General and Transplantation Surgery, University of Pisa
- Krzysztof Jamroziak
- Department of Hematology, Transplantation and Internal Medicine, University of Warsaw
- Evaristo Maiello
- Department of Oncology, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital
- Luca Morelli
- Department of Translational Research and New Technologies in Medicine and Surgery, General Surgery Unit, University of Pisa
- Ludmila Vodickova
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences
- Gregorio Di Franco
- Department of Translational Research and New Technologies in Medicine and Surgery, General Surgery Unit, University of Pisa
- Stefano Landi
- Department of Biology, Unit of Genetics, University of Pisa
- Andrea Szentesi
- Institute for Translational Medicine, Medical School, University of Pécs
- Martin Lovecek
- Department of Surgery I, University Hospital Olomouc
- Marta Puzzono
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute
- Francesca Tavano
- Division of Gastroenterology and Research Laboratory, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital, San Giovanni Rotondo
- Hanneke W. M. van Laarhoven
- Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam
- Alessandro Zerbi
- Pancreatic Unit, IRCCS Humanitas Research Hospital
- Beatrice Mohelnikova-Duchonova
- Department of Oncology, Faculty of Medicine and Dentistry, Palacky University
- Hannah Stocker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Eithne Costello
- Department of Molecular & Clinical Cancer Medicine, University of Liverpool
- Gabriele Capurso
- Digestive and Liver Disease Unit, S Andrea Hospital
- Laura Ginocchi
- Oncological Department, Oncology of Massa Carrara
- Rita T. Lawlor
- ARC-NET Research Centre and Department of Diagnostics and Public Health, Section of Pathology, University of Verona
- Giuseppe Vanella
- Digestive and Liver Disease Unit, S Andrea Hospital
- Francesca Bazzocchi
- Department of Surgery, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital
- Jakob R. Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf
- Anna Latiano
- Division of Gastroenterology and Research Laboratory, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital, San Giovanni Rotondo
- Bas Bueno-de-Mesquita
- Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM)
- Ruggero Ponz de Leon Pisani
- Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS
- Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Pavel Soucek
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University
- Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs
- Maria Gazouli
- Laboratory of Biology, Medical School, National and Kapodistrian University of Athens
- Thilo Hackert
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg
- Juozas Kupcinskas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences
- Lina Poskiene
- Department of Pathology, Lithuanian University of Health Sciences
- Matteo Tacelli
- Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS
- Susanne Roth
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg
- Silvia Carrara
- Department of Gastroenterology, Endoscopic Unit, IRCCS Humanitas Research Hospital
- Francesco Perri
- Division of Gastroenterology and Research Laboratory, Fondazione IRCCS “Casa Sollievo Della Sofferenza” Hospital, San Giovanni Rotondo
- Viktor Hlavac
- Biomedical Center, Faculty of Medicine in Pilsen, Charles University
- George E. Theodoropoulos
- First Department of Propaedeutic Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens
- Olivier R. Busch
- Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam
- Andrea Mambrini
- Oncological Department, Oncology of Massa Carrara
- Casper H. J. van Eijck
- Department of Surgery, Erasmus MC University Medical Center
- Paolo Arcidiacono
- Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS
- Aldo Scarpa
- ARC-NET Research Centre and Department of Diagnostics and Public Health, Section of Pathology, University of Verona
- Claudio Pasquali
- Department DISCOG, Chirurgia Generale 3, University of Padova
- Daniela Basso
- Department DIMED, Laboratory Medicine, University of Padova
- Maurizio Lucchesi
- Oncological Department, Oncology of Massa Carrara
- Anna Caterina Milanetto
- Department DISCOG, Chirurgia Generale 3, University of Padova
- John P. Neoptolemos
- Department of General, Visceral, and Transplantation Surgery, University of Heidelberg
- Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute
- Dainius Janciauskas
- Department of Pathology, Lithuanian University of Health Sciences
- Xuechen Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Roger Chammas
- Department of Radiology and Oncology, Institute of Cancer of São Paulo (ICESP) São Paulo
- Mara Goetz
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ)
- Livia Archibugi
- Digestive and Liver Disease Unit, S Andrea Hospital
- Michael Dannemann
- Estonian Biocentre, Institute of Genomics, University of Tartu
- Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ)
- Sergio Tofanelli
- Department of Biology, Unit of Zoology and Anthropology, University of Pisa
- Daniele Campa
- Department of Biology, Unit of Genetics, University of Pisa
- DOI
- https://doi.org/10.1186/s40659-023-00457-y
- Journal volume & issue
-
Vol. 56,
no. 1
pp. 1 – 9
Abstract
Abstract Background The 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. Results The 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. Conclusions Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.
Keywords
