Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.

Humans Animals Neanderthals / genetics Diabetes Mellitus, Type 2 Polymorphism, Single Nucleotide Carcinoma, Pancreatic Ductal / genetics Pancreatic Neoplasms / genetics
Admixture Association study Eurasians Introgression Neandertal Pancreatic cancer

Journal

Biological research
ISSN: 0717-6287
Titre abrégé: Biol Res
Pays: England
ID NLM: 9308271

Informations de publication

Date de publication:
13 Aug 2023
Historique:
received: 30 06 2022
accepted: 20 07 2023
medline: 16 8 2023
pubmed: 14 8 2023
entrez: 13 8 2023
Statut: epublish

Résumé

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. 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 Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Sections du résumé

BACKGROUND 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 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
CONCLUSIONS CONCLUSIONS
Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Identifiants

DOI: 10.1186/s40659-023-00457-y PMID: 37574541 PMC: PMC10424372
pubmed: 37574541
doi: 10.1186/s40659-023-00457-y
pii: 10.1186/s40659-023-00457-y
pmc: PMC10424372
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

46

Subventions

Organisme : Cancer Research UK
ID : C7690/A26881
Pays : United Kingdom

Informations de copyright

© 2023. Sociedad de Biologia de Chile.

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Auteurs

Margherita Piccardi (M)

Department of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy.

Manuel Gentiluomo (M)

Department of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy.

Stefania Bertoncini (S)

Department of Biology, Unit of Zoology and Anthropology, University of Pisa, Pisa, Italy.

Raffaele Pezzilli (R)

Potenza County Medical Association, Potenza, Italy.

Bálint Erőss (B)

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.

Stefania Bunduc (S)

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.

Faik G Uzunoglu (FG)

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Renata Talar-Wojnarowska (R)

Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.

Tomas Vanagas (T)

Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Cosimo Sperti (C)

Department DISCOG, Chirurgia Generale 1, University of Padova, Padua, Italy.

Martin Oliverius (M)

Department of Surgery, Third Faculty of Medicine, University Hospital Kralovske Vinohrady, Charles University, Prague, Czech Republic.

Mateus Nóbrega Aoki (MN)

Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Curitiba, Brazil.

Stefano Ermini (S)

Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Children's Hospital, Florence, Italy.

Tamás Hussein (T)

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.

Ugo Boggi (U)

Division of General and Transplantation Surgery, University of Pisa, Pisa, Italy.

Krzysztof Jamroziak (K)

Department of Hematology, Transplantation and Internal Medicine, University of Warsaw, Warsaw, Poland.

Evaristo Maiello (E)

Department of Oncology, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.

Luca Morelli (L)

Department of Translational Research and New Technologies in Medicine and Surgery, General Surgery Unit, University of Pisa, Pisa, Italy.

Ludmila Vodickova (L)

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.

Gregorio Di Franco (G)

Department of Translational Research and New Technologies in Medicine and Surgery, General Surgery Unit, University of Pisa, Pisa, Italy.

Stefano Landi (S)

Department of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy.

Andrea Szentesi (A)

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Center for Translational Medicine, Semmelweis University, Budapest, Hungary.
János Szentágothai Research Center, University of Pécs, Pécs, Hungary.

Martin Lovecek (M)

Department of Surgery I, University Hospital Olomouc, Olomouc, Czech Republic.

Marta Puzzono (M)

Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Francesca Tavano (F)

Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.

Hanneke W M van Laarhoven (HWM)

Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.

Alessandro Zerbi (A)

Pancreatic Unit, IRCCS Humanitas Research Hospital, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Milan, Italy.

Beatrice Mohelnikova-Duchonova (B)

Department of Oncology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.

Hannah Stocker (H)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany.

Eithne Costello (E)

Department of Molecular & Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.

Gabriele Capurso (G)

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.

Laura Ginocchi (L)

Oncological Department, Oncology of Massa Carrara, ASL Toscana Nord Ovest, Massa Carrara, Italy.

Rita T Lawlor (RT)

ARC-NET Research Centre and Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy.

Giuseppe Vanella (G)

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.

Francesca Bazzocchi (F)

Department of Surgery, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.

Jakob R Izbicki (JR)

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Anna Latiano (A)

Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.

Bas Bueno-de-Mesquita (B)

Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Ruggero Ponz de Leon Pisani (R)

Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy.

Ben Schöttker (B)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany.

Pavel Soucek (P)

Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.

Péter Hegyi (P)

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.
János Szentágothai Research Center, University of Pécs, Pécs, Hungary.

Maria Gazouli (M)

Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Thilo Hackert (T)

Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.

Juozas Kupcinskas (J)

Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Lina Poskiene (L)

Department of Pathology, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Matteo Tacelli (M)

Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy.

Susanne Roth (S)

Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.

Silvia Carrara (S)

Department of Gastroenterology, Endoscopic Unit, IRCCS Humanitas Research Hospital, Milan, Italy.

Francesco Perri (F)

Division of Gastroenterology and Research Laboratory, Fondazione IRCCS "Casa Sollievo Della Sofferenza" Hospital, San Giovanni Rotondo, Foggia, Italy.

Viktor Hlavac (V)

Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.

George E Theodoropoulos (GE)

First Department of Propaedeutic Surgery, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Olivier R Busch (OR)

Department of Surgery, Amsterdam UMC, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, the Netherlands.

Andrea Mambrini (A)

Oncological Department, Oncology of Massa Carrara, ASL Toscana Nord Ovest, Massa Carrara, Italy.

Casper H J van Eijck (CHJ)

Department of Surgery, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

Paolo Arcidiacono (P)

Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy.

Aldo Scarpa (A)

ARC-NET Research Centre and Department of Diagnostics and Public Health, Section of Pathology, University of Verona, Verona, Italy.

Claudio Pasquali (C)

Department DISCOG, Chirurgia Generale 3, University of Padova, Padua, Italy.

Daniela Basso (D)

Department DIMED, Laboratory Medicine, University of Padova, Padua, Italy.

Maurizio Lucchesi (M)

Oncological Department, Oncology of Massa Carrara, ASL Toscana Nord Ovest, Massa Carrara, Italy.

Anna Caterina Milanetto (AC)

Department DISCOG, Chirurgia Generale 3, University of Padova, Padua, Italy.

John P Neoptolemos (JP)

Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.

Giulia Martina Cavestro (GM)

Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Dainius Janciauskas (D)

Department of Pathology, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Xuechen Chen (X)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany.

Roger Chammas (R)

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.

Mara Goetz (M)

Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Hermann Brenner (H)

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.

Livia Archibugi (L)

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.

Michael Dannemann (M)

Estonian Biocentre, Institute of Genomics, University of Tartu, Tartu, Estonia.

Federico Canzian (F)

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Sergio Tofanelli (S)

Department of Biology, Unit of Zoology and Anthropology, University of Pisa, Pisa, Italy.

Daniele Campa (D)

Department of Biology, Unit of Genetics, University of Pisa, Via Derna 1, 56126, Pisa, Italy. daniele.campa@unipi.it.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Exploring the Neandertal legacy of pancreatic...
questionsmedicales.fr › Eucaryotes › Animaux › Exploring the Neandertal legacy of pancreatic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Néandertaliens › Exploring the Neandertal legacy of pancreatic...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Exploring the Neandertal legacy of pancreatic...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › Exploring the Neandertal legacy of pancreatic...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › Exploring the Neandertal legacy of pancreatic...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Exploring the Neandertal legacy of pancreatic...