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.

1st Department of Propaedeutic Surgery Hippocration General Hospital National and Kapodistrian University of Athens Athens Greece

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

Carol Davila University of Medicine and Pharmacy Bucharest Romania

Center for Translational Medicine Semmelweis University Budapest Hungary

Centre for Nutrition Prevention and Health Services National Institute for Public Health and the Environment 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 Biomedical Sciences Humanitas University Milan 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 and 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

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 São Paulo Sao Paulo Brazil

Department of Surgery 1 University Hospital Olomouc Olomouc Czech Republic

Department of Surgery 3rd Faculty of Medicine University Hospital Kralovske Vinohrady Charles University Prague 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 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

Division of Clinical Epidemiology and Aging Research German Cancer Research Center 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

Division of Pancreatic Diseases Heart and Vascular Center Semmelweis University Budapest Hungary

Division of Preventive Oncology German Cancer Research Center Heidelberg Germany

Estonian Biocentre Institute of Genomics University of Tartu Tartu Estonia

Faculty of Medicine University of São Paulo São Paulo Brazil

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

Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany

German Cancer Consortium Heidelberg Germany

Institute for Translational Medicine Medical School University of Pécs Pécs Hungary

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

János Szentágothai Research Center University of Pécs Pécs 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

Medical Faculty Heidelberg Heidelberg University Heidelberg Germany

Network Aging Research Heidelberg University Heidelberg Germany

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

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

Pancreatic Unit IRCCS Humanitas Research Hospital 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

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