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Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk.
Lu, Ye; Gentiluomo, Manuel; Macauda, Angelica; Gioffreda, Domenica; Gazouli, Maria; Petrone, Maria C; Kelemen, Dezso; Ginocchi, Laura; Morelli, Luca; Papiris, Konstantinos; Greenhalf, William; Izbicki, Jakob R; Kiudelis, Vytautas; Mohelníková-Duchonová, Beatrice; Bueno-de-Mesquita, Bas; Vodicka, Pavel; Brenner, Hermann; Diener, Markus K; Pezzilli, Raffaele; Ivanauskas, Audrius; Salvia, Roberto; Szentesi, Andrea; Aoki, Mateus Nóbrega; Németh, Balázs C; Sperti, Cosimo; Jamroziak, Krzysztof; Chammas, Roger; Oliverius, Martin; Archibugi, Livia; Ermini, Stefano; Novák, János; Kupcinskas, Juozas; Strouhal, Ondrej; Soucek, Pavel; Cavestro, Giulia M; Milanetto, Anna C; Vanella, Giuseppe; Neoptolemos, John P; Theodoropoulos, George E; van Laarhoven, Hanneke W M; Mambrini, Andrea; Moz, Stefania; Kala, Zdenek; Lovecek, Martin; Basso, Daniela; Uzunoglu, Faik G; Hackert, Thilo; Testoni, Sabrina G G; Hlavác, Viktor; Andriulli, Angelo.
Affiliation
  • Lu Y; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Gentiluomo M; Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany.
  • Macauda A; Department of Biology, University of Pisa, Pisa, Italy.
  • Gioffreda D; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Gazouli M; Division of Gastroenterology and Research Laboratory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
  • Petrone MC; Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
  • Kelemen D; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Ginocchi L; Department of Surgery, Medical School, University of Pécs, Pécs, Hungary.
  • Morelli L; Oncological Department, Oncological Unit of Massa Carrara, Azienda Unità Sanitaria Locale (USL) Toscana Nord Ovest, Carrara, Italy.
  • Papiris K; General Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
  • Greenhalf W; Endoscopic Surgery Department, Hippocratio General Hospital of Athens, Athens, Greece.
  • Izbicki JR; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom.
  • Kiudelis V; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Mohelníková-Duchonová B; Department of Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
  • Bueno-de-Mesquita B; Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czechia.
  • Vodicka P; Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
  • Brenner H; Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.
  • Diener MK; Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czechia.
  • Pezzilli R; First Faculty of Medicine, Institute of Biology and Medical Genetics, Prague, Czechia.
  • Ivanauskas A; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Salvia R; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Szentesi A; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Aoki MN; Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
  • Németh BC; Department of Internal Medicine, San Carlo Hospital, Potenza, Italy.
  • Sperti C; Department of Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
  • Jamroziak K; Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy.
  • Chammas R; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
  • Oliverius M; Centre for Translational Medicine, Department of Medicine, University of Szeged, Szeged, Hungary.
  • Archibugi L; Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Curitiba, Brazil.
  • Ermini S; First Department of Medicine, University of Szeged, Szeged, Hungary.
  • Novák J; Department of Surgery-Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DiSCOG), Padua University Hospital, Padua, Italy.
  • Kupcinskas J; Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland.
  • Strouhal O; Department of Radiology and Oncology, Institute of Cancer of São Paulo (ICESP), São Paulo, Brazil.
  • Soucek P; Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
  • Cavestro GM; Department of Surgery, Faculty Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czechia.
  • Milanetto AC; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Vanella G; Digestive and Liver Disease Unit, Sant' Andrea Hospital, Rome, Italy.
  • Neoptolemos JP; Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
  • Theodoropoulos GE; Blood Transfusion Service, Children's Hospital, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy.
  • van Laarhoven HWM; Pándy Kálmán Hospital of Békés County, Gyula, Hungary.
  • Mambrini A; Department of Gastroenterology, Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
  • Moz S; Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czechia.
  • Kala Z; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czechia.
  • Lovecek M; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.
  • Basso D; Division of Experimental Oncology, Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
  • Uzunoglu FG; Department of Surgery-Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DiSCOG), Padua University Hospital, Padua, Italy.
  • Hackert T; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
  • Testoni SGG; Digestive and Liver Disease Unit, Sant' Andrea Hospital, Rome, Italy.
  • Hlavác V; Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
  • Andriulli A; Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Front Oncol ; 11: 771312, 2021.
Article in En | MEDLINE | ID: mdl-34926279
ABSTRACT
Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p<10-5) compared with the additive effects (p>10-3), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10-8). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Language: En Journal: Front Oncol Year: 2021 Document type: Article Affiliation country: Germany
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Language: En Journal: Front Oncol Year: 2021 Document type: Article Affiliation country: Germany