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IDENTIFICATION OF RECESSIVELY INHERITED GENETIC VARIANTS POTENTIALLY LINKED TO PANCREATIC CANCER RISK
Lu, Ye et al. | Date Issued: 2021
Author
Lu, Ye
Gentiluomo, Manuel
Macauda, Angelica
Gioffreda, Domenica
Gazouli, Maria
Petrone, Maria C.
Kelemen, Dezsö
Ginocchi, Laura
Morelli, Luca
Papiris, Konstantinos
Greenhalf, William
Izbicki, Jakob R.
Kiudelis, Vytautas
Mohelníková -Duchoñova, 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.
Laarhoven, Hanneke W. M. van
Mambrini, Andrea
Moz, Stefania
Kala, Zdenek
Lovecek, Martin
Basso, Daniela
Uzunoglu, Faik G.
Hackert, Thilo
Testoni, Sabrina G. G.
Hlavác, Viktor
Andriulli, Angelo
Lucchesi, Maurizio
Tavano, Francesca
Carrara, Silvia
Hegyi, Péter
Arcidiacono, Paolo G.
Busch, Olivier R.
Lawlor, Rita T.
Puzzono, Marta
Boggi, Ugo
Guo, Feng
Małecka-Panas, Ewa
Capurso, Gabriele
Landi, Stefano
Talar-Wojnarowska, Renata
Strobel, Oliver
Gao, Xin
Vashist, Yogesh
Campa, Daniele
Canzian, Federico
Affilliation
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany. / Medical Faculty Heidelberg. University of Heidelberg. Heidelberg, Germany.
Department of Biology. University of Pisa. Pisa, Italy.
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Division of Gastroenterology and Research Laboratory. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza. San Giovanni Rotondo, Italy.
Department of Basic Medical Sciences. Laboratory of Biology. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center IRSSC. San Raffaele Scientific Institute. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS). Milan, Italy.
Department of Surgery. Medical School. University of Pécs, Pécs, Hungary.
Oncological Department. Oncological Unit of Massa Carrara. Azienda Unità Sanitaria Locale (USL). Carrara, Italy.
General Surgery. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa. Pisa, Italy.
Endoscopic Surgery Department. Hippocratio General Hospital of Athens. Athens, Greece.
Department of Molecular and Clinical Cancer Medicine. University of Liverpool. Liverpool, United Kingdom
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg-Eppendorf. Hamburg, Germany.
Department of Gastroenterology. Institute for Digestive Research. Medical Academy. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Department of Oncology. Faculty of Medicine and Dentistry. Palacky University Olomouc and University Hospital Olomouc. Olomouc, Czechia.
Department for Determinants of Chronic Diseases (DCD). National Institute for Public Health and the Environment (RIVM). Bilthoven, Netherlands.
Department of Molecular Biology of Cancer. Institute of Experimental Medicine of the Czech Academy of Sciences. Prague, Czechia. / Faculty of Medicine and Biomedical Center in Pilsen. Charles University. Pilsen, Czechia. / First Faculty of Medicine. Institute of Biology and Medical Genetics. Prague, Czechia.
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.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
Department of Internal Medicine. San Carlo Hospital. Potenza, Italy.
Department of Gastroenterology. Institute for Digestive Research. Medical Academy. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Department of General and Pancreatic Surgery. The Pancreas Institute. University and Hospital Trust of Verona. Verona, Italy.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Centre for Translational Medicine. Department of Medicine. University of Szeged. Szeged, Hungary.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil.
First Department of Medicine. University of Szeged. Szeged, Hungary.
Department of Surgery-Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DiSCOG). Padua University Hospital. Padua, Italy.
Department of Hematology. Transplantation and Internal Medicine. Medical University of Warsaw. Warsaw, Poland.
Instituto do Cancêr de São Paulo. Departamento de Radiologia e Oncologia. São Paulo, Brasil. / Universidade de São Paulo. Faculdade de Medicina. São Paulo, SP, Brasil.
Department of Surgery. Faculty Hospital Kralovske Vinohrady and Third Faculty of Medicine. Charles University. Prague, Czechia.
Digestive and Liver Disease Unit. Sant’ Andrea Hospital. Rome, Italy. / Faculty of Medicine and Psychology. Sapienza University of Rome. Rome, Italy.
Blood Transfusion Service. Children’s Hospital. Azienda Ospedaliero-Universitaria Meyer. Florence, Italy.
Pándy Kálmán Hospital of Békés County. Gyula, Hungary.
Department of Gastroenterology. Institute for Digestive Research. Medical Academy. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Department of Oncology. Faculty of Medicine and Dentistry. Palacky University Olomouc and University Hospital Olomouc. Olomouc, Czechia. / Institute of Molecular and Translational Medicine. Faculty of Medicine and Dentistry. Palacky University Olomouc. Olomouc, Czechia.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czechia.
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.
Department of Surgery-Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DiSCOG). Padua University Hospital. Padua, Italy.
Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center IRSSC. San Raffaele Scientific Institute. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS). Milan, Italy. / Digestive and Liver Disease Unit. Sant’ Andrea Hospital. Rome, Italy. / Faculty of Medicine and Psychology. Sapienza University of Rome. Rome, Italy.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
First Propaedeutic University Surgery Clinic. Hippocratio General Hospital. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
Department of Medical Oncology. Cancer Center Amsterdam. Amsterdam University Medical Centers. University of Amsterdam. Amsterdam, Netherlands.
Oncological Department. Oncological Unit of Massa Carrara. Azienda Unità Sanitaria Locale (USL). Carrara, Italy.
Department of Medicine (DIMED). Padua University Hospital. Padua, Italy.
Department of Surgery. University Hospital Brno Bohunice. Faculty of Medicine. Masaryk University. Brno, Czechia.
Department of Surgery I. Faculty of Medicine and Dentistry. Palacky University Olomouc and University Hospital Olomouc. Olomouc, Czechia.
Department of Medicine (DIMED). Padua University Hospital. Padua, Italy.
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg-Eppendorf. Hamburg, Germany.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center IRSSC. San Raffaele Scientific Institute. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS). Milan, Italy.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czechia.
Division of Gastroenterology and Research Laboratory. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza. San Giovanni Rotondo, Italy.
Oncological Department. Oncological Unit of Massa Carrara. Azienda Unità Sanitaria Locale (USL). Carrara, Italy.
Division of Gastroenterology and Research Laboratory. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza. San Giovanni Rotondo, Italy.
Division of Gastroenterology and Digestive Endoscopy. Department of Gastroenterology. Humanitas Clinical and Research Center Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS). Milan, Italy.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Centre for Translational Medicine. Department of Medicine. University of Szeged. Szeged, Hungary.
Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center IRSSC. San Raffaele Scientific Institute. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS). Milan, Italy.
Department of Surgery. Cancer Center Amsterdam. Amsterdam University Medical Centers. University of Amsterdam. Amsterdam, Netherlands.
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.
Division of General and Transplant Surgery. Pisa University Hospital. Pisa, Italy.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center IRSSC. San Raffaele Scientific Institute. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS). Milan, Italy. / Digestive and Liver Disease Unit. Sant’ Andrea Hospital. Rome, Italy. / Faculty of Medicine and Psychology. Sapienza University of Rome. Rome, Italy.
Department of Biology. University of Pisa. Pisa, Italy.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Centre for Surgical Oncology. Medias Klinikum Burghausen. Burghausen, Germany.
Department of Biology. University of Pisa. Pisa, Italy.
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Abstract
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.
Keywords in Portuguese
câncer de pâncreas
Keywords
Polymorphism, Genetic
Pancreatic Neoplasms
Genome-Wide Association Study
 
Keywords in Spanish
Polimorfismo Genético
Neoplasias Pancreáticas
Estudio de Asociación del Genoma Completo
 
DeCS
Neoplasias Pancreáticas
Polimorfismo Genético
Estudo de Associação Genômica Ampla
 
Publisher
Frontiers Media
Citation
LU, Ye et al. Identification of recessively inherited genetic variants potentially linked to pancreatic Cancer Risk. Frontiers in Immunology, v. 11, n. 771312, p. 1–11, 2021.
DOI
10.3389/fonc.2021.771312
ISSN
2234-943X