Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk.

genetic polymorphisms genome-wide association study pancreatic cancer recessive model susceptibility

Journal

Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867

Informations de publication

Date de publication:
2021
Historique:
received: 06 09 2021
accepted: 16 11 2021
entrez: 20 12 2021
pubmed: 21 12 2021
medline: 21 12 2021
Statut: epublish

Résumé

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

Identifiants

pubmed: 34926279
doi: 10.3389/fonc.2021.771312
pmc: PMC8678088
doi:

Types de publication

Journal Article

Langues

eng

Pagination

771312

Informations de copyright

Copyright © 2021 Lu, Gentiluomo, Macauda, Gioffreda, Gazouli, Petrone, Kelemen, Ginocchi, Morelli, Papiris, Greenhalf, Izbicki, Kiudelis, Mohelníková-Duchoňová, Bueno-de-Mesquita, Vodicka, Brenner, Diener, Pezzilli, Ivanauskas, Salvia, Szentesi, Aoki, Németh, Sperti, Jamroziak, Chammas, Oliverius, Archibugi, Ermini, Novák, Kupcinskas, Strouhal, Souček, Cavestro, Milanetto, Vanella, Neoptolemos, Theodoropoulos, van Laarhoven, Mambrini, Moz, Kala, Loveček, Basso, Uzunoglu, Hackert, Testoni, Hlaváč, Andriulli, Lucchesi, Tavano, Carrara, Hegyi, Arcidiacono, Busch, Lawlor, Puzzono, Boggi, Guo, Małecka-Panas, Capurso, Landi, Talar-Wojnarowska, Strobel, Gao, Vashist, Campa and Canzian.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Ye Lu (Y)

Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany.

Manuel Gentiluomo (M)

Department of Biology, University of Pisa, Pisa, Italy.

Angelica Macauda (A)

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

Domenica Gioffreda (D)

Division of Gastroenterology and Research Laboratory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Maria Gazouli (M)

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

Maria C Petrone (MC)

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.

Dezső Kelemen (D)

Department of Surgery, Medical School, University of Pécs, Pécs, Hungary.

Laura Ginocchi (L)

Oncological Department, Oncological Unit of Massa Carrara, Azienda Unità Sanitaria Locale (USL) Toscana Nord Ovest, Carrara, Italy.

Luca Morelli (L)

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

Konstantinos Papiris (K)

Endoscopic Surgery Department, Hippocratio General Hospital of Athens, Athens, Greece.

William Greenhalf (W)

Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom.

Jakob R Izbicki (JR)

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

Vytautas Kiudelis (V)

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

Beatrice Mohelníková-Duchoňová (B)

Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czechia.

Bas Bueno-de-Mesquita (B)

Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.

Pavel Vodicka (P)

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.

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.

Markus K Diener (MK)

Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

Raffaele Pezzilli (R)

Department of Internal Medicine, San Carlo Hospital, Potenza, Italy.

Audrius Ivanauskas (A)

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

Roberto Salvia (R)

Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy.

Andrea Szentesi (A)

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

Mateus Nóbrega Aoki (MN)

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

Balázs C Németh (BC)

First Department of Medicine, University of Szeged, Szeged, Hungary.

Cosimo Sperti (C)

Department of Surgery-Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DiSCOG), Padua University Hospital, Padua, Italy.

Krzysztof Jamroziak (K)

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

Roger Chammas (R)

Department of Radiology and Oncology, Institute of Cancer of São Paulo (ICESP), São Paulo, Brazil.
Faculty of Medicine, University of São Paulo, São Paulo, Brazil.

Martin Oliverius (M)

Department of Surgery, Faculty Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University, Prague, Czechia.

Livia Archibugi (L)

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.
Digestive and Liver Disease Unit, Sant' Andrea Hospital, Rome, Italy.
Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

Stefano Ermini (S)

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

János Novák (J)

Pándy Kálmán Hospital of Békés County, Gyula, Hungary.

Juozas Kupcinskas (J)

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

Ondřej Strouhal (O)

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.

Pavel Souček (P)

Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Giulia M Cavestro (GM)

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.

Anna C Milanetto (AC)

Department of Surgery-Dipartimento di Scienze Chirurgiche Oncologiche e Gastroenterologiche (DiSCOG), Padua University Hospital, Padua, Italy.

Giuseppe Vanella (G)

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.
Digestive and Liver Disease Unit, Sant' Andrea Hospital, Rome, Italy.
Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

John P Neoptolemos (JP)

Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

George E Theodoropoulos (GE)

First Propaedeutic University Surgery Clinic, Hippocratio General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Hanneke W M van Laarhoven (HWM)

Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.

Andrea Mambrini (A)

Oncological Department, Oncological Unit of Massa Carrara, Azienda Unità Sanitaria Locale (USL) Toscana Nord Ovest, Carrara, Italy.

Stefania Moz (S)

Department of Medicine (DIMED), Padua University Hospital, Padua, Italy.

Zdenek Kala (Z)

Department of Surgery, University Hospital Brno Bohunice, Faculty of Medicine, Masaryk University, Brno, Czechia.

Martin Loveček (M)

Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czechia.

Daniela Basso (D)

Department of Medicine (DIMED), Padua University Hospital, Padua, Italy.

Faik G Uzunoglu (FG)

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

Thilo Hackert (T)

Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

Sabrina G G Testoni (SGG)

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.

Viktor Hlaváč (V)

Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Angelo Andriulli (A)

Division of Gastroenterology and Research Laboratory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Maurizio Lucchesi (M)

Oncological Department, Oncological Unit of Massa Carrara, Azienda Unità Sanitaria Locale (USL) Toscana Nord Ovest, Carrara, Italy.

Francesca Tavano (F)

Division of Gastroenterology and Research Laboratory, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Silvia Carrara (S)

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.

Péter Hegyi (P)

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

Paolo G Arcidiacono (PG)

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.

Olivier R Busch (OR)

Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.

Rita T Lawlor (RT)

Applied Research on Cancer (ARC)-Net Research Center, University and Hospital Trust of Verona, Verona, Italy.

Marta Puzzono (M)

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.

Ugo Boggi (U)

Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy.

Feng Guo (F)

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

Ewa Małecka-Panas (E)

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

Gabriele Capurso (G)

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.
Digestive and Liver Disease Unit, Sant' Andrea Hospital, Rome, Italy.
Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.

Stefano Landi (S)

Department of Biology, University of Pisa, Pisa, Italy.

Renata Talar-Wojnarowska (R)

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

Oliver Strobel (O)

Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

Xin Gao (X)

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

Yogesh Vashist (Y)

Centre for Surgical Oncology, Medias Klinikum Burghausen, Burghausen, Germany.

Daniele Campa (D)

Department of Biology, University of Pisa, Pisa, Italy.

Federico Canzian (F)

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

Classifications MeSH