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POTENTIAL ASSOCIATION BETWEEN PSCA RS2976395 FUNCTIONAL VARIANT AND PANCREATIC CANCER RISK
Corradi, Chiara et al. | Date Issued: 2024
Author
Corradi, Chiara
Lencioni, Giulia
Felici, Alessio
Rizzato, Cosmeri
Gentiluomo, Manuel
Ermini, Stefano
Archibugi, Livia
Mickevicius, Antanas
Lucchesi, Maurizio
Malecka-Wojciesko, Ewa
Basso, Daniela
Arcidiacono, Paolo Giorgio
Petrone, Maria Chiara
Carrara, Silvia
Götz, Mara
Bunduc, Stefania
Holleczek, Bernd
Aoki, Mateus Nóbrega
Uzunoglu, Faik G
Zanette, Dalila Lucíola
Mambrini, Andrea
Jamroziak, Krzysztof
Oliverius, Martin
Lovecek, Martin
Cavestro, Giulia Martina
Milanetto, Anna Caterina
Peduzzi, Giulia
Duchonova, Beatrice Mohelnikova
Izbicki, Jakob R
Zalinkevicius, Rimantas
Hlavac, Viktor
van Eijck, Casper H. J
Brenner, Hermann
Vanella, Giuseppe
Vokacova, Klara
Soucek, Pavel
Tavano, Francesca
Perri, Francesco
Capurso, Gabriele
Hussein, Tamás
Kiudelis, Mindaugas
Kupcinskas, Juozas
Busch, Olivier R
Morelli, Luca
Theodoropoulos, George E
Testoni, Sabrina Gloria Giulia
Adamonis, Kestutis
Neoptolemos, John P
Gazouli, Maria
Pasquali, Claudio
Kormos, Zita
Skalicky, Pavel
Pezzilli, Raffaele
Sperti, Cosimo
Kauffmann, Emanuele
Büchler, Markus W
Schöttker, Ben
Hegyi, Péter
Capretti, Giovanni
Lawlor, Rita T
Canzian, Federico
Campa, Daniele
Affilliation
University of Pisa. Department of Biology. Pisa, Italy.
University of Pisa. Department of Biology. Pisa, Italy.
University of Pisa. Department of Biology. Pisa, Italy.
University of Pisa. Department of Biology. Pisa, Italy.
University of Pisa. Department of Biology. Pisa, Italy.
Children's Hospital. Azienda Ospedaliera-Universitaria Meyer. Blood Transfusion Service. Florence, Italy.
IRSSC San Raffaele Scientific Institute. Pancreas Translational and Clinical Research Center. Pancreato-Biliary Endoscopy and Endoscopic Ultrasound. Milan, Italy / Sant'Andrea Hospital. Digestive and Liver Disease Unit. Rome, Italy.
Lithuanian University of Health Sciences. Department of Surgery. Kaunas, Lithuania.
Azienda USL Toscana Nord Ovest. Oncological Department. Oncology of Massa Carrara. Carrara, Italy.
Medical University of Lodz. Department of Digestive Tract Diseases. Lodz, Poland.
University of Padova. Department DIMED. Laboratory Medicine. Padua, Italy.
IRSSC San Raffaele Scientific Institute. Pancreas Translational and Clinical Research Center. Pancreato-Biliary Endoscopy and Endoscopic Ultrasound. Milan, Italy.
IRSSC San Raffaele Scientific Institute. Pancreas Translational and Clinical Research Center. Pancreato-Biliary Endoscopy and Endoscopic Ultrasound. Milan, Italy.
IRCCS Humanitas Research Hospital. Gastroenterology Department. Endoscoopic Unit. Rozzano, Milan, Italy.
University Hospital Hamburg-Eppendorf. Department of General, Visceral and Thoracic Surgery. Hamburg, Germany.
Carol Davila University of Medicine and Pharmacy. Bucharest, Romania / Fundeni Clinical Institute. Digestive Diseases and Liver Transplantation Center. Bucharest, Romania / Semmelweis University. Center for Translational Medicine. Budapest, Hungary / Semmelweis University. Division of Pancreatic Diseases, Heart and Vascular Center. Budapest, Hungary.
Saarland Cancer Registry. Saarbrücken, Germany.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologia Aplicadas em Saúde. Curitiba, PR, Brasil.
University Hospital Hamburg-Eppendorf. Department of General, Visceral and Thoracic Surgery. Hamburg, Germany.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologia Aplicadas em Saúde. Curitiba, PR, Brasil.
Azienda USL Toscana Nord Ovest. Oncological Department. Oncology of Massa Carrara. Carrara, Italy.
Medical University of Warsaw. Department of Hematology, Transplantation and Internal Medicine. Warsaw, Poland.
Charles University. University Hospital Kralovske Vinohrady. Third Faculty of Medicine. Department of Surgery. Prague, Czech Republic.
University Hospital Olomouc. Olomouc, Czech Republic.
Vita-Salute San Raffaele University. IRCCS San Raffaele Scientific Institute. Gastroenterology and Gastrointestinal Endoscopy Unit. Milan, Italy.
University of Padova. Department of DiSCOG. Padua, Italy.
University of Pisa. Department of Biology. Pisa, Italy.
Palacky University Olomouc. Faculty of Medicine and Dentistry. Olomouc, Czech Republic.
University Hospital Hamburg-Eppendorf. Department of General, Visceral and Thoracic Surgery. Hamburg, Germany.
Lithuanian University of Health Sciences. Clinics of Institute of Endocrinology. Kaunas, Lithuania.
Charles University. Biomedical Center. Faculty of Medicine in Pilsen. Pilsen, Czech Republic.
Erasmus MC University Medical Center. Department of Surgery. Rotterdam, The Netherlands.
German Cancer Research Center (DKFZ). Division of Clinical Epidemiology and Aging Research. Heidelberg, Germany / German Cancer Research Center (DKFZ). National Center for Tumor Diseases (NCT). Division of Preventive Oncology. Heidelberg, Germany / German Cancer Research Center (DKFZ). German Cancer Consortium (DKTK). Heidelberg, Germany.
IRSSC San Raffaele Scientific Institute. Pancreas Translational and Clinical Research Center. Pancreato-Biliary Endoscopy and Endoscopic Ultrasound. Milan, Italy / Sant'Andrea Hospital. Digestive and Liver Disease Unit. Rome, Italy.
Institute of Experimental Medicine of the Czech Academy of Sciences. Department of Molecular Biology of Cancer. Prague, Czech Republic / Charles University. First Faculty of Medicine. Institute of Biology and Medical Genetics. Prague, Czech Republic.
Charles University. Biomedical Center. Faculty of Medicine in Pilsen. Pilsen, Czech Republic.
Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. Division of Gastroenterology and Research Laboratory. San Giovanni Rotondo, Italy.
Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. Division of Gastroenterology and Research Laboratory. San Giovanni Rotondo, Italy.
IRSSC San Raffaele Scientific Institute. Pancreas Translational and Clinical Research Center. Pancreato-Biliary Endoscopy and Endoscopic Ultrasound. Milan, Italy / Sant'Andrea Hospital. Digestive and Liver Disease Unit. Rome, Italy.
Semmelweis University. Center for Translational Medicine. Budapest, Hungary / Semmelweis University. Division of Pancreatic Diseases, Heart and Vascular Center. Budapest, Hungary.
Lithuanian University of Health Sciences. Department of Surgery. Kaunas, Lithuania.
Lithuanian University of Health Sciences. Institute for Digestive Research. Gastroenterology Department. Kaunas. Lithuania.
University of Amsterdam. Amsterdam UMC. Cancer Center Amsterdam. Department of Surgery. Amsterdam, The Netherlands.
University of Pisa. Department of Translational Research and New Technologies in Medicine and Surgery. General Surgery. Pisa, Italy.
National and Kapodistrian University of Athens. Medical School. Hippocratio General Hospital. First Propaedeutic University Surgery Clinic. Athens, Greece.
IRSSC San Raffaele Scientific Institute. Pancreas Translational and Clinical Research Center. Pancreato-Biliary Endoscopy and Endoscopic Ultrasound. Milan, Italy.
Lithuanian University of Health Sciences. Institute for Digestive Research. Gastroenterology Department. Kaunas. Lithuania / University of Amsterdam. Amsterdam UMC. Cancer Center Amsterdam. Department of Surgery. Amsterdam, The Netherlands.
National and Kapodistrian University of Athens. Medical School. Hippocratio General Hospital. First Propaedeutic University Surgery Clinic. Athens, Greece.
National and Kapodistrian University of Athens. Medical School. Department of Basic Medical Sciences. Laboratory of Biology. Athens, Greece.
University of Padova. Department of DiSCOG. Padua, Italy.
Semmelweis University. Division of Pancreatic Diseases, Heart and Vascular Center. Budapest, Hungary.
University Hospital Olomouc. Olomouc, Czech Republic.
Potenza County Medical Association. Potenza, Italy.
University of Padova. Department of DiSCOG. Padua, Italy.
Pisa University Hospital. Division of General and Transplant Surgery. Pisa, Italy.
University of Heidelberg. Department of General Surgery. Heidelberg, Germany.
German Cancer Research Center (DKFZ). Division of Clinical Epidemiology and Aging Research. Heidelberg, Germany.
Semmelweis University. Center for Translational Medicine. Budapest, Hungary / Semmelweis University. Division of Pancreatic Diseases, Heart and Vascular Center. Budapest, Hungary / University of Pécs. Medical School. Institute for Translational Medicine. Pécs, Hungary / University of Pécs. János Szentágothai Research Center. Pécs, Hungary.
IRCCS Humanitas Research Hospital. Pancreatic Surgery Department. Rozzano, Milan, Italy / Humanitas University. Rozzano, Milan, Italy.
University and Hospital Trust of Verona ARC-NET Centre for Applied Research on Cancer. Verona, Italy.
German Cancer Research Center (DKFZ). Genomic Epidemiology Group. Heidelberg, Germany.
University of Pisa. Department of Biology. Pisa, Italy.
Abstract
Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 x 10-5 ). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene accord ing to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.
Keywords in Portuguese
Metilação de DNA
Câncer pancreático
Fatores de risco
Polimorfismo de nucleotídeo único
 
Keywords
DNA methylation
Pancreatic cancer
Risk factors
Single-nucleotide polymorphism
 
DeCS
Metilação de DNA
Neoplasias Pancreáticas
Polimorfismo de Nucleotídeo Único
 
Publisher
UICC / Wiley Online Library
Citation
CORRADI, C. et al. Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk. INTERNATIONAL JOURNAL OF CANCER, v. 155, n. 8, p. 1432-1442, 2024.
DOI
10.1002/ijc.35046
ISSN
1097-0215
Notes
The PanScan and PanC4 genotyping data are available from the database of Genotypes and Phenotypes (dbGaP, study accession numbers phs000206. v5.p3 and phs000648.v1.p1). The PANDoRA data are available upon reasonable request with approval by the PANDoRA Steering Committee and Ethics Committee of the Medical Faculty of Heidelberg University, Germany. The JaPAN data used in this work are available in the JaPAN consortium website (http://www.aichi-med-u.ac.jp/JaPAN/current_initiatives-e.html). The FinnGen R6 dataset of PDAC cases and controls (“finngen_R6_C3_PANCREAS_EXALLC”) is downloadable from the FinnGen official website (https://finngen.gitbook.io/documentation/). Further information is available from the corresponding author upon request.