Association of genetic variants affecting microRNAs and pancreatic cancer risk

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.
Department of Biology. University of Pisa. Pisa, Italy.
Genetic and Molecular Epidemiology Group. Spanish National Cancer Research Centre (CNIO). Madrid, Spain.
First Propaedeutic University Surgery Clinic. Hippocratio General Hospital. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
Department of Oncology. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
General Surgery. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa, Pisa, Italy.
Digestive and Liver Disease Unit. Sant’Andrea Hospita. Rome, Italy. / Faculty of Medicine and Psychology. Sapienza University of Rome. Rome, Italy. / Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. IRSSC San Raffaele Scientific Institute. Milan, Italy.
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg-Eppendorf. Hamburg, Germany.
First Department of Medicine. Medical School. University of Pécs. Pécs, Hungary.
Department of Gastroenterology. Institute for Digestive Research. Medical Academy. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Department of Surgery. Faculty Hospital Kralovske Vinohrady and Third Faculty of Medicine. Charles University. Prague, Czechia.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Ciências e Tecnologias Aplicadas em Saúde. Curitiba, PR, Brasil.
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg-Eppendorf. Hamburg, Germany.
Department of Surgery. Erasmus Medical Center. Erasmus University. Rotterdam, Netherlands.
Laboratory of Biology. Medical School. National and Kapodistrian University of Athens. Athens, Greece.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Oncological Department. Azienda USL Toscana Nord Ovest. Oncological Unit of Massa Carrara. Carrara, Italy.
Department of Gastroenterology. San Carlo Hospital. Potenza, Italy.
Department for Determinants of Chronic Diseases (DCD). National Institute for Public Health and the Environment (RIVM). Bilthoven, Netherlands.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Department of Medicine. Centre for Translational Medicine. University of Szeged. Szeged, Hungary.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czechia.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
General Surgery. Department of Translational Research and New Technologies in Medicine and Surgery. University of Pisa, Pisa, Italy.
Department of Surgery-DiSCOG. Padua University Hospital. Padua, Italy.
Division of General and Transplant Surgery. University of Pisa. Pisa, Italy.
Biomedical Center. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czechia.
Department of General. Visceral and Thoracic Surgery. University Medical Center Hamburg-Eppendorf. Hamburg, Germany.
Blood Transfusion Service. Azienda Ospedaliero-Universitaria Meyer. Children's Hospital. Florence, Italy.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
Oncological Department. Azienda USL Toscana Nord Ovest. Oncological Unit of Massa Carrara. Carrara, Italy.
Digestive and Liver Disease Unit. Sant’Andrea Hospita. Rome, Italy. / Faculty of Medicine and Psychology. Sapienza University of Rome. Rome, Italy. / Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. IRSSC San Raffaele Scientific Institute. Milan, Italy.
Department of Pathology. Cancer Center Amsterdam. Amsterdam University Medical Centers. University of Amsterdam. Amsterdam, Netherlands.
Department of Oncology. Faculty of Medicine and Dentistry. Palacky University Olomouc and University Hospital Olomouc. Olomouc, Czechia.
Blood Transfusion Service. Azienda Ospedaliero-Universitaria Meyer. Children's Hospital. Florence, Italy.
Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. IRSSC San Raffaele Scientific Institute. Milan, Italy.
Department of Hematology. Institute of Hematology and Transfusion Medicine. Warsaw, Poland.
Medical Faculty Heidelberg. University of Heidelberg. Heidelberg, Germany. / Division of Clinical Epidemiology and Aging Research. German Cancer Research Center (DKFZ). Heidelberg, Germany.
Department of Oncology. Faculty of Medicine and Dentistry. Palacky University Olomouc and University Hospital Olomouc. Olomouc, Czechia.
Department of Biomedical Sciences. Humanitas University. Milan, Italy. / Pancreatic Surgery Unit. Humanitas Clinical and Research Center IRCCS. Milan, Italy.
Department of Surgery-DiSCOG. Padua University Hospital. Padua, Italy.
Oncological Department. Azienda USL Toscana Nord Ovest. Oncological Unit of Massa Carrara. Carrara, Italy.
Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc. Olomouc, Czechia.
Division of Experimental Oncology. Gastroenterology and Gastrointestinal Endoscopy Unit. Vita-Salute San Raffaele University. IRCCS San Raffaele Scientific Institute. Milan, Italy.
Department of Medical Oncology. Cancer Center Amsterdam. Amsterdam University Medical Center. University of Amsterdam. Amsterdam, Netherlands.
Division of Gastroenterology and Digestive Endoscopy. Department of Gastroenterology. Humanitas Clinical and Research Center IRCCS. Milan, Italy.
Department of Gastroenterology. Institute for Digestive Research. Medical Academy. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Endoscopic Surgery Department. Hippocratio General Hospital of Athens. Athens, Greece.
Department of Medicine – DIMED. Padua University Hospital. Padua, Italy.
Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. IRSSC San Raffaele Scientific Institute. Milan, Italy.
Szent György University. Teaching Hospital of County Fejér. Székesfehérvár, Hungary.
Department of Radiology and Oncology. Institute of Cancer of São Paulo. São Paulo, Brazil. / Universidade de São Paulo. Faculdade de Medicina. São Paulo, SP, Brasil.
Department of Molecular Biology of Cancer. Institute of Experimental Medicine of the Czech Academy of Sciences. Prague, Czechia. / Biomedical Center and Department of Surgery. Faculty of Medicine in Pilsen. Charles University. Pilsen, Czechia. / First Faculty of Medicine. Institute of Biology and Medical Genetics. Charles University. Prague, Czechia.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
Department of Surgery-DiSCOG. Padua University Hospital. Padua, Italy.
ARC-NET, Center for Applied Research on Cancer. University and Hospital Trust of Verona. Verona, Italy.
Department of Molecular and Clinical Cancer Medicine. University of Liverpool. Liverpool, United Kingdom.
Division of Experimental Oncology. Gastroenterology and Gastrointestinal Endoscopy Unit. Vita-Salute San Raffaele University. IRCCS San Raffaele Scientific Institute. Milan, Italy.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Department of Medicine. Centre for Translational Medicine. University of Szeged. Szeged, Hungary.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Department of Digestive Tract Diseases. Medical University of Lodz. Lodz, Poland.
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 Gastroenterology. Institute for Digestive Research. Medical Academy. Lithuanian University of Health Sciences. Kaunas, Lithuania.
Division of Clinical Epidemiology and Aging Research. German Cancer Research Center (DKFZ). Heidelberg, Germany. / German Cancer Consortium (DKTK). German Cancer Research Center (DKFZ). Heidelberg, Germany.
Institute for Translational Medicine. Medical School. University of Pécs. Pécs, Hungary. / Fundeni Clinical Institute. Bucharest, Romania.
Institute for Risk Assessment Sciences (IRAS). Utrecht University. Utrecht, Netherlands.
Department of General Surgery. University of Heidelberg. Heidelberg, Germany.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Division of Gastroenterology and Research Laboratory. Fondazione IRCCS “Casa Sollievo della Sofferenza” Hospital. San Giovanni Rotondo, Italy.
Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. IRSSC San Raffaele Scientific Institute. Milan, Italy.
Department of Gastroenterology. Institute for Digestive Research. Medical Academy. Lithuanian University of Health Sciences. Kaunas, Lithuania.
ARC-NET, Center for Applied Research on Cancer. University and Hospital Trust of Verona. Verona, Italy.
Digestive and Liver Disease Unit. Sant’Andrea Hospita. Rome, Italy. / Faculty of Medicine and Psychology. Sapienza University of Rome. Rome, Italy. / Pancreato-Biliary Endoscopy and Endosonography Division. Pancreas Translational and Clinical Research Center. IRSSC San Raffaele Scientific Institute. Milan, Italy.
Genetic and Molecular Epidemiology Group. Spanish National Cancer Research Centre (CNIO). Madrid, Spain.
Department of Biology. University of Pisa. Pisa, Italy.
Genomic Epidemiology Group. German Cancer Research Center (DKFZ). Heidelberg, Germany.

Abstract

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case–Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07–1.17, p = 3.03 × 10−6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.

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Frontiers Media

Citation

LU, Ye et al. Association of genetic variants affecting microRNAs and pancreatic cancer risk. Frontiers in Genetics. v. 12, n. 693933, p. 1–11, 2021.

DOI

10.3389/fgene.2021.693933

ISSN

1664-8021

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/49779

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