title: The c.657del5 variant in the NBN gene predisposes to pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is the sixth most frequent cancer type in the Czech Republic with a poor prognosis that could be improved by an early detection and subsequent surgical treatment combined with chemotherapy. Genetic factors play an important role in PDAC risk. We previously identified one PDAC patient harboring the Slavic founder deleterious mutation c.657del5 in the NBN gene, using a panel next-generation sequencing (NGS). A subsequent analysis of 241 unselected PDAC patients revealed other mutation carriers. The overall frequency of c.657del5 in unselected PDAC patients (5/241; 2.07%) significantly differed from that in non-cancer controls (2/915; 0.2%; P=0.006). The result indicates that the NBN c.657del5 variant represents a novel PDAC-susceptibility allele increasing PDAC risk (OR=9.7; 95% CI: 1.9 to 50.2). The increased risk of PDAC in follow-up recommendations for NBN mutation carriers should be considered if other studies also confirm an increased frequency of c.657del5 carriers in PDAC patients from other populations.
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Marianna
authors.initials: M
authors.lastname: Borecka
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Zemankova
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Lhota
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Soukupova
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Kleiblova
authors.affiliation: Department of Oncology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Vocka
authors.affiliation: Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
authors.affiliation: Department of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ticha
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kleibl
authors.affiliation: Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. Electronic address: mjana@lf1.cuni.cz.
authors.forename: Marketa
authors.initials: M
authors.lastname: Janatova
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D003604:Czechoslovakia; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010375:Pedigree
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins
keywords: Inherited risk; Pancreatic ductal adenocarcinoma; The NBN gene