title: Heterozygous p.I171V mutation of theNBNgene as a risk factor for lung cancer development.
abstract: TheNBNgene, also known asNBS1, is located on the chromosome band 8q21.3, and encodes a 754-amino acid-long protein named nibrin. This protein is a member of the MRE1-RAD50-NBN nuclear complex, and is involved in numerouscellprocesses essential for maintaining genomic stability. Heterozygous variants in theNBNgene, including p.I171V, c.657del5 and p.R215W, have been described as risk factors for the development of several malignancies. However, there is no report regarding the association of these mutations with lung cancer thus far. Therefore, the present study aimed to evaluate whether there is an association between the heterozygous p.I171V, c.657del5 and p.R215W variants of theNBNgene and the risk of developing lung cancer. The frequency of these variants was estimated in a group of 453 adults diagnosed with non-small cell lung cancer (NSCLC) and in healthy controls (2,400 for p.I171V, 2,090 for c.657del5 and 498 for p.R215W). The p.I171V variant was assessed by restrictionfragmentlength polymorphism analysis of polymerase chain reaction (PCR) products, usingMunI (MfeI) restriction enzyme, whereas the c.657del5 and p.R215W variants were assessed by thePCR single-strand conformation polymorphism method. A significantly increased risk of developing lung cancer was observed for the p.I171V variant, which was present in 17 (3.75%) of the 453 cases of lung cancer and in 12 (0.5%) of the 2,400 healthy individuals (odds ratio, 7.759; P<0.0001). The results obtained indicated an association between the p.I171V mutation and the development of lung cancer. Therefore, this variant may be considered a risk factor for NSCLC. Prospective studies with larger groups of patients may reveal the potential impact of the p.I171V variant in the occurrence of lung cancer.
authors.affiliation: Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Ewelina Maria
authors.initials: EM
authors.lastname: Kałużna
authors.affiliation: Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Rembowska
authors.affiliation: Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Ziółkowska-Suchanek
authors.affiliation: Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Bogna
authors.initials: B
authors.lastname: Świątek-Kościelna
authors.affiliation: Department of Thoracic Surgery, University of Medical Sciences, Poznań 60-569, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gabryel
authors.affiliation: Department of Thoracic Surgery, University of Medical Sciences, Poznań 60-569, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Dyszkiewicz
authors.affiliation: Department of Molecular Pathology, Institute of Human Genetics of the Polish Academy of Sciences, Poznań 60-479, Poland.
authors.forename: Jerzy Stanisław
authors.initials: JS
authors.lastname: Nowak
keywords: NBN gene; lung cancer risk; nibrin; p.I171V