title: Carrier frequency of mutation 657del5 in the NBS1 gene in a population of Polish pediatric patients with sporadic lymphoid malignancies.
abstract: Nijmegen breakage syndrome (NBS) is a human autosomal recessive disease characterized by genomic instability and enhanced cancer predisposition, in particular to lymphoma and leukemia. Recently, significantly higher frequencies of heterozygous carriers of the Slavic founder NBS1 mutation, 657del5, were found in Russian children with sporadic lymphoid malignancies, and in Polish adults with non-Hodgkin lymphoma (NHL). In addition, the substitution 643C>T (R215W) has also been found in excess among children with acute lymphoblastic leukemia (ALL). In an attempt to asses the contribution of both mutations to the development of sporadic lymphoid malignancies, we analyzed DNA samples from a large group of Polish pediatric patients. The NBS1 mutation 657del5 on one allele was found in 3 of 270 patients with ALL and 2 of 212 children and adolescents with NHL; no carrier was found among 63 patients with Hodgkin lymphoma (HL). No carriers of the variant R215W were detected in any studied group. The relative frequency of the 657del5 mutation was calculated from a total of 6,984 controls matched by place of patient residence, of whom 42 were found to be carriers (frequency = 0.006). In the analyzed population with malignancies, an increased odds ratio for the occurrence of mutation 657del5 was found in comparison with the control Polish population (OR range 1.48-1.85, 95% confidence interval 1.18-2.65). This finding indicates that the frequency of the mutation carriers was indeed increased in patients with ALL and NHL (p < 0.05). Nonetheless, NBS1 gene heterozygosity is not a major risk factor for lymphoid malignancies in childhood and adolescence.
authors.affiliation: Department of Medical Genetics, Children's Memorial Health Institute, 04-730 Warsaw, Al. Dzieci Polskich 20, Poland. chrzanowska@czd.waw.pl
authors.forename: Krystyna H
authors.initials: KH
authors.lastname: Chrzanowska
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.forename: Ewa
authors.initials: E
authors.lastname: Popowska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Gładkowska-Dura
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Małdyk
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Syczewska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: Bozenna
authors.initials: B
authors.lastname: Goryluk-Kozakiewicz
authors.forename: Halina
authors.initials: H
authors.lastname: Bubała
authors.forename: Artur
authors.initials: A
authors.lastname: Gadomski
authors.forename: Anna
authors.initials: A
authors.lastname: Gaworczyk
authors.forename: Bernarda
authors.initials: B
authors.lastname: Kazanowska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kołtan
authors.forename: Marta
authors.initials: M
authors.lastname: Kuźmicz
authors.forename: Teresa
authors.initials: T
authors.lastname: Luszawska-Kutrzeba
authors.forename: Lucyna
authors.initials: L
authors.lastname: Maciejka-Kapuścińska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Stolarska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Stefańska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sznurkowska
authors.forename: Anna
authors.initials: A
authors.lastname: Wakulińska
authors.forename: Maria
authors.initials: M
authors.lastname: Wieczorek
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepański
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kowalczyk
mesh_terms: D000293:Adolescent; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008223:Lymphoma / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011044:Poland / Q000453:epidemiology
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins