title: Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland.
abstract: It has been suggested based on familial data that Nijmegen breakage syndrome (NBS) heterozygotes have an increased risk of malignant tumors. We found 15 carriers of the 657del5 mutation and 8 carriers of the R215W molecular variant of the NBS1 gene among 1,289 consecutive patients from Central Poland with various cancers and only 10 and 4 such carriers, respectively, in 1,620 controls from this region. Most of the 657del5 mutation carriers were found among patients with melanoma (4/105), non-Hodgkin lymphoma (2/42) and breast cancer (4/224) and of the 234 patients with colorectal carcinoma 3 carried the 657del5 mutation and 3 others the R215W molecular variant. The frequencies of 657del5 mutation carriers among patients with melanoma and non-Hodgkin lymphoma and of R215W carriers in patients with colorectal cancer were significantly higher than in controls (p < 0.01, < 0.05 and < 0.05 respectively). The pooled frequencies of 657del5 and R215W mutations in all cancer patients were also significantly higher than in controls (p < 0.05). Two carriers of the 657del5 mutation had second primary tumors. Malignant tumors among parents and siblings of 657del5 mutation carriers (14/77) were twice more frequent than in population controls. Three carriers of this mutation (2 probands with melanoma) reported melanoma in relatives. These results suggest strongly that NBS1 heterozygosity may be associated with elevated risk of some cancers. Larger studies are needed to evaluate the impact of the high frequency of germline NBS1 mutations on the cancer burden in the Slav populations.
authors.affiliation: Department of Immunology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. jsteffen@coi.waw.pl
authors.forename: Jan
authors.initials: J
authors.lastname: Steffen
authors.forename: Raymonda
authors.initials: R
authors.lastname: Varon
authors.forename: Maria
authors.initials: M
authors.lastname: Mosor
authors.forename: Galina
authors.initials: G
authors.lastname: Maneva
authors.forename: Martin
authors.initials: M
authors.lastname: Maurer
authors.forename: Markus
authors.initials: M
authors.lastname: Stumm
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
authors.forename: Maryna
authors.initials: M
authors.lastname: Rubach
authors.forename: Ewa
authors.initials: E
authors.lastname: Kosakowska
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Ruka
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Nowecki
authors.forename: Piotr
authors.initials: P
authors.lastname: Rutkowski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Demkow
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sadowska
authors.forename: Mariusz
authors.initials: M
authors.lastname: Bidziński
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Gawrychowski
authors.forename: Karl
authors.initials: K
authors.lastname: Sperling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D011044:Poland / Q000453:epidemiology; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins