title: Heterozygous carriers of the I171V mutation of the NBS1 gene have a significantly increased risk of solid malignant tumours.
abstract: Homozygous mutation 657del5 within the NBS1 gene is responsible for the majority of Nijmegen breakage syndrome (NBS) cases. NBS patients are characterised by increased susceptibility to malignancies mainly of lymphoid origin. Recently it has been postulated that heterozygous carriers of 657del5 NBS1 mutation are at higher risk of cancer development. The aim of the study was to analyse the frequency of I171V mutation in NBS1 gene in 270 women with breast cancer, 176 patients with larynx cancer, 81 with second primary tumours of head and neck, 131 with colorectal carcinoma and 600 healthy individuals. I171V mutation was present in 17 cancer patients compared with only one in healthy individuals. This constitutes 2.58% in studied patients with malignancies and 0.17% in the control group (P=0.0002; relative risk 1.827; odds ratio 15.886; 95% confidence interval 2.107-119.8). Since DNA was isolated from non malignant cells, all mutations found in cancer patients appeared to be of germinal origin. It can be concluded that NBS1 allele I171V may be a general susceptibility gene in solid tumours.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznań Strzeszyńska 32, Poland. nowakjs@man.poznan.pl
authors.forename: Jerzy
authors.initials: J
authors.lastname: Nowak
authors.forename: Maria
authors.initials: M
authors.lastname: Mosor
authors.forename: Iwona
authors.initials: I
authors.lastname: Ziółkowska
authors.forename: Malgorzta
authors.initials: M
authors.lastname: Wierzbicka
authors.forename: Monika
authors.initials: M
authors.lastname: Pernak-Schwarz
authors.forename: Marta
authors.initials: M
authors.lastname: Przyborska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Roznowski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pławski
authors.forename: Ryszard
authors.initials: R
authors.lastname: Słomski
authors.forename: Danuta
authors.initials: D
authors.lastname: Januszkiewicz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012307:Risk Factors
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins