title: NBS1 657del5 mutation may contribute only to a limited fraction of breast cancer cases in Russia.
abstract: The gene for Nijmegen chromosomal breakage syndrome (NBS1) plays a role in a variety of processes protecting chromosomal stability. Recently, it was suggested in a Polish case-control study that the founder hypomorphic mutation in NBS1, 657del5, which occurs in approximately 0.5% of Slavic subjects, may be associated with an increased risk of breast cancer (BC). We attempted to validate these findings in Russian subjects, who are also of Slavic descent. Heterozygous carriers for the 657del5 mutation were detected in 2 of 173 (1.16%) bilateral breast cancer cases, 5 of 700 (0.71%) unilateral breast cancer patients, 2 of 348 (0.57%) healthy middle-aged females and in 0 of 344 elderly tumor-free women. The difference between the "extreme" cohorts, i.e., biBC patients vs. elderly controls, approached the formal limit of statistic significance (p=0.046). LOH at NBS1 was detected in only 3 of 5 available breast tumors from NBS1 657del5-carriers. In 2 of these tumors, the loss involved the mutant NBS1-allele. Overall, our data suggest that the NBS1 657del5 allele may contribute only to a limited fraction of breast cancer cases in Russia.
authors.affiliation: N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Buslov
authors.forename: Aglaya G
authors.initials: AG
authors.lastname: Iyevleva
authors.forename: Elena V
authors.initials: EV
authors.lastname: Chekmariova
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Suspitsin
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Togo
authors.forename: Ekatherina Sh
authors.initials: ESh
authors.lastname: Kuligina
authors.forename: Anna P
authors.initials: AP
authors.lastname: Sokolenko
authors.forename: Dmitry E
authors.initials: DE
authors.lastname: Matsko
authors.forename: Elena A
authors.initials: EA
authors.lastname: Turkevich
authors.forename: Yulia R
authors.initials: YR
authors.lastname: Lazareva
authors.forename: Oleg L
authors.initials: OL
authors.lastname: Chagunava
authors.forename: Elena M
authors.initials: EM
authors.lastname: Bit-Sava
authors.forename: Vladimir F
authors.initials: VF
authors.lastname: Semiglazov
authors.forename: Peter
authors.initials: P
authors.lastname: Devilee
authors.forename: Cees
authors.initials: C
authors.lastname: Cornelisse
authors.forename: Kaido P
authors.initials: KP
authors.lastname: Hanson
authors.forename: Evgeny N
authors.initials: EN
authors.lastname: Imyanitov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010865:Pilot Projects; D012306:Risk; D012426:Russia
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins