Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <or=55 years.
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Bondy, Melissa L.
Hunt, Kelly K.
Singletary, S. Eva
Ross, Merrick I.
MetadataShow full item record
AbstractDNA double-strand breaks (DSBs) may lead to genomic instability and cancer if unrepaired. Nijmegen breakage syndrome 1 (NBS1) protein is one of the key proteins that participates in recognition and repair of DSBs in humans. We hypothesized that polymorphisms of NBS1 are associated with breast cancer risk. We selected three NBS1 haplotype-tagging polymorphisms (i.e. 924T>C, 8360G>C and 30537G>C) to represent all common (>or=5%) haplotypes reported in the National Institute of Environmental Health Sciences database and to reconstruct haplotypes. In a hospital-based case-control study of 421 non-Hispanic white patients with sporadic breast cancer (C polymorphism. Furthermore, the derived haplotypes were associated with risk in a dose-response manner as the number of variant (risk) alleles (i.e. 8360C, 924C or 30537C) increased (adjusted OR = 1.07, 95% CI = 0.78-1.46 for 1-2 variant alleles; adjusted OR = 2.47, 95% CI = 1.48-4.14 for 3-6 variant alleles; P(trend) = 0.006). These findings suggest that NBS1 polymorphisms and haplotypes may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Large studies are warranted to confirm these findings.
CitationCarcinogenesis 2006, 27 (11):2209-2216
DescriptionBiomarker: three Nijmegen breakage syndrome 1 (NBS1) protein haplotype-tagging polymorphisms (i.e. 924T>C, 8360G>C and 30537G>C) of Effect studied: breast cancer risk; DNA damage. Tissue/biological material/sample size: 30 ml of blood. Method of analysis: PCR-RFLP assay. Study design: case-control study. Study size: 421 cases and 423 controls Impact on outcome (including dose-response): compared with 924TT homozygotes the variant homozygote 924CC carriers had a 4.55-fold increased risk of breast cancer [95% confidence interval (CI) = 1.51-13.7] and that compared with the 8360GG genotype the variant genotypes were also associated with a significantly increased risk [adjusted odds ratio (OR) = 1.33, 95% CI = 1.00-1.78 for 8360CG; adjusted OR = 1.83, 95% CI = 1.14-2.94 for 8360CC]. However, these effects were not observed for the 30537G>C polymorphism. Furthermore, the derived haplotypes were associated with risk in a dose-response manner as the number of variant (risk) alleles (i.e. 8360C, 924C or 30537C) increased (adjusted OR = 1.07, 95% CI = 0.78-1.46 for 1-2 variant alleles; adjusted OR = 2.47, 95% CI = 1.48-4.14 for 3-6 variant alleles; P(trend) = 0.006). KEYWORDS - CLASIFFICATION: Aged;analysis;biomarkers of individual susceptibility: field studies;blood;Breast;Breast Neoplasms;cancer epidemiology;Cell Cycle;Cell Cycle Proteins;Environmental Health;Epidemiology;etiology;European Continental Ancestry Group;Female;field studies;genetic;Genetic Predisposition to Disease;genetics;Genotype;Haplotypes;Homozygote;Humans;Middle Aged;Models,Genetic;Nuclear Proteins;Odds Ratio;Polymorphism,Genetic;Proteins;Research;Risk;