Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <or=55 years.
DNA 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 (<or=55 years) and 423 cancer-free controls who were frequency-matched with the cases by age (+/-5 years and <or=55), we tested our hypothesis and found that 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). 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.
Lu
Jiachun
J
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center Houston, TX 77030, USA.
Wei
Qingyi
Q
Bondy
Melissa L
ML
Li
Donghui
D
Brewster
Abenaa
A
Shete
Sanjay
S
Yu
Tse-Kuan
TK
Sahin
Aysegul
A
Meric-Bernstam
Funda
F
Hunt
Kelly K
KK
Singletary
S Eva
SE
Ross
Merrick I
MI
Wang
Li-E
LE
D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D044465:White People
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins