Carcinogenesis Advance Access published online on May 19, 2006
Carcinogenesis, doi:10.1093/carcin/bgl077
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1 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
* To whom correspondence should be addressed. 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 participate 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 (
Received December 20, 2005
Revised May 11, 2006
Accepted May 13, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women
Jiachun Lu 1,
Qingyi Wei 1 *,
Melissa L. Bondy 1,
Donghui Li 2,
Abenaa Brewster 3,
Sanjay Shete 1,
Tse-Kuan Yu 4,
Aysegul Sahin 5,
Funda Meric-Bernstam 6,
Kelly K. Hunt 6,
S. Eva Singletary 6,
Merrick I. Ross 6,
and
Li-E. Wang 1
55 years
2 Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
3 Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
4 Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
5 Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
6 Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
Qingyi Wei, E-mail: qwei{at}mdanderson.org
Abstract 
5%) haplotypes reported in the National Institute of Environmental Health Sciences (NIEHS) database and to reconstruct haplotypes. In a hospital-based case-control study of 421 non-Hispanic white patients with sporadic breast cancer 
55 years and 423 cancer-free controls who were frequency matched with the cases by age (±5 years and 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; Ptrend = 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.
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