© 2005 Oxford University Press
ARTICLE |
DNA Repair Capacity of Lymphoblastoid Cell Lines From Sisters Discordant for Breast Cancer
Affiliations of authors: Department of Environmental Health Sciences (DOK, MA, JS, GM) and Epidemiology, Mailman School of Public Health (MBT, FFZ, RTS), Columbia University, New York, NY
Correspondence to: Regina M. Santella, Department of Environmental Health Sciences, Rm. 506, Mailman School of Public Health, Columbia University, 701 W. 168th St., New York, NY 10032 (e-mail: rps1{at}columbia.edu)
Background: Interindividual differences in DNA repair capacity may influence cancer risk. We tested whether the nucleotide excision repair pathway was deficient in breast cancer case patients by analyzing sister pairs. Methods: Cell lines derived from sisters discordant for breast cancer (137 families containing 158 case patients and 154 control sisters) were obtained from the Metropolitan New York Registry of Breast Cancer Families. Lymphoblastoid cells were treated with benzo[a]pyrene diolepoxide (BPDE) for 30 minutes and were either harvested immediately or were washed and cultured in complete medium for 4 hours to allow DNA repair. Immunofluorescence using a polyclonal anti-BPDE–DNA primary antibody was used to quantify BPDE–DNA adducts. Percent DNA repair capacity was calculated from the difference between staining immediately after treatment minus that after 4 hours of repair, divided by the initial damage and was categorized into quartiles based on control values. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for age at blood donation, body mass index, and smoking. Statistical tests were two-sided. Results: Mean percent DNA repair capacity was lower in breast cancer case patients than in control subjects (difference = 8.6, 95% CI = 4.3 to 13.8, P = .001). Using the quartile with the highest percent DNA repair capacity as the referent group, adjusted odds ratios of breast cancer increased from 1.23 (95% CI = 0.57 to 2.65) to 2.38 (95% CI = 1.17 to 4.86) to 2.99 (95% CI = 1.45 to 6.17) (Ptrend = .002) as DNA repair capacity decreased. Conclusions: Deficient DNA repair capacity is associated with increased breast cancer risk.
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Editorial about this Article
- Measuring DNA Repair Capacity: Small Steps
- Marianne Berwick and Paolo Vineis
J Natl Cancer Inst 2005 97: 84-85.[Extract] [Full Text] [PDF]
Related Memo to the Media
- Press Release: Deficient DNA Repair Capacity Associated With Increased Risk of Breast Cancer
- Sarah L. Zielinski
J Natl Cancer Inst 2005 97: 81.[Extract] [Full Text]
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