Send to

Choose Destination
Carcinogenesis. 2008 Jul;29(7):1367-72. doi: 10.1093/carcin/bgn140. Epub 2008 Jun 19.

Double-strand breaks repair in lymphoblastoid cell lines from sisters discordant for breast cancer from the New York site of the BCFR.

Author information

Department of Environmental Health Sciences, Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.


Unrepaired DNA double-strand breaks (DSBs) may have serious consequences for cells by inducing chromosomal aberrations, thereby increasing genetic instability and cancer risk. One's capacity to repair DSB is therefore an important factor to consider when estimating cancer risk. We assessed DNA end-joining (EJ) capacity in cell lines derived from sisters discordant for breast cancer to determine if individual differences in DSB repair are a significant risk factor. We used an in vitro phenotypic assay on nuclear extracts from lymphoblasts of 179 subjects including 86 cases and 93 controls. EJ activity was functionally estimated as the ability of extracts to join together monomers of the plasmid pUC18 linearized either with sticky (EcoRI) or blunt ends (HincII). Mean percentage of EJ capacity was slightly lower in cases than controls, both for EcoRI (cases 27.9 +/- 11.1; controls 29.6 +/- 10.7, P = 0.28) and HincII substrates (cases 28.8 +/- 12.2; controls 30.6 +/- 13.0, P = 0.36); however, no significant differences were observed. Categorizing EJ capacity into tertiles and using the highest activity as the referent, we observed elevated associations for each tertile of decreased repair [Odds ratio (OR) = 2.20, 95% confidence interval (CI) = 0.77-6.22 and OR = 4.22, 95% CI thinsp;= 1.22-14.0, P = 0.02], respectively, for EcoRI. Results were not statistically significant for HincII (OR = 1.37, 95% CI = 0.51-3.70 and OR = 2.32, 95% CI = 0.57-9.38, P = 0.24). These data suggest that individual differences in EJ capacity may represent a risk factor predisposing women to breast cancer.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center