A tumorigenic role of the non-homologous end-joining (NHEJ) pathway for the 
repair of DNA double-strand breaks (DSBs) has been suggested by our finding of a 
significant association between increased breast cancer risk and a cooperative 
effect of single-nucleotide polymorphisms in NHEJ genes. To confirm this 
finding, this case-control study detected both in vivo and in vitro DNA 
end-joining (EJ) capacities in Epstein-Barr virus-immortalized peripheral blood 
mononuclear cells (PBMCs) of 112 breast cancer patients and 108 healthy controls 
to identify individual differences in EJ capacity to repair DSB as a risk factor 
predisposing women to breast cancer. PBMCs from breast cancer patients 
consistently showed lower values of in vivo and in vitro EJ capacities than 
those from healthy women (P < 0.05). Logistic regression, simultaneously 
considering the effect of known risk factors of breast cancer, shows that the in 
vitro EJ capacity above the median of control subjects was associated with 
nearly 3-fold increased risks for breast cancer (adjusted odds ratio, 2.98; 95% 
confidence interval, 1.64-5.43). Furthermore, a dose-response relationship was 
evident between risk for breast cancer and EJ capacity, which was analyzed as a 
continuous variable (every unit decrease of EJ capacity being associated with an 
1.09-fold increase of breast cancer risk) and was divided into tertiles based on 
the EJ capacity values of the controls (P for trend < 0.01). The findings 
support the conclusion that NHEJ may play a role in susceptibility to breast 
cancer.