DNA double-strand break repair capacity and risk of breast cancer.
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.
Bau
Da-Tian
DT
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Mau
Yi-Chien
YC
Ding
Shian-Ling
SL
Wu
Pei-Ei
PE
Shen
Chen-Yang
CY
D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D011897:Random Allocation; D012307:Risk Factors