Carcinogenesis Advance Access originally published online on May 10, 2007
Carcinogenesis 2007 28(8):1726-1730; doi:10.1093/carcin/bgm109
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DNA double-strand break repair capacity and risk of breast cancer
1 Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan
2 Cancer Center, China Medical University Hospital, Taichung 40402, Taiwan
3 Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei 11485, Taiwan
4 Life Science Library, Academia Sinica, Taipei 11529, Taiwan
5 Graduate Institute of Environmental Science, China Medical University, Taichung 40402, Taiwan
* To whom correspondence should be addressed. Tel: +886 2 27899036; Fax: +886 2 2782 3047; Email: bmcys{at}ibms.sinica.edu.tw
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.
Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; DSB, double-strand break; DTT, dithiothreitol; EJ, end joining; NHEJ, non-homologous end joining; PBMC, peripheral blood mononuclear cell; SNP, single-nucleotide polymorphism
Received December 29, 2006; revised April 24, 2007; accepted April 30, 2007.
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