Genetic analysis of apoptosis and BRCA1 gene mutations in patients from families with hereditary breast cancer

Aim: The breast cancer susceptibility gene BRCA1 encodes a large multi-functional protein which is implicated as a caretaker of the genome, through its role in regulation of DNA damage response pathways, including apoptosis. Apoptotic cell death plays an important role in the pathogenesis and disease progression of cancer as well as in the response to treatment. The objective of this study was to determine the frequency of BRCA1 germ-line mutations and apoptosis in patients with a family history of cancer.
Material and methods: 124 women from hereditary breast cancer families provided blood for genetic analysis. Blood samples from age-matched healthy individuals (n=108) served as controls. The BRCA1 mutations were determined by PCR-RFLP methods. The apoptotic peripheral blood cells were detected by agarose gel electrophoresis.
Results: Apoptotic cells were identified in 18% (23/124) of patients. There were no significant differences in apoptosis frequencies between patients and controls (p>0.05). Nine Ex20insC and four ExII17delA mutations of the BRCAl gene were identified in apoptosis-positive samples from breast cancer families.
Conclusions: The presence of apoptotic peripheral blood cells in patients suggests a potential role of apoptosis in risk of breast cancer appearance. The lack of detectable BRCA1 germ-line mutations in most cases suggests that there are probably additional, as yet unidentified genes predisposing to this disease.