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The BRCA1 gene product helps to maintain genomic integrity through its participation in the cellular response to DNA damage: specifically, the repair of double-stranded DNA breaks. An impaired cellular response to DNA damage is a plausible mechanism whereby BRCA1 mutation carriers are at increased risk of breast cancer. Hence, an individual's capacity to repair DNA may serve as a useful biomarker of breast cancer risk. The overall aim of the current study was to identify a biomarker of DNA repair capacity that could distinguish between BRCA1 mutation carriers and non-carriers. DNA repair capacity was assessed using three validated assays: the single-cell alkaline gel electrophoresis (comet) assay, the micronucleus test, and the enumeration of gamma-H2AX nuclear foci. DNA repair capacity of peripheral blood lymphocytes from 25 cancer-free female heterozygous BRCA1 mutation carriers and 25 non-carrier controls was assessed at baseline and following cell exposure to gamma-irradiation (2 Gy). We found no significant differences in the mean tail moment, in the number of micronuclei or in the number of gamma-H2AX nuclear foci between the carriers and non-carriers at baseline, and following gamma-irradiation. These data suggest that these assays are not likely to be useful in the identification of women at a high risk for breast cancer.

DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1 mutation carriers