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Biomarkers and Early Detection: Risk Markers and Surrogate Endpoints

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

UT M. D. Anderson Cancer Ctr., Houston, TX

Abstract

A10

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. A marker of DNA repair might also be used as an endpoint in studies designed to evaluate the capacity of different intervention strategies to modify risk.The overall aim of the current study was to identify a biomarker of DNA repair capacity that could help 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 \#915;-H2AX nuclear foci. These assays form a complementary panel of biomarkers for DNA repair, and reflect both molecular and chromosomal repair capacity in vivo. 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 \#915;-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.