Risk assessment in first degree female relatives of breast cancer patients using the alkaline Comet assay

Abstract

First degree female relatives (FDFRs) of breast cancer patients have been reported to have a 2- to 3-fold increase in breast cancer risk as compared with the general population. Assessment of genetic instability (DNA damage and repair efficiency) is an important parameter concerning mutagenesis and carcinogenesis. In an attempt to identify individuals at high risk of breast cancer in the FDFRs of breast cancer patients, two tests were used: the alkaline Comet assay on leucocytes and the micronucleus test (MNT) on buccal epithelial cells. In addition to FDFRs, two other categories of subjects were included: breast cancer patients and controls. The Comet assay was used to study basal DNA damage, DNA susceptibility to a mutagen (N-methyl N-nitro N-nitrosoguanidine) and DNA repair efficiency. In addition, the MNT served as an indicator of chromosome breakage/aneuploidy. A significant increase in DNA damage (basal and after treatment with a mutagen, as well as after allowing repair to take place) and micronucleus frequency was observed from controls to FDFRs and from FDFRs to breast cancer patients. There was considerable variability in the subjects with respect to both of these parameters. Outliers identified among the FDFRs based on 3 SD limits of DNA damage and micronucleus frequency were considered as high risk individuals.