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

First degree female relatives (FDFRs) of breast cancer patients have been r eported to have a 2- to 3-fold increase in breast cancer risk as compared w ith the general population. Assessment of genetic instability (DNA damage a nd repair efficiency) is an important parameter concerning mutagenesis and carcinogenesis. In an attempt to identify individuals at high risk of breas t cancer in the FDFRs of breast cancer patients, two tests mere used: the a lkaline Comet assay on leucocytes and the micronucleus test (MNT) on buccal epithelial cells. In addition to FDFRs, two other categories of subjects w ere included: breast cancer patients and controls. The Comet assay was used to study basal DNA damage, DNA susceptibility to a mutagen (N-methyl N-nit ro N-nitrosoguanidine) and DNA repair efficiency, In addition, the MNT serv ed as an indicator of chromosome breakage/aneuploidy, A significant increas e in DNA damage (basal and after treatment with a mutagen, as well as after allowing repair to take place) and micronucleus frequency was observed fro m controls to FDFRs and from FDFRs to breast cancer patients. There was con siderable variability in the subjects with respect to both of these paramet ers. Outliers identified among the FDFRs based on 3 SD limits of DNA damage and micronucleus frequency were considered as high risk individuals.