Chromosomal radiosensitivity in BRCA1 and BRCA2 mutation carriers

Purpose: The chromosomal radiosensitivity of a selected group of familial breast cancer patients carrying a mutation in BRCAI (n= 11) or BRCA2 (n = 9) and a group of healthy mutation carriers (n = 12) was investigated and compared to a reference group of breast cancer patients without a BRCA 1 /2 mutation (n = 78) and a group of healthy women carrying no mutation (n = 58). Materials and methods: The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus (MN)-assay on fresh blood samples and on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines. For the MN-assay, lymphocytes were exposed in vitro to 3.5 Gy and 2 Gy Co-60 gamma-rays at a high dose rate (HDR) or low dose rate (LDR). 70-h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. For the G2-assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy Co-60 gamma-rays after 71h incubation. Cultures were arrested 90 min after irradiation and chromatid breaks were scored in 50 metaphascs. Results: The group of breast cancer patients with a BRCAI or 2 mutation was on average more radiosensitive than the control group, but not different from breast cancer patients without a BRCA mutation. The radiation response of healthy BRCA1/2 carriers was not significantly different from the control group and also not different from relatives without a BRCA mutation. Comparing the radiation response in EBV cell lines derived from breast cancer patients with or without a BRCA1 mutation revealed no significant difference. Conclusions: Our results reveal that chromosomal radiosensitivity observed in breast cancer patients heterozygous for BRCA1 or 2 mutations, could not be demonstrated in healthy BRCA1/2 mutation carriers. This suggests that mutations in BRCA1 or 2 genes are not playing a main role in chromosomal radiosensitivity, this although BRCA1 and 2 are both involved in DNA repair/signalling processes.