Breast cancer risk genes affecting individual radiosensitivity

Abstract

Abstract Increased radiosensitivity can cause adverse radiotherapy effects. Heterozygote variants in breast cancer risk genes increase cancer risk and may affect radiosensitivity. This study assessed their impact on individual radiosensitivity to determine the radiation risk for gene carriers. Radiosensitivity was analyzed in 273 patients with breast cancer risk gene variants. Using fluorescence in situ hybridization (FiSH), chromosomal aberrations were quantified as breaks per metaphase (B/M) after ex vivo irradiation of blood lymphocytes. Results were compared with healthy controls and breast cancer cases, both without confirmed non-carrier status, limiting gene-specific conclusions. Gene carriers showed slightly increased radiosensitivity (mean 0.488 B/M ± 0.134) compared with healthy controls (0.411 B/M ± 0.088; p  < 0.0001) but similar to breast cancer control group (0.498 B/M ± 0.192; p  = 0.563). In BRCA1/2 carriers, radiosensitivity was slightly increased, while single cases in BARD1 , RAD51 , and MSH variants suggested a possible increase ( p  < 0.003). Radiosensitivity was influenced by gene locus, variant type, age, and cancer history. 24.5% of carriers exceeded a cutoff of ≥ 0.55 B/M, where dose reduction could be considered. Radiosensitivity of breast cancer risk gene carriers varies and is slightly increased. Individuals with increased radiosensitivity risk should consider testing.