Abstract
Radiation therapy is now well tolerated and associated with few side effects. However, people with certain germline genetic variants may be more sensitive to radiation, increasing their risk of experiencing adverse effects from treatment. Increased sensitivity to radiation can be tested in various ways; chromosomal aberrations, which are mutations, are particularly useful for this purpose. Many genetic variants only cause a slight increase in radiation sensitivity such as heterozygous pathogenic variants in the breast cancer risk genes BRCA1 and BRCA2. Variants of tumour suppressor genes, such as TP53, neurofibromatosis (NF1, PTCH1) and retinoblastoma (RB1), cause a slightly higher increase in radiation sensitivity. However, these also carry a high risk of secondary cancers for only a slightly increased level of risk for therapy-related side effects. Some patients with variants have significantly higher levels of radiation sensitivity - up to double the normal level - while others are even more sensitive. Nevertheless, significant variations exist within each specific genetic disorder. This means that radiosensitivity testing should be considered for all patients with a genetic disorder suspected to markedly increase their radiosensitivity, before they undergo radiotherapy. It implies that patients at risk of germline variants, such as children, young people and others at risk with a tumour, should be carefully evaluated and testing for genetic variants should be performed.