Ionizing Radiation and Ultraviolet Light Irradiation‐Associated DNA Damage Increasing Genomic Instability Risk

Cancer frequently develops in association with genomic instability, which includes massive induction of chromosomal structural variants (SVs) and single nucleotide variants (SNVs). SVs are typically caused by erroneous repair of DNA double-strand breaks (DSBs) and are tightly linked to cancer risk. Indeed, cancers often arise under DNA repair-deficient backgrounds such as BRCA1/2 mutations. However, many cancers exhibiting genomic instability occur without detectable defects in canonical repair pathways. The major exogenous risk factors include ionizing radiation (IR) and ultraviolet (UV) light, both of which induce multiple types of DNA damage. Long-standing questions are which specific types of DNA lesions induced by the irradiation contribute to genomic instability and how these lesions promote mutagenesis in cancer-driver genes. In this review, we summarize current knowledge regarding how IR and UV irradiation lead to genomic instability associated with mutation induction in cancer-driver genes.