Ionizing Radiation May Induce Tumors Partly Through the Alteration or Regulation of Mismatch Repair Genes

Ionizing radiation is mutagenic and carcinogenic, and it is reported to induce primary and secondary tumors with intestinal tumors being one of the most commonly observed. However, the pathological and molecular mechanism(s) underlying the radiation-associated tumorigenesis remain unclear. A link between radiation and somatic tumorigenesis partly through genetic, epigenetic alteration and/or regulation of mismatch repair (MMR) genes has been hypothesized for the first time within this review. Clinical observations and experimental findings provide significant support for this association including MMR mutations as well as altered MMR RNA and protein expressions that occurred post-exposure, although existing evidence in published literature is sparse in this niche area. Some speculative mechanisms are suggested with this review to inform future research. Further studies are needed to understand the roles of the MMR system in response to radiation and to test this possible connection which could potentially provide useful and urgently needed information for clinical guidance.