Clinical implications of radiation-induced genomic instability.

Radiation-induced genomic instability encompasses a range of measurable end points such as chromosome destabilization, sister chromatid exchanges, gene mutation and amplification, late cell death and aneuploidy, all of which may be causative factors in the development of clinical disease, including carcinoma. Clinical implications of genomic instability can be broadly grouped into two main areas: as a marker for increased cancer risk/early detection, and as a consequence of radiation therapy (IR) that may be causative of, or a strong marker for, the induction of a therapy-induced second malignancy. Research in human populations has been limited, but broadly encompasses three populations: those exposed to alpha-particle irradiation, those with a cancer diagnosis who were examined for lymphocyte sensitivity to IR as a biomarker for risk of cancer induction, and those who successfully completed radiation therapy for an index cancer and who were examined for the induction of a second malignancy. This review examines each of those populations in turn and offers some potential future research directions to better elucidate the role of radiation-induced genomic instability in clinical disease.