Genetic susceptibility to radiogenic cancer in humans.

The clinical benefits associated with the use of ionizing radiation for diagnostic and therapeutic purposes are well established, particularly in cancer medicine. Unfortunately, it is now clear that prior exposure to radiation is associated with an excess risk of developing malignancy in the exposure field. Indeed, the development of a second primary malignancy is a devastating side effect that can often be attributed to radiotherapy for a first cancer. Research has focused on elucidating the relationship between therapeutic radiation dose and site-specific cancer risk, and how this relationship is affected by host factors such as age, sex, and exposure to other potential carcinogens. By contrast, there is a relative paucity of data on host genetic susceptibility to cancer following cytotoxic and mutagenic radiation exposure. Animal model systems suggest a strong genetic basis underlying susceptibility to radiogenic cancer. In humans, research has focused on investigating loci with relatively rare putative high penetrance risk alleles. However, genetic susceptibility to radiogenic cancer and other late effects of radiation exposure may be determined predominantly by co-inheritance of low penetrance risk alleles, and how these interact with each other (gene-gene interactions), with radiation dose (gene-exposure interactions) and other risk factors.