Genetic susceptibility to late normal tissue injury

The outcome of all cancer therapies, including radiation, has greatly improved in the last 25 years, resulting in a doubling of the number of long-term cancer survivors. However, a subset of these survivors incurs adverse chronic side effects in unavoidably irradiated normal tissues, persisting long after treatment and compromising the quality of life of these patients. Interpatient variability in normal tissue radiation response is well documented and suggested to be under genetic control. Fibrosis, a clinically significant late effect in many irradiated tissues that results in tissue remodeling and loss of function, is a complex genetic trait making identification of the underlying genes difficult. Current clinical and animal studies are providing information on the genetics and molecular basis of late normal tissue injury in the radiation therapy setting, bringing us closer to our dual goal of individualizing treatment by genetic profiling and improving the quality of life of long-term survivors.