Radiobiology research is building the foundation for applying genomics in 
precision radiation oncology. Advances in high-throughput approaches will 
underpin increased understanding of radiosensitivity and the development of 
future predictive assays for clinical application. There is an established 
contribution of genetics as a risk factor for radiotherapy side effects. An 
individual's radiosensitivity is an inherited polygenic trait with an 
architecture that includes rare mutations in a few genes that confer large 
effects and common variants in many genes with small effects. Current thinking 
is that some will be tissue specific, and future tests will be tailored to the 
normal tissues at risk. The relationship between normal and tumor cell 
radiosensitivity is poorly understood. Data are emerging suggesting interplay 
between germline genetic variation and epigenetic modification with growing 
evidence that changes in DNA methylation regulate the radiosensitivity of cancer 
cells and histone acetyltransferase inhibitors have radiosensitizing effects. 
Changes in histone methylation can also impair DNA damage response signaling and 
alter radiosensitivity. An important effort to advance radiobiology in the 
genomic era was establishment of the Radiogenomics Consortium to enable the 
creation of the large radiotherapy cohorts required to exploit advances in 
genomics. To address challenges in harmonizing data from multiple cohorts, the 
consortium established the REQUITE project to collect standardized data and 
genotyping for ~5,000 patients. The collection of detailed dosimetric data is 
important to produce validated multivariable models. Continued efforts will 
identify new genes that impact on radiosensitivity to generate new knowledge on 
toxicity pathogenesis and tests to incorporate into the clinical decision-making 
process.