title: Radiogenomics - current status, challenges and future directions.
abstract: Radiogenomics designates a scientific field that addresses possible associations between genetic germline alterations and normal tissue toxicity after radiotherapy. The ultimate aim of this research is to establish a gene-based predictive test for normal tissue radiosensitivity. During the last 5 years, substantial progress has been achieved in this field. Several compelling associations for SNPs have been demonstrated in large candidate gene studies as well as genome wide association studies. These findings shed new light on radiobiology and expand our understanding of the processes that lead to side effects after radiotherapy. Despite this, certain fundamental challenges still relate to genomic approaches. Based on the latest insights into complex trait genetics and molecular genetics, we provide an analysis of these challenges and propose putative strategies to further advance the field. These strategies include 'big data approaches' and collaborative research within international consortia. Furthermore, research that combines the study of radiation-induced gene expression and genome-wide SNP genotype may discover genetic alterations that regulate the biological response to ionizing radiation. Thus, such integrative approaches may lead to genetic alterations that affect risk of normal tissue toxicity.
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. Electronic address: nicolaj@oncology.au.dk.
authors.forename: Christian Nicolaj
authors.initials: CN
authors.lastname: Andreassen
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
authors.forename: Line Meinertz Hybel
authors.initials: LM
authors.lastname: Schack
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
authors.forename: Louise Vagner
authors.initials: LV
authors.lastname: Laursen
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
mesh_terms: D057225:Data Mining; D030541:Databases, Genetic; D004059:Diffusion of Innovation; D005544:Forecasting; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D023281:Genomics / Q000266:history / Q000379:methods* / Q000639:trends; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine / Q000266:history / Q000379:methods* / Q000639:trends; D040641:Quantitative Trait Loci; D011832:Radiation Injuries / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control; D018787:Radiation Oncology / Q000266:history / Q000379:methods* / Q000639:trends; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D005819:Genetic Markers; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: Complex trait; Expression quantitative trait loci; Normal tissue toxicity; Predictive assay; Radiosensitivity; SNP