title: Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?
abstract: Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review 'omics' approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different 'omics' approaches may be more efficient in identifying critical pathways than pathway analysis based on single 'omics' data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterised by different mechanisms. Thus 'omics' and functional approaches may synergise if they are integrated into radiogenomics 'systems biology' to facilitate the goal of individualised radiotherapy.
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany. Electronic address: carsten.herskind@medma.uni-heidelberg.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Herskind
authors.affiliation: Department of Genetics, University of Leicester, Leicester, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Talbot
authors.affiliation: Department of Radiation Oncology, Mount Sinai School of Medicine, New York, USA; Department of Radiation Oncology, University of Rochester Medical Center, Rochester, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Kerns
authors.affiliation: Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany.
authors.forename: Marlon R
authors.initials: MR
authors.lastname: Veldwijk
authors.affiliation: Department of Radiation Oncology, Mount Sinai School of Medicine, New York, USA; Department of Radiation Oncology, New York University School of Medicine, USA; Department of Dermatology, Mount Sinai School of Medicine, New York, USA.
authors.forename: Barry S
authors.initials: BS
authors.lastname: Rosenstein
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Christie Hospital, Manchester, UK.
authors.forename: Catharine M L
authors.initials: CM
authors.lastname: West
mesh_terms: D020869:Gene Expression Profiling; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040901:Proteomics / Q000379:methods; D011829:Radiation Dosage; D000069079:Radiation Exposure / Q000009:adverse effects*; D011832:Radiation Injuries / Q000235:genetics* / Q000378:metabolism; D011878:Radiotherapy / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D049490:Systems Biology / Q000379:methods*; D018511:Systems Integration
chemical_list: D005819:Genetic Markers
keywords: Gene expression microarrays; Genome-wide association studies; Normal-tissue reaction; Predictive tests; Radiotherapy; Single-nucleotide polymorphisms