Can risk of radiotherapy-induced normal tissue complications be predicted from genetic profiles?
Over the last decade, increasing efforts have been taken to establish associations between various genetic germline alterations and risk of normal tissue complications after radiotherapy. Though the studies have been relatively small and methodologically heterogeneous, preliminary indications have been provided that single nucleotide polymorphisms in the genes TGFB1 and ATM may modulate risk of particularly late toxicity. In addition, rare ATM alterations may enhance complication susceptibility. Nevertheless, we are still far from having an exhaustive understanding of the genetics that may underlie differences in clinical normal tissue radiosensitivity. Recent technical advances and emerging insights to the structure of inter-individual genetic variation open up unprecedented opportunities to dissect the molecular and genetic basis of normal tissue radiosensitivity. However, to fully exploit these new possibilities well-planed large-scale clinical studies are mandatory. Currently, international initiatives are taken to establish the bio banks and databases needed for this task.
Andreassen
Christian Nicolaj
CN
Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. nicolaj@oncology.dk
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005819:Genetic Markers; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000532:radiotherapy*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011831:Radiation Genetics; D011832:Radiation Injuries / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases