Genetic biomarkers of therapeutic radiation sensitivity.
The occurrence of acute or late normal tissue reactions after therapeutic radiotherapy and cellular responses in in vitro radiosensitivity assays do not correlate well suggesting that to date no one test system is suitable for predicting the risk or severity of such reactions. New insights into the underlying molecular mechanisms of this sensitivity are coming from studies that assess associations between common polymorphisms in DNA damage detection and repair genes and the development of adverse reactions to radiotherapy. The presence of such variants may alter protein function and an individual's capacity to repair damaged DNA modifying the response of the normal tissue. Polymorphisms in the XRCC1, ATM, hHR21 and TGFbeta1 genes have been shown to be associated with an increased risk of developing an adverse normal tissue reaction to radiotherapy, whilst one variant in the ATM gene has been reported to be radioprotective. Functional studies, taking into account either the haplotypes or the combined genotypes when multiple polymorphisms in a gene are present, will be necessary to establish the mechanistic basis of these associations. In the future association studies can only benefit from the analysis of multiple genes in large, well-characterized cohorts in particular to identify genetic factors that might specifically influence the temporal occurrence of these adverse reactions.
Fernet
Marie
M
DNA Repair Group, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France.
Hall
Janet
J
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011836:Radiation Tolerance; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; D010750:Phosphoproteins; C429022:RAD21 protein, human; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases