Radiation, DNA damage and cancer.
The characterization of the rare, radiation-sensitive and cancer-prone syndromes, ataxia telangiectasia and Nijmegen breakage syndrome, has demonstrated that genetic predisposition increases the risk of developing cancer after exposure to ionizing radiation (IR). Molecular analyses of these disorders provide valuable insights into the normal function of these two gene products in the cellular response to IR-induced DNA damage. Their contribution to a cellular radiosensitive phenotype and their role in sporadic cancers can now be fully assessed. For example, the gene ataxia telangiectasia mutated (ATM) has recently been shown to be a tumour suppressor gene in T-cell prolymphocytic leukaemia, and there is increasing evidence that individuals with one mutated ATM or Nijmegen breakage syndrome (NBS1) allele have an increased predisposition to cancer.
Hall
J
J
Unit of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France. hall@iarc.fr
Angèle
S
S
D001260:Ataxia Telangiectasia / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D019457:Chromosome Breakage; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins; D011836:Radiation Tolerance / Q000235:genetics*; D013577:Syndrome
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D004247:DNA