Genetic variations in DNA repair genes, radiosensitivity to cancer and susceptibility to acute tissue reactions in radiotherapy-treated cancer patients.
Ionizing radiation is a well established carcinogen for human cells. At low doses, radiation exposure mainly results in generation of double strand breaks (DSBs). Radiation-related DSBs could be directly linked to the formation of chromosomal rearrangements as has been proven for radiation-induced thyroid tumors. Repair of DSBs presumably involves two main pathways, non-homologous end joining (NHEJ) and homologous recombination (HR). A number of known inherited syndromes, such as ataxia telangiectasia, ataxia-telangiectasia like-disorder, radiosensitive severe combined immunodeficiency, Nijmegen breakage syndrome, and LIG4 deficiency are associated with increased radiosensitivity and/or cancer risk. Many of them are caused by mutations in DNA repair genes. Recent studies also suggest that variations in the DNA repair capacity in the general population may influence cancer susceptibility. In this paper, we summarize the current status of DNA repair proteins as potential targets for radiation-induced cancer risk. We will focus on genetic alterations in genes involved in HR- and NHEJ-mediated repair of DSBs, which could influence predisposition to radiation-related cancer and thereby explain interindividual differences in radiosensitivity or radioresistance in a general population.
Department of Pathology, University of Pittsburgh, Pittsburgh, USA. dimitry.chistiakov@eudoramail.com
Dimitry A
DA
Chistiakov
Natalia V
NV
Voronova
Pavel A
PA
Chistiakov
D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics* / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D051135:Rad51 Recombinase / Q000235:genetics; D011830:Radiation Effects; D011831:Radiation Genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing
D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; D051135:Rad51 Recombinase