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Hornhardt, S.* ; Rößler, U.* ; Sauter, W. ; Rosenberger, A.* ; Illig, T. ; Bickeböller, H.* ; Wichmann, H.-E. ; Gomolka, M.*

Genetic factors in individual radiation sensitivity.

DNA Repair 16, 54-65 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Cancer risk and radiation sensitivity are often associated with alterations in DNA repair, cell cycle, or apoptotic pathways. Interindividual variability in mutagen or radiation sensitivity and in cancer susceptibility may also be traced back to polymorphisms of genes affecting e.g. DNA repair capacity. We studied possible associations between 70 polymorphisms of 12 DNA repair genes with basal and initial DNA damage and with repair thereof. We investigated DNA damage induced by ionizing radiation in lymphocytes isolated from 177 young lung cancer patients and 169 cancer-free controls. We also sought replication of our findings in an independent sample of 175 families (in total 798 individuals). DNA damage was assessed by the Olive tail moment (OTM) of the comet assay. DNA repair capacity (DRC) was determined for 10, 30 and, 60. min of repair.Genes involved in the single-strand-repair pathway (SSR; like XRCC1 and MSH2) as well as genes involved in the double-strand-repair pathway (DSR; like RAD50, XRCC4, MRE11 and ATM) were found to be associated with DNA damage. The most significant association was observed for marker rs3213334 (p=0.005) of XRCC1 with basal DNA damage (B), in both cases and controls. A clear additive effect on the logarithm of OTM was identified for the marker rs1001581 of the same LD-block (p=0.039): BCC=-1.06 (95%-CI: -1.16 to -0.96), BCT=-1.02 (95%-CI: -1.11 to -0.93) and BTT=-0.85 (95%-CI: -1.01 to -0.68). In both cases and controls, we observed significantly higher DNA basal damage (p=0.007) for carriers of the genotype AA of marker rs2237060 of RAD50 (involved in DSR). However, this could not be replicated in the sample of families (p=0.781). An alteration to DRC after 30min of repair with respect to cases was observed as borderline significant for marker rs611646 of ATM (involved in DSR; p=0.055), but was the most significant finding in the sample of families (p=0.009).Our data indicate that gene variation impacts measurably on DNA damage and repair, suggesting at least a partial contribution to radiation sensitivity and lung cancer susceptibility.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dna Damage ; Dna Repair ; Dna Repair Pathways ; Polymorphisms ; Radiation Sensitivity; Breast-cancer Patients; Dna-repair Genes; Normal Tissue Complications; Base Excision-repair; Non-hodgkin-lymphoma; Cell Lung-cancer; Mutagen Sensitivity; Mismatch Repair; Comet Assay; Damage Response
ISSN (print) / ISBN 1568-7864
e-ISSN 1568-7856
Journal DNA Repair
Quellenangaben Volume: 16, Issue: 1, Pages: 54-65 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)