Journal Article

Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects

Pavel Vodicka, Rudolf Stetina, Veronika Polakova, Elena Tulupova, Alessio Naccarati, Ludmila Vodickova, Rajiv Kumar, Monika Hanova, Barbara Pardini, Jana Slyskova, Ludovit Musak, Giuseppe De Palma, Pavel Soucek and Kari Hemminki

in Carcinogenesis

Volume 28, issue 3, pages 657-664
Published in print October 2006 | ISSN: 0143-3334
Published online March 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl187
Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects

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We investigated association between polymorphisms in DNA repair genes and the capacity to repair DNA damage induced by γ-irradiation and by base oxidation in a healthy population. Irradiation-specific DNA repair rates were significantly decreased in individuals with XRCC1 Arg399Gln homozygous variant genotype (0.45 ± 0.47 SSB/109 Da) than in those with wild-type genotype (1.10 ± 0.70 SSB/109 Da, P = 0.0006, Mann–Witney U-test). The capacity to repair oxidative DNA damage was significantly decreased among individuals with hOGG1 Ser326Cys homozygous variant genotype (0.37 ± 0.28 SSB/109 Da) compared to those with wild-type genotype (0.83 ± 0.79 SSB/109 Da, P = 0.008, Mann–Witney U-test). Investigation of genotype combinations showed that the increasing number of variant alleles for both XRCC1 Arg399Gln and APE1 Asn148Glu polymorphisms resulted in a significant decrease of irradiation-specific repair rates (P = 0.008, Kruskal–Wallis test). Irradiation-specific DNA repair rates also decreased with increasing number of variant alleles in XRCC1 Arg399Gln in combination with variant alleles for two other XRCC1 polymorphisms, Arg194Trp and Arg280His (P = 0.002 and P = 0.005, respectively; Kruskal–Wallis test). In a binary combination variant alleles of hOGG1 Ser326Cys and APE1 Asn148Glu polymorphisms were associated with a significant decrease in the capacity to repair DNA oxidative damage (P = 0.018, Kruskal–Wallis test). In summary, XRCC1 Arg399Gln and hOGG1 Ser326Cys polymorphisms seem to exert the predominant modulating effect on irradiation-specific DNA repair capacity and the capacity to repair DNA oxidative damage, respectively.

Journal Article.  5775 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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