Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA strand break repair phenotype and genotoxicity in workers exposed to low dose ionising radiations?

Aka, Peter; Mateuca, Raluca; Buchet, Jean-Pierre; Thierens, Hubert; Kirsch‐Volders, Micheline

doi:10.1016/j.mrfmmm.2004.08.002

Cited by 109 publications

(77 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this analysis, a single sporadic deviation from the null hypothesis of no-association and no-linkage for the hOGG1 Ser326Cys site was revealed, but this result failed to meet the stringency of significance after multiple test adjustment. Nevertheless, individuals with at least one hOGG1 Cys326 allele exhibit significantly slower DNA repair rates, as measured with the Comet assay [Aka et al, 2004], and hOGG1 Cys326Cys individuals showed higher levels of oxidative damage following exposure to Cr(VI) . Carriers of this genotype are also at increased risk of orolaryngeal cancer [Elahi et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

“…Single strand breaks are repaired chiefly through the base excision repair pathway (BER) whilst double strand breaks are dealt with through either homologous recombinational repair (HRR), where the undamaged copy in the homologous chromosome or sister chromatid is used as a template for repair, or via nonhomologous end joining (NHEJ) [Hoeijmakers, 2001;Jackson, 2002;Slupphaug et al, 2003]. Polymorphic variation in DNA repair genes has been reported to influence the response to in vitro irradiation as measured by cell cycle delay [Hu et al, 2001], cytogenetic damage [Lunn et al, 2000;Au et al, 2003;Marcon et al, 2003], and DNA single strand break induction and repair using the Comet assay [Aka et al, 2004;Godderis et al, 2004;Rzeszowska-Wolny et al, 2005]. However, whilst variation in DNA repair gene polymorphisms has been reported to influence the in vivo frequencies of micronuclei [Angelini et al, 2005] and unstable chromosome aberrations [Kiuru et al, 2005] following low dose irradiation, no such effect was found when stable translocations were used as the endpoint [Kiuru et al, 2005;Wilding et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Wilding¹,

Curwen²,

Tawn³

et al. 2006

Environ and Mol Mutagen

View full text Add to dashboard Cite

Sixteen candidate polymorphisms (13 SNPs and 3 microsatellites) in nine genes from four DNA repair pathways were examined in 83 subjects, comprising 23 survivors of childhood cancer, their 23 partners, and 37 offspring, all of whom had previously been studied for G 2 chromosomal radiosensitivity. Genotype at the Asp148Glu SNP site in the APEX gene of the base excision repair (BER) pathway was associated with childhood cancer in survivors (P = 0.001, significant even after multiple test adjustment), due to the enhanced frequency of the APEX Asp148 allele among survivors in comparison to that of their partners. Analysis of variance (ANOVA) of G 2 radiosensitivity in the pooled sample, as well as family-based association test (FBAT) of the family-wise data, showed sporadic suggestions of associations between G 2 radiosensitivity and polymorphisms at two sites (the Thr241-Met SNP site in the XRCC3 gene of the homologous recombinational pathway by ANOVA, and the Ser326Cys site in the hOGG1 gene of the BER pathway by FBAT analysis), but neither of these remained significant after multiple-test adjustment. This pilot study provides an intriguing indication that DNA repair gene polymorphisms may underlie cancer susceptibility and variation in radiosensitivity. Environ. Mol. Mutagen. 48:48-57, 2007.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Wilding¹,

Curwen²,

Tawn³

et al. 2006

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…Exposure to ionizing radiation has been linked to cancers of the thyroid, breast and lung as well as leukemias in humans (Ron, 1998), and is known to cause DNA damage requiring the base excision pathway (Wallace, 1994). Not only is there relevance to individuals exposed to low dose ionizing radiation (Aka et al, 2004), but a recent study suggests that XRCC1 polymorphisms may be associated with ineffective radiotherapy in some cancer patients (Moullan et al, 2003).…”

Section: Strategies For Carcinogen Challenge Studiesmentioning

confidence: 99%

Mouse models of XRCC1 DNA repair polymorphisms and cancer

Ladiges

2006

Oncogene

View full text Add to dashboard Cite

DNA damage plays a major role in mutagenesis, carcinogenesis and aging. A gene that is emerging as an essential element in the repair of both damaged bases and single-strand breaks (SSB) is XRCC1. XRCC1 has been shown to have a large number of single-nucleotide polymorphisms (SNPs), several of which are being increasingly studied in cancer epidemiology investigations, in part because of their relative high frequency in the population. Although association trends with specific cancer types have occasionally been shown in a variety of ethnic backgrounds, there are often conflicting reports that weaken any substantial conclusions. The functional significance of these SNPs is still largely unknown. XRCC1 is an excellent prototype to provide a forum for determining how epidemiological cancer association studies with DNA repair gene polymorphisms can be validated or refuted. The focus is on the utilization of in silico data and biochemical studies in cell lines and existing mouse models to help provide a framework for the development of new mutant mouse lines that mimic human polymorphisms. These mouse lines will provide the next generation of mammalian tools for carcinogen exposure studies relevant to human cancer and variations in XRCC1, and provide the basis for investigating groups of genes and polymorphisms in an animal model.

show abstract

“…For example, increased DNA adducts, increased chromosomal damage and increased micronuclei have all been demonstrated in persons with variant genotypes. [25][26][27][28][29] In addition, protein conservation analysis predicts a significant change in function of XRCC3 alleles carrying the variant genotype. 30 Data regarding the functional significance of the RAD51 polymorphism is limited.…”

Section: Introductionmentioning

confidence: 99%

DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group

et al. 2007

View full text Add to dashboard Cite

Polymorphisms of DNA repair genes RAD51 and XRCC3 increase susceptibility to acute myeloid leukemia (AML) in adults, an effect enhanced by deletion of the glutathione-Stransferase M1 (GSTM1) gene. In this study, we genotyped 452 children with de novo AML treated on CCG protocols 2941 and 2961 and compared genotype frequencies with those of normal blood donors, and analyzed the impact of genotype on outcome of therapy. XRCC3 Thr241Met, RAD51 G135C and GSTM1 genotypes did not increase susceptibility to AML when assessed singly. In contrast, when XRCC3 and RAD51 genotypes were examined together a significant increase in susceptibility to AML was seen in children with variant alleles. Analysis of outcome of therapy showed that patients heterozygous for the XRCC3 Thr241Met allele had improved postinduction disease-free survival compared to children homozygous for the major or minor allele, each of whom had similar outcomes. Improved survival was due to reduced relapse in the heterozygous children, and this effect was most marked in children randomized to therapy likely to generate DNA doublestrand breaks (etoposide, daunomycin), compared with antimetabolite (fludarabine, cytarabine) based therapy. In contrast, RAD51 G135C and the GSTM1 deletion polymorphism did not influence outcome of AML therapy in our study population.

show abstract

Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA strand break repair phenotype and genotoxicity in workers exposed to low dose ionising radiations?

Cited by 109 publications

References 33 publications

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Mouse models of XRCC1 DNA repair polymorphisms and cancer

DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group

Contact Info

Product

Resources

About

Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA strand break repair phenotype and genotoxicity in workers exposed to low dose ionising radiations?

Cited by 109 publications

References 33 publications

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G2chromosomal radiosensitivity

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G2chromosomal radiosensitivity

Mouse models of XRCC1 DNA repair polymorphisms and cancer

DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group

Contact Info

Product

Resources

About

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity

Influence of polymorphisms at loci encoding DNA repair proteins on cancer susceptibility and G₂chromosomal radiosensitivity