Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26354780
DOI
10.1093/carcin/bgv127
PII: bgv127
Knihovny.cz E-zdroje
- MeSH
- chromozomální aberace * MeSH
- DNA vazebné proteiny genetika MeSH
- DNA-glykosylasy genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetické asociační studie MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory genetika MeSH
- oprava DNA genetika MeSH
- protein XRCC1 MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- DNA-glykosylasy MeSH
- oxoguanine glycosylase 1, human MeSH Prohlížeč
- protein XRCC1 MeSH
Human cancers are often associated with numerical and structural chromosomal instability. Structural chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBL) arise as consequences of direct DNA damage or due to replication on a damaged DNA template. In both cases, DNA repair is critical and inter-individual differences in its capacity are probably due to corresponding genetic variations. We investigated functional variants in DNA repair genes (base and nucleotide excision repair, double-strand break repair) in relation to CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) in healthy individuals. Chromosomal damage was determined by conventional cytogenetic analysis. The genotyping was performed by both restriction fragment length polymorphism and TaqMan allelic discrimination assays. Multivariate logistic regression was applied for testing individual factors on CAs, CTAs and CSAs. Pair-wise genotype interactions of 11 genes were constructed for all possible pairs of single-nucleotide polymorphisms. Analysed individually, we observed significantly lower CTA frequencies in association with XPD Lys751Gln homozygous variant genotype [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.48-0.85, P = 0.004; n = 1777]. A significant association of heterozygous variant genotype in RAD54L with increased CSA frequency (OR 1.96, 95% CI 1.01-4.02, P = 0.03) was determined in 282 subjects with available genotype. By addressing gene-gene interactions, we discovered 14 interactions significantly modulating CAs, 9 CTAs and 12 CSAs frequencies. Highly significant interactions included always pairs from two different pathways. Although individual variants in genes encoding DNA repair proteins modulate CAs only modestly, several gene-gene interactions in DNA repair genes evinced either enhanced or decreased CA frequencies suggesting that CAs accumulation requires complex interplay between different DNA repair pathways.
Department of Agrobiology and Agrochemistry University of Tuscia 011000 Viterbo Italy
Division of Molecular Genetic Epidemiology German Cancer Research Centre 69120 Heidelberg Germany
Faculty of Medicine Slovak Medical University in Bratislava 83303 Bratislava Slovak Republic
Health Effects Laboratory MILK NILU Norwegian Institute for Air Research 2027 Kjeller Norway
Molecular Biology Service Research Institute for Molecular Pathology 1030 Vienna Austria
Citace poskytuje Crossref.org
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