Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26354780
DOI
10.1093/carcin/bgv127
PII: bgv127
Knihovny.cz E-resources
- MeSH
- Chromosome Aberrations * MeSH
- DNA-Binding Proteins genetics MeSH
- DNA Glycosylases genetics MeSH
- Adult MeSH
- Gene Frequency MeSH
- Genetic Association Studies MeSH
- Polymorphism, Single Nucleotide MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neoplasms genetics MeSH
- DNA Repair genetics MeSH
- X-ray Repair Cross Complementing Protein 1 MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA-Binding Proteins MeSH
- DNA Glycosylases MeSH
- oxoguanine glycosylase 1, human MeSH Browser
- X-ray Repair Cross Complementing Protein 1 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
References provided by Crossref.org
DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations
DNA Mismatch Repair Gene Variants in Sporadic Solid Cancers
DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome
