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Interactions of DNA...
Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects.
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Vodicka, Pavel (author)
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Musak, Ludovit (author)
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Frank, Christoph (author)
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Kazimirova, Alena (author)
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Vymetalkova, Veronika (author)
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Barancokova, Magdalena (author)
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Smolkova, Bozena (author)
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Dzupinkova, Zuzana (author)
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Jiraskova, Katerina (author)
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Vodenkova, Sona (author)
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Kroupa, Michal (author)
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Osina, Oto (author)
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Naccarati, Alessio (author)
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Palitti, Fabrizio (author)
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- Försti, Asta (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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Dusinska, Maria (author)
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Vodickova, Ludmila (author)
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- Hemminki, Kari (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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(creator_code:org_t)
- 2015-09-08
- 2015
- English.
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 36:11, s. 1299-1306
- Related links:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Vodicka, Pavel
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Musak, Ludovit
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Frank, Christoph
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Kazimirova, Alen ...
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Vymetalkova, Ver ...
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Barancokova, Mag ...
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show more...
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Smolkova, Bozena
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Dzupinkova, Zuza ...
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Jiraskova, Kater ...
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Vodenkova, Sona
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Kroupa, Michal
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Osina, Oto
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Naccarati, Aless ...
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Palitti, Fabrizi ...
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Försti, Asta
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Dusinska, Maria
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Vodickova, Ludmi ...
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Hemminki, Kari
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Carcinogenesis
- By the university
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Lund University