Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F15%3A43910303" target="_blank" >RIV/00216208:11120/15:43910303 - isvavai.cz</a>

Alternative codes found

RIV/68378041:_____/15:00454746 RIV/00216208:11110/15:10306920 RIV/00216208:11140/15:10306920

Result on the web

<a href="http://dx.doi.org/10.1093/carcin/bgv127" target="_blank" >http://dx.doi.org/10.1093/carcin/bgv127</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/carcin/bgv127" target="_blank" >10.1093/carcin/bgv127</a>

Result language

angličtina

Original language name

Interactions of DNA repair gene variants modulate chromosomal aberrations in healthy subjects

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Carcinogenesis

ISSN

0143-3334

e-ISSN

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Volume of the periodical

36

Issue of the periodical within the volume

11

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

1299-1306

UT code for WoS article

000366386800006

EID of the result in the Scopus database

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