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Metabolic Gene Variants Associated with Chromosomal Aberrations in Healthy Humans
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SYSNO ASEP 0452304 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Metabolic Gene Variants Associated with Chromosomal Aberrations in Healthy Humans Author(s) Hemminki, K. (DE)
Frank, Ch. (DE)
Försti, A. (DE)
Musak, L. (SK)
Kazimírová, A. (SK)
Barančoková, M. (SK)
Horská, A. (SK)
Vymetálková, Veronika (UEM-P) RID
Smerhovský, Z. (CZ)
Naccarati, Alessio (UEM-P)
Souček, P. (CZ)
Vodičková, Ludmila (UEM-P) RID
Buchancová, J. (SK)
Smolková, B. (SK)
Dusinska, M. (NO)
Vodička, Pavel (UEM-P) RIDNumber of authors 16 Source Title Genes Chromosomes & Cancer. - : Wiley - ISSN 1045-2257
Roč. 54, č. 4 (2015), s. 260-266Number of pages 7 s. Language eng - English Country US - United States Keywords DNA-damage ; cancer ; polymorphisms ; risk ; lymphocytes ; exposure ; repair ; susceptibility ; markers ; GSTT1 Subject RIV EB - Genetics ; Molecular Biology Institutional support UEM-P - RVO:68378041 UT WOS 000350275900006 EID SCOPUS 84923229952 DOI 10.1002/gcc.22239 Annotation Nonspecific chromosomal aberrations (CAs) are found in about 1% of lymphocytes drawn from healthy individuals. They include chromosome-type aberrations (CSAs), which are increased in exposure to ionizing radiation, and chromatid-type aberrations (CTAs) which in experimental systems are formed by DNA binding carcinogens and mutagens. The frequency of CAs is associated with the risk of cancer, but the causes of CAs in general population are unknown. Here, we want to test whether variants in metabolic genes associate with CAs in healthy volunteers. Cases were considered those whose total CA (CAtot) frequency was >2% and for CSA and CTA the limit was >1%. Controls had lower frequencies of CAs. Functional polymorphisms in seven genes were selected for analysis: cytochrome P450 1B1 (CYP1B1), epoxide hydrolase 1 (EPHX1), NAD(P)H:quinone oxidoreductase 1 (NQO1), each coding for phase 1 enzymes, and glutathione S-transferase P1 (GSTP1), glutathione S-transferases M1 (GSTM1) and T1 (GSTT1), coding for enzymes which conjugate reactive metabolites, that is, phase 2 enzymes. The number of volunteers genotyped for each gene varied from 550 to 1,500. Only EPHX1 was individually associated with CAtot; high activity genotypes decreased CAtot. A total of six significant (P < 0.01) pair-wise interactions were observed, most including a GST variant as one of the pair. In all genotype combinations with significant odds ratios for CAs a GST variant was involved. The present data provide evidence that variants in genes coding for metabolic enzymes, which individually have small effects, interact and are associated with CA frequencies in peripheral lymphocytes of healthy volunteers. (c) 2015 Wiley Periodicals, Inc. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2016
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