Metabolic Gene Variants Associated with Chromosomal Aberrations in Healthy Humans

0452304 - ÚEM 2016 RIV US eng J - Journal Article
Hemminki, K. - Frank, Ch. - Försti, A. - Musak, L. - Kazimírová, A. - Barančoková, M. - Horská, A. - Vymetálková, Veronika - Smerhovský, Z. - Naccarati, Alessio - Souček, P. - Vodičková, Ludmila - Buchancová, J. - Smolková, B. - Dusinska, M. - Vodička, Pavel
Metabolic Gene Variants Associated with Chromosomal Aberrations in Healthy Humans.
Genes Chromosomes & Cancer. Roč. 54, č. 4 (2015), s. 260-266. ISSN 1045-2257. E-ISSN 1098-2264
Institutional support: RVO:68378041
Keywords : DNA-damage * cancer * polymorphisms * risk * lymphocytes * exposure * repair * susceptibility * markers * GSTT1
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.960, year: 2015

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.
Permanent Link: http://hdl.handle.net/11104/0253321