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Metabolic gene variants associated with chromosomal aberrations in healthy humans.

Hemminki, Kari LU ; Frank, Christoph LU ; Försti, Asta LU ; Musak, Ludovit; Kazimirova, Alena; Barancokova, Magdalena; Horska, Alexandra; Vymetalkova, Veronika; Smerhovsky, Zdenek and Naccarati, Alessio, et al. (2015) In Genes, Chromosomes and Cancer 54(4). p.260-266
Abstract
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... (More)
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. © 2015 Wiley Periodicals, Inc. (Less)
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Genes, Chromosomes and Cancer
volume
54
issue
4
pages
260 - 266
publisher
John Wiley & Sons
external identifiers
  • pmid:25622915
  • wos:000350275900006
  • scopus:84923229952
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1045-2257
DOI
10.1002/gcc.22239
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English
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yes
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64bd25da-0556-44b9-a569-32e29b473fb0 (old id 5039666)
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http://www.ncbi.nlm.nih.gov/pubmed/25622915?dopt=Abstract
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2015-02-04 17:41:19
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2017-10-29 03:12:17
@article{64bd25da-0556-44b9-a569-32e29b473fb0,
  abstract     = {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 &gt;2% and for CSA and CTA the limit was &gt;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 &lt; 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. © 2015 Wiley Periodicals, Inc.},
  author       = {Hemminki, Kari and Frank, Christoph and Försti, Asta and Musak, Ludovit and Kazimirova, Alena and Barancokova, Magdalena and Horska, Alexandra and Vymetalkova, Veronika and Smerhovsky, Zdenek and Naccarati, Alessio and Soucek, Pavel and Vodickova, Ludmila and Buchancova, Janka and Smolkova, Bozena and Dusinska, Maria and Vodicka, Pavel},
  issn         = {1045-2257},
  language     = {eng},
  number       = {4},
  pages        = {260--266},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Metabolic gene variants associated with chromosomal aberrations in healthy humans.},
  url          = {http://dx.doi.org/10.1002/gcc.22239},
  volume       = {54},
  year         = {2015},
}