Metabolic gene variants associated with chromosomal aberrations in healthy humans.

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Kari Hemminki
  • Christoph Frank
  • Asta Försti
  • Ludovit Musak
  • Alena Kazimirova
  • Magdalena Barancokova
  • Alexandra Horska
  • Veronika Vymetalkova
  • Zdenek Smerhovsky
  • Alessio Naccarati
  • Pavel Soucek
  • Ludmila Vodickova
  • Janka Buchancova
  • Bozena Smolkova
  • Maria Dusinska
  • Pavel Vodicka
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Public Health, Global Health, Social Medicine and Epidemiology
Original languageEnglish
Pages (from-to)260-266
JournalGenes, Chromosomes and Cancer
Volume54
Issue number4
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes