Genetic variation associated with chromosomal aberration frequency: A genome-wide association study

Research output: Contribution to journalArticle


Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10−5 in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. 2018 Wiley Periodicals, Inc.


  • Yasmeen Niazi
  • Hauke Thomsen
  • Bozena Smolkova
  • Ludmila Vodickova
  • Sona Vodenkova
  • Michal Kroupa
  • Veronika Vymetalkova
  • Alena Kazimirova
  • Magdalena Barancokova
  • Katarina Volkovova
  • Marta Staruchova
  • Per Hoffmann
  • Markus M. Nöthen
  • Maria Dušinská
  • Ludovit Musak
  • Pavel Vodicka
  • Kari Hemminki
  • Asta Försti
External organisations
  • German Cancer Research Centre
  • Heidelberg University
  • Slovak Academy of Sciences
  • Institute of Experimental Medicine, Czech Academy of Science
  • Charles University in Prague
  • Slovak Medical University
  • University Hospital Bonn
  • University of Basel
  • University of Bonn
  • Norwegian Institute for Air Research
  • Center for Primary Health Care Research
  • Comenius University
  • University Hospital Martin
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics


  • chromatid-type aberrations, chromosome-type aberrations, GWAS, single-nucleotide polymorphism
Original languageEnglish
JournalEnvironmental and Molecular Mutagenesis
Publication statusPublished - 2018 Oct 3
Publication categoryResearch