Impact of genetic polymorphisms in kinetochore and spindle assembly genes on chromosomal aberration frequency in healthy humans

Research output: Contribution to journalArticle


Genomic instability is a characteristic of a majority of human malignancies. Chromosomal instability is a common form of genomic instability that can be caused by defects in mitotic checkpoint genes. Chromosomal aberrations in peripheral blood are also indicative of genotoxic exposure and potential cancer risk. We evaluated associations between inherited genetic variants in 33 mitotic checkpoint genes and the frequency of chromosomal aberrations (CAs) in the presence and absence of environmental genotoxic exposure. Associations with both chromosome and chromatid type of aberrations were evaluated in two cohorts of healthy individuals, namely an exposed and a reference group consisting of 607 and 866 individuals, respectively. Binary logistic and linear regression analyses were performed for the association studies. Bonferroni-corrected significant p-value was 5 × 10-4 for 99 tests based on the number of analyzed genes and phenotypes. In the reference group the most prominent associations were found with variants in CCNB1, a master regulator of mitosis, and in genes involved in kinetochore function, including CENPH and TEX14, whereas in the exposed group the main association was found with variants in TTK, also an important gene in kinetochore function. How the identified variants may affect the fidelity of mitotic checkpoint remains to be investigated, however, the present study suggests that genetic variation may partly explain interindividual variation in the formation of CAs.


  • Yasmeen Niazi
  • Hauke Thomsen
  • Bozena Smolkova
  • Ludmila Vodickova
  • Soňa Vodenkova
  • Michal Kroupa
  • Veronika Vymetalkova
  • Alena Kazimirova
  • Magdalena Barancokova
  • Katarina Volkovova
  • Marta Staruchova
  • Per Hoffmann
  • Markus M. Nöthen
  • Maria Dusinska
  • Ludovit Musak
  • Pavel Vodicka
  • Kari Hemminki
  • Asta Försti
External organisations
  • German Cancer Research Centre
  • Genewerk GmbH
  • 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
  • Norwegian Institute for Air Research
  • University Hospital Martin
  • Division of Pediatric Neurooncology
  • Hopp Children's Cancer Center
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Cancer and Oncology


  • Chromosomal aberration, Environmental toxicology, Genetic Polymorphism, GWAS, Kinetochore Function, Mitotic checkpoint
Original languageEnglish
Article number503253
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Publication statusPublished - 2020 Oct 1
Publication categoryResearch
Externally publishedYes