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

Niazi, Yasmeen ; Thomsen, Hauke LU orcid ; Smolkova, Bozena ; Vodickova, Ludmila ; Vodenkova, Soňa ; Kroupa, Michal ; Vymetalkova, Veronika ; Kazimirova, Alena ; Barancokova, Magdalena and Volkovova, Katarina , et al. (2020) In Mutation Research - Genetic Toxicology and Environmental Mutagenesis 858-860.
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Chromosomal aberration, Environmental toxicology, Genetic Polymorphism, GWAS, Kinetochore Function, Mitotic checkpoint
in
Mutation Research - Genetic Toxicology and Environmental Mutagenesis
volume
858-860
article number
503253
publisher
Elsevier
external identifiers
  • scopus:85091570864
  • pmid:33198934
ISSN
1383-5718
DOI
10.1016/j.mrgentox.2020.503253
language
English
LU publication?
no
id
11294b47-387f-46e2-b98e-25675b69dcc7
date added to LUP
2020-10-05 08:23:03
date last changed
2024-03-16 02:53:27
@article{11294b47-387f-46e2-b98e-25675b69dcc7,
  abstract     = {{<p>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<sup>-4</sup> 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.</p>}},
  author       = {{Niazi, Yasmeen and Thomsen, Hauke and Smolkova, Bozena and Vodickova, Ludmila and Vodenkova, Soňa and Kroupa, Michal and Vymetalkova, Veronika and Kazimirova, Alena and Barancokova, Magdalena and Volkovova, Katarina and Staruchova, Marta and Hoffmann, Per and Nöthen, Markus M. and Dusinska, Maria and Musak, Ludovit and Vodicka, Pavel and Hemminki, Kari and Försti, Asta}},
  issn         = {{1383-5718}},
  keywords     = {{Chromosomal aberration; Environmental toxicology; Genetic Polymorphism; GWAS; Kinetochore Function; Mitotic checkpoint}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Elsevier}},
  series       = {{Mutation Research - Genetic Toxicology and Environmental Mutagenesis}},
  title        = {{Impact of genetic polymorphisms in kinetochore and spindle assembly genes on chromosomal aberration frequency in healthy humans}},
  url          = {{http://dx.doi.org/10.1016/j.mrgentox.2020.503253}},
  doi          = {{10.1016/j.mrgentox.2020.503253}},
  volume       = {{858-860}},
  year         = {{2020}},
}