Impact of genetic polymorphisms in kinetochore and spindle assembly genes on chromosomal aberration frequency in healthy humans
Language English Country Netherlands Media print-electronic
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
PubMed
33198934
DOI
10.1016/j.mrgentox.2020.503253
PII: S1383-5718(20)30123-6
Knihovny.cz E-resources
- Keywords
- Chromosomal aberration, Environmental toxicology, GWAS, Genetic Polymorphism, Kinetochore Function, Mitotic checkpoint,
- MeSH
- Chromosome Aberrations * MeSH
- Chromosomal Proteins, Non-Histone genetics MeSH
- Cyclin B1 genetics MeSH
- Cyclin-Dependent Kinases genetics MeSH
- Adult MeSH
- Gene Frequency MeSH
- Polymorphism, Single Nucleotide * MeSH
- Cyclin-Dependent Kinase-Activating Kinase MeSH
- Kinetochores metabolism MeSH
- Cohort Studies MeSH
- M Phase Cell Cycle Checkpoints genetics MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Linear Models MeSH
- Odds Ratio MeSH
- Transcription Factors genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- CCNB1 protein, human MeSH Browser
- CENPH protein, human MeSH Browser
- Chromosomal Proteins, Non-Histone MeSH
- Cyclin B1 MeSH
- Cyclin-Dependent Kinases MeSH
- Cyclin-Dependent Kinase-Activating Kinase MeSH
- TEX14 protein, human MeSH Browser
- Transcription Factors MeSH
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.
Department of Molecular Genetic Epidemiology German Cancer Research Center 69120 Heidelberg Germany
Department of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany
References provided by Crossref.org
Genetic and environmental associations of nonspecific chromosomal aberrations
