DNA repair gene polymorphisms and chromosomal aberrations in healthy, nonsmoking population
Language English Country Netherlands Media print-electronic
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
PubMed
33676360
DOI
10.1016/j.dnarep.2021.103079
PII: S1568-7864(21)00035-5
Knihovny.cz E-resources
- Keywords
- Association study, Chromosomal aberrations, DNA repair, Double-strand breaks,
- MeSH
- White People genetics MeSH
- Genome-Wide Association Study MeSH
- Chromosome Aberrations * MeSH
- DNA-Binding Proteins genetics MeSH
- Adult MeSH
- DNA Repair Enzymes genetics MeSH
- RecQ Helicases genetics MeSH
- Werner Syndrome Helicase genetics MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Non-Smokers * MeSH
- DNA Mismatch Repair genetics MeSH
- DNA Repair genetics MeSH
- Computer Simulation MeSH
- Poly(ADP-ribose) Polymerases genetics MeSH
- Replication Protein A genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Healthy Volunteers MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Slovakia MeSH
- Names of Substances
- Bloom syndrome protein MeSH Browser
- DNA-Binding Proteins MeSH
- DNA Repair Enzymes MeSH
- RecQ Helicases MeSH
- Werner Syndrome Helicase MeSH
- NHEJ1 protein, human MeSH Browser
- PARP2 protein, human MeSH Browser
- Poly(ADP-ribose) Polymerases MeSH
- Replication Protein A MeSH
- RPA2 protein, human MeSH Browser
- RPA3 protein, human MeSH Browser
- WRN protein, human MeSH Browser
Nonspecific structural chromosomal aberrations (CAs) can be found at around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. The frequency of CAs has been measured in occupational monitoring and an increased frequency of CAs has also been associated with cancer risk. Alterations in DNA damage repair and telomere maintenance are thought to contribute to the formation of CAs, which include chromosome type of aberrations and chromatid type of aberrations. In the present study, we used the result of our published genome-wide association studies to extract data on 153 DNA repair genes from 866 nonsmoking persons who had no known occupational exposure to genotoxic substances. Considering an arbitrary cut-off level of P< 5 × 10-3, single nucleotide polymorphisms (SNPs) tagging 22 DNA repair genes were significantly associated with CAs and they remained significant at P < 0.05 when adjustment for multiple comparisons was done by the Binomial Sequential Goodness of Fit test. Nucleotide excision repair pathway genes showed most associations with 6 genes. Among the associated genes were several in which mutations manifest CA phenotype, including Fanconi anemia, WRN, BLM and genes that are important in maintaining genome stability, as well as PARP2 and mismatch repair genes. RPA2 and RPA3 may participate in telomere maintenance through the synthesis of the C strand of telomeres. Errors in NHEJ1 function may lead to translocations. The present results show associations with some genes with known CA phenotype and suggest other pathways with mechanistic rationale for the formation of CAs in healthy nonsmoking population.
References provided by Crossref.org
Genetic and environmental associations of nonspecific chromosomal aberrations
