DNA damage and unrepaired or insufficiently repaired DNA double-strand breaks as well as telomere shortening contribute to the formation of structural chromosomal aberrations (CAs). Non-specific CAs have been used in the monitoring of individuals exposed to potential carcinogenic chemicals and radiation. The frequency of CAs in peripheral blood lymphocytes (PBLs) has been associated with cancer risk and the association has also been found in incident cancer patients. CAs include chromosome-type aberrations (CSAs) and chromatid-type aberrations (CTAs) and their sum CAtot. In the present study, we used data from our published genome-wide association studies (GWASs) and extracted the results for 153 DNA repair genes for 607 persons who had occupational exposure to diverse harmful substances/radiation and/or personal exposure to tobacco smoking. The analyses were conducted using linear and logistic regression models to study the association of DNA repair gene polymorphisms with CAs. Considering an arbitrary cutoff level of 5 × 10-3, 14 loci passed the threshold, and included 7 repair pathways for CTA, 4 for CSA, and 3 for CAtot; 10 SNPs were eQTLs influencing the expression of the target repair gene. For the base excision repair pathway, the implicated genes PARP1 and PARP2 encode poly(ADP-ribosyl) transferases with multiple regulatory functions. PARP1 and PARP2 have an important role in maintaining genome stability through diverse mechanisms. Other candidate genes with known roles for CSAs included GTF2H (general transcription factor IIH subunits 4 and 5), Fanconi anemia pathway genes, and PMS2, a mismatch repair gene. The present results suggest pathways with mechanistic rationale for the formation of CAs and emphasize the need to further develop techniques for measuring individual sensitivity to genotoxic exposure.

• Klíčová slova
• DNA repair, association study, chromosomal aberrations, exposure, polymorphism,
• Publikační typ
• časopisecké články MeSH

Microsomal epoxide hydrolase (EPHX1) is an evolutionarily highly conserved biotransformation enzyme for converting epoxides to diols. Notably, the enzyme is able to either detoxify or bioactivate a wide range of substrates. Mutations and polymorphic variants in the EPHX1 gene have been associated with susceptibility to several human diseases including cancer. This review summarizes the key knowledge concerning EPHX1 gene and protein structure, expression pattern and regulation, and substrate specificity. The relevance of EPHX1 for human pathology is especially discussed.

• Klíčová slova
• Disease, EPHX1, Function, Gene, Genotype, Structure,
• MeSH
• alkoholické nemoci jater genetika   metabolismus   MeSH
• epoxid hydrolasy genetika   metabolismus   MeSH
• genetická predispozice k nemoci genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé MeSH
• mutace * MeSH
• nádory genetika   metabolismus   MeSH
• regulace genové exprese enzymů MeSH
• rizikové faktory MeSH
• substrátová specifita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• EPHX1 protein, human MeSH Prohlížeč
• epoxid hydrolasy MeSH

• MeSH
• chromozomální aberace * MeSH
• lidé MeSH
• poškození DNA MeSH
• referenční hodnoty MeSH
• sestřih RNA * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH