DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations
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 radia...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.691947/full |
| _version_ | 1819067498614489088 |
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| author | Yasmeen Niazi Yasmeen Niazi Yasmeen Niazi Hauke Thomsen Hauke Thomsen Bozena Smolkova Ludmila Vodickova Ludmila Vodickova Ludmila Vodickova Sona Vodenkova Michal Kroupa Michal Kroupa Veronika Vymetalkova Veronika Vymetalkova Veronika Vymetalkova Alena Kazimirova Magdalena Barancokova Katarina Volkovova Marta Staruchova Per Hoffmann Per Hoffmann Markus M. Nöthen Maria Dusinska Ludovit Musak Pavel Vodicka Pavel Vodicka Pavel Vodicka Kari Hemminki Kari Hemminki Kari Hemminki Asta Försti Asta Försti Asta Försti |
| author_facet | Yasmeen Niazi Yasmeen Niazi Yasmeen Niazi Hauke Thomsen Hauke Thomsen Bozena Smolkova Ludmila Vodickova Ludmila Vodickova Ludmila Vodickova Sona Vodenkova Michal Kroupa Michal Kroupa Veronika Vymetalkova Veronika Vymetalkova Veronika Vymetalkova Alena Kazimirova Magdalena Barancokova Katarina Volkovova Marta Staruchova Per Hoffmann Per Hoffmann Markus M. Nöthen Maria Dusinska Ludovit Musak Pavel Vodicka Pavel Vodicka Pavel Vodicka Kari Hemminki Kari Hemminki Kari Hemminki Asta Försti Asta Försti Asta Försti |
| author_sort | Yasmeen Niazi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T16:19:13Z |
| format | Article |
| id | doaj.art-67c08dd2adc745f7a352ef04e03c4aa4 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-21T16:19:13Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-67c08dd2adc745f7a352ef04e03c4aa42022-12-21T18:57:38ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-06-011210.3389/fgene.2021.691947691947DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed PopulationsYasmeen Niazi0Yasmeen Niazi1Yasmeen Niazi2Hauke Thomsen3Hauke Thomsen4Bozena Smolkova5Ludmila Vodickova6Ludmila Vodickova7Ludmila Vodickova8Sona Vodenkova9Michal Kroupa10Michal Kroupa11Veronika Vymetalkova12Veronika Vymetalkova13Veronika Vymetalkova14Alena Kazimirova15Magdalena Barancokova16Katarina Volkovova17Marta Staruchova18Per Hoffmann19Per Hoffmann20Markus M. Nöthen21Maria Dusinska22Ludovit Musak23Pavel Vodicka24Pavel Vodicka25Pavel Vodicka26Kari Hemminki27Kari Hemminki28Kari Hemminki29Asta Försti30Asta Försti31Asta Försti32Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, GermanyHopp Children’s Cancer Center (KiTZ), Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, GermanyDepartment of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, GermanyGeneWerk GmbH, Heidelberg, GermanyDepartment of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Bratislava, SlovakiaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, CzechiaFirst Faculty of Medicine, Institute of Biology and Medical Genetics, Charles University, Prague, CzechiaFaculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Prague, CzeciaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, CzechiaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, CzechiaFaculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Prague, CzeciaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, CzechiaFirst Faculty of Medicine, Institute of Biology and Medical Genetics, Charles University, Prague, CzechiaFaculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Prague, CzeciaDepartment of Biology, Faculty of Medicine, Slovak Medical University, Bratislava, SlovakiaDepartment of Biology, Faculty of Medicine, Slovak Medical University, Bratislava, SlovakiaDepartment of Biology, Faculty of Medicine, Slovak Medical University, Bratislava, SlovakiaDepartment of Biology, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia0Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany1Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland0Institute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany2Health Effects Laboratory, Department of Environmental Chemistry, NILU-Norwegian Institute for Air Research, Kjeller, Norway3Jessenius Faculty of Medicine, Biomedical Center Martin, Comenius University in Bratislava, Bratislava, SlovakiaDepartment of Molecular Biology of Cancer, Institute of Experimental Medicine, Czech Academy of Sciences, Prague, CzechiaFirst Faculty of Medicine, Institute of Biology and Medical Genetics, Charles University, Prague, CzechiaFaculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Prague, CzeciaDepartment of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, GermanyFaculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, Prague, Czecia4Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, GermanyDepartment of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, GermanyHopp Children’s Cancer Center (KiTZ), Heidelberg, GermanyDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, GermanyDNA 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.https://www.frontiersin.org/articles/10.3389/fgene.2021.691947/fullchromosomal aberrationsassociation studyDNA repairexposurepolymorphism |
| spellingShingle | Yasmeen Niazi Yasmeen Niazi Yasmeen Niazi Hauke Thomsen Hauke Thomsen Bozena Smolkova Ludmila Vodickova Ludmila Vodickova Ludmila Vodickova Sona Vodenkova Michal Kroupa Michal Kroupa Veronika Vymetalkova Veronika Vymetalkova Veronika Vymetalkova Alena Kazimirova Magdalena Barancokova Katarina Volkovova Marta Staruchova Per Hoffmann Per Hoffmann Markus M. Nöthen Maria Dusinska Ludovit Musak Pavel Vodicka Pavel Vodicka Pavel Vodicka Kari Hemminki Kari Hemminki Kari Hemminki Asta Försti Asta Försti Asta Försti DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations Frontiers in Genetics chromosomal aberrations association study DNA repair exposure polymorphism |
| title | DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations |
| title_full | DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations |
| title_fullStr | DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations |
| title_full_unstemmed | DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations |
| title_short | DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations |
| title_sort | dna repair gene polymorphisms and chromosomal aberrations in exposed populations |
| topic | chromosomal aberrations association study DNA repair exposure polymorphism |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.691947/full |
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