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  • Niazi, YasmeenGerman Cancer Research Centre,Hopp Children’s Cancer Center Heidelberg (KiTZ) (author)

DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-06-16
  • Frontiers Media SA,2021
  • 9 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:69a5566d-0dec-46f7-a348-8f08cc820ff3
  • https://lup.lub.lu.se/record/69a5566d-0dec-46f7-a348-8f08cc820ff3URI
  • https://doi.org/10.3389/fgene.2021.691947DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

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  • Thomsen, HaukeGenewerk GmbH,German Cancer Research Centre(Swepub:lu)med-hth (author)
  • Smolkova, BozenaSlovak Academy of Sciences (author)
  • Vodickova, LudmilaAcademy of Sciences of the Czech Republic,Institute of Experimental Medicine, Czech Academy of Science,Charles University in Prague (author)
  • Vodenkova, SonaInstitute of Experimental Medicine, Czech Academy of Science (author)
  • Kroupa, MichalCharles University in Prague,Institute of Experimental Medicine, Czech Academy of Science (author)
  • Vymetalkova, VeronikaAcademy of Sciences of the Czech Republic,Institute of Experimental Medicine, Czech Academy of Science,Charles University in Prague (author)
  • Kazimirova, AlenaSlovak Medical University (author)
  • Barancokova, MagdalenaSlovak Medical University (author)
  • Volkovova, KatarinaSlovak Medical University (author)
  • Staruchova, MartaSlovak Medical University (author)
  • Hoffmann, PerUniversity of Basel (author)
  • Nöthen, Markus MUniversity of Bonn (author)
  • Dusinska, MariaNorwegian Institute for Air Research (author)
  • Musak, LudovitComenius University (author)
  • Vodicka, PavelInstitute of Experimental Medicine, Czech Academy of Science,Academy of Sciences of the Czech Republic,Charles University in Prague (author)
  • Hemminki, KariLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,Charles University in Prague,German Cancer Research Centre(Swepub:lu)med-khk (author)
  • Försti, AstaLund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,Hopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Centre(Swepub:lu)med-asf (author)
  • German Cancer Research CentreHopp Children’s Cancer Center Heidelberg (KiTZ) (creator_code:org_t)

Related titles

  • In:Frontiers in Genetics: Frontiers Media SA121664-8021

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