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@ARTICLE{Niazi:167820,
author = {Y. Niazi$^*$ and H. Thomsen$^*$ and B. Smolkova and L.
Vodickova and S. Vodenkova and M. Kroupa and V. Vymetalkova
and A. Kazimirova and M. Barancokova and K. Volkovova and M.
Staruchova and P. Hoffmann and M. M. Nöthen and M. Dusinska
and L. Musak and P. Vodicka and A. Försti$^*$ and K.
Hemminki$^*$},
title = {{DNA} repair gene polymorphisms and chromosomal aberrations
in healthy, nonsmoking population.},
journal = {DNA repair},
volume = {101},
issn = {1568-7864},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {DKFZ-2021-00564},
pages = {103079},
year = {2021},
note = {#EA:C050#LA:C020#},
abstract = {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.},
keywords = {Association study (Other) / Chromosomal aberrations (Other)
/ DNA repair (Other) / Double-strand breaks (Other)},
cin = {C050 / HD01 / B062 / C020},
ddc = {570},
cid = {I:(DE-He78)C050-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)B062-20160331 / I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33676360},
doi = {10.1016/j.dnarep.2021.103079},
url = {https://inrepo02.dkfz.de/record/167820},
}