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AuthorSurowy, Harald Martindc.contributor.author
Date of accession2016-03-15T06:25:11Zdc.date.accessioned
Available in OPARU since2016-03-15T06:25:11Zdc.date.available
Year of creation2011dc.date.created
AbstractThe purpose of this study was to elucidate if the cellular DNA repair capacity, genotypes of DNA repair genes and the occurrence of breast cancer can be associated with each other on the same set of probands in a single study. Rarely characterized features of the DNA repair capacity measures were studied as a prerequisite for their use in the definition as an intermediate phenotype of cancer. The study population comprised different cohorts with sporadic or familial breast cancer cases and controls. DNA repair assays were performed in parallel on peripheral blood samples of the probands: the baseline and the radiation induced micronucleus (MN) assay, the baseline and the induced sister chromatid exchange (SCE) assay and the mitotic delay (MD) assay. 23 missense variants in 15 genes were genotyped. An increased induced MN frequency and a decreased MD index were associated with the occurrence of breast cancer. The minor allele of the variant Slx4 S1271F (rs3810813) was enriched in breast cancer cases compared to controls (OR ~ 1.6) and displayed an increase with younger age of the cases. In-silico analysis revealed a probable functional impact on the Slx4 protein. The same variant was also associated with an increase of the induced MN frequency. The minor allele of the variant rs13044759 in the NINL gene was associated with an increased MD index. The measured DNA repair end points are largely independent and can be used to characterize different aspects of the cellular DNA repair capacity. Lymphoblastoid cell lines are not applicable as surrogates for peripheral blood lymphocytes as source of study material. Heritability estimates showed that the MN assays and the MD assay predominantly reflect the influence of genetic factors. Thus, the concordance between the results of the three types of association studies concerning the induced MN and the MD assay supports the view that the cellular DNA repair capacity can be of use as an intermediate phenotype of breast cancer.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 01.10.2008)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v2dc.rights.uri
KeywordDNA repair capacitydc.subject
KeywordEnvironmental influencedc.subject
KeywordGenetic influencedc.subject
KeywordGenotypingdc.subject
KeywordHeritabilitydc.subject
KeywordHomologous recombinationdc.subject
KeywordLymphoblastoid cell linedc.subject
KeywordMicronucleidc.subject
KeywordMicronucleusdc.subject
KeywordMitotic delaydc.subject
KeywordNINLdc.subject
KeywordPeripheral blood lymphocytesdc.subject
KeywordSLX4dc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHBreast neoplasmsdc.subject.mesh
MeSHDNA breaks, double-strandeddc.subject.mesh
MeSHDNA repairdc.subject.mesh
MeSHNeoplasmsdc.subject.mesh
MeSHSister chromatid exchangedc.subject.mesh
TitleCharacterization of cellular DNA repair capacity by molecular and cytogenetic approaches: suitability as intermediate phenotype of cancerdc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-2257dc.identifier.doi
PPN683465422dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-77697dc.identifier.urn
GNDDNS-Reparaturdc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
Date of activation2011-11-30T13:54:04Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 14.358; W: W-H 12.804uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS ID7769uulm.vtsID
CategoryPublikationenuulm.category
Bibliographyuulmuulm.bibliographie


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