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Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer: the influence of dna repair genes variants

2020-09Journal article Open access
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dc.contributor.authorSantos, Luís S.
dc.contributor.authorGil, Octávia M.
dc.contributor.authorSilva, Susana N.
dc.contributor.authorGomes, Bruno C.
dc.contributor.authorFerreira, Teresa C.
dc.contributor.authorLimbert, Edward
dc.contributor.authorRueff, José
dc.date.accessioned2021-03-18T14:56:42Z
dc.date.available2021-03-18T14:56:42Z
dc.date.issued2020-09
dc.description.abstractRadioiodine therapy with131I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that131I-emitted ionizing radiation may induce double-strand breaks in extra-thyroidal tissues, increasing the risk of secondary malignancies. We, therefore, sought to evaluate the induction and 2-year persistence of micronuclei (MN) in lymphocytes from 26131I-treated DTC patients and the potential impact of nine homologous recombination (HR), non-homologous end-joining (NHEJ), and mismatch repair (MMR) polymorphisms on MN levels. MN frequency was determined by the cytokinesis-blocked micronucleus assay while genotyping was performed through pre-designed TaqMan® Assays or conventional PCR-restriction fragment length polymorphism (RFLP). MN levels increased significantly one month after therapy and remained persistently higher than baseline for 2 years. A marked reduction in lymphocyte proliferation capacity was also apparent 2 years after therapy. MLH1 rs1799977 was associated with MN frequency (absolute or net variation) one month after therapy, in two independent groups. Significant associations were also observed for MSH3 rs26279, MSH4 rs5745325, NBN rs1805794, and tumor histotype. Overall, our results suggest that131I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence131I sensitivity, hence its risk-benefit ratio. Further studies are warranted to confirm the potential utility of these single nucleotide polymorphisms (SNPs) as radiogenomic biomarkers in the personalization of radioiodine therapy.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.3390/genes11091083pt_PT
dc.identifier.eid85091147832
dc.identifier.issn2073-4425
dc.identifier.pmcPMC7565468
dc.identifier.pmid32957448
dc.identifier.urihttp://hdl.handle.net/10400.14/32267
dc.identifier.wos000580144300001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectChromosome-defective micronucleipt_PT
dc.subjectDNA repairpt_PT
dc.subjectIodine-131pt_PT
dc.subjectMicronucleus assaypt_PT
dc.subjectPharmacogeneticspt_PT
dc.subjectPharmacogenomic variantspt_PT
dc.subjectPrecision medicinept_PT
dc.subjectSingle nucleotide polymorphismpt_PT
dc.subjectThyroid cancerpt_PT
dc.titleMicronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer: the influence of dna repair genes variantspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage24pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleGenespt_PT
oaire.citation.volume11pt_PT
person.familyNameSantos
person.familyNameMonteiro Gil
person.familyNameNunes Silva
person.givenNameLuis
person.givenNameOctávia
person.givenNameSusana
person.identifier.ciencia-idF11C-1AC5-C419
person.identifier.ciencia-idB61C-8B26-2D4B
person.identifier.ciencia-id8C1F-BB2F-44E3
person.identifier.orcid0000-0001-8906-9976
person.identifier.orcid0000-0002-0366-8124
person.identifier.orcid0000-0002-9122-0732
person.identifier.ridB-5404-2013
person.identifier.ridK-2518-2013
person.identifier.ridA-9678-2013
person.identifier.scopus-author-id23475245800
person.identifier.scopus-author-id7003782574
person.identifier.scopus-author-id7203043130
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication4c8d70d3-5648-4e31-85ec-3a7bf8295d08
relation.isAuthorOfPublication4e87378b-aec5-415d-95ea-49198dd13bb7
relation.isAuthorOfPublicationbaacd890-c6c8-4ea1-9e15-1b2556566907
relation.isAuthorOfPublication.latestForDiscoverybaacd890-c6c8-4ea1-9e15-1b2556566907

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