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Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer

2020-09Artigo científico Acesso aberto
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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.contributor.authorRueff, Jose
dc.contributor.institutionCentre for Toxicogenomics and Human Health (ToxOmics)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblSpringer Science Business Media
dc.date.accessioned2021-01-28T23:40:00Z
dc.date.available2021-01-28T23:40:00Z
dc.date.issued2020-09
dc.descriptionFunding: This research was funded by FCT—Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through Project UID/BIM/00009/2019—Centre for Toxicogenomics and Human Health.
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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent24
dc.format.extent1295597
dc.identifier.doi10.3390/genes11091083
dc.identifier.issn0920-8569
dc.identifier.otherPURE: 20031541
dc.identifier.otherPURE UUID: 6b6464b1-8e61-47f2-a630-f1a1864d3a20
dc.identifier.otherScopus: 85091147832
dc.identifier.otherPubMed: 32957448
dc.identifier.otherWOS: 000580144300001
dc.identifier.otherORCID: /0000-0002-9122-0732/work/91554845
dc.identifier.urihttp://hdl.handle.net/10362/110910
dc.identifier.urlhttps://www.scopus.com/pages/publications/85091147832
dc.language.isoeng
dc.peerreviewedyes
dc.subjectChromosome-defective micronuclei
dc.subjectDNA repair
dc.subjectIodine-131
dc.subjectMicronucleus assay
dc.subjectPharmacogenetics
dc.subjectPharmacogenomic variants
dc.subjectPrecision medicine
dc.subjectSingle nucleotide polymorphism
dc.subjectThyroid cancer
dc.subjectGenetics
dc.subjectGenetics(clinical)
dc.subjectSDG 3 - Good Health and Well-being
dc.titleMicronuclei formation upon radioiodine therapy for well-differentiated thyroid canceren
dc.title.subtitleThe influence of dna repair genes variantsen
dc.typejournal article
degois.publication.issue9
degois.publication.titleGenes
degois.publication.volume11
dspace.entity.typePublication
person.familyNameRueff
person.givenNameJose
person.identifier793666
person.identifier.ciencia-id0E15-908D-EA21
person.identifier.orcid0000-0002-8456-7295
person.identifier.ridE-6426-2013
person.identifier.scopus-author-id7006536439
rcaap.rightsopenAccess
relation.isAuthorOfPublication91a3b5ac-0328-498d-8cb8-08555b202306
relation.isAuthorOfPublication.latestForDiscovery91a3b5ac-0328-498d-8cb8-08555b202306

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