Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer

Detalhes bibliográficos
Autor(a) principal: Santos, Luís S.
Data de Publicação: 2020
Outros Autores: Gil, Octávia M., Silva, Susana N., Gomes, Bruno C., Ferreira, Teresa C., Limbert, Edward, Rueff, José
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/110910
Resumo: Funding: 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.
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spelling Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancerThe influence of dna repair genes variantsChromosome-defective micronucleiDNA repairIodine-131Micronucleus assayPharmacogeneticsPharmacogenomic variantsPrecision medicineSingle nucleotide polymorphismThyroid cancerGeneticsGenetics(clinical)SDG 3 - Good Health and Well-beingFunding: 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.Radioiodine 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.Centre for Toxicogenomics and Human Health (ToxOmics)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNSantos, Luís S.Gil, Octávia M.Silva, Susana N.Gomes, Bruno C.Ferreira, Teresa C.Limbert, EdwardRueff, José2021-01-28T23:40:00Z2020-092020-09-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article24application/pdfhttp://hdl.handle.net/10362/110910eng0920-8569PURE: 20031541https://doi.org/10.3390/genes11091083info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:54:47Zoai:run.unl.pt:10362/110910Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:41:45.236338Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer
The influence of dna repair genes variants
title Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer
spellingShingle Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer
Santos, Luís S.
Chromosome-defective micronuclei
DNA repair
Iodine-131
Micronucleus assay
Pharmacogenetics
Pharmacogenomic variants
Precision medicine
Single nucleotide polymorphism
Thyroid cancer
Genetics
Genetics(clinical)
SDG 3 - Good Health and Well-being
title_short Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer
title_full Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer
title_fullStr Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer
title_full_unstemmed Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer
title_sort Micronuclei formation upon radioiodine therapy for well-differentiated thyroid cancer
author Santos, Luís S.
author_facet Santos, Luís S.
Gil, Octávia M.
Silva, Susana N.
Gomes, Bruno C.
Ferreira, Teresa C.
Limbert, Edward
Rueff, José
author_role author
author2 Gil, Octávia M.
Silva, Susana N.
Gomes, Bruno C.
Ferreira, Teresa C.
Limbert, Edward
Rueff, José
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centre for Toxicogenomics and Human Health (ToxOmics)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Santos, Luís S.
Gil, Octávia M.
Silva, Susana N.
Gomes, Bruno C.
Ferreira, Teresa C.
Limbert, Edward
Rueff, José
dc.subject.por.fl_str_mv Chromosome-defective micronuclei
DNA repair
Iodine-131
Micronucleus assay
Pharmacogenetics
Pharmacogenomic variants
Precision medicine
Single nucleotide polymorphism
Thyroid cancer
Genetics
Genetics(clinical)
SDG 3 - Good Health and Well-being
topic Chromosome-defective micronuclei
DNA repair
Iodine-131
Micronucleus assay
Pharmacogenetics
Pharmacogenomic variants
Precision medicine
Single nucleotide polymorphism
Thyroid cancer
Genetics
Genetics(clinical)
SDG 3 - Good Health and Well-being
description Funding: 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-09
2020-09-01T00:00:00Z
2021-01-28T23:40:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/110910
url http://hdl.handle.net/10362/110910
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0920-8569
PURE: 20031541
https://doi.org/10.3390/genes11091083
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 24
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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