{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:13:30Z","timestamp":1774548810372,"version":"3.50.1"},"reference-count":134,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Radioiodine therapy with 131I remains the mainstay of standard treatment for well-differentiated thyroid cancer (DTC). Prognosis is good but concern exists that 131I-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 26 131I-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\u00ae 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 that 131I therapy may pose a long-term challenge to cells other than thyrocytes and that the individual genetic profile may influence 131I 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.<\/jats:p>","DOI":"10.3390\/genes11091083","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T08:29:43Z","timestamp":1600331383000},"page":"1083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Micronuclei Formation upon Radioiodine Therapy for Well-Differentiated Thyroid Cancer: The Influence of DNA Repair Genes Variants"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8906-9976","authenticated-orcid":false,"given":"Lu\u00eds","family":"S. Santos","sequence":"first","affiliation":[{"name":"Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School; Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"},{"name":"Institute of Health Sciences (ICS), Center for Interdisciplinary Research in Health (CIIS), Universidade Cat\u00f3lica Portuguesa, 3504-505 Viseu, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0366-8124","authenticated-orcid":false,"given":"Oct\u00e1via","family":"M. Gil","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias e Tecnologias Nucleares, Instituto Superior T\u00e9cnico, Universidade de Lisboa, 2695-066 Bobadela, Loures, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9122-0732","authenticated-orcid":false,"given":"Susana","family":"N. Silva","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School; Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-1095","authenticated-orcid":false,"given":"Bruno","family":"C. Gomes","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School; Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]},{"given":"Teresa","family":"C. Ferreira","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Medicina Nuclear, Instituto Portugu\u00eas de Oncologia de Lisboa (IPOLFG), 1099-023 Lisboa, Portugal"}]},{"given":"Edward","family":"Limbert","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Endocrinologia, Instituto Portugu\u00eas de Oncologia de Lisboa (IPOLFG), 1099-023 Lisboa, Portugal"}]},{"given":"Jos\u00e9","family":"Rueff","sequence":"additional","affiliation":[{"name":"Centre for Toxicogenomics and Human Health (ToxOmics), Genetics, Oncology and Human Toxicology, NOVA Medical School; Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, 1169-056 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2019, May 28). Global Cancer Observatory: Cancer Today. 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