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

Luís S. Santos, Octávia M. Gil, Susana N. Silva, Bruno C. Gomes, Teresa C. Ferreira, Edward Limbert, José Rueff

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Abstract

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.

Original languageEnglish
Article number1083
Number of pages24
JournalGenes
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Chromosome-defective micronuclei
  • DNA repair
  • Iodine-131
  • Micronucleus assay
  • Pharmacogenetics
  • Pharmacogenomic variants
  • Precision medicine
  • Single nucleotide polymorphism
  • Thyroid cancer

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