Abstract
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® 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.
Highlights
Thyroid cancer (TC) is the most common endocrine malignancy, accounting for approximately2.1% of cancers diagnosed all over the world
We have previously demonstrated that therapy with 70 mCi 131 I in differentiated thyroid carcinoma (DTC) patients is consistently associated with increased DNA damage levels in peripheral lymphocytes [22,23]
We have previously demonstrated a significant increase in binucleated cells carrying micronuclei (BNMN) frequency in peripheral lymphocytes from 19 DTC patients treated with 70 mCi 131 I [22]
Summary
Thyroid cancer (TC) is the most common endocrine malignancy, accounting for approximately2.1% of cancers diagnosed all over the world. Thyroid cancer (TC) is the most common endocrine malignancy, accounting for approximately. TC incidence is about two to four times higher in women. Genes 2020, 11, 1083 than in men and is one of the most common malignancies in adolescent and young adults (ages 15–39 years), with the median age at diagnosis being lower than that for most other types of cancer [1,2,3]. Papillary (PTC) and follicular (FTC) thyroid carcinoma represent 85–90% and 5–10% of TC cases, respectively. These tumor histotypes retain their morphologic features, being often referred to as differentiated thyroid carcinoma (DTC) [3,4]. The best-established modifiable risk factor for DTC is IR exposure during childhood and adolescence (radioiodines including 131 I, X-radiation, γ-radiation) [2,3,4,5]
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