Circulating biomarkers in papillary thyroid carcinoma: DIO2 polymorphism and hormonal control

• Grant number: 24/15140-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Debora Lucia Seguro Danilovic
• Grantee: Diego Franco Araujo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The conventional treatment for papillary thyroid cancer (PTC) is total thyroidectomy, radioiodine therapy and TSH suppression. This is achieved by replacement of levothyroxine (T4) in supraphysiological doses. Since the biologically active thyroid hormone is T3, in the absence of thyroid production of this hormone, the availability of serum and intracellular T3 to inhibit TSH secretion depends on peripheral conversion of T4 to T3 by deiodinases. The type 2 deiodinase polymorphism, Thr92Ala-DIO2 (rs225014), is associated with lower T3 levels and less response to T4-induced TSH suppression. The oncological consequences of the presence of the Thr92Ala-DIO2 polymorphism in patients with PTC have not been defined. In addition to the need for higher doses of levothyroxine to suppress TSH, it is possible that intracellular T3 deficiency may affect patient prognosis, as T3 has a direct role in immune mechanisms that control cancer. The aim of this study is to evaluate the frequency of genotypes of the deiodinase 2 polymorphism, Thr92Ala-DIO2 (rs225014), in the population of patients with PTC and to relate them to the dose of levothyroxine required for TSH suppression and response to cancer treatment. Peripheral blood samples were collected from 148 patients who have undergone thyroidectomy for PTC. The study of Thr92Ala-DIO2 genotypes will be performed on DNA extracted from peripheral leukocytes by real-time polymerase chain reaction (qRT-PCR) using a commercially available TaqMan assay. The results will be analysed using an allelic discrimination table. The results will be correlated with clinical data and responses to therapy.