Analysis of the Morphofunctional Effects of the SOD2 Gene Polymorphism in Thyroid Tumors

• Grant number: 24/05915-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Laura Sterian
• Grantee: Marina Viana Alves
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Thyroid cells require an efficient reduction-oxidation (REDOX) system to protect them from oxidative stress created by the high circulation of reactive oxygen species (ROS) from their physiological processes. Oxidative damage to DNA by high levels of ROS may be implicated in the genesis and progression of thyroid cancer through mutations in genes involved in the MAPK signaling pathway and the stress-activated MAPK/JNK cascade. The superoxide dismutase 2 (SOD2) gene encodes proteins with detoxifying action that neutralize ROS, but its role has still been little explored. Non-synonymous single nucleotide polymorphisms (nsSNPs) can impact the structure and function of proteins, influencing the susceptibility and evolution of neoplastic processes. To analyze the impact of nsSNPs on the SOD2 gene, seeking their possible clinical utility as biomarkers of susceptibility, evolution or even as a therapeutic target in thyroid cancer, we propose the development of a "pipeline" for analysis of the entire SOD2 coding region using platforms of open source bioinformatics, publicly accessible datasets, and molecular quantum chemistry techniques. We intend to investigate the frequency of genetic alterations and their association with protein expression levels, and validate our results using biological cancer databases. Polymorphic variants that present a minimum allele frequency MAF>0.1 will be investigated through genotyping of 150 patients with thyroid nodules and 150 controls.