• association study
• cancer
• carcinoma
• case-control study
• gene-candidate study
• genotyping
• in silico tools
• KASPar
• SNP
• TaqMan
• thyroid

Thyroid cancer is a common endocrine malignancy. It accounts about 1% of all oncological diseases. There are several histological types and subtypes of thyroid cancer with different cellular origins, characteristics and prognosis. The Well Differentiated Thyroid Carcinoma (WDTC) represents more than 90% of all the forms of thyroid cancer. Among them it is possible to distinguish between Papillary Thyroid Carcinomas (PTC) and Follicular Thyroid Carcinomas (FTC). The thyroid cancer incidence in the world has been increasing in the past years. Although thyroid nodules are frequent their rate of malignancy is low. Many individual and environment factors have been considered as risk factors for thyroid cancer.
The purpose of my thesis was to identify possible genetic polymorphisms, selected in genes somatically mutated in WDTC. For the analysis of genetic single-nucleotide polymorphism (SNP) data we carried out a candidate-gene case-control study.
A case-control association study was conducted with patients with sporadic WDTC and healthy controls from an Italian population. We collected 3277 samples (1558 cases and 1719 controls) and we used the browser Cosmic to select our genes from the top genes somatically mutated in WDTC, especially considering those involved in PTC. Focusing on 5’UTR variants, 3’UTR variants and missense variants, considering the global minor allele frequency (MAF) over 10% and the linkage disequilibrium (LD) between these SNPs, we selected 34 SNPs. We used TaqMan PCR and KASPar SNP Genotyping System to genotype all the individuals. The association between our polymorphisms and the risk of WDTC was evaluated with a multivariate logistic regression analysis.
The results of this study provides evidence that inherited variants in the APC, TSHR, SMAD4, GNAS and EGFR genes can play a role in the etiology of thyroid cancer. We used in silico methods to predict the effect of possible amino acid substitutions on protein function and to understand the molecular events controlling gene expression.