Genetics and Epigenetics of Thyroid Cancer

Thyroid cancer is the most common endocrine malignancy, accounting for about ۳% of all cancers. The main histological subtypes of thyroid cancer include papillary, follicular, medullary, and anaplastic, which account for ۸۰%, ۱۰%, ۵%, and less than ۲%, respectively. According to global statistics, the incidence of thyroid cancer is increasing exponentially, and it is the fifth and sixteenth most common solid malignancy in women and men, respectively. Genetic, epigenetic, hormonal, and environmental factors can influence the occurrence of thyroid cancer. One of the critical factors in evaluating the risk of thyroid cancer is family history. Research shows that the risk of thyroid cancer in people with positive family history is ۲-۳ times higher than in others. According to the findings, some genetic syndromes such as Multiple endocrine neoplasia type ۲ (MEN ۲), Cowden, and familial adenomatous polyposis are related to thyroid cancer. Genetic changes, including point mutations and structural changes, play an essential role in different types of thyroid cancer. For example, a mutation in the BRAF gene, especially the V۶۰۰E mutation, is one of the most common alterations in papillary carcinoma (PTC), leading to the activation of MAPK/ERK signaling and tumor growth. RAS mutations, especially KRAS and HRAS, are more frequently observed in follicular carcinoma (FTC) and contribute to activating growth signaling pathways. Also, the occurrence of mutation in the RET gene in medullary carcinoma (MTC) is significant. This mutation can act as a primary factor in tumor formation and play a significant role in lymphatic metastasis. Epigenetic processes, such as abnormal methylation in the promoter region of tumor suppressor genes such as PTEN, TP۵۳, TIMP۳, RASSF۱A, and SLC۵A۸, and thyroid-specific genes, including sodium/iodine transporter (NIS) and thyroid-stimulating hormone receptor (TSHR), can increase the risk of developing thyroid tumors. In addition to DNA methylation, histone changes are considered epigenetic factors. For example, histone deacetylases (HDACs) increase in thyroid cancer, suppressing tumor suppressor genes, so inhibiting HDACs can be considered a therapeutic strategy. miRNAs regulate gene expression, also known as epigenetic factors in thyroid cancer. Changes in the expression level of miRNAs lead to disruption of signaling pathways and tumorigenesis. For example, miR-۱۸۱a, miR-۱۸۷, let-۷, miR-۲۲۱, miR-۲۲۲, and miR-۱۴۶b are essential in papillary thyroid cancer and can be used as biomarkers for diagnosis and prognosis. Environmental factors like diet, pollution, and stress can also influence epigenetic changes. For example, insufficient iodine intake, oxidative stress, and chronic inflammation can cause epigenetic changes in thyroid cells. As a result, careful examination of genetic and epigenetic changes in thyroid cancer not only helps to understand the biological mechanisms of this disease better but can also lead to the development of new diagnostic and treatment methods. Identifying these changes can help provide targeted treatments, improve patient prognosis, and move towards personalized treatments. Further research in this field can lead to discovering new factors and more effective ways to manage this disease. Therefore, we intend to address the critical genetic and epigenetic factors in the diagnosis and targeted therapy of thyroid cancer.

کلیدواژه ها:

Thyroid Cancer ، Genetic ، Epigenetic ، miRNAs ، Targeted Therapy