Association of metastasis suppressor gene mkk4 and nme1 with gene polymorphism in well-differentiated papillary thyroid cancer

Papillary thyroid cancer is the most common type of thyroid cancer. Although its prognosis is generally good, there are also aggressive forms, thus there are differences in its treatment and follow-up. This study aimed to determine the relationship between nucleoside diphosphate kinase 1 and mitojen activated protein kinase kinase 4 gene polymorphisms, which have been associated with different types of cancer, and papillary thyroid cancer, thereby identifying different genetic pathways as prognostic markers. Our study was designed as a case-control study and included 234 patients with papillary thyroid cancer followed at the Endocrinology and Metabolic Diseases Clinic of Trakya University Medical Faculty, and 242 healthy volunteers. They were evaluated for mitojen activated protein kinase kinase 4 and nucleoside diphosphate kinase 1 gene polymorphisms. The patients' pathological data and treatment responses were collected retrospectively. As a result of the study, the mitojen activated protein kinase kinase 4 guanine-guanine variant was found to be more prevalent in patients with papillary thyroid cancer compared to the thymine-thymine variant (p: 0.01). When allele frequencies for mitojen activated protein kinase kinase 4 were evaluated, the guanine allele was significantly higher in the papillary thyroid cancer patient group, whereas the thymine allele frequency was higher in the control group compared to the patient group (p: 0.011). Furthermore, the guanine allele frequency was found to be significantly higher in the group with lymph node metastasis (p: 0.031). No relationship was found between nucleoside diphosphate kinase 1 polymorphism and papillary thyroid cancer. However, the presence of lymphovascular invasion was found to be higher in the thymine-thymine genotype group compared to the guanine- guanine and guanine-thymine genotype groups (p = 0.017; p = 0.049). In conclusion, although there are studies with different patient groups in the literature, we did not encounter a study conducted specifically on papillary thyroid cancer. Our study is the first in the literature to determine that having mitojen activated protein kinase kinase 4 gene polymorphism increases the risk of developing papillary thyroid cancer. There is a need for more comprehensive studies evaluating the relationship between nucleoside diphosphate kinase 1 and MKK4 gene polymorphisms and papillary thyroid cancer in different ethnic groups.