Evaluation of clock gene RS1801260 and rs11932595 polymorphisms in terms of throid cancer development and prognosis

Aim: Circadian rhythm genes are involved in various physiological pathways, including cell cycle, apoptosis, and DNA repair, and the relationship of circadian rhythm genes with various types of cancer has been determined. In our study, we aimed to investigate the relationship between RS1801260 and RS11932595 single nucleotit polymorphisms on the CLOCK gene, which is involved in the circadian rhythm, and thyroid cancer, which is the most common cancer of the endocrine system. It is thought that our study may illuminate some of the genetic pathways involved in the pathogenesis of thyroid cancer, contribute to the detection of cancer-prone individuals, provide the discovery of new prognostic factors in thyroid cancer, and lead to new studies in this field. Materials and Methods: Our study was designed as a case-control study,150 cases diagnosed with thyroid cancer and 150 healthy volunteers who were followed up at the AÜTF Endocrinology and Metabolic Diseases clinic were included in our study. DNA was isolated from the peripheral blood sample obtained from the participants and the RS1801260 and RS11932595 polymorphisms in the CLOCK gene were analyzed by the PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) method. Anthropometric measurements, sleep quality score and clinical data of the participants were collected. Results: CLOCK gene RS11932595 GG genotype and G allele frequency were found to be significantly lower in the thyroid cancer group than in the control group. Thyroid cancer risk was found to be decreased in those with the G-Allele (OR=0.707 p<0.05). According to our multivariate analysis, having the RS11932595 normal AA genotype increases the risk of developing thyroid cancer by 3.59 fold compared to the mutant GG genotype. (p<0.05 OR=3.59). We did not detect a relationship between RS1801260 polymorphism and thyroid cancer development. However, we found that it was associated with tumor size below 1 cm and having more than one tumor focus at the same time (p<0.05). Although the RS1801260 polymorphism was observed to be associated with lymph node metastasis and recurrence, it was not found to have statistical significance when evaluated by multivariate analysis. In our case group, we found a statistically significant correlation between the risk of relapse and the presence of type 2 diabetes and stimulated TG levels (p<0.05). Conclusion: Having CLOCK gene RS11932595 polymorphisms reduces the risk of developing thyroid cancer. CLOCK gene RS1801260 polymorphism has an effect on tumor histopathological features in thyroid cancer.