Background/Aim: To evaluate the association between TRIB1(rs6987702) and IL-9(rs1859430, rs2069870) genotypes with the development and manifestation of pituitary adenoma (PA). Materials and Methods: The study group included 141 patients with PA and the control group consisted of 287 healthy people. The genotyping of rs6987702, rs1859430 and rs2069870 was carried out using a real-time polymerase chain reaction. Results: Statistically significant results were obtained regarding the rs1859430, but there were no significant results regarding rs6987702. We found that the rs1859430 A/A genotype increased the odds of having recurrent PA six times (p=0.006) under the co-dominant model and four times (p=0.021) under the recessive model. Furthermore, the analysis showed that the G/A genotype increased the odds of having recurrent PA 2.3 times (p=0.003) under the co-dominant model, while G/A and A/A genotypes increased the odds 2.7 times (p=0.011) under the over-dominant model. Conclusion: Certain genotypes of rs1859430 can be associated with PA recurrence. Pituitary adenoma (PA) is a benign pituitary gland tumor, which starts from the cells of adenohypophysis (1). PAs are mainly inactive, but certain types of PAs secrete hormones and become clinically apparent (2). They can also be classified according to their size: microadenomas, which are more commonly found in female and <60 years old patients, and macroadenomas, which are more prevalent in male and >60 years old patients (3-5). According to the latest statistical report of Central Brain Tumor Registry of the United States (CBTRUS), the incidence rate of benign pituitary tumors has increased, and currently they present 16.4% of all primary brain and central nervous system tumors (6). The report of Brain Tumor Register of Japan published in 2017 showed that pituitary gland was a primary location for 22.6% of all brain tumors and 91.1% of them were benign (7). Meta-analysis of 143 studies showed that the recurrence rate depends on the type of PA (8) and varies from 5% to 16% (7). Although the exact mechanism of PA development is still unknown, it may include various immunogenetic factors. Many potential molecular markers, which might be involved in the tumorigenesis of PAs, are currently under investigation. In the present study, one TRIB1 gene polymorphism and two IL-9 gene polymorphisms were selected for further investigation. Tribbles-1 (TRIB1) is a protein, encoded by the TRIB1 gene, most commonly found in the nucleus of a cell. This protein belongs to a group of pseudokinases, which consist of 3 different domains: N-terminal PEST domain, pseudokinase domain and C-terminal COP1 binding peptide domain. TRIB kinases have unique sequences located at the C-terminal end (9). Tribbles-1 is mostly found in myeloid cells. It is thought to be important in intracellular signaling, and thereby, to participate in the management of cell cycle, differentiation, metabolism and proliferation, migration and invasion (9-11). TRIB1 is thought to have oncogenic properties. Miyajima et a...