Evaluation of ret polymorphism and serum levels of RET related parameters in breast cancer

The most common type of cancer in women is breast cancer elucidating the genetic factors underlying the pathology and choosing the treatment method are of great importance. RET is a member of the receptor tyrosine kinase family that is essential for the normal development and maturation of various tissues. RET signaling promotes changes in the tumor microenvironment that alter the stroma and cellular composition surrounding the tumor. Gene polymorphisms of RET and NRTN are one of the focus of studies in the investigation of cancer pathogenesis, risk, invasion and metastasis. Although RET and NRTN polymorphisms have been investigated in various cancers in many ethnicities and populations, there are not enough studies in breast cancer. In this thesis, it was aimed to examine the possible risk between RET gene G691S (rs1799939), L769L (rs1800861), S904S (rs1800863), Neuturin gene IVSI-663 (rs1379868) polymorphisms and breast cancer, and to evaluate RET-related serum NRTN, BDNF, MMP-2 and FAK levels. The study consists of 110 breast cancer patients and 110 healthy controls. RET gene G691S, L769L, S904S and NRTN gene IVSI-663 polymorphisms were detected by PCR-RFLP method. Allele frequencies and genotype distributions of this polymorhisms were determined. Serum NRTN, BDNF, MMP-2 and FAK levels were measured by ELISA method using commercial kits. NRTN gene IVSI-663 polymorphism in G allele has been found to be 1.54 fold increased the risk of breast cancer, however AA genotype has been found 0,43 fold decreased the risk of breast cancer (respectively, p<0.05, p<0.05). The patient and control groups showed a similar profile for RET gene G691S, L769L and S904S allele frequencies and genotype distributions (p>0,05). In the patient group, increase in serum NRTN, BDNF and FAK levels and decrease in MMP-2 levels were found (p<0,05). It is thought that increased breast cancer risk with the G allele in NRTN gene, which is a RET ligand, IVSI-663 polymorphism, as well as the increased serum NRTN, BDNF and FAK levels, will contribute to the diagnosis, prognosis and determination of new treatment strategies.