Research Information System
Thesis Type: Doctorate
Institution Of The Thesis: Gazi University, Sağlık Bilimleri Enstitüsü, BİYOKİMYA (ECZ) ANABİLİM DALI, Turkey
Approval Date: 2021
Thesis Language: Turkish
Student: Tuba TAŞKAN
Supervisor: Aymelek Gönenç
Abstract:
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.
Key Words : RET, Neurturin, Breast Cancer, Polymorphism, BDNF, FAK, MMP-2