Neurturin gene IVSI-663 polymorphism but not RET variants is associated with increased risk for breast cancer.

Abstract

Gene polymorphisms of rearranged during transfection (RET) and its ligand neurturin (NRTN) are one of the focus of studies in the investigation of cancer pathogenesis, invasion, and metastasis. In this study, we aimed to examine the possible risk of breast cancer between RET G691S, L769L, S904S, and NRTN IVSI-663 polymorphisms and to evaluate serum NRTN, brain-derived neurotrophic factor (BDNF), matrix metalloproteinase (MMP)-2, MMP-9, and focal adhesion kinase (FAK) levels. The study consists of 110 breast cancer patients and 110 controls. Polymorphisms were detected by the polymerase chain reaction method from study groups whole blood. The NRTN 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 (P < .05, P < .05, respectively). Study groups showed a similar profile for RET G691S, L769L, S904S allele frequencies and genotype distributions (P > .05). In the patient group, significant increase in serum NRTN and FAK levels and decrease in MMP-2 and MMP-9 levels were found (P < .05, P < .05, P < .05, P < .05, respectively). In summary that increased breast cancer risk with the G allele in NRTN gene IVSI-663 polymorphism, as well as the increased serum NRTN and FAK levels, will contribute to the diagnosis, prognosis and determination of new treatment strategies.