TIMP1 and TIMP3 circulating levels and promoter polymorphisms in breast cancer.

Abstract

BACKGROUND Tissue inhibitors of metalloproteinases (TIMPs) are key regulators of the metalloproteinases that have important roles in different processes including extracellular matrix degradation and tissue remodeling. In this research, we studied the correlation between TIMP1 (rs4898) and TIMP3 (rs9619311) gene variations and their circulating levels with the risk of breast cancer among 100 case-control samples. METHODS The polymorphisms were genotyped by PCR-based Restriction Fragment Length Polymorphism (RFLP). The serum level was analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS The distribution of C/C, C/T and T/T genotypes for TIMP1 were 25%, 46% and 29% in patients and 26%, 39% and 35% in controls, respectively (P=0.56). Moreover, TIMP3 distribution of C/C, C/T and T/T genotypes were 18%, 43% and 39% in patients and 22%, 37% and 41% in controls, respectively (P=0.63). Besides, the results of serum levels showed higher expression of TIMP1 in controls and TIMP3 in breast cancer patients. TIMP1 serum levels in patients and controls were 96±17 ng/ml and 127±20 ng/ml, respectively (P=0.008), and TIMP3 serum levels in patients was increased (44±7 ng/ml) as compared to controls (31±6 ng/ml) (P=0.004). CONCLUSION It is concluded that TIMP1 (rs4898) and TIMP3 (rs9619311) polymorphisms are not significantly related to breast cancer. Moreover, CC and TT genotypes are correlated with increased serum TIMP1 and TIMP3 levels in breast cancer patients, respectively. It is also suggested that serum concentration of TIMP1 and TIMP3 is related to the physiopathology of breast cancer.