RESUMO
The aim of this study was to evaluate the role of GSTM1 null/present, GSTT1 null/present, and GSTP1 polymorphisms in the clinical response to chemotherapy and treatment outcome of breast cancer. The GSTM1, GSTT1, and GSTP1 IIe105Val polymorphism genotypes were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. Conditional logistic regression analysis revealed that breast cancer patients carrying the GG genotype of GSTP1 IIe105Val showed a significantly better response to chemotherapy compared to those expressing the AA genotype [odds ratio = 2.66, 95% confidence interval (CI) = 1.24-5.91, P = 0.007]. The Cox proportional hazards model indicated that the GG genotype of GSTP1 IIe105Val in breast cancer patients was correlated with a lower risk of death from all causes than those with AA genotype. The adjusted hazard ratio (95%CI) for the GG genotype of GSTP1 IIe105Val was 0.44 (0.18-0.99; P = 0.03). In conclusion, the results of our study indicated that the GG genotype of GSTP1 IIe105Val was significantly associated with better response to chemotherapy and longer overall survival, compared to the wide-type genotype.
Assuntos
Neoplasias da Mama/genética , Glutationa S-Transferase pi/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Lumbar intervertebral disc degeneration (IDD) is a common clinical pathology and has become a focus for research in recent years. Matrix metalloproteinases (MMPs) are enzymes responsible for the degradation of almost all extracellular matrix proteins (ECM). The over-expression of MMPs or tissue inhibitors of metalloproteinases (TIMPs) may disrupt the dynamic balance of the ECM. Therefore, in the current study, the expression levels of MMP-1 and TIMP-1 in lumbar IDD patients were evaluated in an attempt to elucidate their role in IDD pathogenesis and progression. In total, 60 IDD patients were recruited as the experimental group, along with 20 cases of lumbar vertebral injury without disc degeneration as the control group. Preoperative venous blood samples were collected, and intervertebral disc tissues were collected from the lesion during surgery. Serum and tissue levels of MMP-1 and TIMP-1 were quantified by enzyme-linked immunosorbent assay and immunohistochemical staining, respectively. Serum and tissue MMP-1 levels in IDD patients were significantly higher than those in the control group (P < 0.05). Additionally, sub-group analysis revealed that severe IDD patients had higher MMP-1 levels compared with mild or moderate IDD patients (P < 0.05). However, there were no significant differences in TIMP- 1 levels in either the serum or tissues of IDD patients compared to patients in the control group (P > 0.05). These results demonstrate that MMP-1 expression is increased in IDD, with higher expression observed in more severe cases, whereas TIMP-1 expression was similarly expressed in both normal and degenerated discs.