Tissue inhibitor matrix metalloproteinase 1 polymorphisms associated with colorectal cancer prognosis in a Han Chinese cohort

Purpose: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an inhibitor of matrix metalloproteinases, known to play a crucial role in tumorigenesis. It has significant predictive value for patients with colorectal cancer (CRC). However, its precise clinical applicability remains unknown. The current study investigated association between TIMP-1 gene polymorphisms and survival in CRC patients. Method: This study enrolled 118 endometrial cancer patients that underwent surgery for CRC between January 2011 and July 2015. Patients were genotyped for TIMP-1 polymorphism (rs4898, 372 T/C). In addition, TIMP-1 levels were assessed using enzyme-linked immunosorbent assay kits. Results: Higher plasma TIMP-1 levels were observed in patients with TIMP-1 rs4898 T allele, compared to patients with non-T alleles (P<0.001). There was significant association with vascular invasion (P=0.002), lymph node metastasis (P=0.038), distant metastasis (P=0.049), TNM stage (P=0.003), Dukes' stage (P=0.045), and recurrence (P=0.005). Kaplan-Meier analysis demonstrated that TIMP-1 rs4898 T allele was associated with lower cumulative overall survival (OS) and recurrence-free survival (RFS) (P<0.001, P<0.001, respectively). Cox proportional hazards modeling showed the TIMP-1 rs4898 T allele to be an independent prognostic predictor for OS (HR=2.607, 95% CI=1.158-5.870, P=0.021) and RFS (HR=2.667, 95% CI=1.194-5.959, P=0.017) in CRC patients. Conclusion: TIMP-1 rs4898 polymorphisms are associated with unfavorable clinicopathological factors, indicating potential clinical predictive value for CRC patient prognosis.