Association Between Vascular Endothelial Growth Factor Gene Polymorphism and Bladder Cancer Risk and its Relationship to Serum Ca19.9, Mmp9 and Timp1 Levels: A Case–Control Study From a Tertiary Care Centre

Abstract

Background: Bladder cancer represents one of the most frequently diagnosed malignancies of the urinary tract and contributes substantially to cancer-related morbidity and mortality worldwide. The development and progression of bladder cancer involve complex interactions between genetic susceptibility, environmental exposures, angiogenesis, extracellular matrix remodeling, and tumor-associated molecular alterations. Vascular endothelial growth factor (VEGF), a key regulator of tumor angiogenesis, plays an important role in tumor growth, invasion, and metastatic potential. Functional genetic variations within the VEGF gene may influence VEGF expression and thereby modify individual susceptibility to bladder cancer. In addition, circulating biomarkers such as carbohydrate antigen 19.9 (CA19.9), matrix metalloproteinase-9 (MMP9), and tissue inhibitor of metalloproteinase-1 (TIMP1) have been implicated in tumor progression and extracellular matrix degradation.
Objectives: To evaluate the association between VEGF gene polymorphism and risk of bladder cancer and to assess its relationship with serum levels of CA19.9, MMP9, and TIMP1 among bladder cancer patients.
Materials and Methods: This original research study was conducted as a hospital-based case–control study in the Department of Urology and biochemistry, Calcutta National Medical College, Kolkata, from 2020 to 2023. A total of 150 participants were enrolled, including 75 histopathologically confirmed bladder cancer patients (cases) and 75 age- and sex-matched healthy individuals (controls). Peripheral blood samples were collected for genetic analysis of VEGF polymorphism and estimation of serum CA19.9, MMP9, and TIMP1 levels. Genotyping was performed using polymerase chain reaction-based methods. Serum biomarker concentrations were assessed using standardized immunoassay techniques. Statistical analysis was performed using SPSS software. Associations between genetic variants, biomarker levels, and bladder cancer risk were evaluated using appropriate statistical tests.
Results: Bladder cancer patients demonstrated a significantly higher frequency of the VEGF risk genotype compared with controls. The VEGF polymorphism was significantly associated with increased bladder cancer susceptibility (OR=2.74, 95% CI: 1.32–5.69, p=0.006). Serum CA19.9, MMP9, and TIMP1 levels were significantly elevated among cases compared with controls (p<0.001). Patients carrying the VEGF variant genotype showed significantly higher circulating MMP9 and TIMP1 concentrations compared with wild-type carriers. A positive correlation was observed between MMP9 and TIMP1 levels among bladder cancer patients (r=0.62, p<0.001).
Conclusion: The present study suggests that VEGF gene polymorphism may contribute to increased susceptibility to bladder cancer and may influence tumor-associated biomarker expression. Altered VEGF-mediated angiogenic pathways together with increased MMP9 and TIMP1 levels may play an important role in bladder cancer progression. VEGF polymorphism combined with serum biomarkers may serve as a potential molecular tool for risk assessment and disease characterization.