Genetic Insights into Bladder Carcinogenesis: Impact of VEGFA -460T>C (rs833061) Polymorphism

Abstract

Background: Vascular endothelial growth factor A (VEGFA) plays a critical role in tumor angiogenesis and cancer progression. Polymorphisms in the VEGFA gene, particularly rs833061 (-460T>C), have been implicated in cancer susceptibility and clinical outcomes. However, the association between VEGFA rs833061 and bladder cancer remains underexplored, particularly in the North Indian population.

Objective: The objective of the present investigation was to evaluate the potential relationship between the VEGFA rs833061 genetic polymorphism and susceptibility to bladder cancer, along with its influence on clinical outcomes, in a North Indian cohort.

Methods: A case-control study was conducted involving 60 bladder cancer patients and 60 healthy individuals (Control group). Genotypic frequencies for the VEGFA rs833061 polymorphism were determined using Amplification refractory mutation system PCR analysis. To determine the magnitude of the association between different genotypes and bladder cancer susceptibility, odds ratios (ORs) along with 95% confidence intervals (CIs) were computed.

Results: A markedly elevated frequency of the T allele was observed in bladder cancer patients (0.56) compared with the control group (0.17) (p < 0.001). Analysis under dominant, recessive, and co-dominant models indicated an enhanced cancer risk for the combined CT+TT genotypes. Notably, individuals carrying the TT genotype exhibited a significantly higher likelihood of developing bladder cancer (OR = 1.89, p = 0.002). In the dominant model, the combined CT + TT genotype conferred a higher cancer risk (OR = 0.051, p = 6.67 × 10⁻¹²). The recessive model also showed a moderate but significant association (OR = 0.273, p = 0.0257). Clinically, the TT genotype correlated with higher tumor grade (p = 0.0024) and advanced disease stage (p = 0.015), indicating a potential role of VEGFA polymorphisms in disease aggressiveness.

Conclusion: Present research demonstrated a significant association between the VEGFA rs833061 polymorphism and bladder cancer risk and progression in studied population. The T allele and TT genotype emerged as potential genetic markers for bladder cancer susceptibility and poor clinical outcomes. The findings indicate that VEGFA rs833061 could function as a predictive biomarker as well as a promising therapeutic target for anti-angiogenic strategies in bladder cancer. Nonetheless, confirmation through larger cohort studies and functional investigations is essential to substantiate these results and elucidate the underlying molecular mechanisms.