Association of Chemokine and Chemokine Receptor Gene Polymorphis (MCP1 A-2518G and CCR2-V64I) with Urinary Bladder Cancer: A Study in Kashmiri Population

Abstract

Epidemiological evidence points to a connection between inflammation and a predisposition for the development of cancer. Several pro-inflammatory gene products have been identified that lead to variations in the production and concentration of inflammatory proteins. A case-control study was conducted in chemokine and chemokine receptor genes (MCP-1 A-2518G and CCR2-V64I) to elucidate the possible role of these SNPs as risk factors in urinary bladder cancer (UBC) development. Using the polymerase chain reaction-restriction fragment length polymorphism approach, we investigated the genotype distribution of 120 bladder cancer patients in comparison with 155 cancer-free controls from the same geographical region. Significant differences were observed in the distribution of genotypes in MCP-1 A-2518G between the control and bladder cancer patients (0.36 vs 0.47; p=0.000). Homozygous variant GG frequency of MCP-1 A-2518G in cases was found to be 20% as against 5.1% in controls (p<0.05). No significant association was found in CCR2-V64I genotypes (p = 0.09) between the controls and patients with the frequency of homozygous variant (64I) being 15% and 20% (0.15 vs. 0.20) respectively. Interestingly, CCR2-V64I heterozygote (wt/64I+64I) frequencies were significantly increased in the higher grades/stages of bladder cancer patients (p< 0.05). Based on above mentioned results, we conclude that the MCP-1 -2518A/G polymorphism is associated with genetic susceptibility to the risk for bladder cancer.