CCR2-64I is a risk factor for development of bladder cancer.

Chemokines are potent proinflammatory cytokines that are implicated in numerous inflammatory diseases. Proinflammatory gene polymorphisms lead to variations in the production and concentration of inflammatory proteins. We investigated a possible association between polymorphisms in chemokine and chemokine receptor genes (MCP-1 A-2518G and CCR2-V64I) and bladder cancer risk. Genotypes were determined by PCR-RFLP assays in 72 bladder cancer patients and 76 unrelated age-matched healthy controls. There were significant differences in the frequencies of the MCP-1 A-2518G (P = 0.012) and CCR2-V64I genotypes (P = 0.004) between the controls and patients. The MCP-1 A-2518G GG genotype frequencies for controls and cases were 0.039 and 0.11, respectively; individuals who had the GG genotype had a 3-fold increased risk of bladder cancer (P = 0.08). The CCR2-64I/64I genotype frequencies for controls and cases were 0.02 and 0.13, respectively; subjects carrying the 64I/64I genotype had a 5.9-fold increased risk of bladder cancer compared to the other genotypes. Individuals carrying the CCR2-V64I heterozygote or homozygous variant genotype (64I/64I + wt/64I) had a 2.9-fold increased risk of bladder cancer compared with the wild-type genotype (wt/wt). CCR2-V64I heterozygote or homozygous wild-type genotype (wt/wt + wt/64I) frequencies were significantly decreased in the patient group compared with controls. We conclude that CCR2-64I is a new risk factor for bladder cancer.