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

• Published in: Genetics and molecular research Vol. 9; no. 2; pp. 685 - 692
• Main Authors: Narter, K F, Agachan, B, Sozen, S, Cincin, Z B, Isbir, T
• Format: Journal Article
• Language: English
• Published: Brazil 01.01.2010
• Subjects: Adult; Aged; Aged, 80 and over; Amino Acid Substitution - genetics; Case-Control Studies; Chemokine CCL2 - genetics; Female; Gene Frequency - genetics; Genetic Predisposition to Disease; Haplotypes - genetics; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Polymorphism, Single Nucleotide - genetics; Precancerous Conditions - genetics; Receptors, CCR2 - genetics; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology
• ISSN: 1676-5680; 1676-5680
• DOI: 10.4238/vol9-2gmr829

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.