title: CCR2-64I is a risk factor for development of bladder cancer.
abstract: 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.
authors.affiliation: Department of Urology, Uskudar State Hospital, Istanbul, Turkey.
authors.forename: K F
authors.initials: KF
authors.lastname: Narter
authors.forename: B
authors.initials: B
authors.lastname: Agachan
authors.forename: S
authors.initials: S
authors.lastname: Sozen
authors.forename: Z B
authors.initials: ZB
authors.lastname: Cincin
authors.forename: T
authors.initials: T
authors.lastname: Isbir
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics*; D054390:Receptors, CCR2 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054390:Receptors, CCR2