Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and clinicopathological characteristics of prostate cancer.

Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
DNA and cell biology (Impact Factor: 2.28). 05/2012; 31(8):1418-24. DOI: 10.1089/dna.2012.1716
Source: PubMed

ABSTRACT The aim of our study was to determine the effect of monocyte chemotactic protein-1 (MCP-1), CC chemokine receptor 2 (CCR2), and CC chemokine receptor 5 (CCR5) gene polymorphisms on the susceptibility and clinicopathological characteristics of prostate cancer. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 156 histopathologically confirmed prostate cancer patients and 152 healthy subjects. Individuals with AA genotype or at least one A allele of CCR2 V64I gene polymorphism had a higher risk for prostate cancer as compared with those with GG genotype (p=0.010 and p=0.028, respectively). CCR5 Δ32/wt genotype and CCR5 Δ32 allele were also found to be involved in the susceptibility to prostate cancer (p=0.028 and p=0.030, respectively). However, there was no significant association between MCP-1-2518 A/G gene polymorphism and prostate cancer risk. Prostate cancer patients carrying AA genotype or at least one A allele of CCR2 V64I had significantly increased risk for high stage disease (p=0.002 and p=0.039, respectively) and metastasis (p=0.004 and p=0.022, respectively). The CCR2 A allele (64I allele) was significantly associated with high T stage (p=0.001) and metastasis (p=0.005) as compared with CCR2 G allele (64V allele). Our data indicate that gene polymorphism of CCR2 V64I may influence the susceptibility and clinicopathological characteristics of prostate cancer and CCR5 Δ32 allele may also be an important risk factor for prostate cancer in Turkish men population.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Fibrocytes are circulating, hematopoietic cells that express CD45 and Col1a1. They contribute to wound healing and several fibrosing disorders by mechanisms that are poorly understood. In this report, we demonstrate that fibrocytes predispose the lung to B16-F10 metastasis by recruiting Ly-6C(+) monocytes. To do so, we isolated fibrocytes expressing CD45, CD11b, CD13, and Col1a1 from the lungs of wild type (WT) and Ccr5(-/-) mice. WT but not Ccr5(-/-) fibrocytes increased the number of metastatic foci when injected into Ccr5(-/-) mice (73 ± 2 versus 32 ± 5; p < 0.001). This process was MMP9 dependent. Injection of WT enhanced GFP(+) fibrocytes also increased the number of Gr-1(Int), CD11b(+), and enhanced GFP(-) monocytes. Like premetastatic-niche monocytes, these recruited cells expressed Ly-6C, CD117, and CD45. The transfer of these cells into Ccr5(-/-) mice enhanced metastasis (90 ± 8 foci) compared with B cells (27 ± 2), immature dendritic cells (31 ± 6), or alveolar macrophages (28 ± 3; p < 0.05). WT and Ccl2(-/-) fibrocytes also stimulated Ccl2 expression in the lung by 2.07 ± 0.05- and 2.78 ± 0.36-fold compared with Ccr5(-/-) fibrocytes (1.0 ± 0.06; p < 0.05). Furthermore, WT fibrocytes did not increase Ly-6C(+) monocytes in Ccr2(-/-) mice and did not promote metastasis in either Ccr2(-/-) or Ccl2(-/-) mice. These data support our hypothesis that fibrocytes contribute to premetastatic conditioning by recruiting Ly-6C(+) monocytes in a chemokine-dependent process. This work links metastatic risk to conditions that mobilize fibrocytes, such as inflammation and wound repair.
    The Journal of Immunology 03/2013; · 5.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Studies investigating the impact of polymorphisms on monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) on the risk of cancer have reported inconsistent results. We performed a meta-analysis of 23 eligible studies to summarize the data describing the association between cancer risk and polymorphisms in MCP-1 A2518G and CCR2 V64I. Q-statistics and I(2) statistics were calculated to examine heterogeneity and summary odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using a random effects model. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, and publication biases were estimated. Overall, MCP-1 and CCR2 polymorphisms showed no significant associations with cancer risk (MCP-1-2518A/G, GG+GA vs. AA: OR=0.94, 95% CI=0.76-1.17; CCR2 V64I, AA+AG vs. GG: OR=1.27, 95% CI=0.87-1.86). However, strong evidence of heterogeneity was found among the investigated studies, and subgroup analyses were therefore conducted according to study location, cancer type, source of controls, and presence of deviation from the Hardy-Weinberg equilibrium (HWE). When the data were stratified by study location, the increased risk of cancer among A allele carriers of CCR2 V64I was observed only in studies conducted in Asian countries (AA+AG vs. GG: OR=1.65; 95% CI=1.25-2.18). This meta-analysis suggests that genetic polymorphisms of CCR2 V64I may influence the susceptibility of cancer in Asian countries. Further well-designed studies with larger sample sizes should be conducted.
    Cytokine 07/2013; · 2.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Objectives The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism. METHODS: Electronic searches of Pubmed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association. RESULTS: Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR=1.84, 95% CI=1.35-2.51, AA vs GA/GG, p=0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR=2.06, 95% CI=1.02-4.15, AA vs GA/GG, p=0.11), cervical cancer (OR=3.34, 95% CI=1.48-7.50, AA vs GG, p=0.56), and oral cancer (OR=2.04, 95% CI=1.46-2.84, GA vs GG, p=0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR=2.31, 95% CI=1.45-3.68, AA vs GA/GG, p=0.16) and Asians (OR=1.88, 95% CI=1.12-3.16, AA vs GA/GG, p=0.92). CONCLUSION: This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.
    Gene 04/2013; · 2.20 Impact Factor