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: 2.06). 05/2012; 31(8):1418-24. DOI: 10.1089/dna.2012.1716
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.
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ABSTRACT: The gene variants of the chemokine and chemokine receptor genes associated with inflammation may be involved in cancer initiation and progression. The aim of this study was to explore the possible association of monocyte chemoattractant protein-1 (MCP-1) A2518G, stromal cell derived factor 1 (SDF-1) 3'A and chemokine receptors CCR2A V64I, CCR5 Δ32, CCR5 59029 and CXCR4 gene polymorphisms with the risk and clinicopathological characteristics of bladder cancer (BC) in a Turkish population. The genotyping was done by PCR and PCR-Restriction Fragment Length Polymorphism (RFLP) methods in 142 histologically confirmed BC patients and 197 controls. The SDF-1 3'AA genotype conferred significantly increased susceptibility to BC. The carriers with AA genotype or at least one A allele of CCR2 had an increased risk of developing BC. CCR5 wt/Δ32 genotype and CCR5 Δ32 allele were also observed to be involved in the susceptibility to BC. Additionally, the combination of CCR2 V64I and CCR5 Δ32 (i.e., GG-wt/Δ32) was found to be associated with BC risk. With respect to the stage of BC, the AA genotype of SDF-1 and at least one T allele of CXCR4 were significantly associated with high T stage as compared to GG genotype of SDF-1 and CC genotype of CXCR4. Furthermore, BC patients with AA genotype or at least one A allele of CCR2 had an increased risk of high grade and stage tumors as compared to those with GG genotype. Our results suggest that the genetic variants of SDF-1 3'A, CCR2A V64I and CCR5 Δ32 gene polymorphisms may modify the BC risk. Furthermore, SDF-1 3'A, CCR2A V64I and CXCR4 gene polymorphisms may contribute to the muscle invasive BC in a Turkish population.
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ABSTRACT: Few studies reported the implication of single nucleotide polymorphisms (SNPs) of monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) in clinical significance of cancer of uterine cervix. We hypothesized that SNPs of MCP-1 and CCR-2 may affect the expression of these genes and then proteins. Therefore, we investigated the influence of the gene polymorphisms of MCP-1 and CCR-2 on the susceptibility and clinicopathologic characteristics of cervical neoplasia in Taiwan women. We recruited 86 patients with invasive cancer and 61 with high-grade dysplasia and 253 control women and selected 1 MCP-1 SNP rs1024611 (-2518G/A) and 1 CCR-2 SNP rs1799864 (190G/A; V64I) to determine their genotypes distribution using polymerase chain reaction-restriction fragment length polymorphism. In comparison to normal individuals with homozygotes GG in MCP-2 SNP, women with GA or AA carried a 2.01 odds ratio of developing cervical cancer. Nevertheless, it was not demonstrated in CCR-2 SNP. Furthermore, women with mutant homozygote (AA) of MCP-1 SNP increased the risk of deep stromal invasion, large tumor diameter, and parametrium invasion of cervical cancer, when compared to those with wild homozygote GG or heterozygote GA. However, women with mutant homozygotes (AA) of CCR-2 SNP did not increase the risk of poor clinicopathologic characteristics. In conclusion, MCP-1 SNP may be correlated with the development, deep stromal invasion, large tumor diameter, and parametrium invasion of cervical cancer but not with cancer recurrence or survival of Taiwan women patients with cancer. However, the SNP of its receptor, CCR-2, is not implicated in cervical cancer.
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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.
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