CCR2-64I gene polymorphism increase susceptibility to oral cancer
ABSTRACT The purpose of this study was to investigate the impact of MCP-1 and its receptor CCR2 gene polymorphisms on the susceptibility and clinicopathological characteristics of oral cancer, as well as the synergistic effect between these gene polymorphisms and well-known risk factors including alcohol, tobacco, and areca consumptions. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for polymorphism analysis, 344 healthy controls and 216 oral cancer patients were recruited to reveal a significant association between V64I CCR2 gene polymorphism and oral cancer susceptibility. After adjusting for other confounders, individuals with GA (AOR=1.84; 95%CI=1.10-3.20) or at least one A allele (AOR=1.78; 95%CI=1.05-3.02) had a higher risk for oral cancer, compared to GG genotypes. Moreover, results also revealed that for subjects with GA or at least one A allele of V64I CCR2 gene polymorphism, those exposed to environmental risk factors possessed a significantly higher risk for oral cancer than those unexposed subjects. Therefore, genetic polymorphism of CCR2-64I may contribute to the susceptibility to oral cancer.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Single nucleotide polymorphisms (SNPs) may affect the development of diseases. The -2518A/G polymorphism in the regulatory region of the monocyte chemo-attractant protein-1 (MCP-1) gene has been reported to be associated with cancer risk. However, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to obtain a more precise estimation of the relationship between the -2518A/G polymorphism and cancer risk. We performed a meta-analysis, including 4,162 cases and 5,173 controls, to evaluate the strength of the association between the -2518A/G polymorphism and cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Overall, the results indicated that the -2518A/G polymorphism was not statistically associated with cancer risk. However, sub-group analysis revealed that individuals with GG genotypes showed an increased risk of cancer in digestive system compared with carriers of the A allele (GG vs. AA: OR = 1.43, 95%CI = 1.05-1.96, Pheterogeneity = 0.08; GG vs. OR = 1.29, 95%CI = 1.02-1.64, Pheterogeneity = 0.14). In addition, the increased risk of GG genotype was also observed in Caucasians (GG vs. OR = 1.81, 95%CI = 1.10-2.96, Pheterogeneity = 0.02). This meta-analysis suggests that the MCP-1 -2518A/G polymorphism may have some relation to digestive system cancer susceptibility or cancer development in Caucasian. Large-scale and well-designed case-control studies are needed to validate the findings.PLoS ONE 12/2013; 8(12):e82855. DOI:10.1371/journal.pone.0082855 · 3.53 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: In an earlier study, the genotypes associated with higher level of transforming growth factor-β1 (TGF-β1) were found to reduce the risk for breast cancer in western Indian women. This observation implied that gene polymorphisms affecting the levels of pro- and anti-inflammatory cytokines may influence the risk for breast cancer in this population. Hence, we performed genotyping for three more functional single-nucleotide polymorphisms (SNPs) responsible for variations in the levels of cytokines associated with inflammation. To that effect, polymorphisms in genes coding for IL-4 (IL-4 C-590T; rs2243250), IFN-γ (IFN-G A + 874T; rs2430561) and MCP-1 (MCP-1 A-2578G; rs1024611) were examined in premenopausal, healthy women (N = 239) and patients with breast cancer (N = 182) from western India. In carriers of the IL-4*590T allele, a reduced risk for the disease (dominant model; OR = 0.61, 95% CI 0.37-0.98) was seen similar to that seen in TGF-B1*10C carriers. An opposite trend was observed with respect to the alleles associated with higher expression of MCP-1 or IFN-γ. In individuals positive for three or more alleles associated with higher levels of either pro- or anti-inflammatory cytokines, an additive effect on the modulation of risk for the disease was evident (for TGF-B1 & IL-4, OR = 0.33, 95% CI 0.12-0.87; for IFN-G & MCP-1, OR = 2.29, 95% CI 0.95-5.51). In the context of contrasting observations in other populations, these results indicate a significant contribution of anti-inflammatory genotypes in the modulation of risk for breast cancer in western Indian women.International Journal of Immunogenetics 10/2013; 41(3). DOI:10.1111/iji.12098 · 1.34 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Bone invasion is a common complication of oral squamous cell carcinoma (OSCC), and this study sought to explore whether suppressed expression of monocyte chemotactic protein-1 (MCP-1) can be used to inhibit the bone invasion by OSCC. Strong staining of MCP-1 protein was observed from 10 archival blocks of OSCC by immunohistochemistry (IHC). Real-time PCR showed MCP-1 mRNA was highly expressed by OSCC cell lines (SCC25, HN5, and Tca8113), and SCC25 cells had the highest expression. An expression construct of a dominant negative variant of MCP-1 with 7 amino acids truncated (7ND), in the vector pcDNA was used to transfect SCC25 cells, and resultant stabilized SCC25 cells (SCC25-7ND) were generated by antibiotic selection. 10% conditioned media (CM, supernatant) of SCC25-7ND cells efficiently inhibited the formation of human osteoclasts grown from CD14(+) monocyte subpopulation, comparing with 10% CM of SCC25 cells. Further, cells of SCC25 or SCC25-7ND were injected onto the surface of calvariae of nude mice to establish an animal model of bone invasion by OSCC. H&E staining showed well-differentiated OSCC was formed in both groups, tumour cells invading the bone while osteoclasts locating in typical resorption lacunae. TRAP staining indicated significantly fewer osteoclasts were found in calvariae with cells of SCC25-7ND in comparison to cells of SCC25. These data demonstrate the relevance of MCP-1 with research on bone invasion by OSCC, and suggest the potential value of MCP-1 as a target to inhibit this common complication. © 2014 Wiley Periodicals, Inc.Journal of Cellular Biochemistry 06/2014; 115(10). DOI:10.1002/jcb.24849 · 3.37 Impact Factor