Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and clinicopathological characteristics of prostate cancer.
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.
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ABSTRACT: Associations between CCL5-403, CCR5-59029, and Delta32 polymorphisms and cancer risk are inconclusive. To derive a more precise estimation of the association, we performed a meta-analysis by searching PubMed, EMBASE, Google scholar, and WanFang databases. A total of 20 eligible articles with 39 studies were included. Of those studies, there were 21 studies for CCR5-Delta32 polymorphism, 9 studies for CCR5-59029 polymorphism, and 9 studies for CCL5-403 polymorphism. Combined analysis revealed no associations between these polymorphisms and cancer risk. However, subgroup analysis by ethnicity suggested that CCR5-59029 polymorphism was associated with the risk of cancer among Asian populations (A vs. G: odds ratio (OR) = 1.36, 95 % confidence interval (CI) 1.13-1.65, P H = 0.27; AA vs. GG: OR = 2.07, 95 % CI 1.37-3.12, P H = 0.17; GA+AA vs. GG: OR = 1.35, 95 % CI 1.03-1.77, P H = 0.92; AA vs. GA+GG: OR = 1.98, 95 % CI 1.01-3.88, P H = 0.08), but not among Caucasian populations. CCL5-403 polymorphism was associated with the risk of cancer among African populations (A vs. G: OR = 0.68, 95 % CI 0.55-0.83, P H = 0.14; AA vs. GG: OR = 0.51, 95 % CI 0.33-0.77, P H = 0.52; AG vs. GG: OR = 0.58, 95 % CI 0.42-0.80, P H = 0.14; AG+AA vs. GG: OR = 0.56, 95 % CI 0.41-0.75, P H = 0.13), but not among Caucasian populations and Asian populations. Overall, this meta-analysis indicated that CCR5-Delta32 was not associated with the risk of cancer. CCR5-59029 polymorphism contributed to cancer risk among Asian populations, and CCL5-403 polymorphism was associated with the decreased risk of cancer among African populations.Tumor Biology 04/2014; · 2.52 Impact Factor
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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
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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