Monocyte chemotactic protein-1 and CC chemokine receptor 2 polymorphisms and prognosis of renal cell carcinoma

Tumour Biol. 2013 Oct;34(5):2741-6. doi: 10.1007/s13277-013-0827-7. Epub 2013 May 9.

Abstract

Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC chemokine receptor 2 (CCR2) play a major role in inflammation and proliferation of cancers. We investigated a possible association between polymorphisms in MCP-1 and CCR2 genes (MCP-1 -2518A/G and CCR2 190G/A or V64I) and the risk as well as prognosis of renal cell carcinoma (RCC). Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 416 RCC cases and 458 age-matched healthy controls. Frequency of MCP-1 2518GG genotype for cases and controls was 0.384 and 0.286, respectively; individuals carrying the GG genotype had a 1.89-fold increased risk of RCC than those with AA genotype (95 % confidence interval [CI] 1.24-2.81, p = 0.002; data were adjusted for age and sex). Frequency of CCR2 190AA (64I/64I) genotype for cases and controls was 0.175 and 0.076, respectively; subjects having AA genotype had a 2.68-fold increased risk of RCC compared to those with the wild-type GG genotype (95 %CI 1.71-4.17, p = 4.3 × 10(-6); data were adjusted for age and sex). When analyzing the survival rate of RCC, patients with MCP-1 -2518GG genotype revealed significantly shorter survival time compared to cases with MCP-1 -2518AA and AG genotypes (p = 0.003). Similarly, RCC cases carrying CCR2 190AA genotype showed significantly shorter survival rate than patients with GG or GA genotypes (p < 0.001). These data suggested that MCP-1 -2518A/G and CCR2 190G/A polymorphisms are new risk factors for RCC and could be used as prognostic markers for this malignancy.

MeSH terms

  • Aged
  • Amino Acid Substitution
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Case-Control Studies
  • Chemokine CCL2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Receptors, CCR2 / genetics*

Substances

  • CCL2 protein, human
  • CCR2 protein, human
  • Chemokine CCL2
  • Receptors, CCR2