MCP-1 Promoter Polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment

Clin Cancer Res. 2007 Nov 1;13(21):6320-6. doi: 10.1158/1078-0432.CCR-07-1029.

Abstract

Purpose: We herein examined whether the single nucleotide polymorphism (SNP) at -2518 of the MCP-1 gene promoter region influences clinical outcomes among nasopharyngeal carcinoma (NPC) patients.

Experimental design: The study population consisted of 411 NPC patients without metastasis at diagnosis. All patients were treated at the Chang Gung Memorial Hospital from March 1994 to November 2004. The MCP-1 SNP-2518 genotype of each patient was determined by TaqMan genotyping kit. Statistical analyses were conducted to compare disease-specific survival (DSS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) of patients according to genotype. MCP-1 expression in tumor biopsies was examined by immunohistochemistry.

Results: Among 411 NPC patients, carriers of AA and AG genotypes were prone to distant metastasis than that of GG genotype (hazard ratio, 2.21; P = 0.017, and hazard ratio, 2.23; P = 0.005, for AA and AG genotype, respectively) after initial radiotherapy. No genotype-specific significant difference was found in DSS, PFS, and LRFS. Furthermore, immunohistochemistry revealed that MCP-1 expression level was higher in NPC tumor cells from GG carriers compared with those from AA and AG carriers.

Conclusions: MCP-1 SNP-2518 may be a valuable genetic marker for assessing the risk of developing distant metastasis after the radiotherapy in NPC patients. Carriers of A allele may require more aggressive chemotherapy implicating a potential marker for personalized medicine. We speculate that a regulatory SNP may be associated with the distant metastasis of NPC. Validation studies are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Carcinoma / genetics*
  • Carcinoma / metabolism*
  • Carcinoma / radiotherapy
  • Chemokine CCL2 / genetics*
  • Chemokine CCL2 / physiology*
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / radiotherapy
  • Neoplasm Metastasis
  • Polymorphism, Genetic*

Substances

  • CCL2 protein, human
  • Chemokine CCL2