Data from <i>MCP-1</i> Promoter Polymorphism at −2518 Is Associated with Metastasis of Nasopharyngeal Carcinoma after Treatment

Abstract

<div>Abstract<p><b>Purpose:</b> We herein examined whether the single nucleotide polymorphism (SNP) at −2518 of the <i>MCP-1</i> gene promoter region influences clinical outcomes among nasopharyngeal carcinoma (NPC) patients.</p><p><b>Experimental Design:</b> 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 <i>MCP-1</i> 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.</p><p><b>Results:</b> Among 411 NPC patients, carriers of AA and AG genotypes were prone to distant metastasis than that of GG genotype (hazard ratio, 2.21; <i>P</i> = 0.017, and hazard ratio, 2.23; <i>P</i> = 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.</p><p><b>Conclusions:</b><i>MCP-1</i> 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.</p></div>