Abstract
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. 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. 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. 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.
Highlights
We examined whether the single nucleotide polymorphism (SNP) at -2518 of the MCP-1 gene promoter region influences clinical outcomes among nasopharyngeal carcinoma (NPC) patients
To test whether MCP-1 expression can be detected in NPC tumors, 37 NPC biopsies were examined by IHC
These results suggested that MCP-1 is overexpressed by NPC tumor cells, and the expression level is associated with the MCP-1 SNP-2518 genotype
Summary
We examined whether the single nucleotide polymorphism (SNP) at -2518 of the MCP-1 gene promoter region influences clinical outcomes among nasopharyngeal carcinoma (NPC) patients. 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. 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-1SNP-2518 may be a valuable genetic marker for assessing the risk of developing distant metastasis after the radiotherapy in NPC patients. In NPC, the overexpression of MCP-1 has been detected in the infiltrated macrophages, leading to intensive leukocyte infiltration [24] It is unclear whether (a) MCP-1 is overexpressed in NPC tumor cells; (b) MCP-1 expression level can be modulated by the functional SNP; and (c) MCP-1 SNP2518 genotype is associated with NPC patients’ prognosis
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