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MCP-1 Promoter Polymorphism at –2518 Is Associated with Metastasis of Nasopharyngeal Carcinoma after Treatment

Authors' Affiliations: ¹ Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; ² Chang Gung Molecular Medicine Research Center and Departments of ³ Life Science and ⁴ Public Health, Chang Gung University, Departments of ⁵ Radiation Oncology, ⁶ Medical Research, ⁷ Pathology, and ⁸ Otolaryngology, Chang Gung Memorial Hospital at Lin-Kou, Taoyuan, Taiwan

Requests for reprints: Y.-S. Chang, Graduate Institute of Basic Medical Sciences, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-shan, Taoyuan 333, Taiwan. Phone: 886-3-211-8683; Fax: 886-3-211-8683; E-mail: ysc{at}mail.cgu.edu.tw or N.-M. Tsang, Department of Radiation Oncology, Chang Gung Memorial Hospital at Lin-kuo, 5 Fu-sin Street, Kwei-shan, Taoyuan 333, Taiwan. E-mail: vstsang{at}adm.cgmh.org.tw.

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.

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