title: MCP-1 Promoter Polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ka-Po
authors.initials: KP
authors.lastname: Tse
authors.forename: Nang-Ming
authors.initials: NM
authors.lastname: Tsang
authors.forename: Kung-Den
authors.initials: KD
authors.lastname: Chen
authors.forename: Hsin-Pai
authors.initials: HP
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
authors.forename: Sheng-Po
authors.initials: SP
authors.lastname: Hao
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hsieh
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000532:radiotherapy; D018932:Chemokine CCL2 / Q000235:genetics* / Q000502:physiology*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000532:radiotherapy; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2