MCP-1 Promoter Polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment.
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.
Tse
Ka-Po
KP
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
Tsang
Nang-Ming
NM
Chen
Kung-Den
KD
Li
Hsin-Pai
HP
Liang
Ying
Y
Hsueh
Chuen
C
Chang
Kai-Ping
KP
Yu
Jau-Song
JS
Hao
Sheng-Po
SP
Hsieh
Ling-Ling
LL
Chang
Yu-Sun
YS
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
C111835:CCL2 protein, human; D018932:Chemokine CCL2