Associations Between Promoter Region-460T/C,-1154G/A Single Nucleotide Polymorphisms In VEGF Gene And The Prognosis Of Nasopharyngeal Carcinoma

Objective To explore the associations between promoter region-460T/C,-1154G/A single nucleotide polymorphisms in VEGF gene and the prognosis of nasopharyngeal carcinoma(NPC)retrospectively analyzed the clinical data and genetic information,so as to provide theoretical basis for individualized treatment of NPC.Method.163 cases with primary histopathologically-confirmed NPC were collected in The Affiliated Hospital of Guangxi Medical Unicersity from December 2011 to December 2012.Peripheral blood sample was taken before the treatment and the VEGF gene promoter region-460T/C-1154G/A single nucleotide polymorphism were detected by direct sequencing method.Intensity-modulated radiation therapy and platinum based chemotherapy was performed in all patients.Chi-square test was applied to compare differences between genetic polymorphism and local recurrence,distant metastasis.Survival rates were calculated by Kaplan-Meier estimation while survival curves were analyzed by log-rank tests.Prognostic factors were analyzed by multivariate analysis with COX proportional hazards survival modeling.All statistical calculations were performed with SPSS 21.0 Windows.Two-sided values less than 0.05 were considered statistically significant.Results1.A retrospective study of 163 NPC patients(51 women,112 men;median age 45 years,age distribution 13-76 years)was identified.Date to February 252015,12 patients were lost to follow up,143 were still alive,and 20 were died.The survival times were 9-38 months,while the median overall survivals were 31 months.2.The T/T,T/C and C/C genotypic distributions of VEGF-460T/C were 52.8%,38.0%,9.2%,respectively.The G/G,G/A and A/A Genotypic distributions of VEGF-1154G/A were 41.7%,39.3%,19.0%,respectively.T/T,T/C,C/C genotype patients with distant metastasis were 6cases,12cases and 2cases,while the number of without distant metastasis were 80cases,50cases and 13cases.The frequency of C allele in distant metastasis group was higher than without distant metastasis group,but there was no significant difference(P=0.077).This results show that the C allele might increase the rick of distant metastasis.3.The estimated 1-,2-,and 3-year overall survival rates for all NPC patients were 98.1%,87.9%,and 87.1%,respectively.The 3-year OS of T/T,T/C,C/C genotypes were 95.1%,76.7%and 86.7%,respectively,and the differences of them were significant(P=0.008);Compared with T/C genotype,the T/C and C/C genotype had a lower 3-year OS(78.8%vs 95.1%;P=0.003).The 3-year OS in patients with G/G,G/A and A/A genotypes were 87.6%,83.9%,93.5%(P=0.465).Univariate analysis showed that N classification,local recurrence,distant metastasis and VEGF-460T/C SNP were the prognostic factors affecting the survival of patients with NPC(P<0.05).Multivariate Cox analysis indicated that local recurrence,distant metastasis and VEGF-460T/C SNP were independent prognostic factors of survival for all NPC patients(P<0.05).4.The estimated 1-,2-,and 3-year LRFS for all NPC patients were 96.3%,93.7%,and 93.7%,respectively.The 3-year LRFS of T/T,T/C,C/C genotypes were 92.8%,95.1%and 93.3%,respectively,and the differences of them were not significant(P=0.862);The 3-year LRFS in patients with G/Q G/A and A/A genotypes were 95.5%,91.9%and 93.5%(P=0.724).There was no significant association between the remaining predictors(age,gender,clinical classification,N classification,T classification,treatment,VEGF-460T/C SNP and VEGF-1154G/A SNP)and local recurrence-free survival base on univariate and multivariate analysis(P>0.05).5.The estimated 1-,2-,and 3-year DMFS for all NPC patients were 92.6%,92.0%,and 85.5%,respectively.The 3-year DMFS of T/T,T/C,C/C genotypes were 90.6%,79.9%and 81.7%,respectively,and the differences of them were not significant(P=0.081);Compared with T/C genotype,the T/C and C/C genotype had a lower 3-year DMFS(79.9%vs 95.3%;P=0.036).The 3-year DMFS in patients with G/G,G/A and AJA genotypes were 88.6%,80.4%,89.3%(P=0.502).Univariate analysis showed that N classification and VEGF-460T/C SNP were the prognostic factors affecting the distant metastasis-free survival of patients with NPC(P<0.05).Multivariate Cox analysis indicated that N classification was an independent prognostic factor of distant metastasis-free survival for all NPC patients(P<0.05).6.In the T/T,T/C,C/C subgroups,the difference of OS,LRFS,DMFS between induction chemotherapy group and no-induction chemotherapy group was no statistically significant(P>0.05).Conclusions1.There is no significant correlation between VEGF-1154G/A polymorphism and M classification,local recurrence;there is no significant correlation between VEGF-460T/C polymorphism and local recurrence,while the C allele might increase the rick of distant metastasis.2.VEGF-460T/C SNP is an independent prognostic for OS,while VEGF-1154G/A SNP is not an effective indicator for the prognosis of NPC.