| Objective: Esophagus carcinoma is the eighth common carcinoma of mortality all over the world,especially higher in China. When EC Patients are diagnosed,most of them are in the intermediate-advanced stage and the malignant cells have already desseminated.At present,chemotherapy is the only effective approach to prevent and control systemic metastasis. Therefore,the chemotherapy plays an important role in EC comprehensive therapy,whether as a main modality for EC patients in advanced stage or as an adjuvant treatment for perioperative patients.It is necessary to predict chemosensitivity of EC in order to make EC chemotherapy more directive,more effeetive and less blind.Many studies show that the ERCC1,GSTP1 gene polymorphisms are associated with the effect of platinum-based treatment.Therefore,in this study,we detected the genetic polymorphisms of ERCC1-C8092A,C19007T and GSTP1-A105G of the advcanced esophageal cancer patients treated with cisplatin-based chemotherapies,analyzed whether the polymorphisms and other clincal and pathological factors were related to tumor remission and PFS(progression free survival),which may provide basis for individualized treatment of EC in clinic.Methods: 107 advanced esophageal cancer patients were enrolled between September 2006 and September 2008 in Anhui provincial hospital and Anhui oncology hospital. They were all treated with cisplatin combined with fluorouracil chemotherapies. The tumor responses and PFS were assessd. The polymorphisms were detected after DNA PCR amplifications,which extracted from peripheral blood karyocytes before the first chemotherapies used. In the end,of 98 patients completed the trials and the data were available.Statistical analysis was performed using SPSS statistical software package 11.0 with P≤0.05 considered as statistically signficant.Univariate analysis by chi-square test and multivarariate analysis by logistic regression model were used for remission rate.PFS curves were calculated according to Kaplan-Meier method.Univariate analysis by log-rank test and multivarariate analysis by Cox regression model were used for PFS.Results: In these 98 patients,there were 69 male and 29 female;66 patients were no yunger than 60 years,32 patients were yunger than 60 years;the pathological types of all were squamous cell carcinoma,and of 27 were poor differentiated,71 were moderately or well differentiated; there were 16 patients'ECOG as 0 , 53 patients'ECOG as 1 and 29 patients'ECOG as 2; there were 15,45 and 38 patients'ERCC1-C8092A genetype as A/A,A/C and C/C respectively; there were 12,33and 53patients'ERCC1-C19007T genetype as T/T,C/T and C/C respectively; there were 4,20and74 patients'GSTP1-A105G genetype as G/G,A/G and A/A respectively. On univariate analysis,ERCC1-C8092 gene polymorphisms related to remission rates and PFS. The patients with ERCC1-C8092A A/C or A/A genotype had a higher response rate than the patients with C/C (51.67% vs 28.95%,P=0.036),and longer PFS(7.5 months vs 4.5 months,P﹤0.0001).There were no significant relationship between response rate and PFS and other genetic polymorphisms.Concolutions:Advanced esophageal cancer patient with ERCC1-C8092A genotypes as A/A or A/C, or well or moderately differentiated tumor cells may get more benefit in cisiplatin-based chemothetrapy. The research suggests that the ERCC1-C8092A genetic polymorphisms may be related with therapeutic responses to cisplatin chemotherapy and PFS in the advanced esophageal cancer. |
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