The Relationship Between Polymorphisms Of MTHFR A1298C Or GST M1and The Treatment Efficacy Or Survival Of The Advanced Gastric Cancer Patients Applied With Capecitabine-based Chemotherapy

Objective:to investigate the relationship between polymorphisms of methylenetetrahyd-rofolate reductase (MTHFR) gene A1298C or glutathione S-transferase (GST) M1gene and the treatment efficacy or survival of the advanced gastric cancer patients(AGC) applied with capecitabine-based chemotherapy.Methods:In the group of patients with a total of71patients,All patients were treated withcapecitabine based chemotherapy and DNA of peripheral blood leukocytes wereobtained before therapy. MTHFR A1298C and GST M1genotypes were detected byPCR-RFLP method. by polymerase chain reaction-restriction fragment lengthpolymorphism(PCR-RFLP)method and analysed by agarose gel electrophoresismethod. All patients were used to capecitabine-based combination chemotherapyregimens, in accordance with the RECIST standards and evaluation of curative effect.The relationship between the response rate and median progression free survival (PFS)and median survival time (MST) in AGC patients with different genotypes wereobserved and analyzed by the methods of multiple logistic regression analysis andcox regression analysis.Results:Of all the71cases,complete remission (CR) in1cases, partial remission (PR) in28cases, the overall response rate (RR) was40.85%(29/71) for RR. The medianprogression-free survival was175days (95%CI:165.677-184.323days) and the mediansurvival time was308days (95%CI:296.751-319.249days).1frequency of gene distribution(1) MTHFRA1298C:the frequency of A/A,A/C and C/C genotype was66.20%,32.39%and1.41%respectively.(2) GST-M1:functional and blank genotype frequency was43.66%and56.34%respectively. The site of the genotype distributions are consistent with Hardy-Weinbergbalance (P>0.05).2The relationship between different genotypes and the response rate:(1) MTHFR A1298C:47cases of A/A genotype in patients，CR1cases, PR23cases,RR=51.06%;in24cases of A/C+C/C genotype in patients,CR0cases,PR5cases,with an efficiency of20.83%, both have significant difference (P=0.014).(2) GST-M1:31cases of functional genotypes in patients,CR0cases,PR12cases，RR=38.71%;40cases of null genotype patients,CR1cases， PR16cases,RR=42.50%;the two had no statistical difference (P=0.747).a multivariate logisticregression analysis showed that only MTHFRA1298C associated with the efficacy.The efficacy of A/A genotype were higher compared to A/C+C/C genotype(OR0.252,95%CI:0.081-0.788).3The relationship between different genotypes and chemotherapy survivalThe results of the Cox regression analysis showed that MTHFR A1298C hadconnected with PFSand OS.(1) The median progression-free survival timeMTHFR A1298C:A/A type median progression-free survival was longer thanA/C+C/C type; they was180days (95%CI:172.755-187.245) and156days (95%CI:127.029-184.971) respectively(X2=6.395,P=0.011).(2) The median survival timeMTHFRA1298C:A/A type median overall survival time was longer thanA/C+C/C type they was323days (95%CI:301.835-344.165) and275days (95%CI:223.912-326.088) respectively (X2=10.155, P=0.001).Conclusion:This study demonstrated that the polymorphism of MTHFRA1298C wereassociated with the therapeutic effect and survival of AGC treated with capecitabinebased combination chemotherapy;their detection for guidance of advanced gastriccancer treated with capecitabine based combination chemotherapy and predict itsefficacy and survival situation has a high clinical value,but GSTM1genetic polym-orphism detection is not.