Predict Effect Of Response And Survival Of Polymorphisms Of XPD, XPA, XRCC1 And GSTP1 In Patients With Advanced Gastric Cancer Treated With Oxaliplatin Based Chemotherapy

Objective:To investigate the correlation between genetic polymorphisms of XPD Lys751Gln,XPA A23G,XRCC1 Arg399Gln and GSTP1 Ile 105Val and response to oxaliplatin-based chemotherapy in patients with advanced gastric cancer.Methods:Collected the peripheral venous blood from 110 patients who with advanced gastric cancer and treated with oxaliplatin-based chemotherapy. PCR-PFLP and gene sequencing analysis were used for analyzing the genetic polymorphisms of XPD Lys751Gln,XPA A23G,XRCC1 Arg399Gln,GSTP1Ile105Val. Therapeutic effectiveness were evaluated after two cycles of chemotherapy according to RECIST criteria. Chemotherapy efficiency, mPFS and MST were computed, and the relationship between genotypes and chemotherapy efficiency and survival were analyzed.Results:1. The effective rate, mPFS and MST was 49.1%,128d and 308d, respectively, in 110 patients with advanced gastric cancer.2. The isoforms distribution of XPD Lys751Gln, XPA A23G, XRCC1 Arg399Gln and GSTP1Ile105Val were all demonstrated Hardy-Weinberg equilibrium.3. The efficiency of chemotherapy was correlated with genetic polymorphisms of XRCC1 Arg399Gln,GSTP1Ile105Val, but not with XPD Lys751Gln,XPA A23G. The effective rate has statistically differences between XRCC1 Arg399Gln Arg/Arg and Arg/Gln+Gln/Gln (62.1% VS 27.9%, X2=12.201, P<0.001). There also has statistically differences between GSTP1 Ile105Val Ile/Ile and Ile/Val+Val/Val (35.7%VS 71.2%, X2=13.052, P<0.001)4. MPFS was correlated with genetic polymorphisms of XRCC1 Arg399Gln and GSTPlIle105Val, that was not correlated with genetic polymorphism of XPD Lys751Gln and XPA A23G. mPFS has statistically differences between Arg399Gln Arg/Arg and Arg/Gln+Gln/Gln in gene XRCC1 (140d VS.84d, X2=13.801, P<0.001). There also has statistically differences between Ile105Val Ile/Ile and Ile/Val+Val/Val in gene GSTP1 (90d VS.150d, X2=18.579, P<0.001).5. MST was correlated with genetic polymorphisms of XRCC1 Arg399Gln and GSTP1Ile105Val, whereas that was not correlated with genetic polymorphism of XPD Lys751Gln and XPA A23G. MST has statistically differences between Arg399Gln Arg/Arg and Arg/Gln+Gln/Gln in gene XRCCl (330d VS.210d, X2=21.249, P<0.001). There also has statistically differences between Ile105Val Ile/Ile and Ile/Val+Val/Val in gene GSTP1(228d VS.356d, X2=21.555, P<0.001)。6. Combination analysis of genetic polymorphism reveals that mPFS has statistically differences among 0 risk genotypes, one risk genotypes and two risk genotypes(X2=28.508, P<0.001). The results of log-rank comparisons are:P<0.001 in 0 VS.1; P<0.001 in 0 VS.2; P=0.053 in 1 VS.2. COX regression analysis reveals that mPFS was correlated with one or two risk genotypes.7. Combination analysis of genetic polymorphism reveals that MST also has statistically differences among these three groups(X2=40.311, P<0.001). The results of log-rank comparisons are:P<0.001 in 0 VS.1; P<0.001 in 0 VS.2; P=0.002 in 1 VS.2. COX regression analysis reveals that MST was correlated with one or two risk genotypes.Conclusions:Genetic polymorphisms of XRCC1 Arg399Gln and GSTP1Ile105Val were correlated with efficiency and survival in patients with advanced gastric cancer treated with oxaliplatin based chemotherapy. Further more, combination analysis has better prediction role in survival.