Xrcc1, Adprt Gene Polymorphism And Ts Gene Expression Experiments And Evidence-based Medical Research And The Relationship Of Tumor Sensitivity To Chemotherapy

Objective: To investigate the association between XRCC1 T-77C, Argl94Trp, Arg399Gln and ADPRT Val762Ala polymorphisms and chemotherapy sensitivity in advanced Non-Small Cell Lung Cancer patients receiving platinum- based chemotherapy, and also analysis the combined predictive effect of the four polymorphisms. Methods: A total of 107 advanced lung cancer patients receiving platinum-based chemotherapy were involved. DNA of peripheral blood leukoeytes was obtained, and genotypes were detected by PCR-RFLP method. The association between genotypes and response rate was evaluated. Logistic regression was used to adjust for sex, year, pathological type, clinical stage, and therapeutic regimen. Results: Compared with the TT genotype, XRCC1 -77 C-allele carriers had a roughly 41% increased efficancy but with no statistical significance (adjusted OR = 1.41, 95% CI: 0.51-3.93). For XRCC1 Argl94Trp polymorphism, XRCC1 194 Arg/Trp carriers had a significant higher response rate than the wild genotype carriers (adjusted OR = 3.61, 95% CI: 1.36-9.63); Also, XRCC1 194 Trp carriers had a significant higher response rate than the wild genotype carriers (adjusted OR = 3.52, 95% CI: 1.36-9.11). For XRCC1 Arg399Gln polymorphism, XRCC1 399 Gln carriers had a lower response rate than the wild genotype carriers (crude OR = 0.42, 95% CI: 0.19-0.93; adjusted OR = 0.52, 95% CI: 0.22-1.26). For ADPRT Val762Ala polymorphism, ADPRT 762Ala carriers had a higher response rate than the wild genotype carriers (adjusted OR = 1.57, 95% CI: 0.67-3.66). Compared with the carriers with sensitive alleles to platinum- based chemotherapy less than three, the carriers with three or four drug sensitive alleles are more sensitive to platinum-based chemotherapy (adjusted OR = 4.51, 95% CI: 1.54-11.19), the carriers with five or six drug sensitive alleles are also more sensitive to platinum-based chemotherapy but with no statistical significance (adjusted OR = 2.92, 95% CI: 0.60-14.23). Conclusions: XRCC1 Argl94Trp polymorphism had a significant impact on response rate in advanced NSCLC patients treated with platinum-based chemotherapy. The XRCC1 l94Trp carriers were more sensitive to platinum-based chemotherapy. The predictive value of XRCC1 Arg399Gln polymorphism needed further confirmation,it seemed that the Arg/Arg carriers were more sensitive to platinum-based chemotherapy. However, no association was found between the XRCC1 T-77C, ADPRT Val762Ala polymorphism and response rate. The combined predictive values of the four polymorphisms may be more powerful than the single one. Objective: The published data about thymidylate synthase (TS) expression and its predictive value in advanced colorectal cancer (CRC) patients receiving fluoropyrimidine-based chemotherapy seemed inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Methods: Studies have been identified by searching PubMed and Embase. Inclusion criteria were advanced CRC patients, received fluoropyrimidine-based chemotherapy, and evaluation of TS expression and overall response rate (ORR). The relative ratio (RR) for ORR in patients with low TS expression over those with high TS expression with 95% confidence interval (CI) was calculated for each study as an estimation of the predictive effect of TS. Results: A total of 24 studies including 1112 patients were involved in this meta-analysis. The overall RR was 2.20 (95% CI, 1.82-2.66; P = 0.000). For studies evaluating TS expression in metastatic lesions, the pooled RR was 3.23 (95% CI, 2.27-4.59; P = 0.000); for studies testing TS expression in primary lesions, a pooled RR of 1.89 (95% CI, 1.45-2.48; P = 0.000) was estimated. Focusing the analysis on IHC-based or RTPCR-based assessments, the pooled RR was 1.83 (95% CI, 1.44-2.34; P = 0.000) and 2.96 (95% CI, 2.07-4.22; P = 0.000), respectively. Conclusions: The results indicated that low TS expression tumors in advanced CRC patients were more sensitive to fluoropyrimidine-based chemotherapy. Subgroup analyses indicated that the predictive value of TS expression evaluated in metastases was more prominent than that of primary lesions, and that TS expression tested by RTPCR was also of greater predictive value than by IHC.