Impact of XRCC1, GSTP1, and GSTM1 Polymorphisms on the Survival of Ovarian Carcinoma Patients Treated with Chemotherapy

Abstract

Background: Single nucleotide polymorphic variants of DNA repair genes may improve drug efficacy through altering expression levels of the encoded proteins. This study evaluated the influence of genetic polymorphism GSTP1 Ile105Val, GSTM1 (null/non-null) and 2 XRCC1 polymorphisms (Arg194Trp and Arg399Gln) on the survival of ovarian carcinoma patients treated with chemotherapy. Methods: 106 patients received treatment with a carboplatin-based or alternative chemotherapy. Polymorphisms were genotyped by pyrosequencing. Results: The genotypes XRCC1 194Arg/Trp and XRCC1 194Trp/Trp conferred no significant risk of death when compared to 194Arg/Arg (hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.33-3.09, and HR 0.89, 95% CI 0.31-2.57, respectively). Similarly, those carrying the XRCC1 399Arg/Gln genotype had no increased risk of death compared to the XRCC1 399Arg/Arg (HR 0.85, 95% CI 0.39-1.86); no homozygous carriers of the glutamine allele (XRCC1 399 Gln/Gln) were detected. The GSTP1 105Ile/Val had no increased risk of death compared to the GSTP1 105Ile/Ile (HR = 1.20, 95% CI = 0.55-2.63) and no homozygous carriers of the valine allele (GSTP1 105Val/Val) were detected in the study. Compared to the non-null genotype of GSTM1, the mortality rate was nonsignificantly reduced in patients with the null genotype (HR 1.07, 95% CI 0.48-2.42). However, overall survival of the patients treated with the carboplatin-based regimen was significantly longer than for those treated with alternative chemotherapy (p_log-rank = 0.006). Conclusions: The present findings suggest that there are no correlations between genotypes and survival.