Association of polymorphic markers of XRCC1, ERCC2, CDKN1A genes with progression free survival of ovarian cancer patients after platinum/taxanesbased chemotherapy

Abstract

Background: The most important goal of current clinical oncology is personalized treatment primarily due to high toxicity of chemotherapeutic drugs. The key drugs used in chemotherapy of ovarian cancer are platinum derivatives, which are both highly effective and highly toxic. Therefore, searching for sensitivity markers for this group of drugs is very relevant. The aim of this work was to study polymorphic markers of XRCC1 and ERCC2 DNA repair genes and the cell cycle regulation gene, CDKN1A, and their relationship with progression-free survival time (PFS), which is a surrogate clinical marker for sensitivity of ovarian cancer to platinum drugs. Materials and methods. The study included 26 patients with advanced ovarian cancer (stage II-IV). Tumor samples were withdrawn from patients before the onset of chemotherapy, during the primary cytoreductive surgery. After surgery, all patients received a standard chemotherapy with paclitaxel and platinum drugs. DNA was isolated from tumor tissue samples using a Diatom DNA Prep 400 kit (Isogen, Russia). The polymorphic markers, Gln399Arg of the XRCC1 gene, Lys751Gln
of the ERCC2 gene, and Ser31Arg of the CDKN1A gene were analyzed by PCR-RFLP and real-time PCR melting curves analysis as a reference. The marker status was compared with the duration of PFS. Results. A tendency towards longer duration of PFS was observed in the presence of the Gln allele of Gln399Arg XRCC1 marker (median PFS, 14.1 months in patients with the Gln allele vs. 10.9 months in the subgroup without the Gln allele; p = 0.095). In the subgroup with optimal cytoreductive surgery, carrying the minor Arg allele of the CDKN1A gene Ser31Arg marker was associated with duration of PFS. In the presence of the minor Arg allele, the PFS duration after platinum-containing chemotherapy was statistically significantly decreased (median PFS, 19.08 months in the absence of Arg allele vs. 12.82 months in the presence of Arg allele, p = 0.035). Conclusion. Polymorphic markers of XRCC1 and CDKN1A genes were found to be related with remission duration after platinum containing chemotherapy of ovarian cancer. This suggests advisability of further studies of these molecular genetic factors on a representative group of patients with ovarian cancer.