Abstract
Objectives: Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway which is activated in the repair of intra- and interstrand DNA crosslink caused by platinum-based treatment. Two single nucleotide polymorphisms (SNPs) of the ERCC1 gene, codon 118 C/T and C8092A, have been reported to be functional, but the influence on platinum resistance and survival is not yet clear. The primary aim of the present study was to investigate whether the two SNPs were associated with resistance to standard combination carboplatin and paclitaxel chemotherapy and the potential prognostic impact in newly diagnosed ovarian cancer patients. Methods: Serum samples from 202 patients with newly diagnosed ovarian cancer were assessed for ERCC1 SNP genotyping using real time PCR. All patients were treated with first line carboplatin/paclitaxel chemotherapy. Results: There were no correlation between the ERCC1 118 C/T and C8092A genotypes and platinum resistance (P = 0.79 and P = 0.36, respectively). Furthermore, the results showed no association to progression free survival (P = 0.18 and P = 0.16, respectively) or overall survival (P = 0.89 and P = 0.78, respectively) for the two SNPs. Conclusions: The ERCC1 118 C/T and C8092A polymorphisms did not have significant influence on clinical outcome defined as platinum resistance, PFS and OS.
Highlights
Differences in chemotherapy response and patient survival may be related to inter individual genetic polymorphisms in patient’s genes since they can change the expression or the function of enzymes related to the metabolism of the chemotherapeutic drug offered to the patient.Ovarian cancer is considered a chemo sensitive tumor as 70% - 85% of patients with advanced ovarian cancer respond to standard combination taxane/platinum-based treatment following primary surgical debulking [1]
Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway which is activated in the repair of intra- and interstrand DNA crosslink caused by platinum-based treatment
The ERCC1 118 C/T and C8092A polymorphisms did not have significant influence on clinical outcome defined as platinum resistance, Progression free survival (PFS) and Overall survival (OS)
Summary
Ovarian cancer is considered a chemo sensitive tumor as 70% - 85% of patients with advanced ovarian cancer respond to standard combination taxane/platinum-based treatment following primary surgical debulking [1]. Despite this apparent efficacy of treatment, the majority of these patients will relapse within a few years and if not already present, chemotherapy resistance will occur. Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway (NER) [5,6,7] This important pathway is activated in the repair of intra- and inter-strand DNA crosslink caused by platinum-based treatment. Excision of the formed DNA adducts is carried out by nucleotide excision repair proteins [8] that recognize the DNA damage and excise the cytotoxic platinum-DNA adducts from the injured DNA strand
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