TITLE:
DNA-repair ERCC1 Gene Polymorphisms in Epithelial Ovarian Cancer and Relation to Platinum Resistance and Survival
AUTHORS:
Karina Dahl Steffensen, Marianne Waldstrøm, Anders Jakobsen
KEYWORDS:
Drug Resistance, Ovarian Cancer, Polymorphisms, ERCC1, DNA Repair, Predictive MARKEr
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.2 No.2,
June
29,
2011
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.