ERCC1, XRCC1, and GSTP1 Polymorphisms and Treatment Outcomes of Advanced Epithelial Ovarian Cancer Patients Treated with Platinum-based Chemotherapy.

Abstract

Objective:The first line regimen for treating epithelial ovarian cancer (EOC) is platinum-based chemotherapy. Various factors impact its effectiveness including polymorphisms of enzymes in platinum-related metabolism processes. Methods:We conducted the study to investigate the association between polymorphisms of ERCC1, XRCC1 and GSTP1, which responsible for platinum’s metabolisms in Thai epithelial ovarian cancer patients. Results:Fifty-two patients with advanced epithelial ovarian cancer were enrolled into this study. Genotyping analysis of ERCC1 (C->A, rs3212986), XRCC1 (A->G, rs25487) and GSTP (A->G, rs1695) were performed which variant allele frequencies were found at 35.6%, 28.9% and 10.6%, respectively. Patients with homozygous variant type (A/A) of ERCC1 C8092A had higher rate of platinum-resistance (75% vs 16.7%, p =0.046). In addition, the significant association of GSTP1 polymorphism and grade 2 anemia was found. Patients with A/G genotype of GSTP1 had higher rate of grade 2 anemia (81.8% vs 46.3%, p =0.036). Conclusions:Genetic polymorphisms of ERCC1, and GSTP1 might be useful biomarkers for prediction of clinical benefit and toxicities of platinum-based chemotherapy in Thai epithelial ovarian cancer patients.