Genetic polymorphisms affecting clinical outcomes in epithelial ovarian cancer patients treated with taxanes and platinum compounds: a Korean population-based study

Abstract

Objective: We sought to evaluate the affect of genetic polymorphisms on clinical outcomes in patients with epithelial ovarian cancer (EOC).

Methods: Clinical data of 118 patients between March 2001 and November 2006 were reviewed. They underwent staging laparotomy followed by adjuvant chemotherapy using taxanes and platinum compounds. We investigated ERCC1 N118N, ERCC1 8092C>A, ERCC2 K751Q, XRCC1 R399Q, XRCC1 R194W, ABCB1 3435C>T, ABCB1 2677G>T/A, GSTP1 I105V, GSTM1 and GSTT1 polymorphisms with single base primer assay.

Results: The multivariate logistic regression analysis revealed that non-null genotype in GSTT1 polymorphism was a poor prognostic factors for overall response (adjusted OR, 0.29; 95% CI, 0.17-0.67), and A/A genotype in GSTP1 I105V polymorphism and T/T or T/A or A/A genotype in ABCB1 2677G>T/A polymorphism were significant risk factors for grade 3 or 4 hematological (adjusted OR, 3.08; 95% CI, 1.12-8.43) and gastrointestinal toxicities (adjusted OR, 9.74; 95% CI, 1.59-15.85), respectively. Moreover, The multivariate Cox's proportional hazard regression analysis showed that C/A or A/A genotype in ERCC1 8092C>A polymorphism and non-null genotype in GSTT1 polymorphism were prognostic factors for poor progression-free survival (adjusted HR, 1.94; 95% CI, 1.07-3.51) and poor overall survival (adjusted HR, 1.65; 95% CI, 1.79-3.42), respectively.

Conclusion: Genetic polymorphisms such as ERCC1 8092C>A, ABCB1 2677G>T/A, GSTP1 I105V and GSTT1 polymorphisms may affect drug response, toxicity and survival in patient with EOC who received taxane- and platinum-based chemotherapy after surgery. However, large-scale, prospective clinical studies are required for evaluating the role of genetic polymorphisms.