Polymorphisms in manganese superoxide dismutase, myeloperoxidase and glutathione-S-transferase and survival after treatment for metastatic breast cancer

Abstract

Treatments for metastatic breast cancer (MBC) are primarily palliative with variable efficacy and outcomes may be influenced by individual differences in drug metabolism. In this study, we examined the association of single nucleotide polymorphisms (SNPs) in genes involved in drug metabolism with progression free survival (PFS) and breast cancer specific survival (BCSS) in 95 patients with MBC that received high dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT). SNPs in the SOD2 (SOD2-01, Val16Ala), MPO (MPO-02, -463 promoter variant) and GSTP1 [GSTP1-01 (Ile105Val), GSTP1-02 (Ala114Val)] genes were examined in DNA isolated from cryopreserved blood products using genotyping assays. Survival was analysed using Cox proportional hazard models and Kaplan-Meier estimates. Patients with the SOD2-01 (TT) genotype had increased risk of disease progression [hazard ratio (HR): 2.52; 95% confidence interval (CI), 1.31-4.85] and breast cancer specific death (HR: 1.92; 95% CI: 1.03-3.57). Risks were increased for patients with both SOD2-01 (TT) and GSTP1-01 (GG or AG) genotypes (HR for disease progression: 2.57, 95% CI: 1.32-5.00 and HR for breast cancer specific death: 2.27; 95% CI: 1.18-4.34). In multivariable analysis, the combined genotype group of SOD2-01 and GSTP1-01 was an independent predictor of PFS and BCSS. HRs progressively increased with increasing number of genotypes associated with worse survival, with p(trend) of 0.005 and 0.006 for PFS and BCSS, respectively. These results suggest that SNPs in genes involved in drug metabolism may influence survival outcome for patients with MBC receiving HDC and ASCT.