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

• Published in: Breast cancer research and treatment Vol. 111; no. 1; pp. 93 - 101
• Main Authors: Bewick, Mary A., Conlon, Michael S. C., Lafrenie, Robert M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2008; Springer; Springer Nature B.V
• Subjects: Adult; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - therapy; Cancer research; Cancer therapies; Chemotherapy; Clinical outcomes; Combined Modality Therapy; Disease-Free Survival; Female; Genotype; Genotype & phenotype; Glutathione Transferase - genetics; Gynecology. Andrology. Obstetrics; Humans; Inactivation, Metabolic - genetics; Kaplan-Meier Estimate; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Oncology; Peroxidase - genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Preclinical Study; Stem Cell Transplantation; Stem cells; Superoxide Dismutase - genetics; Survival analysis; Tumors; Drug metabolism; Metastatic breast cancer; Polymorphisms; Survival; Breast disease; Genetic variability; Superoxide dismutase; Metastasis; Glutathione transferase; Advanced stage; Peroxidase; Drug; Enzyme; Transferases; Genotype; Breast cancer; Malignant tumor; Metabolism; Mammary gland diseases; Treatment; Peroxidases; Oxidoreductases; Pharmacokinetics; Cancer; Polymorphism
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-007-9764-8

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.