AL16ALA-SOD2 polymorphism predicts recurrence risk of breast cancer in patients treated with adjuvant tamoxifen

Abstract

Introduction: Approximately 30% of patients with hormone receptor-positive breast cancer show resistance to tamoxifen, which may result in local or distant recurrence. Based on previous evidence, it can be inferred that tamoxifen sensitivity is influenced by an oxidative genetic imbalance. Objective: To evaluate the association between the genotypes of SOD2 single-nucleotide polymorphisms and the risk of recurrence in patients with luminal breast cancer treated with adjuvant tamoxifen. Methods: This is a retrospective cohort study. Biopsy samples from tumors were used for Val16Ala-SNP real-time PCR genotyping. Other potential markers of apoptosis and proliferation were analyzed by immunohistochemistry. Survival was defined as follow-up of a minimum of 72 months and compared using Cox regression multivariate analysis adjusted for grade, clinical staging, and Bcl-2 and Ki67 markers. Results: 36% patients relapsed, 35% presented with histological grade 3, and 29% had clinical stage III. The frequencies of SOD2 were 35% Ala/Ala, 35% Val/Val, and 30% Ala/Val. Val-allele women tended to be more at risk for recurrence than others (RR = 2.14 (95% CI 0.84–5.47). Patients with the Val allele had a 15% reduction in relapse-free survival, whereas with Ala/Ala, this reduction was only 8%. The expression of Caspase-3 was low in patients with relapse (p = 0.008). Conclusion: This study emphasizes the importance of oxidative response in cancer cells during tamoxifen treatment. The presence of the Val allele showed a strong trend, which could be considered as a hypothesis generator.

Keywords

• Breast cancer
• Relapse
• Val16Ala-SOD2 polymorphism
• Tamoxifen