ABCG2 C421A Polymorphism and Imatinib Response in Chronic Myeloid Leukemia: A Systematic Review and Meta-Analysis

ABSTRACT

OBJECTIVE: To estimate the association between ABCG2 C421A polymorphism and response to imatinib in chronic myeloid leukemia. METHODS: A systematic review was conducted to evaluate the effect of ABCG2 C421A polymorphism on imatinib response. The databases of PubMed, Embase, Web of science, CINAHL with FullText, and Cochrane Library were searched for all published studies from inception to December 2015. The following terms were used with functions of 'AND' and 'OR' 'chronic myeloid leukemia', 'CML', 'drug transporter', 'ABCG2', 'BCRP', 'polymorphisms', 'SNPs', and 'imatinib'. The studies reporting the association between ABCG2 polymorphism and imatinib response were evaluated. RESULTS: A total of 7 studies were included in the present meta-analysis. The pooled analysis showed that ABCG2 c.421CC genotype was significantly associated with poor response to imatinib under the dominant model (CC vs CA+AA; OR 0.56; 95% CI 0.41, 0.77; p = 0.0004). The subgroup analysis of Asian studies demonstrated a significantly lower response in c.421CC genotype than in c.421CA or c.421AA genotype (OR 0.52; 95% CI 0.37, 0.73; p = 0.0002). In subgroup analyses of 5 studies, the patients with the c.421CC genotype exhibited higher risk for worse response than the patients with c.421CA or c.421AA genotype (heterozygote codominant model CC vs. AC; OR 0.49, 95% CI 0.33, 0.73; p = 0.0006; homozygote codominant model CC vs AA; OR 0.43; 95% CI 0.25, 0.75, p = 0.003). CONCLUSION: The ABCG2 c.421CC genotype was significantly associated with poor response to imatinib compared to the c.421CA and c.421AA genotypes in chronic myeloid leukemia, especially in Asian patients.