Lack of association between MDR1 C3435T polymorphism and chemotherapy response in advanced breast cancer patients: evidence from current studies

Abstract

The transmembrane transport of anticancer drugs is mainly regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 gene (MDR1). Since there were controversies regarding the association between MDR1 C3435T polymorphism and response to chemotherapy among patients with advanced breast cancer, a meta-analysis of the link was conducted. A total of 7 studies consist of 464 advanced breast cancer patients relating MDR1 C3435T polymorphism to the response of chemotherapy were included in this meta-analysis. The main analysis revealed a lack of association between the MDR1 C3435T and response to chemotherapy, with odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) of 1.37 (95% CI: 0.78-2.40), 1.17 (95% CI: 0.69-2.01), 1.18 (95% CI: 0.76-1.84) and 1.61 (95%CI: 0.70-3.68) for homozygous comparison, heterozygous comparison, dominant model and recessive model, respectively. The subgroup analysis by ethnicity did not change the pattern of results, with ORs of 0.99 (95% CI: 0.11-9.07), 0.68 (95%CI: 0.29-1.60), 0.81 (95%CI: 0.36-1.85) and 1.51 (95% CI: 0.77-2.96), in homozygous comparison, heterozygous comparison, dominant model and recessive model, respectively in Caucasian, and 1.50 (95% CI: 0.75-3.03), 1.72 (95% CI: 0.85-3.47), 1.59 (95% CI: 0.90-2.80) and 2.29 (95% CI: 0.51-10.35), respectively in Asian. The available evidence indicates that MDR1 C3435T polymorphism cannot be considered as a reliable predictor of response to chemotherapy in patients with advanced breast cancer.