Influence of ABCB1 genetic variants in breast cancer treatment outcomes

摘要

Background: Transportation of anticancer drugs such as anthracyclines across the membrane is regulated by P-glycoprotein encoded by the human multidrug resistance gene 1 (ABCB1). Polymorphisms in the ABCB1 gene (1236C > T, 2677G > T/A, 3435C > T) have been found to be associated with intrinsic and acquired cross resistance to these anticancer drugs. Therefore, the aim of this study is to evaluate the influence of ABCB1 gene polymorphisms in breast cancer treatment outcomes in terms of response and toxicity. Method: Response to neo-adjuvant chemotherapy was evaluated in 100 patients while grade 2-4 toxicity was followed in 207 patients, who had undergone FEC/FAC chemotherapy. Genotyping for ABCB1 polymorphisms was done by PCR-RFLP. Chi square and logistic regression analyses were used to calculate Odd's ratio using SPSS ver 17.0. A meta analysis was also performed using Comprehensive Meta Analysis Ver 2. Results: In response evaluation, 1236C > T polymorphism was significantly associated with treatment response for CT genotype [OR = 5.17(1.3-20.2), P= 0.018] and in dominant model (CC vs CT + TT) [OR = 4.63(1.25-17.0), P= 0.021]. In the toxicity group, the T allele of 1236C>T was associated with grade 2-4 tocxicity [OR 1.48(1.00-2.20), P= 0.049] and the association was also significant in the recessive model [OR 1.88(1.05-3.39), P= 0.033]. For other two SNPs 2677G>T/A and 3435C>T no association was seen with either treatment response or grade 2-4 toxicity. In meta analysis, no overall association was found. Conclusion: In our study, significant association was seen for ABCB1 1236C>T polymorphism with treatment response. The meta analysis did not show overall association with treatment outcomes.