Genotypes and haplotypes of ABCB1 contribute to TAC chemotherapy response in Malaysian triple negative breast cancer patients

Abstract

Triple negative breast cancer (TNBC) which is characterized by absent expression of ER, PR and HER2 receptors, is typically associated with poor treatment response and high recurrence risk rate or metastasis. ABCB1 is a drug efflux enzyme, involved in the drug transport across the membrane. Evidence have shown that, activation (or inactivation) of ABCB1 drug transporter gene may contribute to interindividual variability in treatment response. The present study aimed to investigate the association of SNPs (1236 C>T, 2677 G>T/A and 3435 C>T) and mRNA expression of ABCB1 with chemoresistance on TNBC patients undergoing chemotherapy with Taxane, Adriamycin and Cyclophosphamide (TAC) regimen. Our results showed that, homozygous variant (TT) genotype and variant allele (T) of ABCB1 3435 C>T polymorphism were significantly associated with higher risk for development of chemoresistance. The haplotypes ABCB1 3435T–1236T–2677T and ABCB1 3435T–1236G–2677T also showed significantly higher risk for development of resistance to chemotherapy. The mRNA expression of ABCB1 was significantly down regulated in cancerous as compared to normal adjacent tissues. Interestingly, up-regulation of ABCB1 mRNA expression was observed in patients who showed resistance compared to response to the chemotherapy. Thus, this study concludes that, genotypes and haplotypes of ABCB1 may contribute to the risk of chemoresistance in triple negative breast cancer patients undergoing TAC chemotherapy and may be useful as biomarkers for predicting chemoresistance.