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

Publication date: June 2018Source: Meta Gene, Volume 16Author(s): Ahmad Aizat Abdul Aziz, Md Salzihan Md Salleh, Ibtisam Mohamad, Venkata Murali Krishna Bhavaraju, Maya Mazuwin Yahya, Andee Dzulkarnaen Zakaria, Siew Hua Gan, Ravindran AnkathilAbstractTriple 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...
Source: Meta Gene - Category: Genetics & Stem Cells Source Type: research