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Genetic association of abcg2 gene polymorphisms with tac chemotherapy response in triple negative breast cancer (TNBC) patients

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dc.contributor.authorRashid, Roshaidie Abdul
dc.date.accessioned2026-04-13T02:19:11Z
dc.date.available2026-04-13T02:19:11Z
dc.date.issued2020
dc.description.abstractIntroduction Triple negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer. Due to the lack of hormone receptors, chemotherapy using Taxane-Adriamycin-Cyclophosphamide (TAC) regimen remains the mainstay of TNBC treatment, and is the only choice of treatment available for TNBC. However, TNBC is characterized by high risk of recurrence, metastasis, and chemoresistance, and is associated with inter-individual variability in treatment response. Despite several mechanisms have been implicated in anticancer drug resistance, the exact mechanism of chemoresistance in TNBC remains unclear. A defective transport is a major mechanism of resistance. Transmembrane transport proteins such as breast cancer resistance protein (BCRP) encoded by ABCG2 can cause chemoresistance by means of increased efflux transportation of the drug out of the cell, hindering its molecular action on cancer cells. It was hypothesized that, the genetic variations G34A and C421A of ABCG2 gene, that impair substrate efflux could be associated with chemoresistance in TNBC patients undergoing chemotherapy and designed this study to test this hypothesis. Methodology Blood samples from 76 Malaysian TNBC patients who had undergone Taxane-Adriamycin-Cyclophosphamide (TAC) chemotherapy regimen were collected and stored in EDTA tube. DNA was extracted from these blood samples and genotyped using PCR-RFLP technique. The genotypes were categorized into homozygous wildtype, heterozygous and homozygous variant based on the band sizes on gel electrophoresis. The difference in genotype frequencies between chemoresistant and chemoresponsive groups was determined by using crosstabs analysis. The association between the genotypes and alleles with TAC chemotherapy response was determined by using binary logistic regression analysis deriving Odds Ratio (OR) with confidence interval (CI) of 95% on SPSS version 20.2. Haplotype frequencies between the chemoresistant and chemoresponsive groups of TNBC patients and their association with treatment response was calculated using Haploview software v4.2. Results The heterozygous (GA) and homozygous variant (AA) genotypes of the ABCG2 G34A polymorphism showed a significantly lower risk association with chemoresistance [(OR= 0.303, p=0.029) and (OR= 0.151, p=0.011) respectively]. Whereas the heterozygous (CA) and homozygous variant (AA) genotypes of C421A showed statistically insignificant low risk association with chemoresistance, [OR=0.481, p=0.251; OR=0.412, p=0.113 respectively]. The variant A allele of both SNPs [with OR=0.320, p=0.002 and OR=0.487, p=0.039 respectively] and haplotypes GA, CA and AA [with ORs=0.020, 0.002 and 0.00004, respectively] also showed significantly lower risk association with chemoresistance. It is reasonable to suggest that the variant genotype (AA) and variant allele (A) of G34A and C421A decrease the expression and transporter activity of ABCG2, lower the efflux activity of chemotherapeutic drugs, resulting in increased intracellular accumulation of the drug and thereby improve the efficacy of chemotherapy and lower the risk of chemoresistance. Conclusion These findings suggest that the ABCG2 G34A polymorphism may be useful as a potential biomarker to predict chemotherapy response in TNBC patients
dc.identifier.urihttps://erepo.usm.my/handle/123456789/23883
dc.language.isoen
dc.subjectABCG2
dc.subjectpolymorphisms
dc.titleGenetic association of abcg2 gene polymorphisms with tac chemotherapy response in triple negative breast cancer (TNBC) patients
dc.typeResource Types::text::thesis::master thesis
dspace.entity.typePublication
oairecerif.author.affiliationUniversiti Sains Malaysia
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