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Effect of MDR1 polymorphism on multidrug resistance expression in breast cancer patients
M Taheri1, F Mahjoubi, R Omranipour
1Departament of Clinical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Abstract:
One of the limitations in the treatment of cancer patients with chemotherapy is the development of multidrug resistance (MDR). A well-known mechanism responsible for drug resistance is over-expression of ABC-transporter genes such as MDR1. This gene encodes p-glycoprotein (P-gp), a transmembrane glycoprotein that transports many hydrophobic substrates and anti-cancer drugs out of the cell. MDR1 gene polymorphisms could alter the expression level of P-gp and consequently result in drug resistance. We investigated a possible association between MDR1 gene C3435T polymorphism and its expression in Iranian breast cancer patients. PCR-RFLP was used for the detection of C3435T single nucleotide polymorphism in 54 breast cancer patients and 50 healthy individuals. The expression level of MDR1 was determined by real-time quantitative PCR. We observed no difference in the frequency of C3435T polymorphism between breast cancer patients and healthy controls. However, there was a significant association between MDR1 expression levels and C3435T polymorphism in the patients. C3435T polymorphism may play a role in inducing drug resistance by altering the expression level of the MDR1 gene.
Insights
Multidrug resistance (MDR) in cancer chemotherapy can be influenced by MDR1 gene variations. This study found that while MDR1 C3435T polymorphism didn't differ between groups, it was associated with altered MDR1 gene expression in Iranian breast cancer patients.
Area of Science:
- Genetics
- Oncology
- Pharmacogenomics
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- Over-expression of the MDR1 gene, encoding P-glycoprotein (P-gp), is a key mechanism of MDR.
- MDR1 gene polymorphisms may affect P-gp levels and influence drug resistance.
Purpose of the Study:
- To investigate the association between the MDR1 gene C3435T polymorphism and its expression in Iranian breast cancer patients.
- To explore the role of this polymorphism in the development of chemotherapy resistance.
Main Methods:
- PCR-RFLP was employed to genotype the MDR1 C3435T polymorphism in 54 breast cancer patients and 50 healthy controls.
- Real-time quantitative PCR was used to determine MDR1 gene expression levels.
Main Results:
- No significant difference in the frequency of the MDR1 C3435T polymorphism was observed between breast cancer patients and healthy individuals.
- A significant association was found between MDR1 gene expression levels and the C3435T polymorphism in breast cancer patients.
Conclusions:
- The MDR1 C3435T polymorphism may contribute to chemotherapy resistance in breast cancer by modulating MDR1 gene expression.
- Further research is warranted to elucidate the precise mechanisms linking this polymorphism to drug resistance in cancer treatment.
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