Effects of ABCB1 gene polymorphism on toxicity of Taxene-based Chemotherapy in Bangladeshi Triple Negative Breast Cancer patients.
Authors: Md. Siddiqul Islam1, Jubayer Hosen1, Krishno Dutta1, Ferdin Ehsan1, Zannatul Tunjum Islam1, Umme Rokaya Keya1, Md. Shihad Al Shariar1, Sajed Ahamed Rifat1, Tanvir Mamun Rumy1, Hrishik Iqbal2, Waheed Akter3, Abu Syed Md. Mosadde4, 5
Institution: 1Departement of Pharmacy, Southeast University1 2Renata PLC 3Sir Salimullah Medical College and Midford Hospital, Dhaka 4Quest Bangladesh Biomedical Research Center 5Uttara Adhunik Medical College
Introduction
Triple-negative breast cancer (TNBC) poses a significant therapeutic challenge due to its aggressive nature and limited treatment options. Taxane-based drug response and toxicity may be influenced by variations of ABCB1 gene. The objective of this study was to assess the impact of ABCB1 (rs1045642) polymorphisms on the toxicity of taxane-based chemotherapy in Bangladeshi triple-negative breast cancer patients.
Methods
100 female patients with operable breast cancer who had received docetaxel or paclitaxel containing neoadjuvant chemotherapy were included in this study. The taxane- induced toxicity during the treatment was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. DNA was isolated from patients’ blood and amplified by PCR. Genetic polymorphisms were detected with the PCR-RFLP technique.
Results
It was found that patients with the “TT” genotype of the ABCB1 (rs1045642) gene had a significantly higher risk of developing Anemia (OR = 4.40, 95% CI = 1.06 to 18.09, p = 0.0400) compared to those with the CC genotype. Additionally, patients with the TT and CT plus TT genotypes of the ABCB1 (rs1045642) gene had a significantly higher risk of developing Neutropenia and Gastrointestinal Toxicity compared to those with the CC genotype (OR = 4.38, 95% CI = 0.99 to 19.35, p = 0.0511 and OR = 3.76, 95% CI = 0.95 to 14.87, p = 0.0581 and OR = 4.33, 95% CI = 1.02 to 18.25, p = 0.0457; OR = 3.63, 95% CI = 1.05 to 12.55, p = 0.0416). However, our study did not find any significant relationship between leukopenia and the ABCB1 (rs1045642) gene variant.
Conclusion
Genetic variations in ABCB1 (rs1045642) may influence the toxicity of taxane- based chemotherapy in Bangladeshi TNBC patients. This study sheds light on pharmacogenomics markers for personalized Triple-negative breast cancer treatment, optimizing efficacy and minimizing adverse effects. Key Words: ABCB1, polymorphism, chemotherapy, taxane, triple negative breast cancer.
