Effect of XRCC1 Gene Polymorphism (rs1799782) on Response and Toxicities of Chemotherapy in Bangladeshi Breast Cancer Patients
Authors: Md. Shihad Al Shariar1, Jubayer Hosen1, Lamia Akther1, Mahmud Hasan Rifat1, Tanjum Akter Keya1, Tanvir Mamun Rumy1, Subrota Sutradhar1, Ferdowsi Akter1, Israt Jahan Bulbul1, Yesmin Begum1, Abu Syed Md. Mosaddek2, Kazi Ashraful Islam3, Md. Siddiqul Islam1
Institution: Department of Pharmacy, Southeast University1, Quest Bangladesh Biomedical Research Center2, Institute of Paediatric Neurodisorder and Autism (BSMMU) 3
Introduction
Background: Breast cancer remains a major health concern in Bangladesh, with chemotherapy being a cornerstone of treatment. The XRCC1 gene plays a crucial role in DNA repair, and its polymorphism (rs1799782) may influence chemotherapy response and toxicities. Genetic variations in DNA repair genes have been linked to differential treatment outcomes, making pharmacogenomic studies essential for optimizing cancer therapy. Objectives: This study aims to evaluate the impact of XRCC1 (rs1799782) polymorphism on chemotherapy response and treatment-induced toxicities in Bangladeshi breast cancer patients, providing insights into personalized treatment strategies.
Methods
A total of 400 breast cancer cases and 400 controls were included in this study. Patients undergoing chemotherapy, including cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF/CEF regimens), were genotyped for XRCC1 (rs1799782) polymorphism using the PCR-RFLP technique. Treatment responses were classified as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.
Results
The CC genotype was predominant among patients (89.75%), while CT and TT genotypes were found in 8% and 2.25%, respectively. Patients carrying the T allele (CT+TT genotypes) exhibited a significantly lower response rate to chemotherapy, with increased rates of stable and progressive disease. Furthermore, individuals with the T allele demonstrated a higher incidence of chemotherapy-induced toxicities, including anemia, neutropenia, leukopenia, and gastrointestinal complications (p < 0.05 for all comparisons). The statistical analysis indicated that the CT+TT genotypes were associated with a higher risk of chemotherapy-induced side effects, suggesting a role for XRCC1 polymorphism in influencing treatment tolerance and effectiveness.
Conclusion
XRCC1 (rs1799782) polymorphism influences chemotherapy response and toxicity in Bangladeshi breast cancer patients. The T allele is linked to reduced efficacy and increased adverse effects, highlighting the potential of XRCC1 genotyping for personalized treatment. Larger, multi-ethnic studies are needed for validation.
