Open Access

ARTICLE

The role of polymorphic cytochrome P450 gene (CYP2B6) in B-chronic lymphocytic leukemia (B-CLL) incidence and outcome among Egyptian patients

by MENNA AL-ADL^1,*, MAGDY M. YOUSSEF¹, AHMED EL-SEBAIE², SHERIF REFAAT³, AFAF EL-SAID⁴

1 Division of Biochemistry, Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, 35511, Egypt
2 Hematology Unit, Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, 35511, Egypt
3 Medical Oncology Unit, Oncology Center Mansoura University, Mansoura, 35511, Egypt
4 Department of Genetics, Mansoura University Children’s Hospital, Mansoura, 35511, Egypt

* Corresponding Author: MENNA AL-ADL. Email:

Oncology Research 2024, 32(4), 785-797. https://doi.org/10.32604/or.2024.047021

Received 22 October 2023; Accepted 17 January 2024; Issue published 20 March 2024

Abstract

Cytochromes P450 (CYPs) play a prominent role in catalyzing phase I xenobiotic biotransformation and account for about 75% of the total metabolism of commercially available drugs, including chemotherapeutics. The gene expression and enzyme activity of CYPs are variable between individuals, which subsequently leads to different patterns of susceptibility to carcinogenesis by genotoxic xenobiotics, as well as differences in the efficacy and toxicity of clinically used drugs. This research aimed to examine the presence of the CYP2B6*9 polymorphism and its possible association with the incidence of B-CLL in Egyptian patients, as well as the clinical outcome after receiving cyclophosphamide chemotherapy. DNA was isolated from whole blood samples of 100 de novo B-CLL cases and also from 100 sex- and age-matched healthy individuals. The presence of the CYP2B6*9 (G516T) polymorphism was examined by PCR-based allele specific amplification (ASA). Patients were further indicated for receiving chemotherapy, and then they were followed up. The CYP2B6*9 variant indicated a statistically significant higher risk of B-CLL under different genetic models, comprising allelic (T-allele vs. G-allele, OR = 4.8, p < 0.001) and dominant (GT + TT vs. GG, OR = 5.4, p < 0.001) models. Following cyclophosphamide chemotherapy, we found that the patients with variant genotypes (GT + TT) were less likely to achieve remission compared to those with the wild-type genotype (GG), with a response percentage of (37.5% vs. 83%, respectively). In conclusion, our findings showed that the CYP2B6*9 (G516T) polymorphism is associated with B-CLL susceptibility among Egyptian patients. This variant greatly affected the clinical outcome and can serve as a good therapeutic marker in predicting response to cyclophosphamide treatment.

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