Association of CYP1A1 T3801C (rs4646903) variant with the susceptibility and progression of B-chronic lymphocytic Leukemia (B-CLL) in the Egyptian population

Menna Al-Adl; Afaf El-Said; Ahmed El-Sebaie; Sherif Refaat; Magdy M Youssef

doi:10.1016/j.gene.2023.147673

Association of CYP1A1 T3801C (rs4646903) variant with the susceptibility and progression of B-chronic lymphocytic Leukemia (B-CLL) in the Egyptian population

Gene. 2023 Oct 20:883:147673. doi: 10.1016/j.gene.2023.147673. Epub 2023 Jul 26.

Authors

Menna Al-Adl¹, Afaf El-Said², Ahmed El-Sebaie³, Sherif Refaat⁴, Magdy M Youssef⁵

Affiliations

¹ Division of Biochemistry, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt. Electronic address: mennasalah1992@yahoo.com.
² Genetics Department, Mansoura Children's Hospital, Mansoura, Egypt.
³ Hematology Unit, Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁴ Medical Oncology Unit, Oncology Center Mansoura University, Mansoura, Egypt.
⁵ Division of Biochemistry, Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt.

PMID: 37506988
DOI: 10.1016/j.gene.2023.147673

Abstract

Background: The frequency of hematological malignancies is increasing universally, and over the last few decades, a significant increase in the incidence of B-chronic lymphocytic leukemia (B-CLL) has been observed. Many studies have revealed the involvement of genetic predisposition along with environmental exposure to genotoxic xenobiotics in the leukemogenesis process of B-CLL. CYP1A1 is a vital member of the cytochromes P450 (CYPs) superfamily, which is involved in pro-carcinogens activation into reactive intermediates during phase I xenobiotic biotransformation.

Aim: This study aimed to determine the possible role of the CYP1A1*2A (T3801C, rs4646903) single nucleotide polymorphism (SNP) as a risk factor for developing B-CLL, as well as the impact of this SNP on the disease progression and the clinical outcome.

Patients and methods: The study was conducted on 100 patients newly diagnosed with B-CLL, and 100 healthy individuals with matched ages and sex, served as the control group. CYP1A1 (T3801C) genotyping of all patient and control samples was performed using the PCR-based Restriction Fragment Length Polymorphism (RFLP-PCR) method. In addition, serum levels of both IL-6 and TNF-α were estimated by the ELISA technique.

Results: Higher frequencies of the heterozygous carrier (TC) and homozygous variant (CC) genotypes of the CYP1A1 (T3801C) variant were observed in B-CLL patients compared to the controls (P < 0.001 for both). The frequencies of the CYP1A1 (T3801C) variant indicated a significant elevated risk of B-CLL under various genetic models, including allelic (OR = 8.8, P < 0.001) and dominant (OR = 9.3, P < 0.001) models. In addition, the median IL-6 level was significantly higher in patients with (TC) and (CC) genotypes than in patients with (TT) genotype (P = 0.001 and P < 0.001, respectively). Also, the median TNF-α level was significantly higher in patients with (TC) and (CC) genotypes than in patients with (TT) genotype (P < 0.001 for both).

Conclusion: Our results showed that the CYP1A1*2A (T3801C, rs4646903) SNP increases the susceptibility to B-CLL incidence and is associated with poor disease progression.

Keywords: B-CLL; CYP1A1; Cytochromes P450; Leukemia; SNP; Xenobiotics.

MeSH terms

Case-Control Studies
Cytochrome P-450 CYP1A1 / genetics
Disease Progression
Egypt
Genetic Predisposition to Disease
Genotype
Humans
Interleukin-6 / genetics
Leukemia, Lymphocytic, Chronic, B-Cell* / genetics
Polymorphism, Single Nucleotide
Tumor Necrosis Factor-alpha / genetics

Substances

Cytochrome P-450 CYP1A1
Interleukin-6
Tumor Necrosis Factor-alpha
CYP1A1 protein, human