Genetic insights into acute lymphoblastic leukemia: the role of MDR1 and IL18 polymorphisms in Egyptian children

Résumé

BACKGROUND: The most prevalent cancer in pediatric is acute lymphoblastic leukemia (ALL). The multidrug resistance gene (MDR1) encodes the membrane transport protein P-glycoprotein (P-gp), which acts as an efflux pump. Interleukin 18 (IL18), an 18-kilodalton cytokine, plays a complex role in cancer, exhibiting both anti-cancer and pro-cancer properties. This study aims to investigate the association between polymorphisms in the MDR1 gene (G2677T, rs2032582) and IL18 gene variants (607C > A, rs1946518 and - 137G > C, rs187238) and their potential role in susceptibility to pediatric ALL in an Egyptian population. We hypothesize that specific polymorphisms in MDR1 and IL18 genes are significantly associated with an increased risk of developing pediatric ALL, and that these genetic variants may serve as potential biomarkers for early detection and prognosis. METHODS: MDR1 (G2677T) rs2032582, IL18 (607C > A) rs1946518, and IL18 (-137G > C) rs187238 variants were genotyped in 100 childhood ALL (58 male and 42 female) cases and 100 healthy controls (49 male and 51 female) using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique. RESULTS: The statistical analysis of the results indicated that the MDR1 (G2677T) rs2032582 genotypes (p = 0.051) and allele distribution (p = 0.217) showed no discernible variations between the controls and cases. The data indicate a strong correlation between the TT genotype and an elevated risk of ALL in both sexes. The allele frequency and genotype of IL18 (607C > A) rs1946518 exhibited a significant difference (p = 0.001) between the controls and cases. The results indicated a substantial difference in allele frequency (p = 0.0006) and genotype of the IL18 (-137G > C) polymorphism (p = 0.001) between the controls and cases. CONCLUSIONS: The results suggest that the MDR1 (G2677T) rs2032582 polymorphism may not serve as a dependable prognostic indicator of the disease. In contrast, IL18 (607C > A) rs1946518 and IL18 (-137G > C) rs187238 polymorphisms may affect susceptibility to pediatric leukemia, indicating that IL18 could be a possible biomarker for the early identification of ALL.

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