Tumor necrosis factor-α (TNF-α) −308 G/A and lymphotoxin-α (LT-α) +252 A/G genetic polymorphisms in Egyptian acute lymphoblastic leukemia

Abstract

Acute lymphoblastic leukemia (ALL) is one of the most hematological malignancies of lymphoid origin. It has been proposed that deregulation of cytokines could be linked with pathogenesis, progression, and survival in many diseases. Genetic polymorphisms in two important cytokines like tumor necrosis factor-α (TNF-α) −308 and lymphotoxin-α (LT-α) +252 can disturb both their transcription and expression and lead to their high plasma levels. A difference in the occurrence of the polymorphisms in TNF-α −308 G/A and LT-α +252 A/G in ALL cases among several populations with different ethnicities was observed. The study investigated the occurrence and the role of polymorphisms of tumor necrosis factor genes including TNF-α −308 G>A and LT-α +252 A>G in the development of ALL in Egypt. A case-control study was done on 126 newly diagnosed ALL patients (96 pediatric and 30 adult patients); 130 healthy subjects composed the control group. Polymorphism variants of TNF-α and LT-α genes were studied by PCR-RFLP on genomic DNA of all studied individuals. TNF-α −308 G/A polymorphism was statistically significant in ALL pediatric patients (P value = 0.008) with no association with ALL adult patients. TNF AA homozygous variant genotype and the A allele both showed significant risks of the development of pediatric ALL. However, there was no association between LT-α +252 A/G polymorphism in both pediatric and adult ALL. The results show that TNF AA homozygous variant genotype and A allele showed a significant risk of development of pediatric ALL.