Background: Acute lymphoblastic leukemia (ALL) is the most prevalent pediatric malignancy. It has been linked to
different genetic variations, including those that impact the generation of reactive oxygen species. Neutrophil cytosolic
factor (NCF4) single nucleotide polymorphism (SNP) rs1883112 is one of the implicated genes that may affect
susceptibility to ALL.
Aim of the study: to evaluate the association between NCF4 rs1883112 and susceptibility to develop ALL in Egyptian
children and its correlation to clinical variables, laboratory parameters, and patient outcomes.
Patients and methods: This comparative case-control study was conducted on 100 children less than 18 years old who
were newly diagnosed with ALL, and 100 healthy controls matched in age and sex. Bone marrow aspiration was carried
out principally to permit cytological assessment, immunophenotyping, cytogenetics, molecular genetics, and other
specialized investigations. A molecular study on peripheral blood for the detection of NCF4 rs1883112 polymorphism
by real-time polymerase chain reaction (RT-PCR) was carried out.
Results: The NCF4 rs1883112 polymorphism showed a protective effect against ALL susceptibility, with the GA and
AA genotypes, dominant model, and A allele showing a lower frequency in ALL patients compared to controls (p=
0.001, 0.015, 0.001, and 0.009, respectively). AA genotype was significantly associated with a higher frequency of
t(12;21), and those achieved complete remission. There was no significant association between NCF4 (rs1883112)
genotypes and other cytogenetics or immunophenotyping. The NCF4 rs1883112 dominant genotype hazard ratio was
0.15 for overall survival and 0.24 for disease-free survival by univariate analysis; this remained significant by
multivariate analysis, suggesting that the GA/AA genotype was significantly associated with a lower risk of mortality
and disease relapse.
Conclusion: It is suggested that NCF4 rs1883112 (GA/AA genotype) has a significant protective effect against
susceptibility to ALL development, which is associated with favorable outcomes regarding overall survival and diseasefree survival |
