ARID5B , IKZF1 , GATA3 , CEBPE , and CDKN2A germline polymorphisms and predisposition to childhood acute lymphoblastic leukemia

• Published in: Pediatric hematology and oncology Vol. 41; no. 2; pp. 103 - 11
• Main Authors: Al-Zayan, Nermeen R, Ashour, Mohammed J, Abuwarda, Hadeer N, Sharif, Fadel A
• Format: Journal Article
• Language: English
• Published: England 2024
• Subjects: Case-Control Studies; CCAAT-Enhancer-Binding Proteins - genetics; Child; Cyclin-Dependent Kinase Inhibitor p16; DNA-Binding Proteins - genetics; GATA3 Transcription Factor - genetics; Genetic Predisposition to Disease; Genotype; Germ Cells; Humans; Ikaros Transcription Factor - genetics; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Transcription Factors - genetics; Acute lymphoblastic leukemia; CDKN2A; CEBPE; multifactor dimensionality reduction (MDR); ARID5B; GATA3; IKZF1
• ISSN: 0888-0018; 1521-0669
• DOI: 10.1080/08880018.2023.2234946

Acute lymphoblastic leukemia (ALL) is the most frequent type of pediatric cancer. Germline single nucleotide polymorphisms (SNPs), including
(rs10821936 T/C),
(rs4132601 T/G),
(rs3824662 G/T),
(rs2239633 G/A), and
(rs3731217 A/C) have been linked to pediatric ALL in different populations. Hitherto, no previous studies have tested the relationship between these SNPs and pediatric ALL in Gaza strip. Therefore, we investigated the association between these polymorphisms and the occurrence of childhood ALL in this part of Palestine. This case-control study recruited 100 healthy controls and 78 ALL patients. Allele-specific PCR (AS-PCR) technique was used for SNPs genotyping. Relevant statistical tests were used and the multifactor dimensionality reduction (MDR) approach was applied in the analysis of gene-gene interactions. Minor alleles of
rs10821936 T/C (
 = 0.007) and
rs4132601 T/G (
 = 0.045) were significantly higher in ALL patients. The homozygous (TT) genotype of
rs3824662 G/T (
 = 0.038), (CC) of
rs10821936 T/C (
 = 0.008), and (AC and CC) genotypes of
rs3731217 A/C (
 < 0.0001) were significantly higher in ALL cases. On MDR analysis, the best model for ALL risk was the five-factor model combination of the examined SNPs (CVC = 10/10; TBA = 0.632;
 < 0.0001). This work demonstrates the association of
rs10821936 T/C,
rs4132601 T/G,
rs3824662 G/T, and
rs3731217 A/C polymorphisms with increased risk of pediatric ALL among a patient cohort from Gaza Strip. Further studies with a larger sample size are needed in order to confirm these findings and test the value of these SNPs in prognosis and treatment sensitivity.