Genetic variations in NFKB1 signaling molecules: implications for acute lymphoblastic leukemia in Saudi Arabia

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling regulates immune responses and tumorigenesis. Variations in NF-κB pathway genes may alter susceptibility to acute lymphoblastic leukemia (ALL). To evaluate associations between selected NFKB1 and NFKBIA polymorphisms and ALL risk in a Saudi population. We genotyped NFKB1 (rs93059, rs1287, rs1801) and NFKBIA (rs1050851, rs1957106, rs3138054) in 150 ALL patients and 115 matched controls using TaqMan® assays. Associations were assessed under multiple genetic models, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The NFKB1 rs93059 A allele was associated with reduced ALL risk (OR = 0.68; 95% CI: 0.48-0.97; p = 0.03), with the AA genotype showing protection in codominant (p = 0.03) and recessive (p = 0.02) models. For NFKB1 rs1287, the AA genotype increased risk (OR = 2.75; 95% CI: 1.14-6.62; p = 0.02) in the codominant model. The NFKB1 rs1801 C allele was enriched in patients (OR = 1.54; 95% CI: 1.04-2.23; p = 0.01). No significant associations were observed for NFKBIA variants after multiple-testing correction. NFKB1 rs93059 and rs1801 may influence ALL susceptibility in the Saudi population, underscoring the potential contribution of NF-κB pathway variants to leukemia risk. Functional analyses are warranted to clarify underlying mechanisms.