Insights from Tissue Inhibitor of Metalloproteinase-2 Genotypes to Decipher the Genetic Architecture of Childhood Acute Lymphocytic Leukemia Risk.

BACKGROUND/AIM: Acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic malignancy, particularly affecting children aged 2~5 years. Tissue inhibitor of metalloproteinase-2 (TIMP-2), a key regulator of MMP-2 activity, has been implicated in several cancers, yet its genetic role in childhood ALL remains unexplored.

MATERIALS AND METHODS

This study investigated four polymorphic genotypes, rs8179090, rs4789936, rs2009196, and rs7342880, in 266 Taiwanese children with ALL and 266 matched controls using polymerase chain reaction-restriction fragment length polymorphism methodology.

RESULTS

rs8179090 exhibited a significant association with ALL risk. Individuals with the CC genotype had a markedly increased risk [odds ratio (OR)=4.01, 95% confidence interval (CI)=1.46-11.04, =0.0076], particularly under a recessive model (OR=3.79, 95%CI=1.39-10.36, =0.0105). The C allele frequency was also elevated in cases (20.7%) controls (14.5%) (=0.0100). Stratified analysis showed stronger risk association in children aged ≤3.5 years (CC genotype: OR=5.06, =0.0084) and in boys (CC genotype: OR=5.53, =0.0046). Moreover, CG+CC genotypes were associated with higher clinical risk classification (OR=2.25, =0.0031) and shorter survival (<5 years) (OR=3.68, =0.0003), though no correlation was found with immunophenotypic subtypes. No significant associations were identified for rs4789936, rs2009196, or rs7342880.

CONCLUSION

rs8179090, particularly the CC genotype, may serve as a novel biomarker for childhood ALL susceptibility and prognosis, especially in younger and male patients. Genotyping of this polymorphism could support early risk assessment and personalized clinical management in childhood ALL.