The Genetic Role of Matrix Metalloproteinase-12 in Determining Childhood Acute Lymphocytic Leukemia Risk.
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BACKGROUND/AIM: Childhood acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy among children, yet its molecular etiology remains largely unclear. Matrix metalloproteinase-12 (MMP-12), although less studied than other MMPs, has emerged as a potential player in tumor progression. This study aimed to explore the association of two MMP-12 polymorphisms (rs2276109 and rs652438) with childhood ALL risk and prognosis in a Taiwanese pediatric population. PATIENTS AND METHODS: A total of 266 childhood patients with ALL and 266 age- and sex-matched cancer-free controls were genotyped for MMP-12 rs2276109 and rs652438. Genotypic and allelic distributions were compared, and associations with clinical features were assessed. RESULTS: Neither rs2276109 nor rs652438 was significantly associated with childhood ALL susceptibility. For rs2276109, individuals with AG [odds ratio (OR)=0.84, 95% confidence interval (CI)=0.47-1.50, p=0.6557] or GG genotypes (OR=0.98, 95%CI=0.06-15.82, p=1.0000) had no increased risk compared to AA. Similarly, no significant association was found under dominant or recessive models (dominant: OR=0.84, 95%CI=0.47-1.50, p=0.6614; recessive: OR=1.00, 95%CI=0.06-16.07, p=1.0000). For rs652438, the variant G allele showed no significant risk (OR=1.12, 95%CI=0.76-1.64, p=0.6254). However, rs652438 AG+GG genotypes were significantly correlated with aggressive risk classification (OR=2.17, 95%CI=1.30-3.61, p=0.0040) and shorter survival (<5 years; OR=2.52, 95%CI=1.31-4.84, p=0.0073). CONCLUSION: While MMP-12 rs2276109 and rs652438 polymorphisms do not appear to affect susceptibility to childhood ALL, rs652438 variant genotypes may serve as prognostic biomarkers for disease severity and outcome. Further functional validation and multicenter studies are warranted to confirm these findings and assess their clinical utility in childhood ALL risk stratification.