Association of Tissue Inhibitor of Metalloproteinase 1 rs4898 With Susceptibility to Childhood Acute Lymphoblastic Leukemia in Taiwanese Females

Background/Aim: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, and identification of genetic determinants of disease susceptibility may improve understanding of disease susceptibility and facilitate genetic risk assessment. Tissue inhibitor of metalloproteinase 1 (TIMP1) is a multifunctional regulator of extracellular matrix remodeling, proliferation, and apoptosis. However, the contribution of TIMP1 polymorphisms to childhood ALL susceptibility remains poorly investigated. This study aimed to evaluate whether TIMP1 genetic variants are associated with female childhood ALL risk. Materials and Methods: The study included 118 female childhood ALL patients and 118 age-matched healthy controls from Taiwan. TIMP1 polymorphisms, rs4898, rs6609533, and rs2070584, were genotyped. Genotypic distributions and their associations with ALL risk were evaluated using odds ratios (ORs), 95% confidence intervals (CIs), and p-Values. Results: A significant association was observed between TIMP1 rs4898 and ALL risk (p for trend=0.0024). Compared with the TT reference genotype, the TIMP1 rs4898 CT and CC genotypes exhibited ORs of 1.85 (95%CI=0.97-3.54, p=0.0864) and 2.96 (95%CI=1.46-6.01, p=0.0041), respectively. In the recessive model, TIMP1 rs4898 CC carriers had an OR of 2.04 (95% CI=1.13-3.54, p=0.0232), while the dominant model yielded an OR of 2.24 (95%CI=1.23-4.08, p=0.0119). On the contrary, rs6609533 and rs2070584 showed no significant associations in any model (all p>0.05). Allelic distribution pattern analyses also confirmed the presence of significant differences for TIMP1 rs4898 between the case and control groups (OR=1.82, 95%CI=1.26-2.62, p=0.0017). Conclusion: These findings indicate that TIMP1 rs4898 was associated with childhood ALL susceptibility among Taiwanese females in this cohort. No statistically significant association was observed for rs6609533 or rs2070584. Larger multicenter studies incorporating functional and transcriptomic analyses are warranted to validate these associations and clarify the biological mechanisms underlying TIMP1-related leukemogenesis.