Association of TP53 polymorphic variants rs1042522 and rs1642785 with susceptibility and prognosis of acute lymphoblastic leukemia in a Brazilian Amazon population.
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BACKGROUND: Tumor suppressor genes play a central role in cancer development, and inherited genetic variation may influence both disease susceptibility and clinical outcomes. This study aimed to investigate the frequency and prognostic relevance of TP53 polymorphic variants in patients with acute lymphoblastic leukemia (ALL) from an admixed population in the Brazilian Amazon. METHODS: A population-based case–control study was conducted including 193 patients diagnosed with ALL and 215 healthy controls. Germline TP53 polymorphisms rs1042522 and rs1642785 were genotyped, and allele and genotype frequencies were compared between groups. Associations with ALL susceptibility, relapse, and mortality were evaluated using multiple genetic models adjusted for age and sex. Combined genotype and haplotype analyses were performed, and overall survival was estimated using Kaplan-Meier curves and log-rank tests. RESULTS: The CC genotype and the allele C were more frequent among ALL cases than controls. The allele C of rs1042522 (p = 0.021) and rs1642785 (p = 0.022) was associated with increased susceptibility to ALL. In addition, the allele C of rs1042522 was associated with a higher risk of relapse (p = 0.016) and death (p = 0.009). Protective effects against ALL were observed under the recessive model for rs1042522 (p = 0.019) and the codominant model for rs1642785 (p = 0.013). Both variants showed protective associations with mortality under the log-additive model. Combined genotype analysis revealed that the CG and GG genotypes of rs1042522 were associated with a reduced risk of relapse (p < 0.001). Overall survival analysis showed reduced survival associated with the CC genotype, whereas improved survival was observed for the heterozygous CG genotype. Haplotype analysis indicated that the GG haplotype was associated with a reduced risk of ALL (p = 0.007) and death (p = 0.013). CONCLUSIONS: Our findings suggest that germline TP53 variants rs1042522 and rs1642785 modulate susceptibility and clinical outcomes in ALL, supporting their potential role as prognostic biomarkers. This study highlights the importance of population-based genomic investigations in underrepresented populations.