Influence of variants of the drosha, mir499a, and mir938 genes on susceptibility to acute lymphoblastic leukemia in an admixed population from the brazilian amazon.

ABSTRACT

Acute Lymphoblastic Leukemia (ALL) is the most common type of cancer in children. Polymorphisms that alter the normal function of the microRNAs involved in the development of ALL have been widely investigated, although published data on these polymorphisms in admixed populations are scarce. We investigated the role of 10 polymorphisms in the microRNA and protein-coding genes of the microRNA synthesis complex in susceptibility to pediatric B-cell ALL. The study includes 100 pediatric ALL patients and 180 healthy individuals. The statistical analyses were run in SPSS v.25.0. In the case of the microRNA synthesizing genes, a significant pattern was found in only gene, that is, the rs3805500 polymorphism of DROSHA, in which the homozygous mutant (AA) genotype was associated with a threefold increase in the risk of developing ALL when compared to other genotypes (P=0.004, OR=2.913, CI=1.415-5.998). In the microRNA coding genes, the homozygous mutant rs3746444 genotype of the MIR499A gene was associated with a 17-fold increase in the risk of development of ALL (P<0.001, OR=17.797, CI=5.55-57.016). A protective effect against the development of ALL was also observed in the carriers of the wild homozygous rs2505901 genotype in the MIR938 gene. Our findings highlight the potential of these polymorphisms in the genes involving in the coding of microRNAs for the evaluation of the risk of contracting ALL in the population of the Brazilian Amazon region. These findings contribute to a more complete understanding of the complex etiology of ALL.