Pharmacogenomics and variations in the risk of toxicity during the consolidation/maintenance phases of the treatment of pediatric B-cell leukemia patients from an admixed population in the Brazilian Amazon

Leuk Res. 2018 Nov:74:10-13. doi: 10.1016/j.leukres.2018.09.003. Epub 2018 Sep 15.

Abstract

The treatment of Acute Lymphoblastic Leukemia (ALL) in children has a high clinical success rate, although toxicological complications are frequent, and often result in the interruption of the treatment. Various studies have shown that toxicities resulting from the treatment are influenced by pharmacogenetic variants. Most of this research has focused on relatively homogeneous populations, and the influence of these variants in highly admixed populations, such as that of Brazil, is still poorly understood. The present study investigated the association between pharmacogenetic variants and severe toxicities in pediatric B-cell ALL patients from an admixed population of the Brazilian Amazon. The rs2306283 (of SLCO1B1) mutant allele increased the risk of neurotoxicity threefold, and the homozygous mutant rs9895420 (of ABCC3) genotype was associated with a fivefold increase in protection against severe gastrointestinal toxicity. This indicates that the rs2306283 and rs9895420 polymorphisms may be relevant to the prediction of severe toxicity in pediatric ALL patients.

Keywords: ABCC3; ALL; Pediatrics; Pharmacogenetics; SLCO1B1.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Brazil
  • Child
  • Child, Preschool
  • Consolidation Chemotherapy*
  • Female
  • Humans
  • Infant
  • Liver-Specific Organic Anion Transporter 1 / genetics*
  • Male
  • Multidrug Resistance-Associated Proteins / genetics*
  • Mutation*
  • Pharmacogenomic Testing*
  • Polymorphism, Genetic*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*

Substances

  • Antineoplastic Agents
  • Liver-Specific Organic Anion Transporter 1
  • Multidrug Resistance-Associated Proteins
  • SLCO1B1 protein, human
  • multidrug resistance-associated protein 3