Your browser doesn't support javascript.
loading
Pharmacogenetics of pediatric acute lymphoblastic leukemia in Uruguay: adverse events related to induction phase drugs.
Burgueño-Rodríguez, Gabriela; Méndez, Yessika; Olano, Natalia; Schelotto, Magdalena; Castillo, Luis; Soler, Ana María; da Luz, Julio.
Afiliação
  • Burgueño-Rodríguez G; Laboratorio de Genética Molecular Humana, Departamento de Ciencias Biológicas, CENUR Litoral Norte-Sede Salto, Universidad de la República, Salto, Uruguay.
  • Méndez Y; Red Latinoamericana de Implementación y Validación de Guías Clínicas Farmacogenómicas (RELIVAF-CYTED), Santiago, Chile.
  • Olano N; Servicio Hemato Oncológico Pediátrico (SHOP), Centro Hospitalario Pereira Rossell (CHPR), Montevideo, Uruguay.
  • Schelotto M; Servicio Hemato Oncológico Pediátrico (SHOP), Centro Hospitalario Pereira Rossell (CHPR), Montevideo, Uruguay.
  • Castillo L; Servicio Hemato Oncológico Pediátrico (SHOP), Centro Hospitalario Pereira Rossell (CHPR), Montevideo, Uruguay.
  • Soler AM; Servicio Hemato Oncológico Pediátrico (SHOP), Centro Hospitalario Pereira Rossell (CHPR), Montevideo, Uruguay.
  • da Luz J; Laboratorio de Genética Molecular Humana, Departamento de Ciencias Biológicas, CENUR Litoral Norte-Sede Salto, Universidad de la República, Salto, Uruguay.
Front Pharmacol ; 14: 1278769, 2023.
Article em En | MEDLINE | ID: mdl-38044950
In Uruguay, the pediatric acute lymphoblastic leukemia (ALL) cure rate is 82.2%, similar to those reported in developed countries. However, many patients suffer adverse effects that could be attributed, in part, to genetic variability. This study aims to identify genetic variants related to drugs administered during the induction phase and analyze their contribution to adverse effects, considering individual genetic ancestry. Ten polymorphisms in five genes (ABCB1, CYP3A5, CEP72, ASNS, and GRIA1) related to prednisone, vincristine, and L-asparaginase were genotyped in 200 patients. Ancestry was determined using 45 ancestry informative markers (AIMs). The sample ancestry was 69.2% European, 20.1% Native American, and 10.7% African, but with high heterogeneity. Mucositis, Cushing syndrome, and neurotoxicity were the only adverse effects linked with genetic variants and ancestry. Mucositis was significantly associated with ASNS (rs3832526; 3R/3R vs. 2R carriers; OR: = 6.88 [1.88-25.14], p = 0.004) and CYP3A5 (non-expressors vs. expressors; OR: 4.55 [1.01-20.15], p = 0.049) genes. Regarding Cushing syndrome, patients with the TA genotype (rs1049674, ASNS) had a higher risk of developing Cushing syndrome than those with the TT genotype (OR: 2.60 [1.23-5.51], p = 0.012). Neurotoxicity was significantly associated with ABCB1 (rs9282564; TC vs. TT; OR: 4.25 [1.47-12.29], p = 0.007). Moreover, patients with <20% Native American ancestry had a lower risk of developing neurotoxicity than those with ≥20% (OR: 0.312 [0.120-0.812], p = 0.017). This study shows the importance of knowing individual genetics to improve the efficacy and safety of acute lymphoblastic leukemia.
Palavras-chave
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE País/Região como assunto: America do sul / Uruguay Idioma: En Revista: Front Pharmacol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE País/Região como assunto: America do sul / Uruguay Idioma: En Revista: Front Pharmacol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Suíça