NDA@SZTAKI

Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma

Hegyi, MĂĄrta

Arany, Ádåm

Semsei, Ágnes F

Csordas, Katalin

Eipel, OlivĂŠr

GĂŠzsi, AndrĂĄs

Kutszegi, NĂłra

CsĂłka, Monika

MĂźller, Judit

ErdĂŠlyi, DĂĄniel

Antal, PĂŠter

Szalai, Csaba

KovĂĄcs, GĂĄbor

Impact Journals

2017

RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkolĂłgia

RJ Pediatrics / gyermekgyĂłgyĂĄszat

Inter-individual differences in toxic symptoms and pharmacokinetics of high-dose methotrexate (MTX) treatment may be caused by genetic variants in the MTX pathway. Correlations between polymorphisms and pharmacokinetic parameters and the occurrence of hepato- and myelotoxicity were studied. Single nucleotide polymorphisms (SNPs) of the ABCB1, ABCC1, ABCC2, ABCC3, ABCC10, ABCG2, GGH, SLC19A1 and NR1I2 genes were analyzed in 59 patients with osteosarcoma. Univariate association analysis and Bayesian network-based Bayesian univariate and multilevel analysis of relevance (BN-BMLA) were applied. Rare alleles of 10 SNPs of ABCB1, ABCC2, ABCC3, ABCG2 and NR1I2 genes showed a correlation with the pharmacokinetic values and univariate association analysis. The risk of toxicity was associated with five SNPs in the ABCC2 and NR1I2 genes. Pharmacokinetic parameters were associated with four SNPs of the ABCB1, ABCC3, NR1I2, and GGH genes, and toxicity was shown to be associated with ABCC1 rs246219 and ABCC2 rs717620 using the univariate and BN-BMLA method. BN-BMLA analysis detected relevant effects on the AUC0-48 in the following SNPs: ABCB1 rs928256, ABCC3 rs4793665, and GGH rs3758149. In both univariate and multivariate analyses the SNPs ABCB1 rs928256, ABCC3 rs4793665, GGH rs3758149, and NR1I2 rs3814058 SNPs were relevant. These SNPs should be considered in future dose individualization during treatment.

angol

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/54830/1/oncotarget_08_93881_u.pdf

Hegyi, Mårta and Arany, Ádåm and Semsei, Ágnes F and Csordas, Katalin and Eipel, OlivÊr and GÊzsi, Andrås and Kutszegi, Nóra and Csóka, Monika and Mßller, Judit and ErdÊlyi, Dåniel and Antal, PÊter and Szalai, Csaba and Kovåcs, Gåbor (2017) Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma. Oncotarget, 8 (6). pp. 9388-9398. ISSN 1949-2553

http://real.mtak.hu/54830/

https://doi.org/10.18632/oncotarget.11543

MTMT:3104962; doi:10.18632/oncotarget.11543