Association between SLC19A1 gene polymorphism and high dose methotrexate toxicity in childhood acute lymphoblastic leukaemia and non Hodgkin malignant lymphoma: introducing a haplotype based approach

Author:

Kotnik Barbara Faganel1,Jazbec Janez1,Grabar Petra Bohanec2,Rodriguez-Antona Cristina3,Dolzan Vita2

Affiliation:

1. Department of Oncology and Haematology , University Children’s Hospital , University Medical Centre Ljubljana , Ljubljana , Slovenia

2. Pharmacogenetics Laboratory , Institute of Biochemistry , Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia

3. Hereditary Endocrine Cancer Group Human Cancer Genetics Programme , Spanish National Cancer Research Centre , Madrid , Spain

Abstract

Abstract Background We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0.226 (0.071–0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly reduced the risk for the occurrence of adverse events during treatment with HD-MTX (OR 0.143 (0.023–0.852), p = 0.030). Conclusions SLC 19A1 SNP and haplotype analysis could provide additional information in a personalized HD-MTX therapy for children with ALL/NHML in order to achieve better treatment outcome. However further studies are needed to validate the results.

Publisher

Walter de Gruyter GmbH

Subject

Radiology Nuclear Medicine and imaging,Oncology

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