<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_raon-2017-0040_s_023_w2aab3b7b4b1b6b1aab1c19b1Aa"><h3>Background</h3><p>We investigated the clinical relevance of <italic>SLC 19A1</italic> 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).</p></sec><sec id="j_raon-2017-0040_s_024_w2aab3b7b4b1b6b1aab1c19b2Aa"><h3>Patients and methods</h3><p>Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of <italic>SLC 19A1</italic> single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities.</p></sec><sec id="j_raon-2017-0040_s_025_w2aab3b7b4b1b6b1aab1c19b3Aa"><h3>Results</h3><p>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 &lt; 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).</p></sec><sec id="j_raon-2017-0040_s_026_w2aab3b7b4b1b6b1aab1c19b4Aa"><h3>Conclusions</h3><p><italic>SLC 19A1</italic> 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.</p></sec></abstract>

BackgroundWe 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 methodsEighty-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.ResultsPatients 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).ConclusionsSLC 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.

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

Hereditary Endocrine Cancer Group Human Cancer Genetics Programme

Radiology and Oncology

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

BackgroundWe investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and...

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

Article Category: Research Article

Pubblicato online: 18 set 2017

Pagine: 455 - 462

Ricevuto: 14 feb 2017

Accettato: 18 ago 2017

DOI: https://doi.org/10.1515/raon-2017-0040

© 2017 Barbara Faganel Kotnik, Janez Jazbec, Petra Bohanec Grabar, Cristina Rodriguez-Antona, Vita Dolzan

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.