<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

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.

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

Online veröffentlicht: 18. Sept. 2017

Seitenbereich: 455 - 462

Eingereicht: 14. Feb. 2017

Akzeptiert: 18. Aug. 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.

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