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Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies

Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chine...

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Autores principales: Han, Jian, Liu, Lu, Meng, Li, Guo, Huan, Zhang, Jin, Han, Zhi-Qiang, Hong, Zhen-Ya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739189/
https://www.ncbi.nlm.nih.gov/pubmed/35004279
http://dx.doi.org/10.3389/fonc.2021.759805
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author Han, Jian
Liu, Lu
Meng, Li
Guo, Huan
Zhang, Jin
Han, Zhi-Qiang
Hong, Zhen-Ya
author_facet Han, Jian
Liu, Lu
Meng, Li
Guo, Huan
Zhang, Jin
Han, Zhi-Qiang
Hong, Zhen-Ya
author_sort Han, Jian
collection PubMed
description Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chinese patients diagnosed with hematological malignancies. Patients were genotyped for MTHFR rs1801131, MTHFR rs1801133, and ABCB1 rs1045642 by fluorescence in situ hybridization. Patients with MTHFR rs1801133T allele had a significantly higher risk of hematopoietic toxicity compared with those with CC genotype (p=0.003). With respect to MTHFR rs1801131, patients with CC and AC genotypes had significantly lower frequency of hematopoietic toxicity than patients with AA genotype (p=0.044). In conclusion, we identified an important influence of the SNPs of ABCB1 and MTHFR on MTX-related hematopoietic toxicity in adults with hematological malignancies. To optimize high-dose (HD)-MTX therapy and reduce related hematopoietic toxicity, it is necessary to detect the SNPs of MTHFR and ABCB1 before initiating HD-MTX and deciding the optimal dose of MTX and duration of leucovorin rescue, according to genetic tests and disease type in adults with hematological malignancies.
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spelling pubmed-87391892022-01-08 Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies Han, Jian Liu, Lu Meng, Li Guo, Huan Zhang, Jin Han, Zhi-Qiang Hong, Zhen-Ya Front Oncol Oncology Study of the association between single nucleotide polymorphisms (SNPs) of methotrexate (MTX) pathway genes and MTX-related toxicity in the treatment of hematological malignancies is popular. Here, we studied the association between SNPs of MTHFR and ABCB1 and MTX-related toxicity in 157 adult Chinese patients diagnosed with hematological malignancies. Patients were genotyped for MTHFR rs1801131, MTHFR rs1801133, and ABCB1 rs1045642 by fluorescence in situ hybridization. Patients with MTHFR rs1801133T allele had a significantly higher risk of hematopoietic toxicity compared with those with CC genotype (p=0.003). With respect to MTHFR rs1801131, patients with CC and AC genotypes had significantly lower frequency of hematopoietic toxicity than patients with AA genotype (p=0.044). In conclusion, we identified an important influence of the SNPs of ABCB1 and MTHFR on MTX-related hematopoietic toxicity in adults with hematological malignancies. To optimize high-dose (HD)-MTX therapy and reduce related hematopoietic toxicity, it is necessary to detect the SNPs of MTHFR and ABCB1 before initiating HD-MTX and deciding the optimal dose of MTX and duration of leucovorin rescue, according to genetic tests and disease type in adults with hematological malignancies. Frontiers Media S.A. 2021-12-24 /pmc/articles/PMC8739189/ /pubmed/35004279 http://dx.doi.org/10.3389/fonc.2021.759805 Text en Copyright © 2021 Han, Liu, Meng, Guo, Zhang, Han and Hong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Han, Jian
Liu, Lu
Meng, Li
Guo, Huan
Zhang, Jin
Han, Zhi-Qiang
Hong, Zhen-Ya
Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies
title Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies
title_full Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies
title_fullStr Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies
title_full_unstemmed Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies
title_short Effect of Polymorphisms of ABCB1 and MTHFR on Methotrexate-Related Toxicities in Adults With Hematological Malignancies
title_sort effect of polymorphisms of abcb1 and mthfr on methotrexate-related toxicities in adults with hematological malignancies
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739189/
https://www.ncbi.nlm.nih.gov/pubmed/35004279
http://dx.doi.org/10.3389/fonc.2021.759805
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