The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia

MTHFR is a crucial enzyme in folate metabolism. This study aimed to determine the relationship between MTHFR genetic polymorphism and elimination and toxicities of methotrexate (MTX). To do that, the study enrolled 145 patients diagnosed with acute lymphoblastic leukemia, who received chemotherapy f...

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Autores principales:	Shen Yaqing, Wang Zhujun, Zhou Fen, Jin Runming
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	single nucleotide polymorphism cccg-all-2015 anticancer drug drug toxicity Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c45ec09fdb0f4442a7985f19c4fda67e
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spelling	oai:doaj.org-article:c45ec09fdb0f4442a7985f19c4fda67e2021-12-05T14:10:42ZThe influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia2391-541210.1515/biol-2021-0121https://doaj.org/article/c45ec09fdb0f4442a7985f19c4fda67e2021-11-01T00:00:00Zhttps://doi.org/10.1515/biol-2021-0121https://doaj.org/toc/2391-5412MTHFR is a crucial enzyme in folate metabolism. This study aimed to determine the relationship between MTHFR genetic polymorphism and elimination and toxicities of methotrexate (MTX). To do that, the study enrolled 145 patients diagnosed with acute lymphoblastic leukemia, who received chemotherapy following the Chinese Children’s Cancer Group Acute Lymphoblastic Leukemia (CCCG-ALL)-2015 protocol (clinical trial number: ChiCTR-IPR-14005706). We analyzed the effects of MTHFR C677T and A1298C polymorphisms on MTX elimination and toxicities. Patients with the MTHFR C677T TT genotype could tolerate a significantly higher MTX dose than those with the CC/CT genotype. However, patients with C677T TT genotypes had an increased risk of hypokalemia (1.369 to CC and 1.409 to CT types). The MTX infusion rate in patients with the MTHFR A1298C AC genotype was slightly lower than that in those with CC or AA genotypes. Patients with the A1298C AA genotype had a 1.405-fold higher risk of hepatotoxicity than those with the AC genotype (P > 0.05). There was no significant difference between the prevalence of other toxicities among MTHFR C677T or A1298C genotypes (P > 0.05). Neither MTHFR C677T nor A1298C polymorphisms were significantly associated with delayed MTX clearance. To conclude, MTHFR polymorphisms were not good predictors of MTX-related toxicities.Shen YaqingWang ZhujunZhou FenJin RunmingDe Gruyterarticlesingle nucleotide polymorphismcccg-all-2015anticancer drugdrug toxicityBiology (General)QH301-705.5ENOpen Life Sciences, Vol 16, Iss 1, Pp 1203-1212 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	single nucleotide polymorphism cccg-all-2015 anticancer drug drug toxicity Biology (General) QH301-705.5
spellingShingle	single nucleotide polymorphism cccg-all-2015 anticancer drug drug toxicity Biology (General) QH301-705.5 Shen Yaqing Wang Zhujun Zhou Fen Jin Runming The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
description	MTHFR is a crucial enzyme in folate metabolism. This study aimed to determine the relationship between MTHFR genetic polymorphism and elimination and toxicities of methotrexate (MTX). To do that, the study enrolled 145 patients diagnosed with acute lymphoblastic leukemia, who received chemotherapy following the Chinese Children’s Cancer Group Acute Lymphoblastic Leukemia (CCCG-ALL)-2015 protocol (clinical trial number: ChiCTR-IPR-14005706). We analyzed the effects of MTHFR C677T and A1298C polymorphisms on MTX elimination and toxicities. Patients with the MTHFR C677T TT genotype could tolerate a significantly higher MTX dose than those with the CC/CT genotype. However, patients with C677T TT genotypes had an increased risk of hypokalemia (1.369 to CC and 1.409 to CT types). The MTX infusion rate in patients with the MTHFR A1298C AC genotype was slightly lower than that in those with CC or AA genotypes. Patients with the A1298C AA genotype had a 1.405-fold higher risk of hepatotoxicity than those with the AC genotype (P > 0.05). There was no significant difference between the prevalence of other toxicities among MTHFR C677T or A1298C genotypes (P > 0.05). Neither MTHFR C677T nor A1298C polymorphisms were significantly associated with delayed MTX clearance. To conclude, MTHFR polymorphisms were not good predictors of MTX-related toxicities.
format	article
author	Shen Yaqing Wang Zhujun Zhou Fen Jin Runming
author_facet	Shen Yaqing Wang Zhujun Zhou Fen Jin Runming
author_sort	Shen Yaqing
title	The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
title_short	The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
title_full	The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
title_fullStr	The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
title_full_unstemmed	The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
title_sort	influence of mthfr genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/c45ec09fdb0f4442a7985f19c4fda67e
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The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia

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