TPMT and MTHFR genotype is not associated with altered risk of thioguanine-related sinusoidal obstruction syndrome in pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group.

TitleTPMT and MTHFR genotype is not associated with altered risk of thioguanine-related sinusoidal obstruction syndrome in pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group.
Publication TypeJournal Article
Year of Publication2014
AuthorsWray L, Vujkovic M, McWilliams T, Cannon S, Devidas M, Stork L, Aplenc R
JournalPediatr Blood Cancer
Volume61
Issue11
Pagination2086-8
Date Published2014 Nov
ISSN1545-5017
KeywordsAntimetabolites, Antineoplastic, Child, Child, Preschool, Female, Genotype, Hepatic Veno-Occlusive Disease, Humans, Infant, Male, Methylenetetrahydrofolate Reductase (NADPH2), Methyltransferases, Polymorphism, Single Nucleotide, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Thioguanine
Abstract

Sinusoidal obstruction syndrome is a complication of therapy for pediatric ALL and may be modified by thiopurine methyltransferase activity as well as by MTHFR genotype. We assessed TPMT *3A, *3B, *3C, and MTHFR C677T and A1298C germline genetic polymorphisms among 351 patients enrolled in the thioguanine treatment arm of CCG-1952 clinical trial. TPMT and MTHFR C677T genotypes were not associated with SOS risk. The combination of MTHFR and TPMT variant genotypes was not associated with SOS risk. These suggest that germline genetic variation in TPMT and MTHFR do not significantly alter SOS risk in patients exposed to thioguanine.

DOI10.1002/pbc.25057
Alternate JournalPediatr Blood Cancer
PubMed ID24737678
PubMed Central IDPMC4283196
Grant ListR01CA108862 / CA / NCI NIH HHS / United States
R01CA133881 / CA / NCI NIH HHS / United States
U10 CA098413 / CA / NCI NIH HHS / United States
U10 CA098543 / CA / NCI NIH HHS / United States
U10 CA180886 / CA / NCI NIH HHS / United States
U10 CA180899 / CA / NCI NIH HHS / United States