title: 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.
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.
authors.affiliation: Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wray
authors.forename: Marijana
authors.initials: M
authors.lastname: Vujkovic
authors.forename: Thomas
authors.initials: T
authors.lastname: McWilliams
authors.forename: Shannon
authors.initials: S
authors.lastname: Cannon
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Linda
authors.initials: L
authors.lastname: Stork
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013866:Thioguanine / Q000009:adverse effects*
chemical_list: D000964:Antimetabolites, Antineoplastic; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine
keywords: MTHFR; SOS; TPMT; acute lymphoblastic leukemia; thioguanine; toxicity
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