title: MTHFR 677 (C-->T) polymorphism is not relevant for prognosis or therapy-associated toxicity in pediatric NHL: results from 484 patients of multicenter trial NHL-BFM 95.
abstract: We analyzed the relationship of genetic variation within the methylenetetrahydrofolate reductase gene (MTHFR 677 C-->T) with clinical characteristics, outcome, and therapy-related toxicity in pediatric non-Hodgkin's lymphoma (NHL) in our multicenter trial NHL-BFM 95. In this trial, high-dose methotrexate (MTX) infusion regimens were randomized (4- vs 24-h infusion) in patients with B-cell lymphoma; MTX was applied as 24-h infusion in all patients with lymphoblastic lymphoma and anaplastic large cell lymphoma. Toxicity data were collected per patient and therapy course according to National Cancer Institute Common Toxicity Criteria (NCI-CTC). The genotypes in 484 pediatric patients were distributed as follows: MTHFR 677 CC, 206 patients (42.6%); MTHFR 677 CT, 214 patients (44.2%); and MTHFR 677 TT, 64 patients (13.2%). Lymphoblastic lymphoma was significantly associated with homozygosity for the MTHFR 677 T allele. No association of MTHFR 677 genotype with clinical characteristics (sex, age, and tumor stage), outcome, or therapy-related toxicity could be detected. Therefore, we conclude that the MTHFR 677 C-->T polymorphism does not appear to influence outcome or therapy-associated toxicity in pediatric patients with NHL treated on BFM protocols.
authors.affiliation: Department of Pediatric Hematology and Oncology, Hannover Medical School, Carl-Neuberg-Str 1, D-30625, Hannover, Germany. kseidemann@web.de
authors.forename: Kathrin
authors.initials: K
authors.lastname: Seidemann
authors.forename: Marion
authors.initials: M
authors.lastname: Book
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Ulrike
authors.initials: U
authors.lastname: Meyer
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000483:Alleles; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D012189:Retrospective Studies; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate