No evidence of association of methylenetetrahydrofolate reductase polymorphism with occurrence of second neoplasms after treatment of childhood leukemia

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been associated not only with the risk for acute lymphoblastic leukemia (ALL) in adults and children, but also with increased methotrexate toxicity. The present study aimed to investigate whether MTHFR polymorphisms modify the risk for d...

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Bibliographic Details
Published in:Leukemia & lymphoma 2005-06, Vol.46 (6), p.893-897
Main Authors: Jazbec, Janez, Kitanovski, Lidija, Aplenc, Richard, Debeljak, Maruša, Dol an, Vita
Format: Article
Language:English
Subjects:
Adolescent
Alleles
Antineoplastic Agents - adverse effects
Child
childhood leukemia
Female
Genetic Predisposition to Disease
Genotype
Humans
Infant
Leukemia - complications
Leukemia - drug therapy
Leukemia - pathology
Male
Methotrexate - adverse effects
methylenetetrahydrofolate reductase
Methylenetetrahydrofolate Reductase (NADPH2) - genetics
Neoplasms, Second Primary - etiology
Odds Ratio
Polymorphism, Genetic
Risk
secondary neoplasm
Sequence Analysis, DNA
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Summary:Methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been associated not only with the risk for acute lymphoblastic leukemia (ALL) in adults and children, but also with increased methotrexate toxicity. The present study aimed to investigate whether MTHFR polymorphisms modify the risk for development of secondary malignancies in children treated for ALL with protocols that included high-dose methotrexate. MTHFR genotypes were determined in DNA samples isolated from archived bone marrow smears of 15 patients with a second malignancy and a matched control group of 30 patients who did not developed a second malignancy after the treatment for ALL. The frequencies of MTHFR C677T and A1298C genotypes in all patients were: C677T: CC 40%, CT 46.7% and TT 13.3% and A1298C: AA 46.7%, AC 44.4% and CC 8.9%. The relative risk for second malignancy was not significantly increased in ALL patients having at least one polymorphic C667T [odds ratio (OR) 1.51; 95% confidence interval (CI) 0.43-5.31] or one polymorphic A1298C allele (OR 1; 95% CI 0.29?-?3.46). Our study suggests that MTHFR polymorphisms are not associated with increased risk of second cancer in children treated with high-dose methotrexate.
ISSN:1042-8194
1029-2403
DOI:10.1080/10428190500086428