Abstract | OBJECTIVE: To determine the influence of the genotype and the level of expression of different enzymes involved in folate metabolism on the response to and toxicity of high-dose methotrexate treatment in pediatric osteosarcomas. STUDY DESIGN: DHFR and Reduced folate carrier 1 (RFC1) semiquantitative expression was analyzed in 34 primary and metastatic osteosarcoma tissues by real-time polymerase chain reaction. The following polymorphisms were also analyzed in peripheral blood from 96 children with osteosarcoma and 110 control subjects: C677T, A1298C (MTHFR), G80A (RFC1), A2756G (MTR), C1420T (SHMT), the 28bp-repeat polymorphism, and 1494del6 of the TYMS gene. Treatment toxicity was scored after each cycle according to criteria from the World Health Organization. RESULTS: DHFR and RFC1 expression was lower in initial osteosarcoma biopsy specimens than in metastases (P = .024 and P = .041, respectively). RFC1 expression was moderately decreased in samples with poor histologic response to preoperative treatment (P = .053). Patients with osteosarcoma with G3/G4 hematologic toxicity were more frequently TT than CT/CC for C677T/MTHFR (P = .023) and GG for A2756G/MTR (P = .048 and P = .057 for gastrointestinal and hematologic toxicity, respectively). CONCLUSIONS:
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Authors | Ana Patiño-García, Marta Zalacaín, Lucía Marrodán, Mikel San-Julián, Luis Sierrasesúmaga |
Journal | The Journal of pediatrics
(J Pediatr)
Vol. 154
Issue 5
Pg. 688-93
(May 2009)
ISSN: 1097-6833 [Electronic] United States |
PMID | 19159907
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antimetabolites, Antineoplastic
- Carrier Proteins
- Folate Receptors, GPI-Anchored
- RNA, Messenger
- Receptors, Cell Surface
- Folic Acid
- Tetrahydrofolate Dehydrogenase
- Methotrexate
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Topics |
- Adolescent
- Antimetabolites, Antineoplastic
(administration & dosage, adverse effects)
- Bone Neoplasms
(drug therapy, genetics, mortality)
- Carrier Proteins
(genetics, metabolism)
- Case-Control Studies
- Dose-Response Relationship, Drug
- Drug Resistance, Neoplasm
- Female
- Folate Receptors, GPI-Anchored
- Folic Acid
(genetics, metabolism)
- Gastrointestinal Diseases
(chemically induced)
- Genotype
- Hematologic Diseases
(chemically induced)
- Humans
- Kidney Diseases
(chemically induced)
- Male
- Methotrexate
(administration & dosage, adverse effects)
- Osteosarcoma
(drug therapy, genetics, mortality)
- Polymerase Chain Reaction
- Polymorphism, Genetic
- RNA, Messenger
(metabolism)
- Receptors, Cell Surface
(genetics, metabolism)
- Tetrahydrofolate Dehydrogenase
(genetics, metabolism)
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