Abstract
Methotrexate (MTX) is a folate antagonist inhibiting nucleic acid and methionine synthesis. Methionine is necessary for CNS myelination. In 42 patients with primary CNS lymphoma (PCNSL) treated with a systemic and intraventricular high-dose MTX-based polychemotherapy, the presence of a risk haplotype defined by polymorphisms influencing methionine metabolism referred a relative risk for CNS white matter changes of 4.7 (p = 0.001). The authors conclude that methionine metabolism influences MTX neurotoxicity.
MeSH terms
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Aged
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Brain / drug effects*
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Brain / metabolism
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Brain / pathology
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Central Nervous System Neoplasms / drug therapy*
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DNA Mutational Analysis
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Demyelinating Diseases / chemically induced*
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Demyelinating Diseases / genetics
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Demyelinating Diseases / physiopathology
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Drug Resistance / genetics
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Female
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Folic Acid / metabolism
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Folic Acid Antagonists / administration & dosage
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Folic Acid Antagonists / adverse effects
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Gene Frequency
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Genetic Predisposition to Disease / genetics
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Genetic Testing
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Haplotypes
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Humans
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Lymphoma / drug therapy*
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Male
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Methionine / antagonists & inhibitors
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Methionine / metabolism*
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Methotrexate / administration & dosage
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Methotrexate / adverse effects*
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Middle Aged
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Myelin Sheath / drug effects
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Myelin Sheath / metabolism
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Nerve Fibers, Myelinated / drug effects
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Nerve Fibers, Myelinated / metabolism
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Nerve Fibers, Myelinated / pathology
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Neurotoxins / administration & dosage
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Neurotoxins / adverse effects
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Polymorphism, Genetic / genetics*
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Risk Factors
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S-Adenosylmethionine / metabolism
Substances
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Folic Acid Antagonists
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Neurotoxins
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S-Adenosylmethionine
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Folic Acid
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Methionine
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Methotrexate