Preponderance of methylenetetrahydrofolate reductase C677T homozygosity among leukemia patients intolerant to methotrexate
| Autor: | Federica Sorà, Simona Sica, Luca Laurenti, Patrizia Chiusolo, Luca Mele, Giuseppe Leone, I Casorelli, Giovanni Reddiconto, Luciana Annino |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Maximum Tolerated Dose Risk Assessment Sensitivity and Specificity Gastroenterology chemistry.chemical_compound Predictive Value of Tests Internal medicine Genotype Humans Medicine Genetic Testing Child Methylenetetrahydrofolate Reductase (NADPH2) Aged Probability Retrospective Studies Oxidoreductases Acting on CH-NH Group Donors Acute leukemia Leukemia Polymorphism Genetic Dose-Response Relationship Drug biology business.industry Homozygote Hematology Middle Aged medicine.disease Methotrexate Oncology chemistry Pharmacogenetics Methylenetetrahydrofolate reductase Toxicity Antifolate Immunology biology.protein Female business medicine.drug |
| Zdroj: | Annals of Oncology. 13:1915-1918 |
| ISSN: | 0923-7534 |
| Popis: | Background Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, a common mutation of the gene encoding the enzyme that catalyzes reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a carbon donor in the metabolism of folate, determines a striking reduction in the enzyme activity in carriers of mutation at homozygous status. Patients and methods We retrospectively analyzed the incidence of MTHFR C677T and the influence of genotype on methotrexate (MTX) toxicity in patients with acute leukemia undergoing maintenance chemotherapy. Seventy-eight patients were analyzed and 61 were evaluable for toxicity. MTX toxicity was assessed on bone marrow, liver and mucosae. Results The incidence of the C677T mutation was as expected in the general Italian population with 23.08% of patients being TT, 38.46% of patients CT and 38.46% of patients CC. The TT genotype was significantly associated with an increase of toxicity during MTX administration. No specific pattern of toxicity was detected, although in TT patients myelosuppression and liver toxicity were more pronounced. Conclusions TT genotype may indicate a need to reduce the dose of MTX during prolonged administration. Considering the high prevalence of homozygous individuals in the Italian population, pretreatment screening may be worthwhile. |
| Databáze: | OpenAIRE |
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