Preponderance of methylenetetrahydrofolate reductase C677T homozygosity among leukemia patients intolerant to methotrexate
Preponderance of methylenetetrahydrofolate reductase C677T homozygosity among leukemia patients intolerant to methotrexate
复制标题
DOI：
10.1093/annonc/mdf322
复制
发表时间：
2002-12-01
影响因子：
50.5
通讯作者：
Sica, S
中科院分区：
文献类型：
--
作者：
Chiusolo, P;Reddiconto, G;Sica, S
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.
