RESUMO
BACKGROUND: Folate is an important micronutrient molecule participating in DNA synthesis, methylation and repair mechanisms. Genetic polymorphisms in folate pathway related enzymes including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, thymidylate synthase (TS) 28-bp tandem repeat, and reduced folate carrier (RFC) G80A have been shown to be associated with increased susceptibility for several cancers. The aim of the present study was to evaluate whether single nucleotide polymorphisms in the genes encoding enzymes of the folate pathway predispose to any CNS tumors in Thai children. METHODS: In the present case-control study, we investigated these polymorphisms in genomic DNA from peripheral blood mononuclear cells in 73 Thai children with various types of central nervous system tumors and in 205 age and sex matched controls. RESULTS: Thirty-one out of 73 patients were diagnosed with glial tumors (astrocytoma, oigodendroglioma and ependymoma), 28 with embryonal CNS tumors (medulloblastoma, pinealoblastoma and primitive neuroectodermal tumor), 13 with germ cell tumors and 1 with meningioma. We found that the homozygous CC allele of MTHFR A1298C conferred an increased risk of embryonal CNS tumors (OR: 3.9; 95% CI: 1.3-11.4, p=0.02). CONCLUSION: Our findings thus suggest that folate metabolism may play a role in the pathogenesis of certain specific subtypes of pediatric brain tumor in Thai children, especially embryonal CNS tumors.
Assuntos
Neoplasias do Sistema Nervoso Central/genética , Ácido Fólico/genética , Ácido Fólico/metabolismo , Polimorfismo Genético , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Proteínas de Membrana Transportadoras/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Proteína Carregadora de Folato Reduzido , Tailândia , Timidilato Sintase/genéticaRESUMO
We report a rare case of anaplastic astrocytoma with multicentric central nervous system lesions in a 10-year-old girl presenting with a 1-month history of progressive headache and paraparesis. Neurological examination upon admission revealed papilloedema of both eyes and grade 2/5 weakness of both legs. Cranial and spinal magnetic resonance imaging revealed multiple tumour foci within the suprasellar region, cerebellar hemisphere, cervical and thoracic cords. After an uneventful laminectomy and excision of the tumour at the T8-9 level, a significant improvement of motor function was observed. The histological diagnosis was anaplastic astrocytoma based on the WHO classification. The patient received postoperative radiotherapy and chemotherapy, and was able to walk with the aid of auxiliary crutches. Despite being an uncommon disease in children and being associated with an unfavourable long-term outcome, early diagnosis and appropriate management of this condition may contribute to reduced patient morbidity.
