Folate pathway genetic polymorphisms and susceptibility of central nervous system tumors in Thai children.
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).


CONCLUSIONS
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.
Sirachainan
Nongnuch
N
Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
Wongruangsri
Siranee
S
Kajanachumpol
Saowanee
S
Pakakasama
Samart
S
Visudtibhan
Anannit
A
Nuchprayoon
Issarang
I
Lusawat
Apasri
A
Phudhicharoenrat
Suchart
S
Shuangshoti
Shanop
S
Hongeng
Suradej
S
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D005260:Female; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein; D013785:Thailand; D013940:Thymidylate Synthase / Q000235:genetics
D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D013940:Thymidylate Synthase