Reduced folate carrier-1 G80a gene polymorphism is associated with neuroblastoma's development.
Neuroblastoma is a malignant embryonal tumor of neural crest cells that give rise to the sympathetic nervous system, responsible for 10-70% of all cases of childhood cancer. Because of its early appearance, it has been suggested that risk factors active in the prenatal can be associated with the pathogenesis of neuroblastoma. The aim of this study was to investigate whether the genetic polymorphisms MTHFR C677T and A1298C, MTR A2756G, TYMS 2R/3R and SLC19A1 G80A, involved in folate metabolism, increase the risk of neuroblastoma in Brazilian children. This study comprised 31 Brazilian children (0-14 years old) diagnosed with neuroblastoma compared with 92 controls. Investigation of polymorphisms MTHFR C677T, MTR A2756G and SLC19A1 A80G was performed using PCR-RFLP, the TYMS 2R/3R using PCR and MTHFR A1298C using AS-PCR. The SLC19A1 A80A genotype was significantly associated with the development of neuroblastoma, compared with the control group (Williams G-Test = 0.0286; OR = 5.1667; 95% CI = 1.4481-18.4338; p = 0.0175). When analyzed together, the 80AG+AA genotypes showed a trend toward association (OR = 3.3033; 95% CI = 1.0586-10.3080; p = 0.0563). Our results suggest that individuals carriers of genotype AA for the SLC19A1 gene present risk for the development of neuroblastoma and possibly have difficulty in absorption of folic acid by the cells, and this may adversely affect the metabolism of folate causing genomic instability and promoting the development of cancer. This is the first retrospective/prospective study to examine the relationship between polymorphisms of folate pathway genes and risk of neuroblastoma.
Laboratório de Biologia Molecular, Centro de Oncohematologia Pediátrica (CEONHPE), Hospital Universitário Oswaldo Cruz - HUOC/UPE, Universidade de Pernambuco - UPE, Arnóbio Marques, 310 - Santo Amaro, Recife, 50100-130, Pernambuco, Brazil, dyegomiranda@hotmail.com.
Dyego O
DO
de Miranda
Jemima E X S
JE
Barros
Maria Madalena S
MM
Vieira
Elker L S
EL
Lima
Vera L L
VL
Moraes
Helker A
HA
da Silva
Helder L B O
HL
Garcia
Cássia A
CA
Lima
Adriana V
AV
Gomes
Neide
N
Santos
Maria T C
MT
Muniz
D000293:Adolescent; D001938:Brazil; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)