title: RFC-1 80G>A polymorphism in case-mother/control-mother dyads is associated with risk of nephroblastoma and neuroblastoma.
abstract: OBJECTIVE
  Embryonic tumors are associated with an interruption during normal organ development; they may be related to disturbances in the folate pathway involved in DNA synthesis, methylation, and repair. Prenatal supplementation with folic acid is associated with a decreased risk of neuroblastoma, brain tumors, retinoblastoma, and nephroblastoma. The aim of this study was to investigate the association between MTHFR rs1801133 (C677T) and RFC-1 rs1051266 (G80A) genotypes with the risk of developing nephroblastoma and neuroblastoma.
  
  
  METHODS
  Case-mother/control-mother dyad study. Samples from Brazilian children with nephroblastoma (n=80), neuroblastoma (n=66), healthy controls (n=453), and their mothers (case n=93; control n=75) were analyzed. Genomic DNA was isolated from peripheral blood cells and/or buccal cells and genotyped to identify MTHFR C677T and RFC-1 G80A polymorphisms. Differences in genotype distribution between patients and controls were tested by multiple logistic regression analysis.
  
  
  RESULTS
  Risk for nephroblastoma and neuroblastoma was two- to fourfold increased among children with RFC-1 polymorphisms. An increased four- to eightfold risk for neuroblastoma and nephroblastoma was seen when the child and maternal genotypes were combined.
  
  
  CONCLUSIONS
  Our results suggest that mother and child RFC-1 G80A genotypes play a role on the risk of neuroblastoma and nephroblastoma since this polymorphism may impair the intracellular levels of folate, through carrying fewer folate molecules to the cell interior, and thus, the intracellular concentration is not enough to maintain regular DNA synthesis and methylation pathways.
authors.affiliation: 1 Pediatric Hematology-Oncology Research Program, Instituto Nacional de Câncer , Rio de Janeiro, Brazil .
authors.forename: Rafaela
authors.initials: R
authors.lastname: Montalvão-de-Azevedo
authors.forename: Gisele M
authors.initials: GM
authors.lastname: Vasconcelos
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Vargas
authors.forename: Luiz Claudio
authors.initials: LC
authors.lastname: Thuler
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Camargo
mesh_terms: D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009035:Mothers; D009363:Neoplasm Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051818:Replication Protein C / Q000235:genetics*; D012306:Risk; D009396:Wilms Tumor / Q000453:epidemiology / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; C081632:RFC1 protein, human; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D051818:Replication Protein C