title: Folate pathway gene polymorphisms and risk of childhood brain tumors: results from an Australian case-control study.
abstract: BACKGROUND
  Recent research suggests that maternal folic acid supplementation is associated with a reduced risk of childhood brain tumors (CBT); polymorphisms in folate pathway genes could modify this association or directly influence CBT risk.
  
  
  METHODS
  Associations between risk of CBT and folate pathway polymorphisms were investigated in a population-based case-control study in Australia (2005-2010). Cases were recruited through all Australian pediatric oncology centers and controls by national random digit dialing. Data were available from 321 cases and 552 controls. Six polymorphisms were genotyped in children and parents (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756A>G, MTR 5049C>A, and CBS 2199 T>C). Maternal folic acid use was ascertained via questionnaire. ORs were estimated using unconditional logistic regression. Case-parent trio analyses were also undertaken.
  
  
  RESULTS
  There was weak evidence of a reduced risk of CBT for the MTRR 66GG genotype in the child or father: ORs 0.71 [95% confidence interval (CI), 0.48-1.07]; 0.54 (95% CI, 0.34-0.87), respectively. Maternal prepregnancy folic acid supplementation showed a stronger negative association with CBT risk where the child, mother, or father had the MTRR 66GG genotype (Pinteraction = 0.07, 0.10, and 0.18, respectively).
  
  
  CONCLUSIONS
  Evidence for an association between folate pathway genotypes and CBT is limited in this study. There was possible protection by the MTRR 66GG genotype, particularly when combined with maternal prepregnancy folic acid supplementation; these results are novel and require replication.
  
  
  CONCLUSIONS
  The possible interaction between folic acid supplementation and MTRR 66A>G, if confirmed, would strengthen evidence for prepregnancy folate protection against CBT.
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
authors: Kathryn R
authors: KR
authors: Greenop
authors: Hunter Medical Research Institute, John Hunter Hospital, New South Wales, Australia. School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, Newcastle, New South Wales, Australia. Hunter Area Pathology Service, HNEHealth, Newcastle, New South Wales, Australia.
authors: Rodney J
authors: RJ
authors: Scott
authors: Hunter Medical Research Institute, John Hunter Hospital, New South Wales, Australia. School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia.
authors: John
authors: J
authors: Attia
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
authors: Carol
authors: C
authors: Bower
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
authors: Nicholas H
authors: NH
authors: de Klerk
authors: Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
authors: Murray D
authors: MD
authors: Norris
authors: Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
authors: Michelle
authors: M
authors: Haber
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
authors: Sarra E
authors: SE
authors: Jamieson
authors: School of Surgery, University of Western Australia, Perth, Western Australia, Australia. Department of Clinical Biochemistry, Royal Perth Hospital, Perth, Western Australia, Australia.
authors: Frank M
authors: FM
authors: van Bockxmeer
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia. Department of Paediatric Oncology/Haematology, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.
authors: Nicholas G
authors: NG
authors: Gottardo
authors: Research Portfolio, University of Sydney, Sydney, Australia. School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors: Lesley J
authors: LJ
authors: Ashton
authors: Sax Institute, Haymarket, New South Wales, Australia. Sydney School of Public Health, University of Sydney, New South Wales, Australia.
authors: Bruce K
authors: BK
authors: Armstrong
authors: Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia. Liz.Milne@telethonkids.org.au.
authors: Elizabeth
authors: E
authors: Milne
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001315:Australia / Q000453:epidemiology; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000178:diet therapy / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019587:Dietary Supplements; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000008:administration & dosage / Q000235:genetics*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051150:Methionine Sulfoxide Reductases / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008840:Microfilament Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D014157:Transcription Factors; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C120376:MSRB2 protein, human; D051150:Methionine Sulfoxide Reductases; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human