Abstract for presentation at 11th International Congress of Human Genetics

The role of MTHFR polymorphisms and dietary folate in childhood cancer

  • Dr Anne Ronan, Centre for Clinical Epidemiology and Biostatistics, Faculty of Health, University of Newcastle, Australia, Australia
  • Dr Ammarin Thakkinstian, Centre for Clinical Epidemiology and Biostatistics, Faculty of Health, University of Newcastle, Australia, Thailand
  • Dr Syed Zakaria, Jabatan Pediatrik, Hospital Universiti Kebangsaan Malaysia, Kuala Lumpur,, Malaysia
  • Dr Jongkolnee Settakorn, Department of Pathology, Faculty of Medicine, Chiang Mai University, Thailand, Thailand
  • Sophia Moscovis, Molecular and Cytogenetics Laboratory, Hunter Area Pathology Service, NSW, Australia, Australia
  • Dr Rodney Scott, Molecular and Cytogenetics Laboratory, Hunter Area Pathology Service, NSW, Australia, Australia
  • Dr Frank Alvaro, Pediatric Oncology Unit, John Hunter Children’s Hospital, NSW, Australia, Australia
  • Dr John Attia, Centre for Clinical Epidemiology and Biostatistics, Faculty of Health, University of Newcastle, Australia, Australia

    • Objective: To explore periconceptual genetic and environmental factors in childhood cancer, by measurement of folate intake, occupational exposures to organic solvents and polycyclic aromatic hydrocarbons (PAH), and polymorphisms in folate metabolising enzyme methylene tetrahydrofolate reductase (MTHFR) and xenobiotic metabolising enzyme glutathione-S-transferase M1 (GSTM1).
    Methods: We recruited the families of 39 children with and 49 without cancer for a case-control study. Data were collected using self-administered questionnaires and buccal swabs. Organic solvent exposure was measured using the Finnish Job Exposure Matrix (FINJEM) and dietary folate was evaluated from the Australian Nutritional Tables (AUSNUT).
    Results: An increased risk of childhood cancer, particularly acute lymphoblastic leukaemia (ALL) was seen with the AA or AC genotype at the A1298C polymorphism of the MTHFR gene in the child (adjusted OR = 3.06, 95% CI 1.21-7.71, p = 0.018). Meta-analysis of all reports of this variant in ALL to date confirmed a significant association (combined OR 1.44, 95% CI 1.1-1.9, p = 0.01). However no association with cancer was found for parental pre-conception exposures, dietary or supplemental folate, or interactions between these environmental factors and polymorphisms in GSTM1 or MTHFR.
    Conclusions: The previously reported association between childhood ALL and the MTHFR 1298 AA genotype is repeated here. This is the first study to date to examine the interaction between dietary folate and MTHFR genotype in the causation of childhood cancer. It does not support the role of preconception exposures and diet as risk factors for childhood cancer.

    Conference Organiser - ICMS Pty Ltd