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Exploring a potential mechanistic role of DNA methylation in the relationship between in utero and post-natal environmental exposures and risk of childhood acute lymphoblastic leukaemia.

Authors
  • Timms, Jessica A1, 2
  • Relton, Caroline L3
  • Sharp, Gemma C3
  • Rankin, Judith2
  • Strathdee, Gordon4
  • McKay, Jill A1, 5
  • 1 Institute of Health & Society, Newcastle University, Newcastle, United Kingdom. , (United Kingdom)
  • 2 Research Oncology, King's College London, Guy's Hospital, London.
  • 3 MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom. , (United Kingdom)
  • 4 Northern Institute for Cancer Research, Newcastle University, United Kingdom. , (United Kingdom)
  • 5 Department of Applied Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
International Journal of Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
Dec 01, 2019
Volume
145
Issue
11
Pages
2933–2943
Identifiers
DOI: 10.1002/ijc.32203
PMID: 30740682
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The aetiology of childhood acute lymphoblastic leukaemia (ALL) is unclear. Genetic abnormalities have been identified in a number of ALL cases, although these alone are not sufficient for leukaemic transformation. Various in utero and post-natal environmental exposures have been suggested to alter risk of childhood ALL. DNA methylation patterns can be influenced by environmental exposures, and are reported to be altered in ALL, suggesting a potential mediating mechanism between environment and ALL disease risk. To investigate this, we used a 'meet in the middle' approach, investigating the overlap between exposure-associated and disease-associated methylation change. Genome-wide DNA methylation changes in response to possible ALL-risk exposures (i.e. breast feeding, infection history, day care attendance, maternal smoking, alcohol, caffeine, folic acid, iron and radiation exposure) were investigated in a sub-population of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort using an epigenome-wide association study (EWAS) approach (n = 861-927), and compared to a list of ALL disease-associated methylation changes compiled from published data. Hypergeometric probability tests suggested that the number of directionally concordant gene methylation changes observed in ALL disease and in response to the following exposures; maternal radiation exposure (p = 0.001), alcohol intake (p = 0.006); sugary caffeinated drink intake during pregnancy (p = 0.045); and infant day care attendance (p = 0.003), were not due to chance. Data presented suggests that DNA methylation may be one mediating mechanism in the multiple hit pathway needed for ALL disease manifestation. © 2019 UICC.

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