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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

Research output: Contribution to journalArticlepeer-review

Jessica A Timms, Caroline L Relton, Gemma C Sharp, Judith Rankin, Gordon Strathdee, Jill A McKay

Original languageEnglish
Pages (from-to)2933-2943
Number of pages11
JournalInternational Journal of Cancer
Volume145
Issue number11
DOIs
Published1 Dec 2019

King's Authors

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.

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