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

Timms, Jessica A., Relton, Caroline L., Sharp, Gemma C., Rankin, Judith, Strathdee, Gordon and Mckay, Jill (2019) 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. International Journal of Cancer. ISSN 0020-7136 (In Press)

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Official URL: https://doi.org/10.1002/ijc.32203

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.

Item Type: Article
Uncontrolled Keywords: radiation, alcohol, smoking, caffeine, ALSPAC
Subjects: B900 Others in Subjects allied to Medicine
C400 Genetics
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Paul Burns
Date Deposited: 11 Feb 2019 16:44
Last Modified: 29 Apr 2019 13:07
URI: http://nrl.northumbria.ac.uk/id/eprint/37935

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