The objective of this project will be to determine the ability of early life exposures to induce leukaemia-associated DNA methylation changes in apparently normal cells, which may increase the individual's likelihood of subsequently developing childhood leukaemia. Identification of such links might provide a plausible biological mechanism by which early life exposures could increase leukaemia risk and provide a rational basis for future dietary/environmental interventions aimed at reducing the development of abnormal DNA methylation and thus reducing the risk of leukaemia.

Specific aims: (i)Measure DNA methylation in a panel of genes (that we have previously identified as showing variation in childhood leukaemia cases) in cord blood DNA from a large, intensively characterised birth cohort and relate these findings to a wide range of exposures reported to influence leukaemia risk. (ii)Conduct allele-specific analysis of variation in DNA methylation to determine the allelic distribution of DNA methylation and whether this includes the appearance of highly methylated alleles, similar to those observed in full blown leukaemia.