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Genetic abnormalities have been identified in a number of ALL cases, although these alone are not sufficient for leukaemic transformation. Various <jats:italic>in utero<\/jats:italic> and post\u2010natal 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 \u2018meet in the middle\u2019 approach, investigating the overlap between exposure\u2010associated and disease\u2010associated methylation change. Genome\u2010wide DNA methylation changes in response to possible ALL\u2010risk 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\u2010population of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort using an epigenome\u2010wide association study (EWAS) approach (n\u2009=\u2009861\u2013927), and compared to a list of ALL disease\u2010associated 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 (<jats:italic>p<\/jats:italic>\u2009=\u20090.001), alcohol intake (<jats:italic>p<\/jats:italic>\u2009=\u20090.006); sugary caffeinated drink intake during pregnancy (<jats:italic>p<\/jats:italic>\u2009=\u20090.045); and infant day care attendance (<jats:italic>p<\/jats:italic>\u2009=\u20090.003), 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.<\/jats:p>","DOI":"10.1002\/ijc.32203","type":"journal-article","created":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T05:24:29Z","timestamp":1549862669000},"page":"2933-2943","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Exploring a potential mechanistic role of DNA methylation in the relationship between <i>in utero<\/i> and post\u2010natal environmental exposures and risk of childhood acute lymphoblastic leukaemia"],"prefix":"10.1002","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3687-9312","authenticated-orcid":false,"given":"Jessica A.","family":"Timms","sequence":"first","affiliation":[{"name":"Institute of Health &amp; Society Newcastle University  Newcastle, United Kingdom"},{"name":"Research Oncology King's College London, Guy's Hospital  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Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"McKay","sequence":"additional","affiliation":[{"name":"Institute of Health &amp; Society Newcastle University  Newcastle, United Kingdom"},{"name":"Department of Applied Sciences Northumbria University  Newcastle upon Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6636a3"},{"key":"e_1_2_7_3_1","volume-title":"Childhood Acute Lymphoblastic Leukemia Treatment (PDQ(R)): Health Professional Version, in PDQ Cancer Information Summaries","author":"Board 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