{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T05:40:01Z","timestamp":1756100401226,"version":"3.44.0"},"reference-count":60,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000321","name":"World Cancer Research Fund","doi-asserted-by":"publisher","award":["IIG_FULL_2022_007"],"award-info":[{"award-number":["IIG_FULL_2022_007"]}],"id":[{"id":"10.13039\/501100000321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010052","name":"Northumbria University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001273","name":"CHILDREN with CANCER UK","doi-asserted-by":"publisher","award":["19\u2010316"],"award-info":[{"award-number":["19\u2010316"]}],"id":[{"id":"10.13039\/501100001273","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2025,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Various genetic aberrations are suggested to initiate the development of acute lymphoblastic leukaemia (ALL) but alone are insufficient for disease onset. Epigenetic alteration, such as DNA methylation changes, plays a key role in human health. Evidence suggests DNA methylation may be an intermediate mechanism through which the environment contributes to ALL manifestation. ALL is categorized into subtypes based on leukaemia\u2010associated genetic events, and it is plausible that different exposures pose differing risks for given subtypes. Using our previously established meet\u2010in\u2010the\u2010middle approach, we performed CpG\u2010level analysis to investigate DNA methylation as an intermediate mechanism between risk exposures and ALL. Differentially methylated CpGs (DMCs) were integrated, identifying overlapping methylation, with hypergeometric tests used to assess the probability of concurring methylation considering directionality. DMC analysis reinforced previous gene\u2010level findings suggesting altered DNA methylation associated with maternal radiation exposure, alcohol intake, and plasma folate during pregnancy is also present in the disease. Whilst maternal folate\u2010associated and leukaemia\u2010associated methylation appear consistent across most subtypes, the effect of other exposures appears subtype\u2010specific. We suggest environmentally associated methylation includes driver and\/or \u2018navigator\u2019 changes, the latter influencing biological pathways contributing to ALL. This analysis aids understanding of which risk factors may contribute to specific subtypes or which influence ALL risk more generally.<\/jats:p>","DOI":"10.1002\/ijc.35506","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T23:40:17Z","timestamp":1749512417000},"page":"1600-1612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The potential role of environmentally associated <scp>DNA<\/scp> methylation in childhood acute lymphoblastic leukaemia subtypes"],"prefix":"10.1002","volume":"157","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3600-0079","authenticated-orcid":false,"given":"Jessica R.","family":"Saville","sequence":"first","affiliation":[{"name":"Faculty of Health and Life Sciences, Department of Applied Sciences Northumbria University  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa J.","family":"Russell","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Newcastle University Centre for Cancer, Faculty of Medical Science Newcastle University  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kay","family":"Padget","sequence":"additional","affiliation":[{"name":"Faculty of Health and Life Sciences, Department of Applied Sciences Northumbria University  Newcastle upon Tyne UK"},{"name":"St. George's University, Grenada, Based at Northumbria University  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akram","family":"Ghantous","sequence":"additional","affiliation":[{"name":"Epigenomics and Mechanisms Branch International Agency for Research on Cancer  Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Nordlund","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Molecular Precision Medicine, Science For Life Laboratory Uppsala University  Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill A.","family":"McKay","sequence":"additional","affiliation":[{"name":"Faculty of Health and Life Sciences, Department of Applied Sciences Northumbria University  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201009\u2010808402"},{"key":"e_1_2_11_3_1","unstructured":"Organisation WH.Incidence of Childhood Leukaemia. Vol. Fact Sheet 4.1.2009European Environment and Health Information System.https:\/\/www.euro.who.int\/en\/health\u2010topics\/noncommunicable\u2010diseases\/cancer\/publications\/2009\/4.1\u2010incidence\u2010of\u2010childhood\u2010leukaemia \u2010an\u2010enhis\u2010fact\u2010sheet"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32203"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055\u20109965.EPI\u201013\u20100350"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdp.2005.06.008"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.1.24"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552\u2010018\u20101024\u20101"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2015.08.009"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552\u2010012\u20100004\u20100"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2017.01.003"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000141"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3961\/jpmph.19.020"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2017.04.019"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2021.106983"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552\u2010015\u20100618\u20100"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijheh.2013.12.003"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2017.03.001"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2021.117376"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/jes.2012.115"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu298"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.53"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31014"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102013\u201014\u20109\u2010r105"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015850"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2014.09.004"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10577"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.02.019"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201016\u20102571"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph20075428"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u20108\u2010426"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.24835"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20103347\u20101_6"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2013.01.003"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010021\u201000791\u20101"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1047177"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901518"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185\u2010017\u20102184\u20106"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010animal\u2010020518\u2010115206"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2015.1117889"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201800411"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.15386\/mpr\u20101777"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.54346"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402918"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26735"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102407\u20109\u2010187"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2011.04.010"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102006\u201005\u2010021071"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102015\u201004\u2010639138"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402460"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci12807"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403859"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102012\u201008\u2010452698"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/b978\u20100\u201012\u2010380866\u20100.60010\u20101"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1011022"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010024\u201002118\u20104"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20103016.2001.00325.x"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv072"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13330"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2013\u20103118"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.14367"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.35506","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T05:14:00Z","timestamp":1756098840000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.35506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":60,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,10,15]]}},"alternative-id":["10.1002\/ijc.35506"],"URL":"https:\/\/doi.org\/10.1002\/ijc.35506","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"type":"print","value":"0020-7136"},{"type":"electronic","value":"1097-0215"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"assertion":[{"value":"2024-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}