{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:06:37Z","timestamp":1784016397281,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,10]]},"group-title":"Oncology","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Advancing Translational Science, NIH","award":["UL1 TR001863"],"award-info":[{"award-number":["UL1 TR001863"]}]},{"name":"Yale Center on Climate Change and Health"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute, NIH","doi-asserted-by":"crossref","award":["R01 CA155461"],"award-info":[{"award-number":["R01 CA155461"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>High ambient temperature in early pregnancy has been linked to an increased risk of childhood acute lymphoblastic leukemia (ALL). To better understand biological mechanisms, the current study evaluated potential interaction between temperature and genetic characteristics.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used data from California birth records (1982-2008) and California Cancer Registry (1988-2011) to identify ALL cases (n=3,353) diagnosed \u226414 years of age and non-cancer controls (n=3,530) matched 1:1 on sex, race, ethnicity, and birth year and month. Weekly ambient temperatures throughout pregnancy were assessed on a 1-km grid around the birth address, while genetic data were available from a genome-wide association study using neonatal blood spots. We evaluated the association between ambient temperature and ALL risk by quartiles of established genetic risk score for ALL. Next, we formally tested gene-temperature interactions in the association with ALL, correcting for multiple testing, for genes previously identified with epigenetic changes due to both temperature and ALL. All analyses were adjusted for potential confounders.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    The elevated risk of ALL per 5 \u00b0C increase of weekly mean ambient temperature, confined to early pregnancy, was more pronounced among children with the lowest genetic susceptibility to ALL, especially among Latino children (first quartile: odds ratio [OR] = 1.50, 95% confidence interval [CI]: 1.14-1.97); fourth quartile: OR=1.03, 95% CI: 0.83-1.28). There were significant interactions (p&lt;0.002) between ambient temperature and polymorphisms in\n                    <jats:italic>BNC1<\/jats:italic>\n                    among non-Latino White children, and suggestive interactions (p&lt;0.05) with\n                    <jats:italic>TBPL2<\/jats:italic>\n                    and\n                    <jats:italic>NRXN1<\/jats:italic>\n                    in the full population.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings suggest that there may be interactions between ambient temperature in early pregnancy and offspring genotype in the risk of childhood ALL.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Impact<\/jats:title>\n                  <jats:p>If replicated, these findings could help elucidate the biological mechanisms linking high ambient temperature in early pregnancy and the risk of childhood ALL.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.09.26357608","type":"posted-content","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:30:16Z","timestamp":1783726216000},"source":"Crossref","is-referenced-by-count":0,"title":["Gene-Temperature Interactions and Risk of Childhood Acute Lymphoblastic Leukemia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9581-7384","authenticated-orcid":false,"given":"Tormod","family":"Rogne","sequence":"first","affiliation":[{"name":"Department of Community Medicine and Global Health, University of Oslo, Oslo, Norway"},{"name":"Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Global, Environmental, and Occupational Health, School of Public Health, University of Maryland, College Park, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangge","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua L.","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Metayer","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"Wiemels","sequence":"additional","affiliation":[{"name":"Center for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California Keck School of Medicine, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7679-8704","authenticated-orcid":false,"given":"Andrew T.","family":"DeWan","sequence":"additional","affiliation":[{"name":"Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071401000857000_2026.07.09.26357608v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03395-8"},{"key":"2026071401000857000_2026.07.09.26357608v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30487"},{"key":"2026071401000857000_2026.07.09.26357608v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S2542-5196(24)00121-9"},{"key":"2026071401000857000_2026.07.09.26357608v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-024-00731-z"},{"key":"2026071401000857000_2026.07.09.26357608v1.5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202011-4063OC"},{"key":"2026071401000857000_2026.07.09.26357608v1.6","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-21-1140"},{"key":"2026071401000857000_2026.07.09.26357608v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02596-9"},{"key":"2026071401000857000_2026.07.09.26357608v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3656"},{"key":"2026071401000857000_2026.07.09.26357608v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13069-6"},{"key":"2026071401000857000_2026.07.09.26357608v1.10","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000001121"},{"key":"2026071401000857000_2026.07.09.26357608v1.11","doi-asserted-by":"publisher","DOI":"10.3334\/ORNLDAAC\/1840"},{"key":"2026071401000857000_2026.07.09.26357608v1.12","unstructured":"California Department of Health Care Services. DHCS County Code Reference Table. California Department of Health Care Services. 2022. URL: https:\/\/gis.dhcs.ca.gov\/datasets\/a83122d79b1f4b85b3637d8a462fc2d9_7\/about (Accessed 12 May 2024)."},{"key":"2026071401000857000_2026.07.09.26357608v1.13","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i969"},{"key":"2026071401000857000_2026.07.09.26357608v1.14","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.326.7382.219"},{"key":"2026071401000857000_2026.07.09.26357608v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32203"},{"key":"2026071401000857000_2026.07.09.26357608v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2019.113840"},{"key":"2026071401000857000_2026.07.09.26357608v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2021.117700"},{"key":"2026071401000857000_2026.07.09.26357608v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2022.107655"},{"key":"2026071401000857000_2026.07.09.26357608v1.19","doi-asserted-by":"publisher","DOI":"10.4161\/epi.27585"},{"key":"2026071401000857000_2026.07.09.26357608v1.20","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-9-r105"},{"key":"2026071401000857000_2026.07.09.26357608v1.21","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20398"},{"key":"2026071401000857000_2026.07.09.26357608v1.22","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"2026071401000857000_2026.07.09.26357608v1.23","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-publhealth-012420-105014"},{"key":"2026071401000857000_2026.07.09.26357608v1.24","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1205919"},{"key":"2026071401000857000_2026.07.09.26357608v1.25","doi-asserted-by":"publisher","DOI":"10.4161\/epi.4.3.8752"},{"key":"2026071401000857000_2026.07.09.26357608v1.26","unstructured":"GeneCards. BNC1. 2025."},{"key":"2026071401000857000_2026.07.09.26357608v1.27","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52760"},{"key":"2026071401000857000_2026.07.09.26357608v1.28","unstructured":"GeneCards. NRXN1. 2025. URL: https:\/\/www.genecards.org\/cgi-bin\/carddisp.pl?gene=NRXN1 (Accessed 15 August 2025)."},{"key":"2026071401000857000_2026.07.09.26357608v1.29","unstructured":"GeneCards. TBPL2. 2025."},{"key":"2026071401000857000_2026.07.09.26357608v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2022.05.004"},{"key":"2026071401000857000_2026.07.09.26357608v1.31","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000686"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.09.26357608","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:00:20Z","timestamp":1784016020000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.07.09.26357608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":31,"URL":"https:\/\/doi.org\/10.64898\/2026.07.09.26357608","relation":{},"subject":[],"published":{"date-parts":[[2026,7,10]]},"subtype":"preprint"}}