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This work aimed to investigate this association accounting for genetic polymorphisms of the Th2 pathway cytokines (<jats:italic>IL4<\/jats:italic>, <jats:italic>IL10<\/jats:italic>, <jats:italic>IL13<\/jats:italic>, and <jats:italic>IL4R<\/jats:italic>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Analyses were based on the French case\u2010control study ESTELLE (2010\u20102011). The complete sample included 629 ALL cases and 1421 population\u2010based controls frequency\u2010matched on age and gender. The child's medical history was collected through standardized maternal interview. Biological samples were collected, and genotyping data were available for 411 cases and 704 controls of European origin. Odds ratios (OR) were estimated using unconditional regression models adjusted for potential confounders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the complete sample, a significant inverse association was observed between ALL and reported history of allergic rhinitis or sinusitis (OR\u00a0=\u00a00.65 [0.42\u20100.98]; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04), but there was no obvious association with allergies overall. There was an interaction between genetic polymorphisms in <jats:italic>IL4<\/jats:italic> and <jats:italic>IL4R<\/jats:italic> (<jats:italic>P<\/jats:italic><jats:sub>interaction =<\/jats:sub> 0.003), as well as a gene\u2010environment interaction between <jats:italic>IL4R<\/jats:italic>\u2010rs1801275 and a reported history of asthma (IOR\u00a0=\u00a00.23; <jats:italic>P<\/jats:italic><jats:sub>int\u00a0<\/jats:sub>=\u00a00.008) and eczema (IOR\u00a0=\u00a00.47; <jats:italic>P<\/jats:italic><jats:sub>int\u00a0<\/jats:sub>=\u00a00.06). We observed no interaction with the candidate polymorphisms in <jats:italic>IL4<\/jats:italic> and <jats:italic>IL13<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that the association between allergic symptoms and childhood ALL could be modified by <jats:italic>IL4R<\/jats:italic>\u2010rs1801275, and that this variant could also interact with a functional variant in <jats:italic>IL4<\/jats:italic> gene. Although they warrant confirmation, these results could help understand the pathological mechanisms under the reported inverse association between allergy and childhood ALL.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29402","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T08:33:19Z","timestamp":1634805199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Allergies, genetic polymorphisms of Th2 interleukins, and childhood acute lymphoblastic leukemia: The ESTELLE study"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9549-2498","authenticated-orcid":false,"given":"Roula","family":"Ajrouche","sequence":"first","affiliation":[{"name":"CRESS, Universit\u00e9 de Paris INSERM, UMR 1153 Epidemiology of Childhood and Adolescent Cancers Team  Villejuif France"},{"name":"Faculty of Pharmacy Lebanese University  Hadath 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