ArticlemedRxiv : the preprint server for health sciences2026
Gene-Temperature Interactions and Risk of Childhood Acute Lymphoblastic Leukemia.
Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
10 authors.
Funding
Abstract
Background: 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. Methods: We used data from California birth records (1982-2008) and California Cancer Registry (1988-2011) to identify ALL cases (n=3,353) diagnosed ≤14 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. Results: The elevated risk of ALL per 5 °C 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<0.002) between ambient temperature and polymorphisms in Conclusions: Our findings suggest that there may be interactions between ambient temperature in early pregnancy and offspring genotype in the risk of childhood ALL. Impact: If replicated, these findings could help elucidate the biological mechanisms linking high ambient temperature in early pregnancy and the risk of childhood ALL.
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Registered trials
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