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  • 1
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 30, No. 8 ( 2021-08-01), p. 1526-1535
    Kurzfassung: Prenatal immune development may play an important role in the etiology of childhood acute lymphoblastic leukemia (ALL). Methods: Seven cytokines, IL1β, IL4, IL6, IL8, GM-CSF, TNFα, and VEGF, were analyzed in blood spots collected at birth from 1,020 ALL cases and 1,003 controls participating in the California Childhood Leukemia Study. ORs and 95% confidence intervals (95% CI) associated with an interquartile range increment in cytokine levels were calculated using logistic regression, adjusting for sociodemographic and birth characteristics. Results: We found that patients with ALL were born with higher levels of a group of correlated cytokines than controls [IL1β: OR of 1.18 (95% confidence interval [CI], 1.03–1.35); IL8: 1.19 (1.03–1.38); TNFα: 1.15 (1.01–1.30); VEGF: 1.16 (1.01–1.33)] , especially among children of Latina mothers (ORs from 1.31 to 1.40) and for ALL with high hyperdiploidy (ORs as high as 1.27). We found that neonatal cytokine levels were correlated with neonatal levels of endogenous metabolites which had been previously associated with ALL risk; however, there was no evidence that the cytokines were mediating the relationship between these metabolites and ALL risk. Conclusions: We posit that children born with altered cytokine levels are set on a trajectory towards an increased risk for subsequent aberrant immune reactions that can initiate ALL. Impact: This is the first study to evaluate the interplay between levels of immunomodulatory cytokines at birth, prenatal exposures, and the risk of childhood ALL.
    Materialart: Online-Ressource
    ISSN: 1055-9965 , 1538-7755
    Sprache: Englisch
    Verlag: American Association for Cancer Research (AACR)
    Publikationsdatum: 2021
    ZDB Id: 2036781-8
    ZDB Id: 1153420-5
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    In: Clinical Science, Portland Press Ltd., Vol. 135, No. 8 ( 2021-04-30), p. 1053-1063
    Kurzfassung: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Thirdhand smoke (THS) is the residual tobacco contamination that remains after the smoke clears. We investigated the effects of THS exposure in utero and during early life in a transgenic Cdkn2a knockout mouse model that is vulnerable to the development of leukemia/lymphoma. Female mice, and their offspring, were exposed from the first day of pregnancy to weaning. Plasma cytokines, body weight and hematologic parameters were measured in the offspring. To investigate THS exposure effects on the development of leukemia/lymphoma, bone marrow (BM) was collected from control and THS-exposed mice and transplanted into BM-ablated recipient mice, which were followed for tumor development for 1 year. We found that in utero and early-life THS exposure caused significant changes in plasma cytokine concentrations and in immune cell populations; changes appeared more pronounced in male mice. Spleen (SP) and BM B-cell populations were significantly lower in THS-exposed mice. We furthermore observed that THS exposure increased the leukemia/lymphoma-free survival in BM transplantation recipient mice, potentially caused by THS-induced B-cell toxicity. A trend towards increased solid tumors in irradiated mice reconstituted with THS-exposed BM stimulates the hypothesis that the immunosuppressive effects of in utero and early-life THS exposure might contribute to carcinogenesis by lowering the host defense to other toxic exposures. Our study adds to expanding evidence that THS exposure alters the immune system and that in utero and early-life developmental periods represent vulnerable windows of susceptibility for these effects.
    Materialart: Online-Ressource
    ISSN: 0143-5221 , 1470-8736
    Sprache: Englisch
    Verlag: Portland Press Ltd.
    Publikationsdatum: 2021
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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