American Association for Cancer Research
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Table S7 from Correlates of Prenatal and Early-Life Tobacco Smoke Exposure and Frequency of Common Gene Deletions in Childhood Acute Lymphoblastic Leukemia

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posted on 2023-03-31, 01:00 authored by Adam J. de Smith, Maneet Kaur, Semira Gonseth, Alyson Endicott, Steve Selvin, Luoping Zhang, Ritu Roy, Xiaorong Shao, Helen M. Hansen, Alice Y. Kang, Kyle M. Walsh, Gary V. Dahl, Roberta McKean-Cowdin, Catherine Metayer, Joseph L. Wiemels

Association analyses of joint effects of prenatal and postnatal tobacco smoke exposures on the number of deletions in the child's leukemia using multivariable Poisson regressions.


National Institute of Environmental Health Sciences

National Cancer Institute

Tobacco-Related Disease Research Program

Alex's Lemonade Stand Foundation

U.K. Children with Cancer Foundation

Swiss National Science Foundation

Sutter-Stöttner Foundation

SICPA Foundation



Tobacco smoke exposure has been associated with risk of childhood acute lymphoblastic leukemia (ALL). Understanding the relationship between tobacco exposures and specific mutations may yield etiologic insights. We carried out a case-only analysis to explore whether prenatal and early-life tobacco smoke exposure influences the formation of leukemogenic genomic deletions. Somatic copy number of 8 genes frequently deleted in ALL (CDKN2A, ETV6, IKZF1, PAX5, RB1, BTG1, PAR1 region, and EBF1) was assessed in 559 pretreatment tumor samples from the California Childhood Leukemia Study. Parent and child's passive tobacco exposure was assessed using interview-assisted questionnaires as well as DNA methylation in aryl-hydrocarbon receptor repressor (AHRR), a sentinel epigenetic biomarker of exposure to maternal smoking during pregnancy. Multivariable Poisson regressions were used to test the association between the smoking exposures and total number of deletions. Deletion burden varied by subtype, with a lower frequency in high-hyperdiploid and higher frequency in ETV6–RUNX1 fusion ALL. The total number of deletions per case was positively associated with tobacco smoke exposure, in particular for maternal ever-smoking (ratio of means, RM, 1.31; 95% CI, 1.08–1.59), maternal smoking during pregnancy (RM, 1.48; 95% CI, 1.12–1.94), and during breastfeeding (RM, 2.11; 95% CI, 1.48–3.02). The magnitude of association with maternal ever-smoking was stronger in male children compared with females (Pinteraction = 0.04). The total number of deletions was also associated with DNA methylation at the AHRR epigenetic biomarker (RM, 1.32; 95% CI, 1.02–1.69). Our results suggest that prenatal and early-life tobacco smoke exposure increase the frequency of somatic deletions in children who develop ALL. Cancer Res; 77(7); 1674–83. ©2017 AACR.