Abstract 662: Effect of tobacco smoking on the risks of childhood acute lymphocytic and myeloid leukemias, by phenotypic and cytogenetic subtype
Authors: Catherine S. Metayer, Luoping Zhang, Joe L. Wiemels, Karen Bartley, Joshua Schiffman, Xiaomei Ma, Melinda Aldrich, Steve Selvin, Martyn Smith, Patricia A. Buffler
Journal: Cancer Research (2012)

Abstract Background: Tobacco smoke contains several myelotropic carcinogens (i.e., benzene, 1,3 butadiene and formaldehyde) and is strongly suspected of damaging pluripotential hematopoietic stem cells. Objective: To examine the role of tobacco smoking in the etiology of childhood acute lymphocytic leukemia (ALL) and myeloid leukemia (AML), defined by phenotypic feature and type of chromosomal aberrations at diagnosis, such as translocation t(12:21) or high hyperdiploidy (51+ chromosomes). Method: Children (0-14 years old) newly diagnosed with ALL (n=839) and AML (n=145) were enrolled in a case-control study in California (1995-2008). Population-based controls (n=1226) were matched to cases on age, sex, Hispanic status, and maternal race. Parents provided information on exposure to tobacco smoking before and after their child's birth. Conventional karyotype and fluorescence in situ hybridization (FISH) data were abstracted from the medical reports. Additional FISH assays using pre-treatment bone marrow specimens were conducted to complete cytogenetic classification. Unconditional logistic regression analyses were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for developing leukemia, using binary variable for ever/never smoked (ORbinary) and continuous variable for number of cigarettes smoked per day (ORcig). All models included the matching factors and household income. Results: In univariate analyses, elevated risks of B-cell ALL (n=722) were associated with pre-conception paternal smoking (“PCPS”) (ORcig= 1.02; 95% CI:1.00-1.03; p=0.04) and child's passive smoking (“CPS”) after birth (ORbinary=1.32; 95% CI:1.21-3.50; p=0.02). Analyses using mutually exclusive exposure variables (i.e., only “PCPS,” only “CPS,” and both “PCPS-CPS,” compared to no smoking) showed that the elevated risk of B-cell ALL was limited to children exposed to both “PCPS-CPS” (OR=1.50, 95% CI:1.10-2.04). The magnitude of this association increased for 133 B-cell ALL cases harboring chromosomal translocation t(12;21) (OR=2.37; 95% CI:1.41-4.01). Weaker associations were seen between “PCPS” and “CPS” and B-cell ALL harboring other chromosome translocations (n=82) or deletions (n=63). Tobacco smoking did not appear to be associated with hyperdiploid B-cell ALL (n=228) and T-cell ALL (n=70). Child's passive smoking conferred a 1.5-fold increased risk of AML (95% CI:0.98-2.26; p=0.06), with a higher risk observed for those with chromosome aberrations linked to a “favorable” prognosis (ORbinary=1.94; p=0.07; n=80). No excess risks were seen with maternal smoking during pregnancy, after accounting for other sources of smoking. Conclusions: Exposure to tobacco smoking is an important predictor of childhood ALL, and possibly AML. The observed risks contrast by phenotypic and cytogenetic subtype, providing insights in the etiology of the disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 662. doi:1538-7445.AM2012-662