Abstract
BackgroundRecent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL). We sought to evaluate the role of genes involved in xenobiotic transport and metabolism in childhood ALL risk, both alone and in conjunction with household chemical exposures previously found to be associated with childhood ALL risk.MethodsWe conducted a population-based epidemiologic study of 377 cases and 448 controls in California, utilizing a haplotype-based approach to evaluate 42 xenobiotic transport and metabolism genes in conjunction with data on self-reported household chemical exposures.ResultsWe identified significant associations of childhood ALL risk with haplotypes of ABCB1, ARNT, CYP2C8, CYP1A2, CYP1B1, and IDH1. In addition, certain haplotypes showed significant joint effects with self-reported household chemical exposures on risk of childhood ALL. Specifically, elevated risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1, respectively.ConclusionsOur results provide support for a role of xenobiotic transport and metabolism pathways in risk of childhood ALL and indicate that genes in these pathways may modulate the risk of disease associated with use of common household chemicals. Additional studies are needed to confirm these findings and localize specific causal variants.Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-012-9947-4) contains supplementary material, which is available to authorized users.
Highlights
Leukemia is the most common cancer among children under 15 years of age, accounting for 32 % of all childhood malignancies [1]
Background Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL)
The 42 xenobiotic transport and metabolism pathway genes we examined are listed in Supplementary Table A
Summary
Leukemia is the most common cancer among children under 15 years of age, accounting for 32 % of all childhood malignancies [1]. In order to exert their effects, these potentially harmful xenobiotic (exogenous) chemicals must first gain entry into target cells and undergo cellular metabolic processes that alter their activity. Membrane transporters such as those encoded by the multiple drug resistance (ABCB1/MDR1) gene act as efflux pumps to expel compounds from the cell and are strategically expressed in regions of the body that act as epithelial barriers or perform excretory functions [12]. Recent studies suggest that environmental exposures to pesticides, tobacco, and other xenobiotic chemicals may increase risk of childhood acute lymphoblastic leukemia (ALL).
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