Variation in xenobiotic transport and metabolism genes, household chemical exposures, and risk of childhood acute lymphoblastic leukemia.
BACKGROUND
Recent 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.


METHODS
We 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.


RESULTS
We 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.


CONCLUSIONS
Our 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.
Division of Epidemiology, UC Berkeley School of Public Health, University of California Berkeley, 1995 University Ave, , Berkeley, CA 94704, USA. anandc@berkeley.edu
Anand P
AP
Chokkalingam
Catherine
C
Metayer
Ghislaine A
GA
Scelo
Jeffrey S
JS
Chang
Kevin Y
KY
Urayama
Melinda C
MC
Aldrich
Neela
N
Guha
Helen M
HM
Hansen
Gary V
GV
Dahl
Lisa F
LF
Barcellos
John K
JK
Wiencke
Joseph L
JL
Wiemels
Patricia A
PA
Buffler
D000293:Adolescent; D001692:Biological Transport; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure / Q000009:adverse effects / Q000706:statistics & numerical data*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010575:Pesticides / Q000493:pharmacokinetics / Q000506:poisoning; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D015262:Xenobiotics / Q000493:pharmacokinetics* / Q000506:poisoning*
D010575:Pesticides; D015262:Xenobiotics