Abstract
Objective: The multidrug resistance (MDR) 1 gene encodes a membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic xenobiotics by way of an ATP-dependent cellular efflux mechanism. Among children enrolled in the Northern California Childhood Leukemia Study, we examined the susceptibility conferred by MDR1 single nucleotide polymorphisms (SNP) and predicted haplotypes and whether they modify the association between indoor insecticide exposure and risk of childhood acute lymphoblastic leukemia (ALL).
Methods: Buccal cell DNA from ALL cases (n = 294) and controls (n = 369) individually matched on gender, date of birth, Hispanic status, and maternal race were whole genome amplified and genotyped for four MDR1 SNPs, T−129C (rs3213619), C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642). Detailed and time-specific information on household pesticide use was obtained using in-home interviews with the mother.
Results: Allele frequencies in non-Hispanic White and Hispanic controls were similar, and with the exception of T−129C, seemed to be in strong linkage disequilibrium. Overall, the SNPs considered individually or within haplotypes (C1236T-G2677T/A-C3435T) were not significantly associated with childhood ALL. However, we observed strong evidence of a differential effect of indoor insecticide exposure (interaction odds ratio, 0.31; 95% confidence interval, 0.15-0.64; P = 0.025) on risk of ALL between carriers and noncarriers of haplotype CGC.
Conclusion: These preliminary data suggest that children carrying the haplotype CGC may be less susceptible to the leukemogenic effects of indoor insecticide exposures. Future studies are needed to confirm these findings. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1172–7)
- acute lymphoblastic leukemia
- gene-environment interaction
- haplotype
- MDR1
- pesticides
Footnotes
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Grant support: National Institutes of Environmental Health Sciences grants P42 ES04705 and R01 ES09137, and the charity CHILDREN with LEUKAEMIA (United Kingdom).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Note: J.L. Wiemels is a Scholar of the Leukemia and Lymphoma Society of America.
- Accepted March 13, 2007.
- Received January 11, 2007.
- Revision received March 6, 2007.
Volume 16, Issue 6
