MDR1 gene variants, indoor insecticide exposure, and the risk of childhood acute lymphoblastic leukemia.
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.


CONCLUSIONS
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.
Urayama
Kevin Y
KY
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143-0560, USA.
Wiencke
John K
JK
Buffler
Patricia A
PA
Chokkalingam
Anand P
AP
Metayer
Catherine
C
Wiemels
Joseph L
JL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D016902:Air Pollution, Indoor / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D019450:Genes, MDR; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007306:Insecticides / Q000009:adverse effects*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced* / Q000235:genetics*; D012307:Risk Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007306:Insecticides