MDR1 Gene Variants, Indoor Insecticide Exposure, and the Risk of Childhood Acute Lymphoblastic Leukemia

DOI: 10.1158/1055-9965.EPI-07-0007 Published June 2007

Article Figures & Data

Table 1.

Allele frequencies in non-Hispanic White and Hispanic control children

SNP	Allele	Non-Hispanic White			Hispanic			P*
SNP	Allele			n	Frequency (%)	n	Frequency (%)	P*
T−129C	T	165	94.9	151	95.7
T−129C		C		5.1		4.3	0.617
C1236T	C	168	55.4	150	53.3
C1236T		T		44.6		46.7	0.609
G2677T/A	G	165	53.6	150	57.3
		T		43.3		38.0
		A		3.1		4.7	0.274
C3435T	C	170	46.2	152	54.6
C3435T		T		53.8		45.4	0.032

↵* Pearson χ² test was used to test the difference in allele frequencies between non-Hispanic Whites and Hispanic control children.

Table 2.

Analysis of MDR1 SNPs and risk of childhood ALL

↵* ORs and 95% CI were calculated using conditional logistic regression (matching factors: date of birth, sex, Hispanic status, and maternal race).

Table 3.

Analysis of MDR1 haplotypes and risk of childhood ALL

	C1236T	G2677T/A	C3435T	Cases	Controls	OR (95% CI)*
Hap 1	C	G	C	38.8	40.3	0.92 (0.58-1.45)
Hap 2	C	G	T	8.0	8.8	0.83 (0.37-1.88)
Hap 3	T	G	C	6.1	5.5	1.07 (0.41-2.75)
Hap 4	T	T	T	38.3	37.3	1.09 (0.68-1.75)
Hap 5^†	x	A	x	3.5	3.8	0.91 (0.28-2.92)
Hap 6^‡	Other					5.2	4.3	1.54 (0.50-4.72)
Gene copies				588	738
Global likelihood ratio test^§									P = 0.970

↵* Haplotype ORs and 95% CIs were calculated using conditional logistic regression modeling haplotype probabilities (matching factors: date of birth, sex, Hispanic status, and maternal race). Each haplotype is compared with all other haplotypes.
↵† Group of haplotypes that contain the variant A allele at the G2677T/A locus (includes CAC, CAT, TAC, and TAT).
↵‡ Group of rare haplotypes with frequencies <5% and not part of Hap 5 (includes CTC, CTT, TGT, and TTC).
↵§ Global likelihood ratio test done over all haplotypes. Estimates of exact P values were computed using Monte Carlo methods with 10,000 permutations.

Table 4.

Main effects for MDR1 diplotypes and indoor insecticide exposure and risk of childhood ALL

	Cases (n = 294)	Controls (n = 369)	OR (95% CI)*
MDR1 diplotype
Hap 1 (CGC)^†
Other/other	111 (37.8)	125 (33.9)	1.00 (Reference)
≥One copy	183 (62.3)	244 (66.1)	0.88 (0.63-1.21)
Hap 4 (TTT)^†
Other/other	108 (36.7)	138 (37.4)	1.00 (Reference)
≥One copy	186 (63.2)	231 (62.6)	1.03 (0.74-1.44)
Indoor insecticide exposure^‡
No	54 (18.4)	92 (24.9)	1.00 (Reference)
Yes	240 (81.6)	277 (75.1)	1.65 (1.10-2.47)

↵* ORs and 95% CIs were calculated using conditional logistic regression (matching factors: date of birth, sex, Hispanic status, and maternal race). The analysis of indoor insecticide exposure was additionally adjusted for household income.
↵† The order of the MDR1 SNP loci in the haplotypes is C1236T, G2677T/A, and C3435T.
↵‡ Indoor insecticide exposure anytime from 1 y before child's birth through the first 3 y of life. Exposure(s) occurring within the year before diagnosis for cases and corresponding date for controls was discarded for the analyses.

Table 5.

Analysis of interaction between common MDR1 haplotypes, indoor insecticide exposure, and risk of childhood ALL

↵* ORs and 95% CIs were calculated using conditional logistic regression (matching factors: date of birth, sex, Hispanic status, and maternal race) adjusting for household income.
↵† Interaction OR (OR_Interaction) based on the multiplicative model of interaction defined as the ratio of the joint effect of the MDR1 haplotype and indoor insecticide exposure and product of the individual effects [OR_Interaction = OR_GE / (OR_GE′ × OR_G′_E)].