Urayama Kevin Y, Wiencke John K, Buffler Patricia A, Chokkalingam Anand P, Metayer Catherine, Wiemels Joseph L
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143-0560, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1172-7. doi: 10.1158/1055-9965.EPI-07-0007.
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).
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.
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.
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.
多药耐药（MDR）1基因编码一种名为P-糖蛋白的膜转运蛋白，该蛋白通过ATP依赖的细胞外排机制在保护细胞免受亲脂性外源性物质侵害方面发挥重要作用。在参与北加利福尼亚儿童白血病研究的儿童中，我们研究了MDR1单核苷酸多态性（SNP）和预测单倍型所赋予的易感性，以及它们是否会改变室内接触杀虫剂与儿童急性淋巴细胞白血病（ALL）风险之间的关联。
对294例ALL病例和369例对照的颊细胞DNA进行全基因组扩增，并对四个MDR1 SNP（T-129C（rs3213619）、C1236T（rs1128503）、G2677T/A（rs2032582）和C3435T（rs1045642））进行基因分型，这些病例和对照在性别、出生日期、西班牙裔身份和母亲种族方面进行了个体匹配。通过与母亲进行家庭访谈，获取了关于家庭农药使用的详细且特定时间的信息。
非西班牙裔白人和西班牙裔对照中的等位基因频率相似，除T-129C外，似乎处于强连锁不平衡状态。总体而言，单独考虑或在单倍型（C1236T-G2677T/A-C3435T）内的SNP与儿童ALL均无显著关联。然而，我们观察到有强有力的证据表明，室内接触杀虫剂（交互优势比，0.31；95%置信区间，0.15 - 0.64；P = 0.025）对CGC单倍型携带者和非携带者的ALL风险有不同影响。
这些初步数据表明，携带CGC单倍型的儿童可能对室内接触杀虫剂的致白血病作用不太敏感。需要进一步的研究来证实这些发现。
