Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Blood. 2010 Mar 4;115(9):1765-7. doi: 10.1182/blood-2009-09-241513. Epub 2009 Dec 30.
Recent genome-wide association data have implicated genetic variation at 7p12.2 (IKZF1), 10q21.2 (ARIDB5), and 14q11.2 (CEBPE) in the etiology of B-cell childhood acute lymphoblastic leukemia (ALL). To verify and further examine the relationship between these variants and ALL risk, we genotyped 1384 cases of precursor B-cell childhood ALL and 1877 controls from Germany and the United Kingdom. The combined data provided statistically significant support for an association between genotype at each of these loci and ALL risk; odds ratios (OR), 1.69 (P = 7.51 x10(-22)), 1.80 (P = 5.90 x 10(-28)), and 1.27 (P = 4.90 x 10(-6)), respectively. Furthermore, the risk of ALL increases with an increasing numbers of variant alleles for the 3 loci (OR(per-allele) = 1.53, 95% confidence interval, 1.44-1.62; P(trend) = 3.49 x 10(-42)), consistent with a polygenic model of disease susceptibility. These data provide unambiguous evidence for the role of these variants in defining ALL risk underscoring approximately 64% of cases.
最近的全基因组关联数据表明，7p12.2（IKZF1）、10q21.2（ARIDB5）和 14q11.2（CEBPE）的遗传变异与 B 细胞儿童急性淋巴细胞白血病（ALL）的病因有关。为了验证和进一步研究这些变体与 ALL 风险之间的关系，我们对来自德国和英国的 1384 例前体 B 细胞儿童 ALL 病例和 1877 例对照进行了基因分型。综合数据为这些位点的基因型与 ALL 风险之间的关联提供了统计学上的支持；优势比（OR）分别为 1.69（P = 7.51 x10(-22)）、1.80（P = 5.90 x 10(-28)）和 1.27（P = 4.90 x 10(-6)）。此外，随着这 3 个位点的变异等位基因数量的增加，ALL 的风险也会增加（OR（每等位基因）= 1.53，95%置信区间，1.44-1.62；P（趋势）= 3.49 x 10(-42)），符合疾病易感性的多基因模型。这些数据提供了明确的证据，证明这些变体在定义 ALL 风险方面的作用，突出了大约 64%的病例。
