Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.
Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.
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DOI：
10.1038/ng.430
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发表时间：
2009-09
期刊：
影响因子：
30.8
通讯作者：
Houlston RS
中科院分区：
文献类型：
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作者：
Papaemmanuil E;Hosking FJ;Vijayakrishnan J;Price A;Olver B;Sheridan E;Kinsey SE;Lightfoot T;Roman E;Irving JA;Allan JM;Tomlinson IP;Taylor M;Greaves M;Houlston RS
为了确定儿童急性淋巴细胞白血病（ALL）的风险变异体，我们对2个病例 - 对照系列进行了全基因组关联研究，分析了总共907例ALL病例和2398例对照的291423个标签单核苷酸多态性（SNP）基因型。我们在7p12.2（IKZF1，rs4132601；比值比 = 1.69，P = 1.20×10⁻¹⁹）、10q21.2（ARIDB5，rs7089424；比值比 = 1.65，P = 6.69×10⁻¹⁹）和14q11.2（CEBPE，rs2239633；比值比 = 1.34，P = 2.88×10⁻⁷）处确定了ALL的风险位点。10q21.2（ARIDB5）的风险关联似乎对伴有超二倍体的B细胞前体ALL亚群具有选择性。这些数据表明，常见的低外显率易感等位基因会增加儿童患ALL的风险，并为这种血液癌症的病因提供了新的见解；值得注意的是，所有3个风险变异体都定位于参与B细胞祖细胞转录调控和分化的基因上。
To identify risk variants for childhood acute lymphoblastic leukemia (ALL) we conducted a genome-wide association study of 2 case-control series, analyzing the genotypes of 291,423 tagging SNP genotypes in a total of 907 ALL cases and 2,398 controls. We identified risk loci for ALL at 7p12.2 (IKZF1, rs4132601; OR = 1.69, P = 1.20 x 10-19), 10q21.2 (ARIDB5, rs7089424; OR = 1.65, P = 6.69 x 10-19) and 14q11.2 (CEBPE, rs2239633; OR = 1.34, P = 2.88 x 10-7). The 10q21.2 (ARIDB5) risk association appears to be selective for the subset of B-cell precursor ALL with hyperdiploidy. These data show that common low-penetrance susceptibility alleles contribute to the risk of developing childhood ALL and provide novel insight into disease causation of this hematological cancer; notably all 3 risk variants map to genes involved in transcriptional regulation and differentiation of B-cell progenitors.