Papaemmanuil Elli, Hosking Fay J, Vijayakrishnan Jayaram, Price Amy, Olver Bianca, Sheridan Eammon, Kinsey Sally E, Lightfoot Tracy, Roman Eve, Irving Julie A E, Allan James M, Tomlinson Ian P, Taylor Malcolm, Greaves Mel, Houlston Richard S
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Nat Genet. 2009 Sep;41(9):1006-10. doi: 10.1038/ng.430. Epub 2009 Aug 16.
To identify risk variants for childhood acute lymphoblastic leukemia (ALL), we conducted a genome-wide association study of two case-control series, analyzing the genotypes with respect to 291,423 tagging SNPs in a total of 907 ALL cases and 2,398 controls. We identified risk loci for ALL at 7p12.2 (IKZF1, rs4132601, odds ratio (OR) = 1.69, P = 1.20 x 10(-19)), 10q21.2 (ARID5B, 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 (ARID5B) 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 new insight into disease causation of this specific hematological cancer. Notably, all three risk variants map to genes involved in transcriptional regulation and differentiation of B-cell progenitors.
为了确定儿童急性淋巴细胞白血病（ALL）的风险变异，我们对两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例对照中291,423个标签单核苷酸多态性（SNP）的基因型。我们在7p12.2（IKZF1，rs4132601，优势比（OR）= 1.69，P = 1.20×10^(-19)）、10q21.2（ARID5B，rs7089424，OR = 1.65，P = 6.69×10^(-19)）和14q11.2（CEBPE，rs2239633，OR = 1.34，P = 2.88×10^(-7)）发现了ALL的风险位点。10q21.2（ARID5B）风险关联似乎对具有超二倍体的B细胞前体ALL亚组具有选择性。这些数据表明，常见的低外显率易感性等位基因会增加儿童ALL的发病风险，并为这种特定血液系统癌症的病因提供了新的见解。值得注意的是，所有三个风险变异均映射到参与B细胞祖细胞转录调控和分化的基因。
