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Link to original content: https://pubmed.ncbi.nlm.nih.gov/19684604
Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia - PubMed Skip to main page content
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. 2009 Sep;41(9):1006-10.
doi: 10.1038/ng.430. Epub 2009 Aug 16.

Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia

Elli Papaemmanuil  1 , Fay J Hosking, Jayaram Vijayakrishnan, Amy Price, Bianca Olver, Eammon Sheridan, Sally E Kinsey, Tracy Lightfoot, Eve Roman, Julie A E Irving, James M Allan, Ian P Tomlinson, Malcolm Taylor, Mel Greaves, Richard S Houlston
Affiliations

Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia

Elli Papaemmanuil et al. Nat Genet. 2009 Sep.

Abstract

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.

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Conflict of interest statement

Competing Interests Statement

The authors declare no competing financial interests

Figures

Figure 1
Figure 1. LD structure and association results for each of the disease-associated regions:
(A) 7p12.2; (B) 10q21.2 and (C) 14q11.2. Chromosomal positions based on NCBI build 36 coordinates, showing Ensemble (release 48) genes. Armitage trend test P values (as –log10 values; left y axis) are shown for SNPs analyzed. Recombination rates in HapMap CEU across the region are shown in black (right y axis). Also shown are the relative positions of genes mapping to each region of association. Exons of genes have been redrawn to show the relative positions in the gene, therefore maps are not to physical scale.
Figure 2
Figure 2. Relationship between lymphocyte mRNA expression levels of IKZF1 and rs4132601 genotype.
See this image and copyright information in PMC

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