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

Journal article

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.

Authors: Papaemmanuil, E; Hosking, F; Vijayakrishnan, J; Price, A; Olver, B

• Publication status: Published
• Journal: Nature genetics
• Volume: 41
• Issue: 9
• Pages: 1006-1010
• Publication date: 2009-09-01
• DOI: 10.1038/ng.430
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Case-Control Studies; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Base Sequence; Recombination, Genetic; Molecular Sequence Data; Genome-Wide Association Study; Humans; Gene Frequency; Alleles; Chromosomes, Human, Pair 14; Introns; Child; Chromosomes, Human, Pair 10; Chromosomes, Human, Pair 7; Child, Preschool; Confidence Intervals; Meta-Analysis as Topic; Risk Factors; Base Pairing; DNA-Binding Proteins; Ikaros Transcription Factor; Probability; CCAAT-Enhancer-Binding Proteins; Polymorphism, Single Nucleotide; Transcription Factors; Linkage Disequilibrium; Haplotypes; Genetic Predisposition to Disease; Odds Ratio; Genotype; Physical Chromosome Mapping; Genetic Variation