Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia
Copyright policy )Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia
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.
- University of Salford United Kingdom
- University of York United Kingdom
- Wellcome Centre for Human Genetics United Kingdom
- Leeds Teaching Hospitals NHS Trust United Kingdom
- Solent NHS Trust United Kingdom
Chromosomes, Human, Pair 14, Base Sequence, Genotype, Chromosomes, Human, Pair 10, Genetic Variation, Article, DNA-Binding Proteins, Ikaros Transcription Factor, Gene Frequency, Haplotypes, Case-Control Studies, Child, Preschool, CCAAT-Enhancer-Binding Proteins, Confidence Intervals, Humans, Genetic Predisposition to Disease, Child, Base Pairing, Alleles, Chromosomes, Human, Pair 7, Genome-Wide Association Study
Chromosomes, Human, Pair 14, Base Sequence, Genotype, Chromosomes, Human, Pair 10, Genetic Variation, Article, DNA-Binding Proteins, Ikaros Transcription Factor, Gene Frequency, Haplotypes, Case-Control Studies, Child, Preschool, CCAAT-Enhancer-Binding Proteins, Confidence Intervals, Humans, Genetic Predisposition to Disease, Child, Base Pairing, Alleles, Chromosomes, Human, Pair 7, Genome-Wide Association Study
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