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

Abstract

Richard Houlston and colleagues report results of a genome-wide association study of childhood acute lymphoblastic leukemia. Identified risk loci include IKZF1 on 7p12.2 and ARID5B on 10q21.2, which encode transcription factors involved in the differentiation of B-cell progenitors. 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 × 10−19), 10q21.2 (ARID5B, rs7089424, OR = 1.65, P = 6.69 × 10−19) and 14q11.2 (CEBPE, rs2239633, OR = 1.34, P = 2.88 × 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.