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.
Papaemmanuil
Elli
E
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Hosking
Fay J
FJ
Vijayakrishnan
Jayaram
J
Price
Amy
A
Olver
Bianca
B
Sheridan
Eammon
E
Kinsey
Sally E
SE
Lightfoot
Tracy
T
Roman
Eve
E
Irving
Julie A E
JA
Allan
James M
JM
Tomlinson
Ian P
IP
Taylor
Malcolm
M
Greaves
Mel
M
Houlston
Richard S
RS
D000483:Alleles; D020029:Base Pairing; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002879:Chromosomes, Human, Pair 10; D002883:Chromosomes, Human, Pair 14; D002897:Chromosomes, Human, Pair 7; D016001:Confidence Intervals; D004268:DNA-Binding Proteins / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D007438:Introns; D015810:Linkage Disequilibrium; D015201:Meta-Analysis as Topic; D008969:Molecular Sequence Data; D016017:Odds Ratio; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology* / Q000235:genetics; D011336:Probability; D011995:Recombination, Genetic; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics
C503805:ARID5B protein, human; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497239:IKZF1 protein, human; D014157:Transcription Factors; C070790:CEBPE protein, human; D051740:Ikaros Transcription Factor
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