Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood.
Recent genome-wide association data have implicated genetic variation at 7p12.2 (IKZF1), 10q21.2 (ARIDB5), and 14q11.2 (CEBPE) in the etiology of B-cell childhood acute lymphoblastic leukemia (ALL). To verify and further examine the relationship between these variants and ALL risk, we genotyped 1384 cases of precursor B-cell childhood ALL and 1877 controls from Germany and the United Kingdom. The combined data provided statistically significant support for an association between genotype at each of these loci and ALL risk; odds ratios (OR), 1.69 (P = 7.51 x10(-22)), 1.80 (P = 5.90 x 10(-28)), and 1.27 (P = 4.90 x 10(-6)), respectively. Furthermore, the risk of ALL increases with an increasing numbers of variant alleles for the 3 loci (OR(per-allele) = 1.53, 95% confidence interval, 1.44-1.62; P(trend) = 3.49 x 10(-42)), consistent with a polygenic model of disease susceptibility. These data provide unambiguous evidence for the role of these variants in defining ALL risk underscoring approximately 64% of cases.
Prasad
Rashmi B
RB
Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Hosking
Fay J
FJ
Vijayakrishnan
Jayaram
J
Papaemmanuil
Elli
E
Koehler
Rolf
R
Greaves
Mel
M
Sheridan
Eamonn
E
Gast
Andreas
A
Kinsey
Sally E
SE
Lightfoot
Tracy
T
Roman
Eve
E
Taylor
Malcolm
M
Pritchard-Jones
Kathy
K
Stanulla
Martin
M
Schrappe
Martin
M
Bartram
Claus R
CR
Houlston
Richard S
RS
Kumar
Rajiv
R
Hemminki
Kari
K
D000483:Alleles; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D006113:United Kingdom
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