title: Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood.
abstract: 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.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Rashmi B
authors.initials: RB
authors.lastname: Prasad
authors.forename: Fay J
authors.initials: FJ
authors.lastname: Hosking
authors.forename: Jayaram
authors.initials: J
authors.lastname: Vijayakrishnan
authors.forename: Elli
authors.initials: E
authors.lastname: Papaemmanuil
authors.forename: Rolf
authors.initials: R
authors.lastname: Koehler
authors.forename: Mel
authors.initials: M
authors.lastname: Greaves
authors.forename: Eamonn
authors.initials: E
authors.lastname: Sheridan
authors.forename: Andreas
authors.initials: A
authors.lastname: Gast
authors.forename: Sally E
authors.initials: SE
authors.lastname: Kinsey
authors.forename: Tracy
authors.initials: T
authors.lastname: Lightfoot
authors.forename: Eve
authors.initials: E
authors.lastname: Roman
authors.forename: Malcolm
authors.initials: M
authors.lastname: Taylor
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
mesh_terms: 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
chemical_list: 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