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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...

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Main Authors: Bokkasa, Rashmi Prasad (Author) , Hosking, Fay J. (Author) , Vijayakrishnan, Jayaram (Author) , Papaemmanuil, Elli (Author) , Köhler, Rolf (Author) , Greaves, Mel (Author) , Sheridan, Eamonn (Author) , Gast, Andreas (Author) , Kinsey, Sally E. (Author) , Lightfoot, Tracy (Author) , Roman, Eve (Author) , Taylor, Malcolm (Author) , Pritchard-Jones, Kathy (Author) , Stanulla, Martin (Author) , Schrappe, Martin (Author) , Bartram, Claus R. (Author) , Houlston, Richard S. (Author) , Kumar, Rajiv (Author) , Hemminki, Kari (Author)
Format: Article (Journal)
Language:English
Published: March 4, 2010
In: Blood
Year: 2010, Volume: 115, Issue: 9, Pages: 1765-1767
ISSN:1528-0020
DOI:10.1182/blood-2009-09-241513
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood-2009-09-241513
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Author Notes:Rashmi B. Prasad, Fay J. Hosking, Jayaram Vijayakrishnan, Elli Papaemmanuil, Rolf Koehler, Mel Greaves, Eamonn Sheridan, Andreas Gast, Sally E. Kinsey, Tracy Lightfoot, Eve Roman, Malcolm Taylor, Kathy Pritchard-Jones, Martin Stanulla, Martin Schrappe, Claus R. Bartram, Richard S. Houlston, Rajiv Kumar, and Kari Hemminki

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245 1 0 |a Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood  |c Rashmi B. Prasad, Fay J. Hosking, Jayaram Vijayakrishnan, Elli Papaemmanuil, Rolf Koehler, Mel Greaves, Eamonn Sheridan, Andreas Gast, Sally E. Kinsey, Tracy Lightfoot, Eve Roman, Malcolm Taylor, Kathy Pritchard-Jones, Martin Stanulla, Martin Schrappe, Claus R. Bartram, Richard S. Houlston, Rajiv Kumar, and Kari Hemminki 
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520 |a 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 ×10−22), 1.80 (P = 5.90 × 10−28), and 1.27 (P = 4.90 × 10−6), respectively. Furthermore, the risk of ALL increases with an increasing numbers of variant alleles for the 3 loci (ORper-allele = 1.53, 95% confidence interval, 1.44-1.62; Ptrend = 3.49 × 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. 
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