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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

Prasad, Rashmi B LU ; Hosking, Fay J.; Vijayakrishnan, Jayaram; Papaemmanuil, Elli; Koehler, Rolf; Greaves, Mel; Sheridan, Eamonn; Gast, Andreas; Kinsey, Sally E. and Lightfoot, Tracy, et al. (2010) In Blood 115(9). p.7-1765
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... (More)

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.

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@article{b1cd7107-d2fb-4ef0-a756-9acf0f9ce1af,
  abstract     = {<p>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.</p>},
  author       = {Prasad, Rashmi B and Hosking, Fay J. and Vijayakrishnan, Jayaram and Papaemmanuil, Elli and Koehler, Rolf and Greaves, Mel and Sheridan, Eamonn and Gast, Andreas and Kinsey, Sally E. and Lightfoot, Tracy and Roman, Eve and Taylor, Malcolm and Pritchard-Jones, Kathy and Stanulla, Martin and Schrappe, Martin and Bartram, Claus R. and Houlston, Richard S and Kumar, Rajiv and Hemminki, Kari},
  issn         = {1528-0020},
  keyword      = {Alleles,CCAAT-Enhancer-Binding Proteins,Case-Control Studies,Child,Chromosomes, Human, Pair 10,Chromosomes, Human, Pair 14,Chromosomes, Human, Pair 7,DNA-Binding Proteins,Female,Genetic Predisposition to Disease,Genotype,Germany,Humans,Ikaros Transcription Factor,Male,Middle Aged,Models, Genetic,Odds Ratio,Polymorphism, Single Nucleotide,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma,Transcription Factors,United Kingdom,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {03},
  number       = {9},
  pages        = {7--1765},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in precursor B-cell acute lymphoblastic leukemia of childhood},
  url          = {http://dx.doi.org/10.1182/blood-2009-09-241513},
  volume       = {115},
  year         = {2010},
}