Abstract

Childhood acute lymphoblastic leukemia (ALL) (age 0–14 years) is 20% more common in Latino Americans than non-Latino whites. We conduct a genome-wide association study in a large sample of 3263 Californian children with ALL (including 1949 of Latino heritage) and 3506 controls matched on month and year of birth, sex, and ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic Epidemiology Research on Aging Cohort. Replication of the strongest genetic associations is performed in two independent datasets from the Children’s Oncology Group and the California Childhood Leukemia Study. Here we identify new risk loci on 17q12 near IKZF3/ZPBP2/GSDMB/ORMDL3, a locus encompassing a transcription factor important for lymphocyte development (IKZF3), and at an 8q24 region known for structural contacts with the MYC oncogene. These new risk loci may impact gene expression via local (four 17q12 genes) or long-range (8q24) interactions, affecting function of well-characterized hematopoietic and growth-regulation pathways.

Details

Title
GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21
Author
Wiemels, Joseph L 1 ; Walsh, Kyle M 2 ; de Smith, Adam J 3 ; Metayer, Catherine 4 ; Gonseth, Semira 5   VIAFID ORCID Logo  ; Hansen, Helen M 6 ; Francis, Stephen S 7 ; Ojha, Juhi 3 ; Smirnov, Ivan 6 ; Barcellos, Lisa 4 ; Xiao, Xiaorong 4 ; Morimoto, Libby 4 ; McKean-Cowdin, Roberta 8 ; Wang, Rong 9 ; Yu, Herbert 10   VIAFID ORCID Logo  ; Hoh, Josephine 9 ; DeWan, Andrew T 9 ; Ma, Xiaomei 9 

 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA; Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA; Department of Preventative Medicine, University of Southern California, Los Angeles, CA, USA 
 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA 
 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA 
 School of Public Health, University of California Berkeley, Berkeley, CA, USA 
 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; Department of Preventative Medicine, University of Southern California, Los Angeles, CA, USA 
 Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA 
 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; Department of Epidemiology, School of Community Health Sciences, University of Nevada Reno, Reno, NV, USA 
 Department of Preventative Medicine, University of Southern California, Los Angeles, CA, USA 
 Department of Chronic Diseases Epidemiology, School of Public Health, Yale University, New Haven, CT, USA 
10  University of Hawaii Cancer Center, Honolulu, HI, USA 
Pages
1-8
Publication year
2018
Publication date
Jan 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1988934678
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.