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Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children

Leukemia volume 27, pages 2416–2419 (2013)Cite this article

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Hispanic children have a 10–30% greater incidence rate of ALL than non-Hispanic whites, and nearly double the rate observed in African-Americans.1 Ethnic differences in ALL incidence may be explained by population-level differences in the frequency of genetic risk factors, including those first discovered in genome-wide association studies of European-ancestry populations.2, 3, 4, 5 As Hispanics are an admixed population with European, African and Native American ancestry, differences in ALL incidence observed in Hispanics may be attributable to genetic risk factors associated with Native American ancestry.

Increased Native American ancestry has been linked to increased risk of relapse among Hispanic children with ALL,6 but no study has yet investigated the contribution of genome-wide Native American ancestry to ALL incidence. Using genome-wide SNP data from 298 Hispanic children with B cell ALL and 456 matched controls from the California Childhood Leukemia Study (CCLS), we investigated whether genome-wide Native-American ancestry was associated with increased risk of B-cell ALL. Additionally, we assessed whether the risk alleles at loci identified in genome-wide association studies of European-ancestry populations (IKZF1, CDKN2A, PIP4K2A, ARID5B, CEBPE) were more common in individuals with greater levels of Native American ancestry. Finally, we quantified the contribution of these validated risk loci to the increased ALL incidence observed in Hispanics relative to populations of European or African ancestry.

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Acknowledgements

This work was supported by National Institutes of Health grants: R25CA112355 (KMW), R01CA155461 (JLW, XM), R01CA126831 (JKW) and R01ES009137 (APC, LH, CM, GVD, MLL, KB, LFB, JLW, and PAB). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. K M Walsh and A P Chokkalingam: The first two authors should be regarded as joint first authors.

Authors and Affiliations

  1. Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA

    K M Walsh

  2. Division of Neuroepidemiology, Department of Neurological Surgery, University of California, San Francisco, CA, USA

    K M Walsh, I V Smirnov & J K Wiencke

  3. School of Public Health, University of California, Berkeley, CA, USA

    A P Chokkalingam, L-I Hsu, C Metayer, K Bartley, L F Barcellos & P A Buffler

  4. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    A J de Smith & J L Wiemels

  5. Yale School of Public Health, Yale School of Medicine, New Haven, CT, USA

    D I Jacobs & X Ma

  6. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA

    G V Dahl

  7. Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, CA, USA

    M L Loh

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  1. K M Walsh
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Correspondence to K M Walsh.

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Walsh, K., Chokkalingam, A., Hsu, LI. et al. Associations between genome-wide Native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children. Leukemia 27, 2416–2419 (2013). https://doi.org/10.1038/leu.2013.130

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