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Inherited Risk for Childhood Leukemia

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The Hereditary Basis of Childhood Cancer

Abstract

Childhood leukemia is the most common pediatric malignancy, diagnosed in nearly a third of pediatric cancer patients. Awareness and identification of the hereditary component of childhood leukemia continues to increase. Childhood leukemia, especially acute lymphoblastic leukemia (ALL), has been attributed to a dysregulated immune system with different patterns of infectious exposure at a young age. Candidate gene studies have revealed inconsistent associations with specific SNPs related to folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies (GWAS) have demonstrated stronger associations with SNPs in B-cell development genes and increased risk for childhood ALL. Identical twins have been described with childhood leukemia due to presumed placental transfer, but non-twin siblings with childhood leukemia also have been very rarely reported suggesting a genetic link to disease susceptibility. In this chapter, we review the known hereditary cancer syndromes associated with leukemia which can be divided into six categories: (1) DNA repair syndromes, (2) RASopathies, (3) bone marrow failure syndromes, (4) immunodeficiency syndromes, (5) germline predisposition to leukemia, and (6) congenital syndromes.

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Acknowledgments

We acknowledge the assistance of the Genetic Counseling Shared Resource supported by P30 CA042014 awarded to Huntsman Cancer Institute. We also acknowledge the careful review and suggestions of Mel F. Greaves, PhD, in the Haemato-Oncology Research Unit in the Division of Molecular Pathology at The Institute of Cancer Research in the United Kingdom.

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Authors and Affiliations

  1. Family Cancer Assessment Clinic, High Risk Cancer Research Clinics, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Jennie Vagher, Luke Maese, Amanda Gammon, Wendy Kohlmann & Joshua D. Schiffman

  2. Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

    Luke Maese & Joshua D. Schiffman

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  1. Jennie Vagher
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  2. Luke Maese
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Correspondence to Joshua D. Schiffman .

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  1. University of Toronto, Departments of Pediatrics and Medical Biophysics, The Hospital for Sick Children, Division of Hematology/Oncology, Toronto, ON, Canada

    David Malkin

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Vagher, J., Maese, L., Gammon, A., Kohlmann, W., Schiffman, J.D. (2021). Inherited Risk for Childhood Leukemia. In: Malkin, D. (eds) The Hereditary Basis of Childhood Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-74448-9_11

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