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Review
. 2021 Dec 24:9:805757.
doi: 10.3389/fpubh.2021.805757. eCollection 2021.

Risk Factors for Childhood Leukemia: Radiation and Beyond

Janine-Alison Schmidt  1 , Sabine Hornhardt  1 , Friederike Erdmann  2   3 , Isidro Sánchez-García  4 , Ute Fischer  5 , Joachim Schüz  3 , Gunde Ziegelberger  1
Affiliations
Review

Risk Factors for Childhood Leukemia: Radiation and Beyond

Janine-Alison Schmidt et al. Front Public Health. .

Abstract

Childhood leukemia (CL) is undoubtedly caused by a multifactorial process with genetic as well as environmental factors playing a role. But in spite of several efforts in a variety of scientific fields, the causes of the disease and the interplay of possible risk factors are still poorly understood. To push forward the research on the causes of CL, the German Federal Office for Radiation Protection has been organizing recurring international workshops since 2008 every two to three years. In November 2019 the 6th International Workshop on the Causes of CL was held in Freising and brought together experts from diverse disciplines. The workshop was divided into two main parts focusing on genetic and environmental risk factors, respectively. Two additional special sessions addressed the influence of natural background radiation on the risk of CL and the progress in the development of mouse models used for experimental studies on acute lymphoblastic leukemia, the most common form of leukemia worldwide. The workshop presentations highlighted the role of infections as environmental risk factor for CL, specifically for acute lymphoblastic leukemia. Major support comes from two mouse models, the Pax5+/- and Sca1-ETV6-RUNX1 mouse model, one of the major achievements made in the last years. Mice of both predisposed models only develop leukemia when exposed to common infections. These results emphasize the impact of gene-environment-interactions on the development of CL and warrant further investigation of such interactions - especially because genetic predisposition is detected with increasing frequency in CL. This article summarizes the workshop presentations and discusses the results in the context of the international literature.

Keywords: acute lymphoblastic leukemia; childhood leukemia; environmental exposure; genetic susceptibility; magnetic fields; radiation; risk factors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Risk factors (potential and established) for childhood acute lymphoblastic leukemia (ALL). A large body of research has targeted a wide range of possible risk factors for childhood ALL, including genetic risk factors (indicated in blue) and environmental risk factors (indicated in green). The interaction of genetic and environmental risk factors (gene-environment-interaction) may have an impact on ALL development. Inherited genetic susceptibility is detected with increasing frequency in childhood leukemia as well as preleukemic fusion genes as predisposing factors. The impact of epigenetic alterations (possibly induced by oncogenes or environmental exposures) on ALL development is yet unclear. Among the recognized environmental risk factors are high and low birth weight and sex as well as high to moderate doses of ionizing radiation. The relevance of infections as risk factor for ALL has strengthened considerably in the last decade. In contrast, evidence for an association between a higher risk for ALL and exposure to low/very low doses of ionizing radiation, extremely low frequency magnetic fields (e.g., from power lines), and other environmental risk factors (like pesticides or air pollution), respectively, has yet to be verified.
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