Risk Factors for Childhood Leukemia: Radiation and Beyond.

Janine-Alison Schmidt,Ute Fischer,Gunde Ziegelberger,Friederike Erdmann,Joachim Schüz,Isidro Sánchez-García,Sabine Hornhardt

doi:10.3389/fpubh.2021.805757

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.

Highlights

Leukemia is the most frequent cancer in children, with a proportion of about 30% of all cancers diagnosed in children before the age of 15 years [1]
Experimental Findings Previous hazard identification and risk assessments by International Agency for Research on Cancer (IARC), the World Health Organization (WHO), and the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) considered evidence from experimental animal studies on the association of extremely low-frequency magnetic fields (ELF-MF) and leukemia as inadequate [114, 120, 121], and such studies have been hampered by the fact that no animal model existed that resembled the human disease appropriately
Presented mouse models included the Cdkn2a deficient/ETV6-RUNX1 mouse model, the PAX5-ELN mouse model, and the Sca1-ETV6-RUNX1 mouse model already described in section Experimental Evidence for an InfectionMediated Childhood Leukemogenesis, Cdkn2a deficient/ETV6RUNX1 as well as PAX5-ELN transgenic mice developed neoplasms with a high incidence of up to 50-80%, respectively [122, 123]

Summary

Introduction

Leukemia is the most frequent cancer in children, with a proportion of about 30% of all cancers diagnosed in children before the age of 15 years [1]. It is currently not known how much the frequency of the ETV6-RUNX1 fusion genes differs across infant populations around the world, and future studies have to show how the presence and frequency of preleukemic clones in blood at birth affects the risk of the newborn for developing ALL later in life.

Results

Conclusion