3.3. Molecular genetic analysis ("deep sequencing") of B-cell ALL patients

3.3.a Interdisciplinary study to investigate a relationship between environmental, genetic factors and leukaemia in B-cell ALL patients – feasibility study

Research contractor: Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University Mainz
Start: 1 February 2021
End: 30 April 2022

Background

Leukaemia is the most common childhood cancer in Germany and worldwide. However, despite considerable research, the causes of this disease are still largely unknown.

To date, ionising radiation is one of the few factors that have been shown to increase the risk of developing leukaemia. Although several other factors have been associated with an increased risk of childhood leukaemia, the evidence available is too weak to prove a causal relationship.

These include environmental risk factors such as extremely low frequency magnetic fields (ELF-MF), air pollution, and pesticides as well as lifestyle factors such as alcohol or smoking. Various genetic factors that either newly occur in the child or are inherited from the parents are associated with an increased risk of disease.

It is assumed that the development of childhood leukaemia is a multi-factorial process; both genetic factors and environmental influences are involved. However, it is unclear whether and how these factors influence each other.

Objectives

This project will investigate the feasibility of a main interdisciplinary study to answer the question whether paediatric ALL (acute lymphoblastic leukaemia) patients of different genetic sub-groups differ with respect to previous (including paternal and maternal) exposures to environmental risk factors – here specifically to ELF-MF. For this purpose, the main study is to be embedded in an ongoing or newly starting clinical paediatric leukaemia study and conducted within the framework of this. The present feasibility study is intended to clarify the possibilities of integration as well as the feasibility and significance of such an interdisciplinary main study.

Implementation

In a first step, the relevant state of the art in science and technology will be reviewed in order to identify possible environmental and genetic risk factors associated with childhood leukaemia and to evaluate them according to their relevance. Relevance is assessed based on the level of evidence as well as the level of the potential risk factor and the prevalence thereof. Furthermore, ongoing and newly started ALL clinical trials will be identified and contacted.

If there is a willingness to be involved, a pilot study will be planned, taking into account data protection and ethical aspects. The planning will also include the creation of a questionnaire based on the risk factors identified and evaluated, the selection of a suitable measurement method to record the exposure of ALL patients to low-frequency magnetic fields, and the creation of a concept for recording relevant genetic factors in cooperation with a scientific advisor.

In the final step, the feasibility of the pilot study and the interdisciplinary main study will be evaluated based on the findings obtained. A final report will be written. Among other things, this will list appropriate paediatric ALL clinical trials for embedding, privacy and ethics committee constraints, time lines, costs, and potential case numbers for the main study. On this basis, it will derive recommendations for conducting a pilot study and main study.

3.3.b Interdisciplinary study to investigate a correlation between environmental and genetic factors and leukaemia in B-cell ALL patients – pilot study

In order to investigate possible links between leukaemia development and environmental and genetic factors in patients with B-cell ALL, an interdisciplinary study will be embedded in and conducted within a paediatric clinical leukaemia study. The feasibility of such a study is currently being examined in the ongoing project 3.3.a. The further course of action depends on the results and recommendations of this feasibility study.