Potential screening assays for individual radiation sensitivity and susceptibility and their current validation state

Abstract

Purpose: The workshop on ‘Individual Radiosensitivity and Radiosusceptibility’ organized by MELODI and CONCERT on Malta in 2018, evaluated the current state of assays to identify sensitive and susceptible subgroups. The authors provide an overview on potential screening assays detecting individuals showing moderate to severe early and late radiation reactions or are at increased risk to develop cancer upon radiation exposure.

Conclusion: It is necessary to separate clearly between tissue reactions and stochastic effects such as cancer when comparing the existing literature to validate various test systems. Requirements for the assays are set up. The literature is reviewed for assays that are reliable and robust. Sensitivity and specificity of the assays are regarded and scrutinized for modifying factors. Accuracy of an assay system is required to be more than 90% to balance risks of adverse reactions against risk to fail to cure the cancer. No assay/biomarker is in routine use. Assays that have shown predictive potential for radiosensitivity include SNPs, the RILA assay, and the pATM assay. A tree of risk guideline for radiologists is provided to assist medical treatment decisions. Recommendations for effective research include the setup of common retrospective and prospective cohorts/biobanks to validate current and future tests.

Keywords:

• Radiation sensitivity
• cancer susceptibility
• adverse radiation effects
• predicting tests

Disclosure statement

No potential conflict of interest was reported by the authors.

Authors’ contributions

Maria Gomolka: Coordination, outline, recommendations, graphs, decision tree of risk.

Benjamin Blyth: Responsible for biomarkers radiosusceptibility, graphs, text editing.

Michel Bourguignon: Responsible for introduction, test requirements.

Christophe Badie: Contribution to biomarkers radiosusceptibiliy.

Annette Schmitz: Contribution for introduction, test requirements.

Christopher Talbot: Responsible for biomarkers radiosensitivity.

Christoph Hoeschen: Writing support.

Sisko Salomaa: Responsible for biomarkers noncancer diseases.

Additional information

Funding

We thank the MELODI Association and CONCERT European Joint Programme [H2020 Euratom grant number 662287] for the financial support of the 2018 workshop.

Notes on contributors

Maria Gomolka

Dr. Maria Gomolka is a biologist and senior scientist in the working group Radiationbiology of the Federal Office for Radiation Protection, Oberschleissheim, Germany. She focuses on radiation sensitivity, biobanking of radiation exposed individuals and biomarker development for radiation protection.

Benjamin Blyth

Dr. Benjamin Blyth is a researcher in the Department of Radiation Oncology at the Peter MacCallum Cancer Centre. His research interests include radiation carcinogenesis and individual responses to radiation therapy.

Michel Bourguignon

Prof. Dr. med. Michel Bourguignon is Professor of Biophysics and Nuclear Medicine of the University Paris-Saclay/UVSQ. Half of his career (1978–1996) was dedicated to research in nuclear medicine with the French Atomic Energy Commission (CEA). In the second half (1996–2014), he had major national responsibilities in radiological protection with the ministry of Health and the French nuclear safety authority (ASN). He is currently Editor in chief of Radioprotection.

Christophe Badie

Dr. Christophe Badie leads the Cancer Genetics and Cytogenetics group at Public Health England. He has 25 years of experience in research on radiation effects on health. His group is carrying out research into the fundamental mechanisms by which radiation causes cancer especially the chromosomal and molecular mechanisms that underlie radiation-induced leukemia initiation, development, and susceptibility. He has also identified and developed biomarkers of radiation exposure, sensitivity, toxicity, and long-term effects and published multiple research papers in this area.

Annette Schmitz

Dr. Annette Schmitz is a research scientist working at CEA; the French Atomic Energy Commission. She contributed to human and animal genome cartography and developed research into the contribution of human genetic diversity to radiosensitivity of blood cells, with the aim of developing and validating biomarkers for individual radiosensitivity.

Christopher Talbot

Dr. Christopher Talbot is a senior lecturer in medical genetics at the University of Leicester. His recent work has sought to find predictors for radiotherapy side effects using a variety of approaches including genetics, cell biomarkers, and circadian biology.

Christoph Hoeschen

Prof. Dr. Christoph Hoeschen is professor for medical systems engineering at Otto-von-Guericke University Magdeburg. He studied physics, worked in the national metrology institute of Germany, a university radiology department and at a Helmholtz center before. He participated in various European projects and is member of the German radiation protection board as well as of various scientific organizations and editorial boards.

Sisko Salomaa

Dr. Sisko Salomaa is professor of radiobiology at the University of Eastern Finland and coordinator for national radiation safety research programme (Cores.fi). She is leading the CONCERT work package on Integration and Strategic Research Agenda Development for radiation protection research. She is representative of Finland to UNSCEAR and member of ICRP Committee 1 on Radiation Effects.