Advisory Group on Ionising Radiation (AGIR): Subgroup on Human Radiosensitivity

Terms of reference

Inbred strains of mice show marked differences in sensitivity to both the lethal and carcinogenic effects of radiation leading to the expectation that human populations would also show heterogeneity. One of the early reports from the AGIR considered human radiosensitivity. The 1999 report, Genetic heterogeneity in the population and its implications for radiation risk, concluded 'There are considerable advances needed, both technical and in the understanding of cancer genetics, before genetic testing for individual hypersensitivity to the carcinogenic action of ionising radiation becomes feasible'. The report did however anticipate that identification of susceptible individuals was likely to be possible in the future and acknowledged the ability to identify sensitive individuals could raise ethical problems. Cancer genetics is now much better understood, albeit still incompletely, and evidence for genetic variation in radiosensitivity comes from a variety of sources.

The subgroup will:

• review the evidence for variation in human radiosensitivity.

  This will include both genetic and non-genetic sources of variation. Evidence will likely be drawn from studies of human syndromes, cellular radiosensitivity assays, radiotherapy reaction studies, experimental animal radiosensitivity and cancer susceptibility studies, epidemiological analyses including age and gender specific aspects, and studies of interaction between radiation and other agents (eg radon and smoking) or processes such as inflammatory reactions.

• consider the likely impact of this variation on cancer induction at low doses and medical aspects of radiation protection.

  It is acknowledged that much of the available evidence will be based on relatively high dose studies. However the subgroup aims to use this understanding to anticipate effects of variation on situations that arise in practical radiological protection. This will require understanding of the mechanisms that underlie radiosensitivity.

• explore the possible ethical implications for radiological protection of differences in response to radiation within the population in the light of current knowledge.

  The current system of protection is based on population average estimates of risk. A greater appreciation of the human variation in sensitivity to adverse health effects is anticipated and ways are likely to be identified to assess the sensitivity of individuals or sub-populations. The implications of these variations on the radiological protection system will need to be considered not only from a scientific viewpoint but also in terms of ethical implications.

Membership

Chairman

Professor Malcolm Taylor, University of Birmingham

Members

Dr Gillian Barnett, University of Cambridge
Professor Frances Balkwill, OBE, Institute of Cancer at St Bartholomew's
Professor Bryn Bridges, OBE, University of Sussex
Dr Angus Dawson, Keele University
Professor Jolyon Hendry, University of Oxford
Dr Louise Izatt, Guy's and St Thomas' NHS Foundation Trust
Professor Penny Jeggo, University of Sussex
Dr Paul Pharoah, University of Cambridge
Dr Richard Wakeford, University of Manchester
Professor Catherine West, University of Manchester
 

Secretariat

Dr Christophe Badie, HPA
Dr Simon Bouffler, HPA
 

Observer

Dr Stuart Conney, Department of Health

Work plan

The subgroup will review the available human and experimental data on variation in radiosensitivity due to genetic and other causes and interaction with other agents.This will include consideration of human epidemiological studies, studies of the clinical reactions to radiotherapy, animal studies of radiosensitivity and human cellular and molecular studies. Mechanisms of radiosensitivity will also be considered. The subgroup aims to reach an understanding of the extent of variation of radiosensitivity in the human population, the factors that contribute to the variation, and the mechanistic basis for variation. Consideration will be given to the implications of heterogeneity of radiosensitivity at the low doses of interest in radiological protection as well as at the higher doses that are employed in radiotherapy and that may occur in accidents/incidents involving unauthorised exposures.  An important part of the work is to consider the ethical implications of this understanding of risk at the individual level for radiation protection standards. The subgroup aims to identify knowledge gaps and promising directions for future research.

Meeting dates

July 2010, November 2010, March 2011, July 2011 and October 2011

Last reviewed: 12 December 2011