Low-dose Extrapolation of Radiation-related Cancer Risk
ICRP Publication 99Ann. ICRP 35 (4), 2005
Abstract - This report considers the evidence relating to cancer risk associated with exposure to low doses of low linear energy transfer radiation, and particularly doses below current recommended limits for protection of radiation workers and the general public. The focus is on evidence regarding linearity of the dose–response relationship for all cancers considered as a group, but not necessarily individually, at low doses [the so-called linear, non-threshold (LNT) hypothesis]. It looks at the possibility of establishing a universal threshold dose below which there is no risk of radiation-related cancer. The report is organised by scientific discipline, beginning with epidemiological studies of exposed human populations. Extrapolation of risk estimates based on observations at moderate to high doses continues to be the primary basis for estimation of radiation-related risk at low doses and dose rates. The fundamental role of radiation-induced DNA damage in the induction of mutations and chromosome aberrations provides a framework for the analysis of risks at low radiation doses and low-dose-rate exposures. Although cells have a vast array of damage response mechanisms, these mechanisms are not foolproof, and it is clear that damaged or altered cells are capable of escaping these pathways and propagating. Cellular consequences of radiation-induced damage include chromosome aberrations and somatic cell mutations. Current understanding of mechanisms and quantitative data on dose and time–dose relationships support the LNT hypothesis. Emerging results with regard to radiation-related adaptive responses, genomic instability, and bystander effects suggest that the risk of low-level exposure to ionising radiation is uncertain, and a simple extrapolation from high-dose effects may not be wholly justified in all instances. However, although there are intrinsic uncertainties at low doses and low dose rates, direct epidemiological measures of radiation cancer risk necessarily reflect all mechanistic contributions including those from induced genomic instability, bystander effects, and, in some cases, adaptive responses, and therefore may provide insights about these contributions. Experimental approaches using animal models support the view that the response for early initiating events is likely to correspond to that for the induction of cytogenetic damage. On this basis, mechanistic arguments support a linear response in the low-dose region. Quantitative analyses of dose responses for tumourigenesis and for life shortening in laboratory animals also support this prediction. These studies also support a dose and dose rate effectiveness factor (DDREF) in the range of about 2 when data are extrapolated to low doses from effects induced by doses in the range of 2–3 Gy. A formal quantitative uncertainty analysis combines the different uncertain components of estimated radiation-related cancer risk with and without allowing for the uncertain possibility of a universal low-dose threshold. Unless the existence of a threshold is assumed to be virtually certain, the effect of introducing the uncertain possibility of a threshold is equivalent to that of an uncertain increase in the value of DDREF, i.e. merely a variation on the result obtained by ignoring the possibility of a threshold.
The report concludes that while existence of a low-dose threshold does not seem to be unlikely for radiation-related cancers of certain tissues, the evidence does not favour the existence of a universal threshold. The LNT hypothesis, combined with an uncertain DDREF for extrapolation from high doses, remains a prudent basis for radiation protection at low doses and low dose rates.