The Evidence for Excess Risk of Cancer and Non-Cancer Disease at Low Doses and Dose Rates.

The question of whether there are excess radiation-associated health risks at low dose is controversial. We present evidence of excess cancer risks in a number of (largely pediatrically or in utero exposed) groups exposed to low doses of radiation (<0.1 Gy). Moreover, the available data on biological mechanisms do not provide support for the idea of a low-dose threshold or hormesis for any of these endpoints. There are emerging data suggesting risks of cardiovascular disease and cataract at low doses, but this is less well established. This large body of evidence does not suggest and, indeed, is not statistically compatible with any very large threshold in dose (>10 mGy), or with possible beneficial effects from exposures. The presented data suggest that exposure to low-dose radiation causes excess cancer risks and quite possibly also excess risks of various non-cancer endpoints.

Gamma-radiation levels outdoors in Great Britain based on K, Th and U geochemical data.

Gamma-rays from naturally occurring radionuclides are a major component of background radiation. They are an important tool for geology and are also important for radiation protection. In this paper we use over a quarter of a million geochemical measurements of concentrations of potassium, thorium and uranium in soils and in stream sediments to estimate outdoor gamma-ray dose rates across Great Britain. The soil concentrations are generally at a depth of 5-20 cm with some at 35-50 cm. Soil measurements will give spatially relatively precise estimates, but as soil data are not available for much of Scotland, stream sediment data are used there. Kriging methods are used to estimate surface concentrations of K, Th and U and dose rates are imputed from these concentrations. Our results are compared with measurement surveys of both outdoor and indoor gamma-ray dose rates. Recently there has been interest in exploring the carcinogenic risks of low dose radiation by investigating associations between childhood cancer rates and doses from natural background gamma radiation. To achieve adequate statistical power, such studies must be so large that it is impractical to assess exposures by direct measurements in the homes of study subjects. Instead the exposures must be modelled. The results presented here will be an important input to such work.

Modelling the bimodal distribution of indoor gamma-ray dose-rates in Great Britain.

Gamma radiation from naturally occurring sources (including directly ionizing cosmic-rays) is a major component of background radiation. An understanding of the magnitude and variation of doses from these sources is important, and the ability to predict them is required for epidemiological studies. In the present paper, indoor measurements of naturally occurring gamma-rays at representative locations in Great Britain are summarized. It is shown that, although the individual measurement data appear unimodal, the distribution of gamma-ray dose-rates when averaged over relatively small areas, which probably better represents the underlying distribution with inter-house variation reduced, appears bimodal. The dose-rate distributions predicted by three empirical and geostatistical models are also bimodal and compatible with the distributions of the areally averaged dose-rates. The distribution of indoor gamma-ray dose-rates in the UK is compared with those in other countries, which also tend to appear bimodal (or possibly multimodal). The variation of indoor gamma-ray dose-rates with geology, socio-economic status of the area, building type, and period of construction are explored. The factors affecting indoor dose-rates from background gamma radiation are complex and frequently intertwined, but geology, period of construction, and socio-economic status are influential; the first is potentially most influential, perhaps, because it can be used as a general proxy for local building materials. Various statistical models are tested for predicting indoor gamma-ray dose-rates at unmeasured locations. Significant improvements over previous modelling are reported. The dose-rate estimates generated by these models reflect the imputed underlying distribution of dose-rates and provide acceptable predictions at geographical locations without measurements.

Spatial prediction of naturally occurring gamma radiation in Great Britain.

Gamma radiation from natural sources is an important component of background radiation, and correlates with childhood leukaemia risk in Great Britain. The geographic variation of indoor gamma radiation dose-rates in Great Britain is explored using various geo-statistical methods. A multi-resolution Gaussian-process model using radial basis functions with 2, 4, or 8 components, is fitted via maximum likelihood, and a non-spatial model is also used, fitted by ordinary least squares. Because of the dataset size (N = 10,199), four other parametric spatial models are fitted by variogram-fitting. A randomly selected 70:30 split is used for fitting:validation. The models are evaluated based on their predictive performance as measured by Mean Absolute Error, Mean Squared Error, as well as Pearson correlation and rank-correlation between predicted and actual dose-rates. Each of the four parametric models (Matérn, Gaussian, Bessel, Spherical) fitted the empirical variogram well, and yielded similar predictions at >50 km separation, although with more substantial differences in predicted variograms at <50 km. The multi-resolution Gaussian-process model with 8 components had the best predictive accuracy among the models considered. The Spherical, Bessel, Matérn, Gaussian and ordinary least squares models had progressively worse predictive performance, the ordinary least squares model being particularly poor in this respect.

Levels of naturally occurring gamma radiation measured in British homes and their prediction in particular residences.

Gamma radiation from natural sources (including directly ionising cosmic rays) is an important component of background radiation. In the present paper, indoor measurements of naturally occurring gamma rays that were undertaken as part of the UK Childhood Cancer Study are summarised, and it is shown that these are broadly compatible with an earlier UK National Survey. The distribution of indoor gamma-ray dose rates in Great Britain is approximately normal with mean 96 nGy/h and standard deviation 23 nGy/h. Directly ionising cosmic rays contribute about one-third of the total. The expanded dataset allows a more detailed description than previously of indoor gamma-ray exposures and in particular their geographical variation. Various strategies for predicting indoor natural background gamma-ray dose rates were explored. In the first of these, a geostatistical model was fitted, which assumes an underlying geologically determined spatial variation, superimposed on which is a Gaussian stochastic process with Matérn correlation structure that models the observed tendency of dose rates in neighbouring houses to correlate. In the second approach, a number of dose-rate interpolation measures were first derived, based on averages over geologically or administratively defined areas or using distance-weighted averages of measurements at nearest-neighbour points. Linear regression was then used to derive an optimal linear combination of these interpolation measures. The predictive performances of the two models were compared via cross-validation, using a randomly selected 70 % of the data to fit the models and the remaining 30 % to test them. The mean square error (MSE) of the linear-regression model was lower than that of the Gaussian-Matérn model (MSE 378 and 411, respectively). The predictive performance of the two candidate models was also evaluated via simulation; the OLS model performs significantly better than the Gaussian-Matérn model.

Residential mobility and associated factors in relation to the assessment of exposure to naturally occurring radiation in studies of childhood cancer.

Migration, that is the study subjects moving from one residential address to another, is a complication for epidemiological studies where exposures to the agent of interest depend on place of residence [corrected]. In this paper we explore migration in cases from a large British case-control study of childhood cancer and natural background radiation. We find that 44% of cases had not moved house between birth and diagnosis, and about two-thirds were living within 2 km of their residence at birth. The estimated dose at the diagnosis address was strongly correlated with that at the birth address, suggesting that use of just the birth address in this case-control study does not lead to serious bias in risk estimates. We also review other individual-based studies of naturally occurring radiation, with particular emphasis on those from Great Britain. Interview-based case-control and cohort studies can potentially establish full residential histories for study subjects and make direct measurements of radiation levels in the dwellings in question. However, in practice, because of study size and difficulties in obtaining adequate response rates, interview-based studies generally do not use full residential histories, and a substantial proportion of dose estimates often derive from models rather than direct measurements. More seriously, problems of incomplete response may lead to bias, not just to loss of power. Record-based case-control studies, which do not require direct contact with study subjects, avoid such problems, but at the expense of having only model-based exposure estimates that use databases of measurements.

Case-control study of paternal occupation and social class with risk of childhood central nervous system tumours in Great Britain, 1962-2006.

BACKGROUND: Paternal occupational exposures have been proposed as a risk factor for childhood central nervous system (CNS) tumours. This study investigates possible associations between paternal occupational exposure and childhood CNS tumours in Great Britain. METHODS: The National Registry of Childhood Tumours provided all cases of childhood CNS tumours born and diagnosed in Great Britain from 1962 to 2006. Controls without cancer were matched on sex, period of birth and birth registration sub-district. Fathers' occupations were assigned to one or more of 33 exposure groups. A measure of social class was also derived from father's occupation at the time of the child's birth. RESULTS: Of 11 119 cases of CNS tumours, 5 722 (51%) were astrocytomas or other gliomas, 2 286 (21%) were embryonal and 985 (9%) were ependymomas. There was an increased risk for CNS tumours overall with exposure to animals, odds ratio (OR) 1.40 (95% confidence intervals (CIs) 1.01, 1.94) and, after adjustment for occupational social class (OSC), with exposure to lead, OR 1.18 (1.01, 1.39). Exposure to metal-working oil mists was associated with reduced risk of CNS tumours, both before and after adjustment for OSC, OR 0.87 (0.75, 0.99).Risk of ependymomas was raised for exposure to solvents, OR 1.73 (1.02,2.92). For astrocytomas and other gliomas, risk was raised with high social contact, although this was only statistically significant before adjustment for OSC, OR 1.15 (1.01,1.31). Exposure to paints and metals appeared to reduce the risk of astrocytomas and embryonal tumours, respectively. However, as these results were the result of a number of statistical tests, it is possible they were generated by chance.Higher social class was a risk factor for all CNS tumours, OR 0.97 (0.95, 0.99). This was driven by increased risk for higher social classes within the major subtype astrocytoma, OR 0.95 (0.91, 0.98). CONCLUSION: Our results provide little evidence that paternal occupation is a significant risk factor for childhood CNS tumours, either overall or for specific subtypes. However, these analyses suggest that OSC of the father may be associated with risk of some childhood CNS cancers.

A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980-2006.

We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27,447) born and diagnosed in Great Britain during 1980-2006 and matched cancer-free controls (36,793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother's residence at the child's birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P=0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI -4, 11; P=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power ~50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels.

Case-control study of paternal occupation and childhood leukaemia in Great Britain, 1962-2006.

BACKGROUND: Paternal occupational exposures have been proposed as a risk factor for childhood leukaemia. This study investigates possible associations between paternal occupational exposure and childhood leukaemia in Great Britain. METHODS: The National Registry of Childhood Tumours provided all cases of childhood leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls were matched on sex, period of birth and birth registration subdistrict. Fathers' occupations were assigned to 1 or more of 33 exposure groups. Social class was derived from father's occupation at the time of the child's birth. RESULTS: A total of 16 764 cases of childhood leukaemia were ascertained. One exposure group, paternal social contact, was associated with total childhood leukaemia (odds ratio 1.14, 1.05-1.23); this association remained significant when adjusted for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid leukaemia showed increased risk with paternal exposure to social contact before adjustment for social class. Risk of other leukaemias was significantly increased by exposure to electromagnetic fields, persisting after adjustment for social class. For total leukaemia, the risks for exposure to lead and exhaust fumes were significantly <1. Occupationally derived social class was associated with risk of LL, with the risk being increased in the higher social classes. CONCLUSION: Our results showed some support for a positive association between childhood leukaemia risk and paternal occupation involving social contact. Additionally, LL risk increased with higher paternal occupational social class.

Doses to the red bone marrow of young people and adults from radiation of natural origin.

Natural radiation sources comprise cosmic rays, terrestrial gamma rays, radionuclides in food and inhaled isotopes of radon with their decay products. These deliver doses to all organs and tissues including red bone marrow (RBM), the tissue in which leukaemia is thought to originate. In this paper we calculate the age-dependent annual RBM doses from natural radiation sources to young people and to adults at average levels of exposure in the UK. The contributions to dose are generally less complex than in the case of doses to foetuses and young children where it is necessary to take into account transfer of radionuclides across the placenta, intakes in mother's milk and changes in gut uptake in young infants. However, there is high uptake of alkaline earths and of similar elements in the developing skeleton and this significantly affects the doses from radioisotopes of these elements, not just in the teens and twenties but through into the fifth decade of life. The total equivalent dose to the RBM from all natural sources of radiation at age 15 years is calculated to be about 1200  µSv a year at average UK levels, falling to rather less than 1100  µSv per year in later life; the gentle fall from the late teens onwards reflects the diminishing effect of the high uptakes of radioisotopes of the alkaline earths and of lead in this period. About 60% of the equivalent dose is contributed by the low linear energy transfer (LET) component. Radionuclides in food make the largest contribution to equivalent doses to RBM and much the largest contribution to the absorbed dose from high LET radiation (mainly alpha particles).

The statistical power of epidemiological studies analyzing the relationship between exposure to ionizing radiation and cancer, with special reference to childhood leukemia and natural background radiation.

The etiology of childhood leukemia remains generally unknown, although risk models based on the Japanese A-bomb survivors imply that the dose accumulated from protracted exposure to low-level natural background ionizing radiation materially raises the risk of leukemia in children. In this paper a novel Monte Carlo score-test methodology is used to assess the statistical power of cohort, ecological and case-control study designs, using the linear low-dose part of the BEIR V model derived from the Japanese data. With 10 (or 20) years of follow-up of childhood leukemias in Great Britain, giving about 4600 (or 9200) cases, under an individual-based cohort design there is 67.9% (or 90.9%) chance of detecting an excess (at 5% significance level, one-sided test); little difference is made by extreme heterogeneity in risk. For an ecological design these figures reduce to 57.9% (or 83.2%). Case-control studies with five controls per case achieve much of the power of a cohort design, 61.1% (or 86.0%). However, participation bias may seriously affect studies that require individual consent, and area-based studies are subject to severe interpretational problems. For this reason register-based studies, in particular those that make use of predicted doses that avoid the need for interviews, have considerable advantages. We argue that previous studies have been underpowered (all have power <80%), and some are also subject to unquantifiable biases and confounding. Sufficiently large studies should be capable of detecting the predicted risk attributable to natural background radiation.

Dose to red bone marrow of infants, children and adults from radiation of natural origin.

Natural radiation sources contribute much the largest part of the radiation exposure of the average person. This paper examines doses from natural radiation to the red bone marrow, the tissue in which leukaemia is considered to originate, with particular emphasis on doses to children. The most significant contributions are from x-rays and gamma rays, radionuclides in food and inhalation of isotopes of radon and their decay products. External radiation sources and radionuclides other than radon dominate marrow doses at all ages. The variation with age of the various components of marrow dose is considered, including doses received in utero and in each year up to the age of 15. Doses in utero include contributions resulting from the ingestion of radionuclides by the mother and placental transfer to the foetus. Postnatal doses include those from radionuclides in breast-milk and from radionuclides ingested in other foods. Doses are somewhat higher in the first year of life and there is a general slow decline from the second year of life onwards. The low linear energy transfer (LET) component of absorbed dose to the red bone marrow is much larger than the high LET component. However, because of the higher radiation weighting factor for the latter it contributes about 40% of the equivalent dose incurred up to the age of 15.

Cancer in the offspring of female radiation workers: a record linkage study.

This study uses record linkage between the National Registry of Childhood Tumours (NRCT) and the National Registry for Radiation Workers to re-assess our earlier finding that the offspring of women radiation workers exposed to ionising radiation before the child's conception may be at an increased risk of childhood cancer. An additional 16,964 childhood cancer patients taken from the NRCT, together with the same number of matched controls, are included. Pooled analyses, based on the new and original datasets, include 52,612 cases and their matched controls. Relative risks (RRs) for maternal employment as a radiation worker, maternal exposure or not during the relevant pregnancy and pattern of employment relative to conception and diagnosis dates were calculated.The new data provide no evidence of an increased risk of childhood cancer associated with maternal preconception radiation work and thus do not support our earlier finding of a raised risk in the offspring of female radiation workers. Considering the pooled data, a weak association was found between maternal radiation work during pregnancy and childhood cancer in offspring although the evidence is limited by the small numbers of linked cases and controls.

The proportion of childhood leukaemia incidence in Great Britain that may be caused by natural background ionizing radiation.

The aetiology of childhood leukaemia remains generally unknown, although exposure to moderate and high levels of ionizing radiation, such as those experienced during the atomic bombings of Japan or from radiotherapy, is an established cause. Risk models based primarily on studies of the Japanese atomic bomb survivors imply that low-level exposure to ionizing radiation, including ubiquitous natural background radiation, also raises the risk of childhood leukaemia. Using two sets of recently published leukaemia risk models and estimates of natural background radiation red-bone-marrow doses received by children, about 20% of the cases of childhood leukaemia in Great Britain are predicted to be attributable to this source. However, for one of these sets of risk models this attributable fraction is materially dependent on how the radiation-induced risk is assumed to be transferred between the Japanese atomic bomb survivors and Western children. Over a range of annual doses representing the range (0.5-2.5 mSv/year) experienced by most populations, the attributable proportion for the preferred risk-transfer model varies between 8 and 30%, with small deviations from a linear relationship that are largely due to the saturation of the model, although again this range of attributable fractions depends on the assumed transfer of risk between populations.

Studies of occupational radiation exposure and health: experience from the UK National Registry for Radiation Workers.

Studies of persons exposed to radiation in the course of their work are directly relevant to the task of estimating the health risks of protracted radiation exposures. However, such investigations are not always easy to undertake, and not all studies are equally informative. Considerable care is required, therefore, in order to be able to draw reliable inferences from studies of radiation workers. This paper highlights some important aspects concerning the design, conduct and interpretation of such investigations, with reference to experience gained from a large long-term study of radiation workers in the United Kingdom (the National Registry for Radiation Workers, NRRW). Key findings from the NRRW are summarised, together with a brief description of a recent international study and of work in progress.

Effective and organ doses from thoron decay products at different ages.

The dosimetry of radon-220, often known as thoron, and its decay products has received less attention than has that of radon-222. Dose coefficients used by international bodies such as UNSCEAR and ICRP and by the UK's former National Radiological Protection Board are based on calculations from the 1980s. We present calculations for thoron decay products using the most recent ICRP models. These indicate that the effective dose is dominated by the doses to lung and that, under the present models, these doses are somewhat higher than under the previous consensus. Conversely, the present models give doses to organs outside the respiratory tract that are somewhat lower than those previously calculated. Dose coefficients for children are somewhat higher than those for adults. However, breathing rates for children are lower than those for adults and there are no great differences in annual doses.

Variations in radiation exposures of adults and children in the UK.

Members of the UK population receive radiation doses from a number of sources including cosmic radiation, from uranium, thorium and their decay products, particularly radon, and from medical sources. On average, members of the UK population receive an effective dose of about 200 mSv over their lifetime. This results in a risk of fatal cancer of about 1%. However, the radiation dose is not the same to all individuals. Some components give doses that vary systematically from one region to another. Doses may also vary greatly from one individual to another. The rate at which the dose is accumulated may vary as the individual ages. Different organs and tissues do not necessarily receive the same dose. This paper discusses these factors and attempts to quantify them. Cosmic rays deliver doses which vary little across the body or between individuals. Terrestrial gamma rays also deliver more or less uniform whole-body doses, but the difference between individuals can be greater. Radionuclides in food deliver doses which vary both across the body and between individuals. These variations are even more marked in the case of doses from radon and from medical exposures.

What are the risks from medical X-rays and other low dose radiation?

The magnitude of the risks from low doses of radiation is one of the central questions in radiological protection. It is particularly relevant when discussing the justification and optimization of diagnostic medical exposures. Medical X-rays can undoubtedly confer substantial benefits in the healthcare of patients, but not without exposing them to effective doses ranging from a few microsieverts to a few tens of millisieverts. Do we have any evidence that these levels of exposure result in significant health risks to patients? The current consensus held by national and international radiological protection organizations is that, for these comparatively low doses, the most appropriate risk model is one in which the risk of radiation-induced cancer and hereditary disease is assumed to increase linearly with increasing radiation dose, with no threshold (the so-called linear no threshold (LNT) model). However, the LNT hypothesis has been challenged both by those who believe that low doses of radiation are more damaging than the hypothesis predicts and by those who believe that they are less harmful, and possibly even beneficial (often referred to as hormesis). This article reviews the evidence for and against both the LNT hypothesis and hormesis, and explains why the general scientific consensus is currently in favour of the LNT model as the most appropriate dose-response relationship for radiation protection purposes at low doses. Finally, the impact of the LNT model on the assessment of the risks from medical X-rays and how this affects the justification and optimization of such exposures is discussed.

The development of the UK radon programme.

The natural radioactive gas, radon, is responsible for the largest component of the radiation dose received by the average UK citizen. The risks of exposure to radon have been demonstrated and quantified in epidemiological studies of those exposed at work and in the home. In the UK, measures are in place to identify and help control the exposures in those houses where levels are highest, to limit levels in new buildings and to control exposures in the workplace. This paper outlines the development of the programme, with special reference to the identification and remediation of homes with high radon levels.