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An earlier analysis examined the possibility of bias in the Life Span Study (LSS) cohort by studying Japanese A-bomb survivors with bomb-related acute injuries and those without such injuries. The authors reported significantly higher radiation risks, both for cancers and non-cancers, among those survivors with acute injuries compared with those without. The risks were reported to be particularly large among survivors aged <10 or > or =55 years of age at the time of bombings. The aim of this paper is to examine these findings more closely using the LSS acute effects data. All the analyses were carried out using Poisson regression. Relative risk models were fitted with adjustment for sex and other factors. Significant differences in relative risk between survivors with epilation and burns and those without epilation and burns are found for leukaemia. There is also some evidence for heterogeneity in the leukaemia risk between survivors with two or more acute injuries and those with no injuries, but the evidence is disappeared when survivors with one or more injuries are compared with those without injuries. For solid cancers, cardiovascular disease and all deaths combined, the risks do not differ to a statistically significant extent between survivors with and without injuries. There is no statistically significant heterogeneity in risk across age-at-exposure categories for survivors with injuries. For all deaths combined, relative risk estimates and their uncertainties are significantly higher for survivors exposed at ages <10 years when compared with other exposure ages, but risks are not significantly raised for survivors exposed at > or =55 years of age. With the exception of leukaemia, the findings from the present work are inconsistent with those of Stewart and Kneale.

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.

Statistically significant increases in non-cancer disease mortality with radiation dose have been observed among survivors of the atomic bombings of Hiroshima and Nagasaki. The increasing trends arise particularly for diseases of the circulatory, digestive, and respiratory systems. Rates for survivors exposed to a dose of 1 Sv are elevated by about 10%, a smaller relative increase than that for cancer. The aetiology of this increased risk is not yet understood. Neither animal nor human studies have found clear evidence for excess non-cancer mortality at the lower range of doses received by A-bomb survivors. In this paper, we examine the age and time patterns of excess risks in the A-bomb survivors. The results suggest that the excess relative risk of non-cancer disease mortality might be highest for exposure at ages 30-49 years, and that those exposed at ages 0-29 years might have a very low excess relative risk compared with those exposed at older ages. The differences in excess relative risk for different age-at-exposure groups imply that the dose response relationships for non-cancer disease mortality need to be modelled with adjustment for age-at-exposure.

An epidemiological study was set up in the 1980s of UK participants in the UK atmospheric nuclear weapons testing programme. A large cohort of test participants was established along with a closely matched comparison or control group. Three analyses of mortality and cancer incidence have been carried out. This review describes the development of the evidence on possible effects on test participants with especial emphasis on the most recent analysis. Other sources of evidence, particularly from studies of other groups of test participants, are also considered. It was concluded that overall levels of mortality and cancer incidence in UK nuclear weapons test participants were similar to those in a matched control group, and overall mortality was lower than expected from national rates. There was no evidence of an increased raised risk of multiple myeloma among test participants in recent years, and the suggestion in the first analysis of this cohort of a raised myeloma risk relative to controls is likely to have been a chance finding. There was some evidence of a raised risk of leukaemia other than chronic lymphatic leukaemia among test participants relative to controls, particularly in the early years after the tests. Whilst this could be a chance finding, the possibility that test participation caused a small absolute risk of leukaemia other than chronic lymphatic leukaemia cannot be ruled out.

This review gives a general account of how and why epidemiological studies of UK participants in the nuclear weapons test programme were set up. There is a short description of the circumstances in which the tests were planned and executed and a discussion of the general considerations involved in designing studies to show whether the health of test participants suffered as a result of the tests. The companion review article summarises the results of the epidemiological studies.

This paper investigates some problems with the Colorado Plateau uranium miners cohort when fitting the mechanistic model of carcinogenesis of Moolgavkar et al. (MVK model) to nested case-control data for lung cancers. The influence of data for hard rock mining and work histories on the model fitting is examined and found to be highly influential. The question of selecting the most appropriate number of controls per case is also considered. Analyses were carried out assuming that the hard rock mining exposure occurred prior to all other work histories and that miners received no exposure between work histories. The use of less than 15 controls per case was found to seriously restrict the quality of fit of the models. The best fitting, most reliable model contained linear effects of radon exposure on the first mutation rate, the rate of differentiation, and the rate of death of the intermediate cells. An effect of smoking on the growth of the intermediate cells was also included in the model. It is concluded that owing to the complexity of the MVK model and the limited amount of information in this dataset, the reliability of the Colorado Plateau dataset for fitting this type of model, particularly in a case-control format, is questionable.

An earlier case-control study found no evidence of paternal preconceptional irradiation (PPI) as a cause of childhood leukaemia and non-Hodgkin's lymphoma (LNHL). Although fathers of children with LNHL were more likely to have been radiation workers, the risk was most marked in those with doses below the level of detection. The timing of paternal employment as a radiation worker has now been examined. The previously reported elevated risk of LNHL in the children of male radiation workers was limited to those whose fathers were still radiation workers at conception or whose employment also continued until diagnosis. Children whose fathers stopped radiation work prior to their conception were found to have no excess risk of LNHL. It was not possible to distinguish between the risks associated with paternal radiation work at conception and at the time of diagnosis. A reanalysis of the original study hypothesis incorporating updated dosimetric information gave similar results to those obtained previously. In particular, the risks of LNHL did not show an association with radiation doses received by the father before conception. It seems likely that the increased risk of LNHL among the children of male radiation workers is associated with an increased exposure to some infective agent consequent on high levels of population mixing.

Aims: To extend and analyse follow up of mortality and cancer incidence among men who took part in the UK's atmospheric nuclear weapon tests and experimental programmes 40-50 years ago, with particular reference to multiple myeloma and leukaemia., Methods: A total of 21,357 servicemen and male civilians from the UK who participated in the tests and a control group of 22,333 male controls were followed over the period 1952-98. Analyses were conducted of mortality from various causes, and of mortality and incidence for 27 types of cancer., Results: Rates of mortality from all causes continued to be similar among test participants and controls with the longer follow up, with standardised mortality ratios (SMRs) of 89 and 88 respectively over the full follow up period. For all cancers, the corresponding SMRs were 93 for participants and 92 for controls. Mortality from multiple myeloma was consistent with national rates both for participants and controls, and the relative risk (RR) of myeloma incidence among participants relative to controls was 1.14 (90% CI 0.74 to 1.74) over the full follow up period and 0.79 (90% CI 0.45 to 1.38) during the extended period of follow up (1991-98). Over the full follow up period, leukaemia mortality among participants was consistent with national rates, while rates among controls were significantly lower, and there was a suggestion of a raised risk among test participants relative to controls (RR 1.45, 90% CI 0.96 to 2.17); the corresponding RR for leukaemia incidence was 1.33 (90% CI 0.97 to 1.84). After excluding chronic lymphatic leukaemia (CLL), which is not thought to be radiation inducible, the RR of leukaemia mortality increased to 1.83 (90% CI 1.15 to 2.93), while that for incidence was little changed. Analysis of subgroups of participants with greater potential for exposure provided little evidence of increased risks, although the numbers of men involved were smaller and the statistical power was therefore less. Among other types of cancer, only for liver cancer incidence was there evidence of differences in rates between participants and controls in both the earlier and in the additional period of follow up. Mortality rates among test participants from causes other than cancer were generally similar to those among the controls., Conclusions: Overall levels of mortality and cancer incidence in UK nuclear weapons test participants have continued to be similar to those in a matched control group, and overall mortality has remained lower than expected from national rates. There was no evidence of an increased raised risk of multiple myeloma among test participants in recent years, and the suggestion in the first analysis of this study of a raised myeloma risk is likely to have been a chance finding. There was some evidence of a raised risk of leukaemia other than CLL among test participants relative to controls, particularly in the early years after the tests, although a small risk may have persisted more recently. This could be a chance finding, in view of low rates among the controls and the generally small radiation doses recorded for test participants. However, the possibility that test participation caused a small absolute risk of leukaemia other than CLL cannot be ruled out.

Purpose: To compare quantitative estimates of lifetime cancer risk in humans for exposures to internally deposited radionuclides and external radiation. To assess the possibility that risks from radionuclide exposures may be underestimated., Materials and Methods: Risk estimates following internal exposures can be made for a small number of alpha-particle-emitting nuclides. (1) Lung cancer in underground miners exposed by inhalation to radon-222 gas and its short-lived progeny. Studies of residential (222)Rn exposure are generally consistent with predictions from the miner studies. (2) Liver cancer and leukaemia in patients given intravascular injections of Thorotrast, a thorium-232 oxide preparation that concentrates in liver, spleen and bone marrow. (3) Bone cancer in patients given injections of radium-224, and in workers exposed occupationally to (226)Ra and (228)Ra, mainly by ingestion. (4) Lung cancer in Mayak workers exposed to plutonium-239, mainly by inhalation. Liver and bone cancers were also seen, but the dosimetry is not yet sufficiently good enough to provide quantitative estimates of risks. Comparisons can be made between risk estimates for radiation-induced cancer derived for radionuclide exposure and those derived for the A-bomb survivors, exposed mainly to low-LET (linear energy transfer) external radiation. Data from animal studies, using dogs and rodents, allow comparisons of cancer induction by a range of alpha- and beta-/gamma-emitting radionuclides. They provide information on relative biological effectiveness (RBE), dose-response relationships, dose-rate effects and the location of target cells for different malignancies., Results: For lung and liver cancer, the estimated values of risk per Sv for internal exposure, assuming an RBE for alpha-particles of 20, are reasonably consistent with estimates for external exposure to low-LET radiation. This also applies to bone cancer when risk is calculated on the basis of average bone dose, but consideration of dose to target cells on bone surfaces suggests a low RBE for alpha-particles. Similarly, for leukaemia, the comparison of risks from alpha-irradiation ((232)Th and progeny) and external radiation suggest a low alpha RBE; this conclusion is supported by animal data. Risk estimates for internal exposure are dependent on the assumptions made in calculating dose. Account is taken of the distribution of radionuclides within tissues and the distribution of target cells for cancer induction. For the lungs and liver, the available human and animal data provide support for current assumptions. However, for bone cancer and leukaemia, it may be that changes are required. Bone cancer risk may be best assessed by calculating dose to a 50 micro m layer of marrow adjacent to endosteal (inner) bone surfaces rather than to a single 10 micro m cell layer as currently assumed. Target cells for leukaemia may be concentrated towards the centre of marrow cavities so that the risk of leukaemia from bone-seeking radionuclides, particularly alpha emitters, may be overestimated by the current assumption of uniform distribution of target cells throughout red bone marrow., Conclusions: The lifetime risk estimates considered here for exposure to internally deposited radionuclides and to external radiation are subject to uncertainties, arising from the dosimetric assumptions made, from the quality of cancer incidence and mortality data and from aspects of risk modelling; including variations in baseline rates between populations for some cancer types. Bearing in mind such uncertainties, comparisons of risk estimates for internal emitters and external radiation show good agreement for lung and liver cancers. For leukaemia, the available data suggest that the assumption of an alpha-particle RBE of 20 can result in overestimates of risk. For bone cancer, it also appears that current assumptions will overestimate risks from alpha-particle-emitting nuclides, particularly at low doses.

Epidemiological studies of the survivors of the atomic bombings of Hiroshima and Nagasaki have been conducted over many years. These studies have examined, inter alia, mortality and cancer incidence among the survivors. This paper summarises the form of the studies undertaken, outlines the main findings and describes how these results can be used in deriving estimates of radiation risks. In doing so, some areas of uncertainty and open issues are highlighted, such as the magnitude of lifetime cancer risks and the evidence for raised risks of non-cancer diseases at low doses. Continued follow-up of the survivors will be important in shedding further light on these issues.

Purposes: To model radon-induced lung cancer in uranium miners using a quasi-biological model of carcinogenesis., Materials and Methods: Fitting of generalizations of the stochastic two-mutation carcinogenesis model of Moolgavkar, Venzon and Knudson to a case-control dataset nested within the cohort and to the full cohort of lung cancer mortality in the Colorado Plateau uranium miners, taking account of exposure to cigarette smoke and to radon daughters., Results: Models with three mutations gave adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. The overall fit of the two-mutation model to the case-control data was somewhat worse than that of the three-mutation model. For both the optimal two- and three-mutation models radon daughters and cigarette smoke were assumed to act on the first mutation rate. In the optimal two-mutation model, radon daughters also modified the intermediate cell death or differentiation rate. In the optimal three-mutation model, radon daughters modified the second mutation rate. In all models, the action of radon daughters and cigarette smoke was markedly non-linear, particularly in their action on the mutation rates. The optimal two- and three-mutation models fitted to the cohort data were of slightly different form to those fitted to the case-control data. The model fits to the cohort data are preferred to those to the case-control data on grounds of plausibility., Conclusions: Quasi-biological carcinogenesis models with three mutations give adequate descriptions of the time and age patterns of radon-daughter-induced excess lung tumour mortality. The overall fit of the two-mutation model is somewhat worse than that of the three-mutation model.

Purposes: To assess the degree of overestimation in low-dose cancer risk when models linear in dose are fitted to cancer data., Materials and Methods: Examination of the quadratic and the linear coefficients (in dose) in the Japanese atomic bomb survivor cancer incidence data, based on follow-up to 1987 and taking separate account of random errors in DS86 neutron and DS86 gamma dose estimates and systematic errors in Hiroshima DS86 neutron dose estimates., Results: When the 0-4Gy dose range is used, the low-dose extrapolation factor for all solid tumours, assessing the degree to which low-dose cancer risks are overestimated by fitting a model linear in dose, is 1.06 (95% CI 0.78, 1.62) and so is not significantly different from 1; the associated ratio of the quadratic to the linear coefficients is 0.06 Sv(-1) (95% CI -0.22, 0.67). The best estimate of the low-dose extrapolation factor for leukaemia is 2.47 (95% CI 1.24, > 1,000). The ratio of the quadratic to the linear coefficients is 1.81 Sv(-1) (95% CI 0.21, > 1,000). When various types and groupings of solid tumours are considered there is not generally any strong evidence for upward curvature; for only two out of the six solid tumour groupings are there indications of appreciable upward curvature in the dose response, and in no instance is this statistically significant. Consideration of a lower dose range (0-2Gy rather than 0-4 Gy) results in the low-dose extrapolation factor for solid tumours increasing to 1.21 (95% CI 0.81, 2.45), with corresponding increases for solid tumour subtypes; the corresponding quantity for leukaemia decreases to 1.73 (95% CI 0.79, 147.67). Three out of the six solid tumour subtypes now show appreciable upward curvature. If there is additional adjustment of the Hiroshima neutron dose estimates over the 0-2 Gy dose range, the low-dose extrapolation factor for all solid tumours increases still further, to 1.43 (95% CI 0.97, 2.72), whereas for leukaemia this quantity is further reduced, to 1.58 (95% CI 0.90, 10.58)., Conclusions: There is marked upward curvature in the dose response for leukaemia. For solid tumours there is little indication of upward curvature in the dose response over the 0-4 Gy dose range, although over the 0-2 Gy dose range and after adjustment of Hiroshima DS86 neutron dose estimates the upward curvature is more pronounced. Uncertainties in the likely adjustments to the Hiroshima DS86 neutron dose estimates imply that these findings should be treated with caution.

In this paper the radiation-associated relative risks of second primary cancer incidence in groups treated for first primary cancer by radiotherapy are compared with radiation-associated relative risk estimates in the Japanese atomic bomb survivor cancer incidence data. For four cancer sites, namely lung cancer, bone cancer, ovarian cancer and leukaemia, the relative risks in the comparable (age at exposure, time since exposure, sex matched) subsets of the Japanese data are significantly greater than those in the majority of second cancer studies. Even when the differences between the relative risks in the Japanese atomic bomb survivors and the medical series do not approach conventional levels of statistical significance, relative risks tend to be higher in the Japanese data than in the second cancer studies. At least for leukaemia, the discrepancy between the Japanese and second cancer risks can be largely explained by cell-sterilisation effects. There are few indications of modification of radiation-associated second cancer relative risk among those treated with adjuvant chemotherapy, nor are there strong indications of modification of radiation-associated relative risk by heritable genetic factors. If anything, there is evidence that second cancer relative excess risks are lower among those patients with cancer-prone disorders than among non-susceptible patients. However, the higher underlying cancer risk in some of these medically exposed populations should also be considered, in particular for those with cancer-prone conditions, so that the absolute excess risk is sometimes higher than in the Japanese data.

The dose-response relationship for radiation-induced leukemia was examined in a pooled analysis of three exposed populations: Japanese atomic bomb survivors, women treated for cervical cancer, and patients irradiated for ankylosing spondylitis. A total of 383 leukemias were observed among 283,139 study subjects. Considering all leukemias apart from chronic lymphocytic leukemia, the optimal relative risk model had a dose response with a purely quadratic term representing induction and an exponential term consistent with cell sterilization at high doses; the addition of a linear induction term did not improve the fit of the model. The relative risk decreased with increasing time since exposure and increasing attained age, and there were significant (P < 0.00001) differences in the parameters of the model between datasets. These differences were related in part to the significant differences (P = 0.003) between the models fitted to the three main radiogenic leukemia subtypes (acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia). When the three datasets were considered together but the analysis was repeated separately for the three leukemia subtypes, for each subtype the optimal model included quadratic and exponential terms in dose. For acute myeloid leukemia and chronic myeloid leukemia, there were reductions of relative risk with increasing time after exposure, whereas for acute lymphocytic leukemia the relative risk decreased with increasing attained age. For each leukemia subtype considered separately, there was no indication of a difference between the studies in the relative risk and its distribution as a function of dose, age and time (P > 0.10 for all three subtypes). The nonsignificant indications of differences between the three datasets when leukemia subtypes were considered separately may be explained by random variation, although a contribution from differences in exposure dose-rate regimens, inhomogeneous dose distribution within the bone marrow, inadequate adjustment forcell sterilization effects, or errors in dosimetry could have played a role.

Six statistics are compared in a simulation study for their ability to identify geographical areas with a known excess incidence of a rare disease. The statistics are the standardized incidence ratio, the empirical Bayes method of Clayton and Kaldor, Poisson probability, a statistic based on the 'Breslow T' test (BT) and two statistics based on the 'Potthoff-Whittinghill' test (PW) for extra-Poisson variance. Two alternative processes of clustering are simulated in which high-risk locations could be caused by environmental sources or could be sites of microepidemics of an infectious agent contributing to a rare disease such as childhood leukaemia. The simulation processes use two parameters (proportion of cases found in clusters and mean cluster size) which are varied to embrace a variety of situations. Real and artificial data sets of small area populations are considered. The most extreme of the artificial sets has all areas of equal population size. The other data sets use the small census areas (municipalities) in Finland since these have extremely heterogeneous population size distribution. Subset selection allows examination of this variability. Receiver operator curve methodology is used to compare the efficacy of the statistics in identifying the cluster areas; statistics are compared for the proportion of true high-risk areas identified in the top 1 per cent and 10 per cent of ranked areas. One of the PW statistics performed consistently well under all circumstances, although the results for the BT statistic were marginally better when only the top 1 per cent of ranked areas was considered. The standardized incidence ratio performed consistently worst., (Copyright 1999 National Radiological Protection Board.)

The National Registry for Radiation Workers (NRRW) is the largest epidemiological study of UK radiation workers. Following the first analysis published in 1992, a second analysis has been conducted using an enlarged cohort of 124,743 workers, updated dosimetry and personal data for some workers, and a longer follow-up. Overall levels of mortality were found to be less than those expected from national rates; the standardised mortality ratio for all causes was 82, increasing to 89 after adjusting for social class. This 'healthy worker effect' was particularly strong for lung cancer and for some smoking-related non-malignant diseases. Analysis of potential radiation effects involved testing for any trend in mortality risk with external dose, after adjusting for likely confounding factors. For leukaemia, excluding chronic lymphatic leukaemia (CLL), the central estimate of excess relative risk (ERR) per Sv was similar to that estimated for the Japanese atomic bomb survivors at low doses (without the incorporation of a dose-rate correction factor); the corresponding 90% confidence limits for this trend were tighter than in the first analysis, ranging from just under four times the risk estimated at low doses from the Japanese atomic bomb survivors to about zero. For the grouping of all malignancies other than leukaemia, the central estimate of the trend in risk with dose was closer to zero than in the first analysis; also, the 90% confidence limits were tighter than before and included zero. Since results for lung cancer and non-malignant smoking-related diseases suggested the possibility of confounding by smoking, an examination was made, as in the first analysis, of all malignancies other than leukaemia and lung cancer. In this instance the central estimate of the ERR per Sv was similar to that from the A-bomb data (without the incorporation of a dose-rate correction factor), with a 90% confidence interval ranging from about four times the A-bomb value to less than zero. For multiple myeloma there was an indication of an increasing trend in risk with external dose (p = 0.06), although the evidence for this trend disappeared after omitting workers monitored for exposure to internal emitters. The second NRRW analysis provides stronger inferences than the first on occupational radiation exposure and cancer mortality; the 90% confidence intervals for the risk per unit dose are tighter than before, and now exclude values which are greater than four times those seen among the Japanese A-bomb survivors, although they are also generally consistent with an observation of no raised risk. Furthermore, there is evidence, of borderline statistical significance, of an increasing risk for leukaemia excluding CLL, and, as with solid cancers, the data are consistent with the A-bomb findings.

Generalized relative and absolute risk models, in which various functions of time and age modify the excess relative or absolute risk of radiation-induced cancer, are fitted to the Japanese atomic bomb survivor cancer incidence data set. Among generalized relative risk models, those in which a product of powers of time since exposure and attained age modify the relative risk provide the best fit. There are indications that the Armitage-Doll model (in its formulation as a generalized relative risk model) provides a poor fit to the data, possibly in part because of increasing age-adjusted cancer incidence rates in the Japanese cohort. Generalized absolute risk models, and in particular models in which either powers of time since exposure and attained age, or powers of time since exposure and age at exposure modify the excess absolute risk, provide a superior fit to any of the generalized relative risk models for all solid cancer sites analysed together. When six cancer subtypes are examined separately, only for respiratory cancers does this finding remain true, and for two other sites (female breast cancer and thyroid cancer) the generalized relative risk model yields a better fit than the generalized absolute risk model.

A cohort of 4,400 persons treated for various cancers of childhood in France and the UK was followed up over an extended period to assess risks of subsequent brain tumour in relation to the radiotherapy and chemotherapy that the children received for their first cancer. Elevated risks of subsequent brain tumours were associated with first central nervous system (CNS) tumour (two-sided p = 0.0002) and neurofibromatosis (two-sided p = 0.001). There was also elevated brain tumour risk (two-sided p = 0.003) associated with ionising radiation exposure, the risk being concentrated among benign and unspecified brain tumours. The radiation-related risk of benign and unspecified brain tumours was significantly higher than that of malignant brain tumours (two-sided p< or =0.05); there was no significant change of malignant brain tumour risk with ionising radiation dose (two-sided p > 0.2). In general, there were no strong associations between alkylating agent dose and brain tumour risk. The only significant association between brain tumour risk and alkylating agent dose was in relation to compounds used (bleomycin, chloraminophen) that are thought not to deliver substantial doses to the brain; the statistical significance of the trend with dose depended on a single case, and thus must be considered a weak result.

Purposes: To investigate the evidence for a threshold in the cancer dose-response curve., Materials and Methods: Japanese atomic bomb survivor cancer mortality data, based on follow-up to 1990, was used, taking account of random errors in DS86 dose estimates., Results: For all solid cancers analysed together, there is a significant positive dose response (two-sided p<0.05) if all survivors who received <0.5 Sv are considered, but the significance vanishes if doses of <0.2 Sv are considered; the same is also true for leukaemia. For solid cancer mortality there is no indication of curvilinearity in the dose response: no statistically significant improvement in fit to a linear relative risk model is provided by addition of quadratic or threshold dose terms. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to solid cancer mortality data, the best estimate of the threshold is < 0.00 Sv (95% CI <0.00-0.13). If a linear-quadratic-threshold model is used the best estimate of the threshold is < 0.00 Sv (95% CI < 0.00-0.15). For leukaemia mortality there is highly statistically significant upward curvature in the dose response. In particular, if a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to the leukaemia data, the best estimate of the threshold is 0.16 Sv (95% CI 0.05-0.40) (two-sided p=0.001 for test of departure of threshold from 0). However, there is no evidence for a threshold effect (two-sided p = 0.16) when a quadratic term is included in the dose response: the best estimate of threshold in this case is 0.09Sv (95% CI <0.00-0.29). Moreover, addition of a quadratic term improves the fit of a linear-threshold model at borderline levels of statistical significance (two-sided p = 0.07). Therefore, the most parsimonious description of the leukaemia dose response is provided by a linear-quadratic function of dose., Conclusions: There is no evidence of threshold-type departures from the linear-quadratic dose response either for solid tumours or for leukaemia in the Japanese atomic bomb survivor mortality data.

The Japanese atomic bomb survivor incidence data set and data on five other groups exposed to ionizing radiation in childhood are analysed and evidence found for a reduction in the radiation-induced relative risk of cancers other than leukaemia with increasing time since exposure. Overall, reductions of 5.7-6.1 per cent per year of time since exposure are indicated, depending on the time at which the reduction is presumed to start, and all the reductions are statistically significant at the 5 per cent level. There is no significant heterogeneity in the speed of the reductions in relative risk with time by cohort, by cancer type, sex, or age at exposure group. There is a significant reduction of relative risk with increasing age at exposure, but adjustment for age at exposure does not markedly affect the time trends of relative risk. For all of the groups considered, there is a statistically significant increase in the excess absolute risk with increasing time since exposure. However, by contrast with the relative homogeneity of the time trends of relative risk, there is statistically significant heterogeneity by cancer type within the Japanese cohort (P = 0.05) and between the cohorts (P < 0.0001) in the speed of increase of the excess absolute risk with time since exposure.

Recently released data on cancer incidence in Japanese atomic bomb survivors are analyzed using a variety of relative risk models that take account of errors in estimates of dose to assess the dose response at low doses. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to solid cancer data, a threshold of more than about 0.2 Sv is inconsistent with the data, whereas these data are consistent with there being no threshold. Among solid cancer subtypes there is strong evidence for a possible dose threshold only for nonmelanoma skin cancer. If a relative risk model with a threshold (the dose response is assumed linear above the threshold) is fitted to the leukemia data, a threshold of more than about 0.3 Sv is inconsistent with the data. In contrast to the estimates for the threshold level for solid cancer data, the best estimate for the threshold level in the leukemia data is significantly different from zero even when allowance is made for a possible quadratic term in the dose response, albeit at borderline levels of statistical significance (p = 0.04). There is little evidence for curvature in the leukemia dose response from 0.2 Sv upwards. However, possible underestimation of the errors in the estimates of the dose threshold as a result of confounding and uncertainties not taken into account in the analysis, together with the lack of biological plausibility of a threshold, makes interpretation of this finding questionable.

Objectives: To test the "Gardner hypothesis" that childhood leukaemia and non-Hodgkin lymphoma can be caused by fathers' exposure to ionising radiation before the conception of the child, and, more generally, to investigate whether such radiation exposure of either parent is a cause of childhood cancer., Design: Case-control study., Setting: Great Britain., Subjects: 35,949 children diagnosed as having cancer, together with matched controls., Main Outcome Measures: Parental employment as radiation worker as defined by inclusion in the National Registry for Radiation Workers and being monitored for external radiation before conception of child; cumulative dose of external ionising radiation for various periods of employment before conception; dose during pregnancy., Results: After cases studied by Gardner and colleagues were excluded, fathers of children with leukaemia or non-Hodgkin lymphoma were significantly more likely than fathers of controls to have been radiation workers (relative risk 1.77, 95% confidence interval 1.05 to 3.03) but there was no dose-response relation for any of the exposure periods studied; indeed, the association was greatest for those with doses below the level of detection. No increased risk was found for fathers with a lifetime preconception dose of 100 mSv or more, or with a dose in the 6 months before conception of 10 mSv or more. There was no increased risk for the group of other childhood cancers. Mothers' radiation work was associated with a significant increase of childhood cancer (relative risk 5.00, 1.42 to 26.94; based on 15 cases and 3 controls). Only four of the case mothers and no controls were radiation workers during pregnancy., Conclusions: These results do not support the hypothesis that paternal preconception irradiation is a cause of childhood leukaemia and non-Hodgkin lymphoma; the observed associations may be chance findings or results from exposure to infective or other agents. If there is any increased risk for the children of fathers who are radiation workers, it is small in absolute terms: in Britain the average risk by age 15 years is 6.5 per 10,000; our best estimate, using all available data, is that the increase is 5.4 per 10,000. For mothers, the numbers are too small for reliable estimates of the risk, if any, to be made.

Epidemiologic evaluation of the relation between magnetic field exposures and cancer depends critically on study design, particularly the methods used for exposure assessment. We incorporated a complex magnetic field exposure assessment protocol into a large incident case-control study of childhood leukemia. We measured residential magnetic fields using a standard protocol in current and former homes of 638 cases and 620 controls and determined wire codes for 414 case-control pairs. We chose a time-weighted average of magnetic field measurements in each eligible home, weighted by the time the subject lived in each home as the main exposure metric for each subject. We found that 24-hour bedroom magnetic field measurements adequately characterize children's residential exposure and that measuring other rooms contributes only slightly to the estimate of average residential exposure to magnetic fields. Front door measured fields provide useful exposure information when interior measurements are missing. If feasible, measuring multiple homes in which the subject has resided is preferable to measuring a single home. A similar distribution of wire codes for controls agreeing or refusing to participate in our study implies that risk estimates derived from wire code data will not be influenced by response bias.

The recently released data on cancer incidence in the Japanese atomic bomb survivors are analysed using a variety of relative risk models which take account of errors in estimates of dose to assess the dose-response at low doses. For all solid cancers analysed together there is a significant positive dose-response (at the one-sided 2.5% significance level) if all survivors who received < 0.5 Sv are considered, but the significance vanishes if doses of < 0.2 Sv are considered. If a relative risk model with a threshold (the dose-response being assumed linear above the threshold) is fitted to the solid cancer data, a threshold of more than about 0.2 Sv is inconsistent with the data, whereas these data are consistent with there being no threshold. Linear-quadratic models and linear-quadratic models with an exponential cell-sterilization term provide no better fit than the linear model. For the three main radiation-inducible leukaemia subtypes analysed together (acute lymphatic leukaemia, acute myeloid leukaemia and chronic myeloid leukaemia) there is a significant positive dose-response (at the one-sided 2.5% significance level) if all survivors who received < 0.5 Sv are considered, but the significance vanishes if doses of < 0.2 Sv are considered. If a relative risk model with a threshold (the dose-response being assumed linear above the threshold) is fitted to the leukaemia data, a thresh-old of more than about 0.3 Sv is inconsistent with the data. In contrast with the solid cancer data, the best estimate for the threshold level in the leukaemia data is significantly different from zero, even when allowance is made for a possible quadratic term in the dose-response, albeit at borderline levels of statistical significance (p = 0.04). There is little evidence for curvature in the leukaemia dose-response from 0.2 Sv upwards. However, the possible underestimation of the errors in the estimates of the dose threshold as a result of confounding and uncertainties not taken into account in the analysis, together with the lack of biological plausibility of a threshold, makes the interpretation of this finding questionable.

Generalizations of the two-mutation carcinogenesis model of Moolgavkar, Venzon and Knudson (MVK) are fitted to England and Wales lymphocytic leukaemia incidence data covering the period 1971-1988. Both acute lymphocytic leukaemia (ALL) and chronic lymphocytic leukaemia (CLL) can be fitted by a model with two mutations. These two-mutation models are such that the first (but not the second) mutation rate and the susceptible stem cell population vary rapidly with age. CLL is also adequately fitted by a model with three mutations, and the mutation rates and the variation in the stem cell population numbers implied by the three-mutation model are more plausible than those of the two-mutation model. For CLL there are no significant differences between the sexes in either of the optimal models fitted, but this is not the case for ALL. Thus the original MVK model adequately describes population rates of lymphocytic leukaemia in England and Wales.

In order to conduct valid epidemiological studies of nuclear power plant workers, good information on the workers' radiation dose histories is essential. Dose records held by a major dosimetry service company and on the Nuclear Regulatory Commission's Radiation Exposure Information and Recording System have been compared for a sample of 99 workers. About half of the workers in the sample had no records on the Radiation Exposure Information and Recording System, since they had not terminated employment at a Nuclear Regulatory Commission-licensed facility; accordingly, their career doses (as recorded by the service company) were generally higher than those for workers on the Radiation Exposure Information and Recording System. For nearly half of the workers with records on both databases, the total dose recorded for terminated employments at nuclear power plants differed by at least a factor of 5 between the databases. In absolute terms, these differences were of the order of 100 mSv or more. An approach that utilized both the Radiation Exposure Information and Recording System and the dosimetry service company's records might be of value in constructing dose histories for a large epidemiological study. However, the comparisons presented here support the initiatives of the Nuclear Regulatory Commission to request licensees to report voluntarily career doses for current employees. These data are essential if a large and valid epidemiological study of nuclear plant workers is to be conducted in the foreseeable future.

Following recent research in Great Britain, the geographic incidence of leukemia and non-Hodgkin's lymphoma among White children in three metropolitan regions of the United States (San Francisco-Oakland, CA; Detroit, MI; and Atlanta, GA) during 1978-82 has been analyzed using census tract-specific data. There was no evidence of a general tendency for cases to cluster geographically, in contrast to results from Britain. Further, rates did not vary with median income or education levels for census tracts. However, there was a statistically significant increasing trend in incidence rates with increasing population density: relative risk for highest relative to lowest category = 1.4 (95% percent confidence interval [CI] = 1.1-2.0) for White population density, and 1.4 (CI = 1.0-2.0) for total population density. The interpretation of these findings is unclear and further investigation is required. It is possible that population density is acting as a surrogate for some virus-related factor.

The study is based on a collaboration between the Cancer Registry of Norway, the Norwegian Radiation Protection Authority, and National Radiological Protection Board (NRPB, UK). The association between indoor radon exposure and lung cancer was studied in 427 municipalities. NRPB detectors were sent to 10,000 households, and 7,500 of the detectors were returned. Data from a nation-wide survey of smoking habits in 1964-1965 were available. Data on asbestos exposure were also used in a regression analysis. The reporting to the Cancer Registry of all new cases of cancer is fairly complete, as hospital departments and institutes of pathology are obliged to report all cancer cases. The histologically confirmed lung cancer cases were grouped into squamous-cell carcinoma, small-cell carcinoma, adenocarcinoma and other or non-specified histological types. The age-adjusted rate of lung cancer by histological type was the dependent variable in the regression analysis. A consistent increase in incidence of lung cancer was seen with increasing tobacco consumption, but no positive trend could be shown with increasing radon exposure in the descriptive presentation of the data. In the regression analysis, however, the incidence of small-cell anaplastic lung tumors in females increased significantly with increasing radon exposure. When based on the regression coefficients, the fraction of lung cancers attributable to radon is about 2-4%. However, systematic errors cannot be excluded in an ecological study such as presented here.

Objective: To study cause specific mortality of radiation workers with particular reference to associations between fatal neoplasms and level of exposure to radiation., Design: Cohort study., Setting: United Kingdom., Subjects: 95,217 radiation workers at major sites of the nuclear industry., Main Outcome Measure: Cause of death., Results: Most standardised mortality ratios were below 100: 83 unlagged, 85 with a 10 year lag for all causes; 84 unlagged, 86 lagged for all cancers; and 80 for all known other causes, indicating a "healthy worker effect." The deficit of lung cancer (75 unlagged, 76 lagged) was significant at the 0.1% level. Standardised mortality ratios were significantly raised (214 unlagged, 303 lagged) for thyroid cancer, but there was no evidence for any trend with external recorded radiation dose. Dose of external radiation and mortality from all cancers were weakly correlated (p = 0.10), and multiple myeloma was more strongly correlated (p = 0.06); for leukaemia, excluding chronic lymphatic, the trend was significant (p = 0.03; all tests one tailed). The central estimates of lifetime risk derived from these data were 10.0% per Sv (90% confidence interval less than 0 to 24%) for all cancers and 0.76% per Sv (0.07 to 2.4%) for leukaemia (excluding chronic lymphatic leukaemia). These are, respectively, 2.5 times and 1.9 times the risk estimates recommended by the International Commission on Radiological Protection, but 90% confidence intervals are large and the commission's risk factors fall well within the range. The positive trend with dose for all cancers, from which the risk estimate was derived, was not significant. The positive association between leukaemia (except chronic lymphatic leukaemia) was significant and robust in subsidiary analyses. This study showed no association between radiation exposure and prostatic cancer., Conclusion: There is evidence for an association between radiation exposure and mortality from cancer, in particular leukaemia (excluding chronic lymphatic leukaemia) and multiple myeloma, although mortality from these diseases in the study population overall was below that in the general population. The central estimates of risk from this study lie above the most recent estimates of the International Commission on Radiological Protection for leukaemia (excluding chronic lymphatic leukaemia) and for all malignancies. However, the commission's risk estimates are well within the 90% confidence intervals from this study. Analysis of combined cohorts of radiation workers in the United States indicated lower risk estimates than the commission recommends, and when the American data are combined with our analysis the overall risks are close to those estimated by the commission. This first analysis of the National Registry for Radiation Workers does not provide sufficient evidence to justify a revision in risk estimates for radiological protection purposes.

Study Objective: The aim was to evaluate and improve the completeness of follow up in a cohort study of mortality carried out using the UK National Health Service (NHS) Central Registers., Setting: This was a follow up study of UK servicemen who served abroad in the 1950s and 1960s, including those who participated in the UK atmospheric nuclear weapon tests and experimental programmes., Design: Details of men for whom follow up achieved using the NHS Central Registers was unsatisfactory were submitted to the Department of Social Security (DSS) for tracing, as were details of men born before 1916 and reported by the NHS Central Registers as currently registered with a general practitioner, and a 1% sample of remaining men born in or after 1916., Measurements and Main Results: The additional follow up increased the number of deaths fully identified in the cohort by 6.5%. Mortality among those untraced on the NHS Central Registers was substantially greater than in the cohort as a whole (10.2% v 6.9%). Among those reported by the NHS Central Registers as not currently registered with a general practitioner, 2.7% were found to have died, as were 1.1% of men born before 1916 and currently reported to be registered with a general practitioner. As expected there was clear evidence that information about emigrations supplied by both the NHS Central Registers and DSS is far from complete., Conclusion: Standardised mortality ratios based on follow up via the NHS Central Registers alone are likely to be somewhat low, and this should be borne in mind when interpreting the data.

Various methods can be used to project the risks of radiation-induced cancer estimated in cohort studies beyond the period of follow-up and to other populations. The epidemiological evidence for the choice of risk projection model is reviewed based on data from studies such as those of the Japanese atomic bomb survivors and UK ankylosing spondylitis patients given x-ray therapy. The results of risk projections based on various approaches are presented, including those suggested by UNSCEAR and by the BEIR V Committee. It is emphasised that the continued follow-up of populations such as the Japanese atomic bomb survivors is of great importance in estimating lifetime risks, and that further parallel analyses are required to examine how risks vary across populations.

The Registrar General's decennial supplements on occupational mortality provide only limited information on mortality in the armed forces in the United Kingdom. Mortality has therefore been studied among a group of 30,619 United Kingdom servicemen who served abroad in tropical or desert areas in the 1950s and 1960s, and who remained in the services for a total of at least five years. Mortality from all causes of death, all neoplasms, and all other known non-violent causes was lower than that expected from rates for all men in England and Wales, whereas mortality from accidents and violence was raised. These differences remained after adjustment for social class, affected both officers and other ranks, and had not disappeared even after the men had been followed up for at least 20 years. When mortality from 20 specific cancers and 10 other disease groups was examined there were significant excesses for cancers of the oesophagus (standardised mortality ratio (SMR) = 146; p = 0.03) and prostate (SMR = 156; p = 0.03), and significant deficits for cancers of the lung (SMR = 73; p less than 0.001), stomach (SMR = 66; p = 0.002), bladder (SMR = 53; p = 0.02), other specified neoplasms (SMR = 48; p = 0.001), coronary heart disease (SMR = 76; p less than 0.001), bronchitis, emphysema, and chronic obstructive lung disease (SMR = 42; p less than 0.001), and for five further groups of diseases unrelated to smoking or alcohol. Examination of mortality in each of the three services separately identified two specific hazards in the Royal Navy; seven deaths from mesothelioma occurred compared with less than 2.06 expected (p less than 0.005), and there was also an excess of neoplasms and of other diseases associated with alcohol (SMRs of 181 and 229; p = 0.002 and less than 0.001). Mortality from smoking related diseases other than those associated with alcohol was low in all three services, particularly among officers.

Altogether 22,347 men who participated in the United Kingdom's atmospheric nuclear weapon tests and experimental programmes in Australia and the Pacific Ocean between 1952 and 1967 were identified from the archives of the Ministry of Defence and followed up. Their mortality and incidence of cancer were compared with those in 22,326 matched controls selected from the same archives. The risk of mortality in the participants relative to that in the controls was 1.01 for all causes and 0.96 for all neoplasms. Thirty eight causes of death were examined separately. Significant differences in mortality were found for leukaemia, multiple myeloma, and other injury and poisoning, with higher rates in the participants, and for cancers of the prostate and kidney and chronic bronchitis, with higher rates in the controls. The mortality from leukaemia and multiple myeloma in the participants was slightly greater than would have been expected from national values (standardised mortality ratios of 113 and 111, respectively), but in the controls it was substantially lower (standardised mortality ratios of 32 and 0, respectively). Examination of the rates of leukaemia and multiple myeloma in groups of participants showed very little difference between groups characterised by recorded doses of external radiation or type of test participation and failed to indicate any specific hazard. Evidence obtained from participants who reported themselves voluntarily (or were reported by relatives or friends) suggested that 17% of participants may have been omitted from the main study group but that any resulting bias was small. Most of the differences observed between the participants and controls were interpreted as due to chance, but some may be due to differences in smoking habits. Participation in the test programme did not seem, in itself, to have caused any detectable effect on the participants' expectation of life, apart from possibly causing small risks of developing leukaemia and multiple myeloma.

The heat uptake that resulted from immersing the hand and wrist into a water-filled calorimeter maintained at temperatures between 37-40 degrees C was measured under standard conditions in a group of eight subjects of either sex. The rate of heat transfer (W) increased exponentially with temperature and was a function of hand or body size and age, but not sex. The heat transfer rate normalized to hand mass (W.kg-1) was determined by temperature and age: best-fit mean values (and 95% confidence limits of the population) were 6.0 W.kg-1 (3.2-11.2 W.kg-1) at an immersion temperature of 37 degrees C and 25.4 W.kg-1 (13.7-47.0 W.kg-1) at 40 degrees C. The application of these results to limits on specific energy absorption rate induced in the hands and wrists by radiofrequency dielectric heat sealer welders is discussed.

An excess of leukemias in children has been observed between 1950 and 1980 in the village of Seascale (population about 3,000) which is situated approximately 3 km to the south of Sellafield nuclear fuel reprocessing plant in West Cumbria, England. Radiation doses from all the main sources of radiation exposure of the population and risks of radiation-induced leukemia have been calculated for children born and living in Seascale during the period of operation of the plant. For the Seascale study population of 1225 children and young persons, followed to age 20 y, or followed until 1980 for those born after 1960, 0.016 radiation-induced leukemias are predicted from the Sellafield discharges. This corresponds to an average risk to children in the population of about one in 75,000. For the four fatal leukemias observed in the study population (0.5 expected from United Kingdom statistics) to be attributed to the operations at Sellafield, the average risk would have to be increased by a factor of about 250, to one in 300. Although there is some uncertainty about the releases from the plant and concentrations of radionuclides in environmental materials in the Sellafield area, particularly for the early years of its operation, the possibility that the doses calculated and the risk coefficients used for radiation-induced leukemia could be so substantially wrong is very unlikely. The number of radiation-induced leukemias from all radiation sources is calculated to be 0.1, which corresponds to a risk of about one in 12,250 for the average child in the study population. About two-thirds of the risk is from natural radiation, 16% from the Sellafield discharges, and nuclear weapons fallout and medical exposure each contribute about 9%. The models used for calculating radiation doses from intakes of radionuclides were based upon those recommended by the International Commission on Radiological Protection (ICRP). This presented a number of difficulties in the assessment, which included the lack of any generally accepted age-related dosimetric models, particularly for bone-seeking radionuclides; limited information on gut transfer factors for radionuclides incorporated in foodstuffs; and no dosimetric models for the fetus. These and other problems identified in the analysis that require more information are discussed.