Cancer Incidence In Atomic Bomb Survivors Research Articles

Promoting Action of Radiation in the Atomic Bomb Survivor Cancer Incidence Data

Promoting Action of Radiation in the Atomic Bomb Survivor Cancer Incidence Data

Flexible dose-response models for Japanese atomic bomb survivor data: Bayesian estimation and prediction of cancer risk

Generalised absolute risk models were fitted to the latest Japanese atomic bomb survivor cancer incidence data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates. The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population cancer risks for a current UK population. Because of evidence for irregularities in the low-dose dose response, flexible dose-response models were used, consisting of a linear-quadratic-exponential model, used to model the high-dose part of the dose response, together with piecewise-linear adjustments for the two lowest dose groups. Following an assumed administered dose of 0.001 Sv, lifetime leukaemia radiation-induced incidence risks were estimated to be 1.11 x 10(-2) Sv(-1) (95% Bayesian CI -0.61, 2.38) using this model. Following an assumed administered dose of 0.001 Sv, lifetime solid cancer radiation-induced incidence risks were calculated to be 7.28 x 10(-2) Sv(-1) (95% Bayesian CI -10.63, 22.10) using this model. Overall, cancer incidence risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk.

A comparison of the degree of curvature in the cancer incidence dose-response in Japanese atomic bomb survivors with that in chromosome aberrations measured in vitro

Purposes : To compare the degree of curvature in the dose-response for chromosome aberrations and for radiation-induced cancer. Materials and methods : Comparison of the ratio of the quadratic and linear coeffcients (in dose) in Japanese atomic bomb survivor cancer incidence data, based on follow-up to 1987 and taking account of random errors in DS86 dose estimates with the same ratio in four datasets of chromosome aberrations in peripheral blood lymphocytes measured in vitro and exposed to 60 Co gamma radiation. Results : There are no statistically significant differences between the four in vitro datasets in the ratio of the quadratic to the linear coeffcients for dicentrics or chromosome translocations, nor are there indications of differences between this ratio for dicentrics and that for complete chromosome translocations (p >0.1 in all cases). If the 0-4 Gy dose range is used in the Japanese atomic bomb survivor data, the ratio of the quadratic to the linear coeffcients for all solid cancers is 0.06 Sv 1 (95% CI 0.22, 0.67) and so is not significantly different from 0; this ratio is statistically highly inconsistent (p <0.0001) with the analogous ratio estimated for the in vitro chromosome aberration data (4.20Sv 1; 95% CI 3.06, 6.51). By contrast, there are no statistically significant differences (p =0.42) between the ratio of the quadratic to the linear coeffcients for leukaemia incidence in the Japanese cohort, 1.81 Sv 1 (95% CI 0.21, > 1000), with that for chromosome aberrations in vitro. These results are not markedly changed if the 0-2 Gy dose range is used in the Japanese atomic bomb survivor data. Conclusions : It is unlikely that in vitro chromosome aberrations could be a correlate for the initiating radiogenic lesions leading to radiation-induced solid cancers. However, taken together with certain other biological information, it may not be unreasonable on this basis to use in vitro chromosome aberrations in peripheral blood lymphocytes as a correlate of the radiogenic lesions leading to radiation-induced leukaemia.

Derivation of low-dose extrapolation factors from analysis of curvature in the cancer incidence dose response in Japanese atomic bomb survivors

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 0-4 Gy 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, > 1000). The ratio of the quadratic to the linear coefficients is 1.81 Sv -1 (95% CI 0.21, > 1000). 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 (0-2 Gy 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.

Describing time and age variations in the risk of radiation-induced solid tumour incidence in the Japanese atomic bomb survivors using generalized relative and absolute risk models.

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.

Variations with time and age in the relative risks of solid cancer incidence after radiation exposure

The Japanese atomic bomb survivor cancer incidence dataset and data on five groups exposed to radiation for medical reasons 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 and age at exposure. The rate of the reductions in relative risk with time since exposure are not significantly different for those exposed in childhood and for those exposed in adulthood, if adjustment is made for the effects on the relative risk of age at exposure. For those irradiated in childhood, there is a statistically significant annual reduction of 5.8% (95% CI 2.8, 8.9) in excess relative risk, and there are no strong indications of inter-cohort heterogeneity in the speed of reduction of relative risk. After adjustment for the effects of age at exposure, there is a significant annual reduction of 3.6% (95% CI 1.6, 5.6) in excess relative risk in all age-at-exposure groups. There are significant reductions of 5.2% (95% CI 3.7, 6.8) in excess relative risk per year of age at exposure. There are statistically significant ( P = 0.04) interactions between the exponential adjustments to the excess relative risk for age at exposure and time since exposure in the Japanese data, but no indications ( P = 0.38) of such interactions when powers of time since exposure and attained age are used to adjust the excess relative risk, so that the fit of the model with power adjustments is to be preferred to that of the model with exponential adjustments. There is no significant heterogeneity by cancer type within the Japanese atomic bomb survivor data in the variation of relative risk with time and age. There are indications that the model which assumes a variation in risk dependent only on attained age fits all the datasets analysed together significantly worse ( P = 0.11) than one which allows for different rates of change of risk as a function of time since exposure and age at exposure. The lack of fit of the attained-age model is much more striking in the Japanese bomb survivor incidence data ( P = 0.02), which has much the greatest power of any of the datasets analysed to differentiate time and age trends in excess risk. A variety of relative risk models are used to evaluate solid cancer mortality and incidence risks for a current UK population. High dose-rate solid cancer mortality risks are estimated to lie in the range 6.9% - 13.8% Sv-1. High dose-rate solid cancer incidence risks are calculated to lie in the range 12.1% - 22.0% Sv-1. The preferred generalised relative risk model, with adjustments to the excess relative risk proportional to a product of powers of time since exposure and attained age, predicts solid cancer mortality risks of 9.0% Sv-1 and solid cancer incidence risks of 15.0% Sv-1.

Estimates of neutron relative biological effectiveness derived from the Japanese atomic bomb survivors

Purpose: To investigate neutron relative biological effectiveness. Materials and methods: The latest Japanese atomic bomb survivor cancer incidence and mortality datasets with the current (DS86) dosimetry system are analysed using generalized relative risk models and generalized absolute risk models, both with and without recently indicated adjustments to the Hiroshima DS86 neutron dose estimates. Results: Without adjustments to the Hiroshima neutron doses, the best estimate of neutron relative biological effectiveness for all tumours in the incidence data is 63.3 (95% CI 0-275.3) when a generalized relative risk model is used; when a generalized absolute risk model is used in the incidence data the best estimate is 53.5 (95% CI 0-201.0); when a generalized relative risk model is used in the mortality data, the best estimate is 287.7 (95% CI 38.0- 103). When likely adjustments are made to the Hiroshima neutron doses the best estimate of neutron relative biological effectiveness in the incidence data using a generalized relative risk model is 15.1 (95% CI 0-51.4); when a generalized absolute risk model is used in the incidence data the best estimate is 9.0 (95% CI 0-32.9); when a generalized relative risk model is used in the mortality data the best estimate is 55.1 (95% CI 9.5-280.3). Although there are no significant differences between groupings of the solid tumour sites in their estimated neutron relative biological effectiveness, there are indications that the neutron relative biological effectiveness of solid tumours is lower than that of leukaemia, whether or not adjustments are made to the Hiroshima neutron dose estimates. Uncertainties in the likely adjustments to the DS86 Hiroshima neutron and gamma dose estimates as well as uncertainties in the modelling of excess risk in the two cities (Hiroshima and Nagasaki) imply that these findings should be treated with caution. Conclusions: Likely adjustments to the Hiroshima neutron dose estimates imply a substantial increase in information on neutron relative biological effectiveness. Whether or not adjustments are made to the Hiroshima neutron doses, there are indications of inconsistency between the estimates of neutron relative biological effectiveness for solid tumours and leukaemia. Dosimetric and modelling uncertainties mean that these findings should be treated with caution.