Japanese Atomic Bomb Research Articles

Updated estimates of the proportion of childhood leukaemia incidence in Great Britainthat may be caused by natural background ionising radiation

The aetiology of childhood leukaemia remains generally unknown, although exposure tomoderate and high levels of ionising radiation, such as was experienced during the atomicbombings of Japan or from radiotherapy, is an established cause. Risk models basedprimarily upon studies of the Japanese A-bomb survivors imply that low-level exposure toionising radiation, including to ubiquitous natural background radiation, also raises the riskof childhood leukaemia. In a recent paper (Wakeford et al 2009 Leukaemia 23 770–6) weestimated the proportion of childhood leukaemia incidence in Great Britain attributableto natural background radiation to be about 20%. In this paper we employ thetwo sets of published leukaemia risk models used previously, but use recentlypublished revised estimates of natural background radiation doses received by thered bone marrow of British children to update the previous results. Using thenewer dosimetry we calculate that the best estimate of the proportion of cases ofchildhood leukaemia in Great Britain predicted to be attributable to this source ofexposure is 15–20%, although the uncertainty associated with certain stages in thecalculation (e.g. the nature of the transfer of risk between populations and the pertinentdose received from naturally occurring alpha-particle-emitting radionuclides)is significant. The slightly lower attributable proportions compared with thosepreviously derived by Wakeford et al (Leukaemia 2009 23 770–6) are largely due tothe lower doses (and in particular lower high LET doses) for the first year oflife.

A Model of Cardiovascular Disease Giving a Plausible Mechanism for the Effect of Fractionated Low-Dose Ionizing Radiation Exposure

Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally exposed groups receiving small daily radiation doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1) concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and cancer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapolation would be appropriate for this endpoint.

Lung cancer susceptibility among atomic bomb survivors in relation to CA repeat number polymorphism of epidermal growth factor receptor gene and radiation dose

Lung cancer is a leading cause of cancer death worldwide. Prevention could be improved by identifying susceptible individuals as well as improving understanding of interactions between genes and etiological environmental agents, including radiation exposure. The epidermal growth factor receptor (EGFR)-signaling pathway, regulating cellular radiation sensitivity, is an oncogenic cascade involved in lung cancer, especially adenocarcinoma. The cytosine adenine (CA) repeat number polymorphism in the first intron of EGFR has been shown to be inversely correlated with EGFR production. It is hypothesized that CA repeat number may modulate individual susceptibility to lung cancer. Thus, we carried out a case-cohort study within the Japanese atomic bomb (A-bomb) survivor cohort to evaluate a possible association of CA repeat polymorphism with lung cancer risk in radiation-exposed or negligibly exposed (<5 mGy) A-bomb survivors. First, by dividing study subjects into Short and Long genotypes, defined as the summed CA repeat number of two alleles < or = 37 and > or = 38, respectively, we found that the Short genotype was significantly associated with an increased risk of lung cancer, specifically adenocarcinoma, among negligibly exposed subjects. Next, we found that prior radiation exposure significantly enhanced lung cancer risk of survivors with the Long genotype, whereas the risk for the Short genotype did not show any significant increase with radiation dose, resulting in indistinguishable risks between these genotypes at a high radiation dose. Our findings imply that the EGFR pathway plays a crucial role in assessing individual susceptibility to lung adenocarcinoma in relation to radiation exposure.

Cancer and non-cancer effects in Japanese atomic bomb survivors**Presented as an invited paper at the 21st LH Gray Conference ‘The Radiobiology—RadiationProtection Interface’, Royal College of Physicians, Edinburgh 4–6 June 2008.

The survivors of the atomic bombings in Hiroshima and Nagasaki are a general populationof all ages and sexes and, because of the wide and well characterised range of dosesreceived, have been used by many scientific committees (International Commission onRadiological Protection (ICRP), United Nations Scientific Committee on the Effects ofAtomic Radiation (UNSCEAR), Biological Effects of Ionizing Radiations (BEIR)) as thebasis of population cancer risk estimates following radiation exposure. Leukaemia was thefirst cancer to be associated with atomic bomb radiation exposure, with preliminaryindications of an excess among the survivors within the first five years after the bombings.An excess of solid cancers became apparent approximately ten years after radiationexposure. With increasing follow-up, excess risks of most cancer types have beenobserved, the major exceptions being chronic lymphocytic leukaemia, and pancreatic,prostate and uterine cancer. For most solid cancer sites a linear dose response isobserved, although in the latest follow-up of the mortality data there is evidence (p = 0.10) for an upward curvature in the dose response for all solid cancers. The only cancer siteswhich exhibit (upward) curvature in the dose response are leukaemia, and non-melanomaskin and bone cancer. For leukaemia the dose response is very markedly upwardcurving, indeed largely describable as a pure quadratic dose response, particularlyin the low dose (0–2 Sv) range. Even 55 years after the bombings over 40% ofthe Life Span Study cohort remain alive, so continued follow-up of this group isvital for completing our understanding of long-term radiation effects in people.In general, the relative risks per unit dose among the Japanese atomic bomb survivors aregreater than those among comparable subsets in studies of medically exposed individuals.Cell sterilisation largely accounts for the discrepancy in relative risks between these twopopulations, although other factors may contribute, such as the generally higher underlyingcancer risks in the medical series than in the Japanese atomic bomb survivors. Risks amongoccupationally exposed groups such as nuclear workforces and underground miners aregenerally consistent with those observed in the Japanese atomic bomb survivors. Ingeneral, consistent patterns of variation of risk with age at exposure are also seen inall studies—risks for all cancer types diminish with increasing age at exposure.There are also excess risks of various types of non-malignant disease in the Japanese atomicbomb survivors, in particular cardiovascular, respiratory and digestive diseases. Indeed,risks are elevated to much the same degree for a number of non-malignant diseaseendpoints, suggestive of bias. However, in contrast with the cancer data, there is much lessconsistency in the pattern of risk between the atomic bomb survivors and other exposedgroups; for example, radiation-associated respiratory and digestive diseases have not beenseen in these other groups. Although cardiovascular risks have been seen elsewhere,particularly in medically exposed groups, in contrast with the cancer data there is muchless consistency in risk between studies: risks per unit dose in epidemiological studiesvary over at least two orders of magnitude, possibly as a result of confoundingfactors. In the absence of a convincing mechanistic explanation of epidemiologicalevidence, at present a cause-and-effect interpretation of the reported statisticalassociations for cardiovascular disease is unreliable but cannot be excluded. Furtherepidemiological and biological evidence will allow a firmer conclusion to be drawn.

The radiobiology/radiation protection interface in healthcare

The current knowledge of radiation effects is reviewed and implications for itsapplication in healthcare considered. The 21st L H Gray conference gathered leadingexperts in radiobiology, radiation epidemiology, radiation effect modelling, and theapplication of radiation in medicine to provide an overview of the subject. Thelatest radiobiology research in non-targeted effects such as genomic instability andthe bystander effect challenge the old models, but the implications for healtheffects on humans are uncertain. Adaptive responses to external stresses, of whichradiation is one, have been demonstrated in cells and animal models, but it is notknown how these might modify human dose–effect relationships. Epidemiologicalevidence from the Japanese A-bomb survivors provides strong evidence that thereis a linear relationship between the excess risk of cancer and organ dose thatextends from about 50 mSv up to 2.5 Sv, and results from pooled data for multipleepidemiological studies indicate that risks extend down to doses of 20 mSv. Thus linearextrapolation of the A-bomb dose–effect data provides an appropriate basis forradiological protection standards at the present time. Risks from higher dose diagnosticprocedures fall within the range in which health effects can be demonstrated.There is therefore reason for concern about the rise in the number of computedtomography (CT) scans performed in many countries, and in particular the use of CTfor screening of asymptomatic individuals. New radiotherapy techniques allowhigh dose radiation fields to be conformed more effectively to target volumes,and reduce doses to critical organs, but they tend to give a higher and moreuniform dose to the whole body which may increase the risk of second cancer. It isimportant that radiation protection practitioners keep abreast of developments inunderstanding of radiation effects and advise the medical community about theimplications of fundamental research when planning medical applications for thefuture.

Predicting Future Excess Events in Risk Assessment

Risk characterization in a study population relies on cases of disease or death that are causally related to the exposure under study. The number of such cases, so-called "excess" cases, is not just an indicator of the impact of the risk factor in the study population, but also an important determinant of statistical power for assessing aspects of risk such as age-time trends and susceptible subgroups. In determining how large a population to study and/or how long to follow a study population to accumulate sufficient excess cases, it is necessary to predict future risk. In this study, focusing on models involving excess risk with possible effect modification, we describe a method for predicting the expected magnitude of numbers of excess cases and assess the uncertainty in those predictions. We do this by extending Bayesian APC models for rate projection to include exposure-related excess risk with possible effect modification by, e.g., age at exposure and attained age. The method is illustrated using the follow-up study of Japanese Atomic-Bomb Survivors, one of the primary bases for determining long-term health effects of radiation exposure and assessment of risk for radiation protection purposes. Using models selected by a predictive-performance measure obtained on test data reserved for cross-validation, we project excess counts due to radiation exposure and lifetime risk measures (risk of exposure-induced deaths (REID) and loss of life expectancy (LLE)) associated with cancer and noncancer disease deaths in the A-Bomb survivor cohort.

Cancer risk above 1 Gy and the impact for space radiation protection

Analyses of the epidemiological data on the Japanese A-bomb survivors, who were exposed to γ-rays and neutrons, provide most current information on the dose–response of radiation-induced cancer. Since the dose span of main interest is usually between 0 and 1 Gy, for radiation protection purposes, the analysis of the A-bomb survivors is often focused on this range. However, estimates of cancer risk for doses larger than 1 Gy are becoming more important for long-term manned space missions. Therefore in this work, emphasis is placed on doses larger than 1 Gy with respect to radiation-induced solid cancer and leukemia mortality. The present analysis of the A-bomb survivors data was extended by including two extra high-dose categories and applying organ-averaged dose instead of the colon-weighted dose. In addition, since there are some recent indications for a high neutron dose contribution, the data were fitted separately for three different values for the relative biological effectiveness (RBE) of the neutrons (10, 35 and 100) and a variable RBE as a function of dose. The data were fitted using a linear and a linear-exponential dose–response relationship using a dose and dose-rate effectiveness factor (DDREF) of both one and two. The work presented here implies that the use of organ-averaged dose, a dose-dependent neutron RBE and the bending-over of the dose–response relationship for radiation-induced cancer could result in a reduction of radiation risk by around 50% above 1 Gy. This could impact radiation risk estimates for space crews on long-term mission above 500 days who might be exposed to doses above 1 Gy. The consequence of using a DDREF of one instead of two increases cancer risk by about 40% and would therefore balance the risk decrease described above.

Risks Associated with Low Doses and Low Dose Rates of Ionizing Radiation: Why Linearity May Be (Almost) the Best We Can Do

Deterministic and stochastic effects associated with high-dose ionizing radiation (x-ray) exposure have been known for almost as long as ionizing radiation itself (1–3). At lower doses, radiation risks are primarily stochastic effects, in particular, somatic effects (cancer) rather than the deterministic effects characteristic of higher-dose exposure (4–6). In contrast to deterministic effects, for stochastic effects, scientific committees generally assume that at sufficiently low doses there is a positive linear component to the dose response—that is, that there is no threshold (4–6). This does not preclude there being higher-order (eg, quadratic) powers of dose in the dose response that may be of importance at higher doses. It is on this basis that models linear (or linear-quadratic) in dose are often used to extrapolate the experience of the Japanese atomic bomb survivors (who were typically exposed at a high dose rate to moderate doses [average, 0.1 Sv]) to estimate risks from low doses and low dose rates (4–6). Most population-based cancer risk estimates are based primarily on the Japanese atomic bomb survivor Life Span Study (LSS) cohort data (4–6). However, evidence of excess risks comes from a large number of other studies as well. In the parallel editorial (7), evidence is presented for possible real (or at least “practical”) thresholds or “hormetic” (beneficial) effects of low doses of ionizing radiation. As we summarize here, and in contrast to the arguments of Tubiana et al (7), we judge that there is little epidemiologic or biologic evidence for these for cancer. The arguments are of three forms: (a) assessment of the degree of curvature in the cancer dose response within the Japanese atomic bomb survivors and other exposed groups (in particular, departure from linear or linear-quadratic curvature), (b) consistency of risks between the Japanese and other moderate- and low-dose cohorts, and (c) assessment of biologic data on mechanisms. Most of the information on radiation-induced cancer risk comes from (a) the Japanese atomic bomb survivors, (b) medically exposed populations, (c) occupationally exposed groups, and (d) environmentally exposed groups (6). In the higher-dose radiation therapy studies, where doses received are very much higher than in the LSS, sometimes in the range at which cell sterilization occurs, excess cancer risks per unit dose tend to be less than in comparable subsets of the LSS (8,9). However, as we show, risks in moderate- and low-dose medically and occupationally exposed groups are generally consistent with those in the LSS.

Mortality and cancer incidence following occupational radiation exposure: third analysis of the National Registry for Radiation Workers.

Mortality and cancer incidence were studied in the National Registry for Radiation Workers in, relative to earlier analyses, an enlarged cohort of 174 541 persons, with longer follow-up (to 2001) and, for the first time, cancer registration data. SMRs for all causes and all malignant neoplasms were 81 and 84 respectively, demonstrating a ‘healthy worker effect’. Within the cohort, mortality and incidence from both leukaemia excluding CLL and the grouping of all malignant neoplasms excluding leukaemia increased to a statistically significant extent with increasing radiation dose. Estimates of the trend in risk with dose were similar to those for the Japanese A-bomb survivors, with 90% confidence intervals that excluded both risks more than 2–3 times greater than the A-bomb values and no raised risk. Some evidence of an increasing trend with dose in mortality from all circulatory diseases may, at least partly, be due to confounding by smoking. This analysis provides the most precise estimates to date of mortality and cancer risks following occupational radiation exposure and strengthens the evidence for raised risks from these exposures. The cancer risk estimates are consistent with values used to set radiation protection standards.

Ionising radiation and cancer risks: What have we learned from epidemiology?

Purpose: Epidemiologic studies of persons exposed to ionising radiation offer a wealth of information on cancer risks in humans. The Life Span Study cohort of Japanese A-bomb survivors, a large cohort that includes all ages and both sexes with a wide range of well-characterised doses, is the primary resource for estimating carcinogenic risks from low linear energy transfer external exposure. Extensive data on persons exposed for therapeutic or diagnostic medical reasons offer the opportunity to study fractionated exposure, risks at high therapeutic doses, and risks of site-specific cancers in non-Japanese populations. Studies of persons exposed for occupational and environmental reasons allow a direct evaluation of exposure at low doses and dose rates, and also provide information on different types of radiation such as radon and iodine-131. This article summarises the findings from these studies with emphasis on studies with well-characterised doses.Conclusions: Epidemiologic studies provide the necessary data for quantifying cancer risks as a function of dose and for setting radiation protection standards. Leukaemia and most solid cancers have been linked with radiation. Most solid cancer data are reasonably well described by linear-dose response functions although there may be a downturn in risks at very high doses. Persons exposed early in life have especially high relative risks for many cancers, and radiation-related risk of solid cancers appears to persist throughout life.

Leukaemia following childhood radiation exposure in the Japanese atomic bomb survivors and in medically exposed groups

Incidence and mortality risks of radiation-associated leukaemia are surveyed in the Japanese atomic bomb (A-bomb) survivors exposed in early childhood and in utero. Leukaemia incidence and mortality risks are also surveyed in 16 other studies of persons who received appreciable doses of ionizing radiation in the course of treatment in childhood and for whom there is adequate dosimetry and cancer incidence or mortality follow-up. Relative risks tend to be lower in the medical series than in the Japanese A-bomb survivors. The relative risks in the medical studies tend to diminish with increasing average therapy dose. After taking account of cell sterilisation and dose fractionation, the apparent differences between the relative risks for leukaemia in the Japanese A-bomb survivors and in the medical series largely disappear. This suggests that cell sterilisation largely accounts for the discrepancy between the relative risks in the Japanese data and the medical studies. Excess absolute risk has also been assessed in four studies, and there is found to be more variability in this measure than in excess relative risk. In particular, there is a substantial difference between the absolute risk in the Japanese atomic bomb survivor data and those in three other (European) populations. In summary, the relative risks of leukaemia in studies of persons exposed to appreciable doses of ionizing radiation in the course of treatment for a variety of malignant and non-malignant conditions in childhood are generally less than those in the Japanese A-bomb survivor data. The effects of cell sterilisation can largely explain the discrepancy between the Japanese and the medical series.

Cancer risk estimates from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy

Most information on the dose-response of radiation-induced cancer is derived from data on the A-bomb survivors who were exposed to gamma-rays and neutrons. Since, for radiation protection purposes, the dose span of main interest is between 0 and 1 Gy, the analysis of the A-bomb survivors is usually focused on this range. However, estimates of cancer risk for doses above 1 Gy are becoming more important for radiotherapy patients and for long-term manned missions in space research. Therefore in this work, emphasis is placed on doses relevant for radiotherapy with respect to radiation-induced solid cancer. The analysis of the A-bomb survivor's data was extended by including two extra high-dose categories (4-6 Sv and 6-13 Sv) and by an attempted combination with cancer data on patients receiving radiotherapy for Hodgkin's disease. In addition, since there are some recent indications for a high neutron dose contribution, the data were fitted separately for three different values for the relative biological effectiveness (RBE) of the neutrons (10, 35 and 100) and a variable RBE as a function of dose. The data were fitted using a linear, a linear-exponential and a plateau-dose-response relationship. Best agreement was found for the plateau model with a dose-varying RBE. It can be concluded that for doses above 1 Gy there is a tendency for a nonlinear dose-response curve. In addition, there is evidence of a neutron RBE greater than 10 for the A-bomb survivor data. Many problems and uncertainties are involved in combing these two datasets. However, since very little is currently known about the shape of dose-response relationships for radiation-induced cancer in the radiotherapy dose range, this approach could be regarded as a first attempt to acquire more information on this area. The work presented here also provides the first direct evidence that the bending over of the solid cancer excess risk dose response curve for the A-bomb survivors, generally observed above 2 Gy, is due to cell killing effects.

Are cancer risks associated with exposures to ionising radiation from internal emitters greater than those in the Japanese A-bomb survivors?

After ingestion or inhalation of radionuclides, internal organs of the human body will be exposed to ionising radiation. Current risk estimates of radiation-associated cancer from internal emitters are largely based on extrapolation of risk from high-dose externally exposed groups. Concerns have been expressed that extrapolated risk estimates from internal emitters are greatly underestimated, by factors of ten or more, thus implying a severe underestimation of the true risks. Therefore, data on cancer mortality and incidence in a number of groups who received exposure predominantly from internal emitters are examined and excess relative risks per Sv are compared with comparable (age at exposure, time since exposure, gender) matched subsets of the Japanese atomic bomb survivor cohort. Risks are examined separately for low LET and high LET internal emitters. There are eight studies informative for the effects of internal low LET radiation exposure and 12 studies informative for the effects of internal high LET radiation. For 11 of the 20 cancer endpoints (subgroups of particular study cohorts) examined in the low LET internal emitter studies, the best estimate of the excess relative risk is greater than the corresponding estimate in the Japanese atomic bomb survivors and for the other nine it is less. For four of these 20 studies, the relative risk is significantly (2-sided P < 0.05) different from that in the Japanese atomic bomb survivors, in three cases greater than the atomic bomb survivor relative risk and in one case less. Considering only those six low LET studies/endpoints with 100 or more deaths or cases, for four out of six studies/endpoints the internal emitter risk is greater than that in the Japanese atomic bomb survivors. For seven of the 24 cancer endpoints examined in the high LET internal emitter studies the best estimate of the ERR in the internal emitter study is greater than the corresponding estimate in the Japanese atomic bomb survivors and for the other 17 it is less. For six studies, the relative risk is significantly (2-sided P < 0.05) different from that in the Japanese atomic bomb survivors, in one case greater than the atomic bomb survivor relative risk and in five cases less. Considering only those eight high LET studies/endpoints with 100 or more deaths or cases, for five out of eight studies/endpoints the internal emitter risk is greater than that in the Japanese atomic bomb survivors. These results suggest that excess relative risks in the internal emitter studies do not appreciably differ from those in the Japanese atomic bomb survivors. However, there are substantial uncertainties in estimates of risks in the internal emitter studies, particularly in relation to lung cancer associated with radon daughter (alpha particle) exposure, so a measure of caution should be exercised in these conclusions.

A short review of model selection techniques for radiation epidemiology

A common type of statistical challenge, widespread across many areas of research, involves the selection of a preferred model to describe the main features and trends in a particular data set. The objective of model selection is to balance the quality of fit to data against the complexity and predictive ability of the model achieving that fit. Several model selection techniques, including two information criteria, which aim to determine which set of model parameters the data best support, are reviewed here. The techniques rely on computing the probabilities of the different models, given the data, rather than considering the allowed values of the fitted parameters. Such information criteria have only been applied to the field of radiation epidemiology recently, even though they have longer traditions of application in other areas of research. The purpose of this review is to make two information criteria more accessible by fully detailing how to calculate them in a practical way and how to interpret the resulting values. This aim is supported with the aid of some examples involving the computation of risk models for radiation-induced solid cancer mortality fitted to the epidemiological data from the Japanese A-bomb survivors. These examples illustrate that the Bayesian information criterion is particularly useful in concluding that the weight of evidence is in favour of excess relative risk models that depend on age-at-exposure and excess relative risk models that depend on age-attained.

Low dose radiation and cancer in A-bomb survivors: latency and non-linear dose-response in the 1950-90 mortality cohort.

BackgroundAnalyses of Japanese A-bomb survivors' cancer mortality risks are used to establish recommended annual dose limits, currently set at 1 mSv (public) and 20 mSv (occupational). Do radiation doses below 20 mSv have significant impact on cancer mortality in Japanese A-bomb survivors, and is the dose-response linear?MethodsI analyse stomach, liver, lung, colon, uterus, and all-solid cancer mortality in the 0 – 20 mSv colon dose subcohort of the 1950–90 (grouped) mortality cohort, by Poisson regression using a time-lagged colon dose to detect latency, while controlling for gender, attained age, and age-at-exposure. I compare linear and non-linear models, including one adapted from the cellular bystander effect for α particles.ResultsWith a lagged linear model, Excess Relative Risk (ERR) for the liver and all-solid cancers is significantly positive and several orders of magnitude above extrapolations from the Life Span Study Report 12 analysis of the full cohort. Non-linear models are strongly superior to the linear model for the stomach (latency 11.89 years), liver (36.90), lung (13.60) and all-solid (43.86) in fitting the 0 – 20 mSv data and show significant positive ERR at 0.25 mSv and 10 mSv lagged dose. The slope of the dose-response near zero is several orders of magnitude above the slope at high doses.ConclusionThe standard linear model applied to the full 1950–90 cohort greatly underestimates the risks at low doses, which are significant when the 0 – 20 mSv subcohort is modelled with latency. Non-linear models give a much better fit and are compatible with a bystander effect.

INDICATIONS OF THE NEUTRON EFFECT CONTRIBUTION IN THE SOLID CANCER DATA OF THE A-BOMB SURVIVORS

Risk estimates for radiation-induced cancer are primarily based on the follow-up of the Japanese A-bomb survivors. Their exposures were due to gamma rays and neutrons, and, currently--with the assumed low RBE = 10 of neutrons and reference to the colon dose--the late radiation effects are almost fully attributed to the gamma rays. Solid cancer risk estimates for different organ sites are assessed here, and an inconspicuous but statistically highly significant trend of larger values is found for the organs closer to the body surface; i.e., the organs with less body shielding and, therefore, with larger neutron dose-fractions. Underestimation of the RBE of neutrons can explain this apparent correlation. The trend of ERR/Gy vs. depth ceases to be statistically significant for RBE values close to 100. The suggestion of high RBE values and the corresponding reduction of gamma-ray risk estimates is found to be in line with log-likelihood computations in terms of AMFIT, which provide for the solid cancer mortality of the A-bomb survivors the minimum deviance for RBE = 100 with a 95% confidence lower limit of 25. The present assessment had to use the data made publicly available by RERF. In this form they contain city-, sex-, age-, and dose-categories, but--instead of a separate neutron-dose category--only the mean neutron dose for each data cell. The tentative conclusions that are here obtained should, therefore, be examined by a more definitive analysis, either in terms of grouped data with a separate classification of neutron doses or, ideally, in terms of person by person calculations to be performed at RERF with individually estimated neutron doses.

Possible selection effects for radiation risk estimates in Japanese A-bomb survivors: reanalysis of acute radiation symptoms data

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.

Age-at-exposure effects on risk estimates for non-cancer mortality in the Japanese atomicbomb survivors

Statistically significant increases in non-cancer disease mortality with radiation dose havebeen observed among survivors of the atomic bombings of Hiroshima and Nagasaki. Theincreasing trends arise particularly for diseases of the circulatory, digestive, andrespiratory systems. Rates for survivors exposed to a dose of 1 Sv are elevatedby about 10%, a smaller relative increase than that for cancer. The aetiologyof this increased risk is not yet understood. Neither animal nor human studieshave found clear evidence for excess non-cancer mortality at the lower range ofdoses received by A-bomb survivors. In this paper, we examine the age and timepatterns of excess risks in the A-bomb survivors. The results suggest that the excessrelative risk of non-cancer disease mortality might be highest for exposure at ages30–49 years, and that those exposed at ages 0–29 years might have a very low excessrelative risk compared with those exposed at older ages. The differences in excessrelative risk for different age-at-exposure groups imply that the dose responserelationships for non-cancer disease mortality need to be modelled with adjustment forage-at-exposure.

Radiation: Any Dose Is Too High

Any exposure to radiation may cause cell damage that could lead to cancer, according to a June 2005 report from the National Research Council. The risk noted by the report, though small, is a third higher than the risk of 8.46 cancers per 10,000 people exposed to 1 rem (or 10 millisieverts [mSv]) currently used by U.S. regulators. The report contradicts critics who believe there is a threshold below which radiation is harmless; it also fails to support those who say low doses of radiation cause greater health damage per unit dose than high levels. The seventh Biological Effects of Ionizing Radiation (BEIR) report, sponsored by several federal agencies, assessed and updated the health risks from low linear energy transfer (low-LET) radiation, which deposits little energy in a cell and thus tends to cause little damage. The last BEIR report that addressed these health risks was published in 1990. Richard Monson, a professor of epidemiology at the Harvard School of Public Health and chair of the group that conducted the study, says, “We judged that the most reasonable shape is a line through the origin.” Simply put, this means any low-LET ionizing radiation may increase the risk of a cell becoming cancerous—there is no threshold below which there is no risk—and as exposure increases, so does the health risk. Researchers refer to this straight line as the linear-no-threshold model. Less than 20% of people’s low-level radiation exposure comes from anthropogenic sources. The Earth and cosmic sources emit the remainder. Nearly 80% of human-induced exposure comes from medical procedures, about 15% from products like tobacco and building materials, and around 5% from exposure at work. For the purpose of the BEIR VII report, the authoring committee defined low-LET radiation as levels up to about 100 mSv. For comparison, a chest X ray averages around 0.1 mSv. The committee concluded it’s likely that about 1 out of 100 people would develop a tumor or leukemia from exposure to 100 mSv above background. Of that same 100 people, experts would expect 42 to develop cancers for other reasons, but at the press conference marking the release of the report, the committee said it did not fully exclude the possibility of some radiation exposure being a factor in those cases. The BEIR VII report employed statistical data to draw its conclusions and reviewed studies of people exposed at work and in medical settings. It also relied heavily on data from the Japanese atomic bomb survivors. As these survivors age, more is revealed about the relationship between radiation exposure and eventual health outcomes. Investigators have also improved their estimate of the levels of exposure this population received. But critics question the heavy reliance on the Japanese survivors because of the “healthy survivor” effect—those who survived the bombing might have been hardier than those who died early on, potentially skewing the results. Many researchers say the latest report helps reaffirm the general accuracy of federal standards in place for limiting health risks from low-level radiation. “We believe the data are more convincing than fifteen years ago and show that the radiation protection standards we use are reasonable,” says Monson. Mike Boyd, a health physicist who works on setting and updating those standards for the Environmental Protection Agency, concurs. “I don’t think we’ll be changing any federal standards,” he says. “I’m not willing to say there will be no impact. This report will go into our estimation of risk and could lead to refinements, but generally standards should stay the same.” Although most scientists agree the report incorporated the majority of pertinent data up through 2003, information about low-LET radiation continues to emerge. One hypothesis under investigation, says biologist Andrew Wyrobek of Lawrence Livermore National Laboratory, is the possible adaptive response cells developed over eons of natural exposure. Other hypotheses include genetic instability (the idea that some cells already have genetic mutations and are thus more prone to becoming cancerous, given the incentive) and the “bystander effect” (in which cells respond adversely to nearby irradiation although they themselves weren’t hit directly). These concepts were among those reviewed for the BEIR VII report but were not incorporated into the risk estimates. Most experts agree that the BEIR VII report won’t be the last in the series. “Right now there is just a lot we don’t know about how cells react to very low doses of radiation,” says Wyrobek. “But with multiple exposures from more and more people undergoing medical diagnostics in the low-dose range, and increased amounts of radioactive waste, it’s important to understand these ranges better.” Says Boyd, “I will be excited to see some future academy report after we find out more about how radiation affects cells at very low doses.”

Relationship of hepatocellular carcinoma to soya food consumption: A cohort‐based, case‐control study in Japan

To determine if the risk of hepatocellular carcinoma (HCC) is reduced by consumption of soya foods, we conducted a case-control study within a cohort of Japanese A-bomb survivors. We compared the prediagnosis consumption of isoflavone-rich miso soup and tofu to HCC risk, adjusting for hepatitis B (HBV) and C (HCV) viral infections, the major HCC risk factors in this population. The study included 176 pathologist-confirmed cases of HCC diagnosed in 1964-1988 and 560 controls who died of diseases other than liver cancer. We examined dietary information collected at least 2 years before diagnosis or death and tissue-based measures of viral hepatitis. Using logistic regression, crude ORs were 0.5 (95% CI 0.29-0.95) and 0.5 (95% CI 0.20-0.99) for high vs. low miso soup and tofu intake, respectively. Adjusting for year of birth, sex, HBV, HCV and other factors, the OR for miso soup was unchanged at 0.5 (95% CI 0.14-1.55), and miso results were similar when ORs were recalculated separately for earlier and later birth cohorts to assess consistency of results. The adjusted OR for tofu was 0.9 (95% CI 0.20-3.51). We also found a statistically significant (p < 0.0001) interaction between sex and HCV, with risk of HCC being substantially higher for women. We conclude that consumption of miso soup and other soya foods may reduce HCC risk.