The Genetics Panel of the NAS BEAR I Committee (1956): epistolary evidence suggests self-interest may have prompted an exaggeration of radiation risks that led to the adoption of the LNT cancer risk assessment model.

This paper extends a series of historical papers which demonstrated that the linear-no-threshold (LNT) model for cancer risk assessment was founded on ideological-based scientific deceptions by key radiation genetics leaders. Based on an assessment of recently uncovered personal correspondence, it is shown that some members of the United States (US) National Academy of Sciences (NAS) Biological Effects of Atomic Radiation I (BEAR I) Genetics Panel were motivated by self-interest to exaggerate risks to promote their science and personal/professional agenda. Such activities have profound implications for public policy and may have had a significant impact on the adoption of the LNT model for cancer risk assessment.

Military participants at U.S. Atmospheric nuclear weapons testing--methodology for estimating dose and uncertainty.

Methods were developed to calculate individual estimates of exposure and dose with associated uncertainties for a sub-cohort (1,857) of 115,329 military veterans who participated in at least one of seven series of atmospheric nuclear weapons tests or the TRINITY shot carried out by the United States. The tests were conducted at the Pacific Proving Grounds and the Nevada Test Site. Dose estimates to specific organs will be used in an epidemiological study to investigate leukemia and male breast cancer. Previous doses had been estimated for the purpose of compensation and were generally high-sided to favor the veteran's claim for compensation in accordance with public law. Recent efforts by the U.S. Department of Defense (DOD) to digitize the historical records supporting the veterans' compensation assessments make it possible to calculate doses and associated uncertainties. Our approach builds upon available film badge dosimetry and other measurement data recorded at the time of the tests and incorporates detailed scenarios of exposure for each veteran based on personal, unit, and other available historical records. Film badge results were available for approximately 25% of the individuals, and these results assisted greatly in reconstructing doses to unbadged persons and in developing distributions of dose among military units. This article presents the methodology developed to estimate doses for selected cancer cases and a 1% random sample of the total cohort of veterans under study.

Potential impacts of radon, terrestrial gamma and cosmic rays on childhood leukemia in France: a quantitative risk assessment.

Previous epidemiological studies and quantitative risk assessments (QRA) have suggested that natural background radiation may be a cause of childhood leukemia. The present work uses a QRA approach to predict the excess risk of childhood leukemia in France related to three components of natural radiation: radon, cosmic rays and terrestrial gamma rays, using excess relative and absolute risk models proposed by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Both models were developed from the Life Span Study (LSS) of Japanese A-bomb survivors. Previous risk assessments were extended by considering uncertainties in radiation-related leukemia risk model parameters as part of this process, within a Bayesian framework. Estimated red bone marrow doses cumulated during childhood by the average French child due to radon, terrestrial gamma and cosmic rays are 4.4, 7.5 and 4.3 mSv, respectively. The excess fractions of cases (expressed as percentages) associated with these sources of natural radiation are 20 % [95 % credible interval (CI) 0-68 %] and 4 % (95 % CI 0-11 %) under the excess relative and excess absolute risk models, respectively. The large CIs, as well as the different point estimates obtained under these two models, highlight the uncertainties in predictions of radiation-related childhood leukemia risks. These results are only valid provided that models developed from the LSS can be transferred to the population of French children and to chronic natural radiation exposures, and must be considered in view of the currently limited knowledge concerning other potential risk factors for childhood leukemia. Last, they emphasize the need for further epidemiological investigations of the effects of natural radiation on childhood leukemia to reduce uncertainties and help refine radiation protection standards.

Occupational lymphohematopoietic cancer in Korea.

The purpose of this study was to review the existing studies on lymphohematopoietic (LHP) cancer in Korea, estimate the prevalence of workers exposed to carcinogens, and determine the population attributable fraction (PAF) of leukemia. Two case series and 4 case reports were reviewed. Using official statistics, the prevalence of benzene exposure and ionizing radiation exposure was estimated. Based on the prevalence of exposure and the relative risk, The PAF of leukemia was calculated. Between 1996 and 2005, 51 cases of LHP cancer were reported from the compensation system. Greater than 50% of occupational LHP cancer was leukemia, and the most important cause was benzene. In a cohort study, the standardized incidence ratio was 2.71 (95% CI, 0.56-7.91). The prevalence of exposure was 2.5% and 2.2% in 1995 and 2000, respectively. Using the 1995 prevalence, 3.6-4.8% and 0.1% of cases with leukemia were attributable to benzene and ionizing radiation exposure, respectively, which resulted in 39.7-51.4 cases per year. Benzene is the most important cause of occupational leukemia in Korea. Considering the estimated PAF in this study, the annual number of occupational LHP cancer (51 cases during 10-yr period), might be underreported within the compensation system.

Assessment of environmental exposures from agricultural pesticides in childhood leukaemia studies: challenges and opportunities.

Pesticides are ubiquitous in environments of many rural communities due to drift from agricultural applications and home/garden use. Studies of childhood leukaemia predominantly relied on retrospective pesticide exposure assessment and parental recall of use or proximity to fields or pesticide applications. Sample size requirements mostly preclude the collection of individual-level exposure information, biomarkers or environmental measurements of pesticides prospectively in cohorts. Yet such measures can be used in nested case-control approaches or for validating exposure models that can be applied to large populations. Recently developed models incorporate geographic information system technology and environmental databases of pesticide and/or crop data to assess exposure. Models developed in California to estimate residential exposures are presented by linking addresses to agricultural pesticide application data and land-use maps. Results from exposure validation and simulation studies and exposure measurement error issues are discussed.

Exposure assessment and other challenges in non-ionizing radiation studies of childhood leukaemia.

Studies of electromagnetic fields (EMF) and the development of childhood leukaemia face unique difficulties. EMF are imperceptible, ubiquitous, have multiple sources, and can vary greatly over time and distances. Childhood leukaemia and high average exposures to magnetic fields are both quite rare. Thus, a major challenge in EMF epidemiology is the small number of highly exposed cases and the necessity for retrospective assessment of exposure. Only studies designed to minimize bias while maximizing our ability to detect an association, should one exist, would have a potential to contribute to our understanding. New approaches are needed; the most promising in the extremely low-frequency range involves a study of a highly exposed cohort of children who have lived in apartments next to built-in transformers or electrical equipment rooms. Another promising avenue is an investigation of possible joint effects of environmental exposures and genetic co-factors. An exposure assessment methodology for residential radiofrequency fields is still in its infancy. Rapid changes in technology and exponential increases in its use make exposure assessment more difficult and urgent.

A multilevel analysis of long-term psychological distress among Belarusians affected by the Chernobyl disaster.

BACKGROUND: Radiation contamination and sociopolitical instability following the Chernobyl nuclear power plant disaster have had a profound impact on Belarus. OBJECTIVE: To investigate the factors that impact long-term mental health outcomes of this population almost 20 years after the disaster. STUDY DESIGN: Cross-sectional study. METHODS: In-person interviews were conducted with 381 men and women from two geographic areas of differing radiation contamination within Belarus. Participants completed surveys of demographics, psychosocial factors and psychological distress. Individual-level characteristics were combined with household-level measures of radiation contamination exposure and family characteristics to create multilevel predictive models of psychological distress. RESULTS: Between-household effects accounted for 20% of variability in depression and anxiety scores, but only 8% of variability in somatization scores. Degree of chronic daily stressors showed a significant positive relationship with psychological distress, whereas mastery/controllability showed a significant inverse relationship with distress. At household level, perceived family problems, but not level of residential radiation contamination, was the best predictor of distress. CONCLUSIONS: Multilevel modelling indicates that long-term psychological distress among Belarusians affected by the Chernobyl disaster is better predicted by stress-moderating psychosocial factors present in one's daily life than by level of residential radiation contamination.

Iowa radon leukaemia study: a hierarchical population risk model for spatially correlated exposure measured with error.

This paper presents a Bayesian model that allows for the joint prediction of county-average radon levels and estimation of the associated leukaemia risk. The methods are motivated by radon data from an epidemiologic study of residential radon in Iowa that include 2726 outdoor and indoor measurements. Prediction of county-average radon is based on a geostatistical model for the radon data which assumes an underlying continuous spatial process. In the radon model, we account for uncertainties due to incomplete spatial coverage, spatial variability, characteristic differences between homes, and detector measurement error. The predicted radon averages are, in turn, included as a covariate in Poisson models for incident cases of acute lymphocytic (ALL), acute myelogenous (AML), chronic lymphocytic (CLL), and chronic myelogenous (CML) leukaemias reported to the Iowa cancer registry from 1973 to 2002. Since radon and leukaemia risk are modelled simultaneously in our approach, the resulting risk estimates accurately reflect uncertainties in the predicted radon exposure covariate. Posterior mean (95 per cent Bayesian credible interval) estimates of the relative risk associated with a 1 pCi/L increase in radon for ALL, AML, CLL, and CML are 0.91 (0.78-1.03), 1.01 (0.92-1.12), 1.06 (0.96-1.16), and 1.12 (0.98-1.27), respectively.

EMF and health.

Electric and magnetic fields are ubiquitous in the modern society, and concerns have been expressed regarding possible adverse effects of these exposures. This review covers epidemiologic research on health effects of exposures to static, extremely low-frequency (ELF), and radio frequency (RF) fields. Research on ELF fields has been performed for more than two decades, and the methodology and quality of studies have improved over time. Studies have consistently shown increased risk for childhood leukemia associated with ELF magnetic fields, whereas ELF fields most likely are not a risk factor for breast cancer and cardiovascular disease. There are still inadequate data for other outcomes. More recently, focus has shifted toward RF exposures from mobile telephony. There are no persuasive data suggesting a health risk, but this research field is still immature with regard to the quantity and quality of available data. This technology is constantly changing and there is a need for continued research on this issue. Almost no epidemiologic data are available for static fields.

Research strategies for magnetic fields and cancer.

Widespread concerns about whether electric and magnetic fields (EMF) could adversely affect human health have been raised in epidemiologic studies reported since the 1980s. Possible EMF health effects have been widely publicized in the popular press since that time. We consider here three possible mechanisms of action of EMF on childhood leukemia. We identify the first as "magnetic fields": this hypothesis relates the average level of magnetic field to the incidence of childhood leukemia. We identify a second, recently proposed, mechanism as "contact current": this hypothesis relates the low voltage and consequent current that occurs on the domestic water pipe, due to U.S. grounding practices, as a source for exposure of children. The third hypothesis is that the relationship observed is spurious. Using a modified example taken from the work of Von Winterfeldt and Keeney, we use Decision Analysis to estimate the value of information for distinguishing between the three hypotheses. We believe that this improves on the usual process for deciding on research budgets. Depending on which hypothesis we favor a priori, the value of being informed ranges from US 101 dollars to US 233 dollars per "problem household." Since there could be as many as 2 million such households, the value of information for resolving this issue could approach half a billion dollars! We find that there is no value of information for finding the odds ratio given the contact current hypothesis. In writing this article, we have consciously kept the computations as simple as possible so as to engage the reader's attention and interest. In a penultimate section, we suggest numerous possible extensions for a group interested in discussing and deciding on the value of research on the relationship between magnetic fields and cancer.

An ecological analysis of leukemia incidence around the highest 137Cs concentration in Poland.

Cancer has long been known to be a hazard of exposure to ionizing radiation. However, the assessment of health effects from exposure to radiation is a matter of considerable controversy. This paper presents results of a retrospective study of leukemia incidence (203-207, ICD-9) around the highest 137Cs pollution in Poland (as an effect of the Czarnobyl disaster and/or military bomb tests). The data relating to all the registered leukemias in males and females originated from the Regional Cancer Registry in Opole. The information on 137Cs concentration rates in Opole province was derived from the state monitoring provided by the Polish Geological Institute in Warsaw. The spatial analysis--based on the random-effects Poisson regression model--was carried out via the Markov Chain Monte Carlo (MCMC) technique (Gibbs sampling) using BUGS software. The model incorporated epidemiological data and an ecological covariate--isotope concentrations--and provided a framework for estimating the strength of a dose-response relationship. The differences in incidence levels were quantified by traditional standardized morbidity ratios (SMRs) and presented in thematic maps as well as in combined charts of distance-disease-dose relations. Additionally, to assess spatial disease clustering, a Tango test was adopted. The results of this ecological study suggest that the 137Cs concentrations did not have any negative influence on the exposed population.

[Assessment of the risk of radiation-induced leukaemia in the vicinity of nuclear installations: the Nord-Cotentin radio-ecological study]. / Evaluation du risque de leucémie radio-induite à proximité d'installations nucléaires: l'étude radio-écologique Nord-Cotentin.

BACKGROUND: A radioecological study has been launched in 1997 to perform a realistic assessment of radiation doses received by the population aged 0 to 24 years who lived in the vicinity of the La-Hague nuclear reprocessing plant (Nord-Cotentin, France), and to estimate the associated risk of leukaemia between 1978 and 1996. METHODS: The Working Group in charge of the study included representatives of French radiation protection institutes, nuclear operators, members of environmental organisations and international experts. The methodology retained developed three steps RESULTS: The reconstructed cohort included 6656 individuals born between 1954 and 1996, who lived in the study area for at least one year between 1978 and 1996 before the age of 25. The number of person-years between 1978 and 1996 is 69 308. On the basis of the calculated doses, the estimated number of radiation-induced leukaemia attributable to releases from local nuclear installations was less than 0.002 for the period 1978-1996. CONCLUSIONS: This result constitutes a best estimate of the risk of radiation-induced leukaemia among young people in the canton of Beaumont-Hague. Nevertheless, this estimation must be interpreted in the light of the limits inherent to the risk assessment process and some participants of the Working Group expressed some reservations. The estimated number of radiation-induced leukaemia attributable to local nuclear installations is low in comparison to the 4 cases of leukaemia observed by epidemiological studies during the same period. It is therefore very unlikely that releases from local nuclear installations could notably explain the high incidence of leukaemia observed among young people in the canton of Beaumont-Hague.

Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors.

We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. The estimated cumulative probability of developing morphologic t-MDS/t-AML was 8.6% +/- 2.1% at 6 years. Multivariate analysis of the entire cohort revealed stem cell priming with VP-16 (RR = 7.7, P = 0.002) to be independently associated with an increased risk of t-MDS/t-AML. The influence of pretransplant therapy on subsequent t-MDS/t-AML risk was determined by a case-control study. Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12. 3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection. (Blood. 2000;95:1588-1593)

[Electrical field exposure and human health. Risk assessment and problems relative to bureaucratic procedures and to the role of instituitional organizations in control and prevention]. / Esposizione a campi elettromagnetici e salute dell'uomo. Valutazione del rischio e problematiche relative all'iter normativo e al ruolo degli organi istituzionali nel controllo e nella prevenzione.

After closely analyzing the phenomenon regarding the immense increase and diffusion of equipment which generates low- and high-frequency electromagnetic fields, the AA emphasize both the methodological and interpretive difficulties of assessing the effects produced on public health. They maintain the need to exercise caution in determining the tolerable limits of exposure, and in particular long-term ones. Finally, after analyzing the bureaucratic procedure which led to the formulation of Decree No. 381 of 1998, they express the hope that the various Regions will set themselves high-quality objectives when promulgating the necessary legislation, so as to minimize the risk factor.

Monte Carlo mixture model of lifetime cancer incidence risk from radiation exposure on shuttle and international space station.

Estimating uncertainty in lifetime cancer risk for human exposure to space radiation is a unique challenge. Conventional risk assessment with low-linear-energy-transfer (LET)-based risk from Japanese atomic bomb survivor studies may be inappropriate for relativistic protons and nuclei in space due to track structure effects. This paper develops a Monte Carlo mixture model (MCMM) for transferring additive, National Institutes of Health multiplicative, and multiplicative excess cancer incidence risks based on Japanese atomic bomb survivor data to determine excess incidence risk for various US astronaut exposure profiles. The MCMM serves as an anchor point for future risk projection methods involving biophysical models of DNA damage from space radiation. Lifetime incidence risks of radiation-induced cancer for the MCMM based on low-LET Japanese data for nonleukemia (all cancers except leukemia) were 2.77 (90% confidence limit, 0.75-11.34) for males exposed to 1 Sv at age 45 and 2.20 (90% confidence limit, 0.59-10.12) for males exposed at age 55. For females, mixture model risks for nonleukemia exposed separately to 1 Sv at ages of 45 and 55 were 2.98 (90% confidence limit, 0.90-11.70) and 2.44 (90% confidence limit, 0.70-10.30), respectively. Risks for high-LET 200 MeV protons (LET=0.45 keV/micrometer), 1 MeV alpha-particles (LET=100 keV/micrometer), and 600 MeV iron particles (LET=180 keV/micrometer) were scored on a per particle basis by determining the particle fluence required for an average of one particle per cell nucleus of area 100 micrometer(2). Lifetime risk per proton was 2.68x10(-2)% (90% confidence limit, 0.79x10(-3)%-0. 514x10(-2)%). For alpha-particles, lifetime risk was 14.2% (90% confidence limit, 2.5%-31.2%). Conversely, lifetime risk per iron particle was 23.7% (90% confidence limit, 4.5%-53.0%). Uncertainty in the DDREF for high-LET particles may be less than that for low-LET radiation because typically there is very little dose-rate dependence. Probability density functions for high-LET radiation quality and dose-rate may be preferable to conventional risk assessment approaches. Nuclear reactions and track structure effects in tissue may not be properly estimated by existing data using in vitro models for estimating RBEs. The method used here is being extended to estimate uncertainty in spacecraft shielding effectiveness in various space radiation environments.

Residential wire codes: reproducibility and relation with measured magnetic fields.

OBJECTIVES: To investigate the reproducibility of wire codes to characterise residential power line configurations and to determine the extent to which wire codes provide a proxy measure of residential magnetic field strength in a case-control study of childhood leukaemia conducted in nine states within the United States. METHODS: Misclassification of wire codes was assessed with independent measurements by two technicians for 187 residences. The association between categories of wire code and measured level of magnetic field was evaluated in 858 residences with both a wire code measurement and a 24 hour measurement of the magnetic field in the bedroom. The strength of the association between category of wire code and risk of leukaemia was examined in two regions with different average levels of magnetic field in homes with high categories of wire code. RESULTS: The reproducibility of any of three different classifications of wire codes was excellent (kappa > or = 0.89). Mean and median magnetic fields, and the percentage of homes with high magnetic fields increased with increasing category for each of the wire code classification schemes. The size of the odds ratios for risk of leukaemia and high categories of wire code did not reflect the mean levels of the magnetic field in those categories in two study regions. CONCLUSION: Misclassification of categories of wire code is not a major source of bias in the study. Wire codes provide a proxy measure of exposure to residential magnetic fields. If magnetic fields were a risk factor for leukaemia, however, there would be some attenuation of risk estimates based on wire codes because of misclassification of exposure to magnetic fields at both extremes of the wire code range. The lack of an association between high categories of wire code and risk of leukaemia cannot be explained by a failure of the wire code classification schemes to estimate exposure to magnetic fields in the study area.

Leukemia: lessons from the Japanese experience.

Probably more has been learned about radiation-induced leukemia from intensive study of Japanese atomic bomb survivors than about radiation damage to any other organ system. This has been the result of an intensive binational effort at the Atomic Bomb Casualty Commission and the Radiation Effects Research Foundation in Hiroshima and Nagasaki to monitor the occurrence of leukemia in a large group of atomic bomb survivors over a period of more than 50 years (the Life Span Study). The focus in the leukemia studies has been on disease latency, time of peak incidence rates, clinical course, shape of the dose-response curve and changes in risk over time for various types of leukemia in relationship to shielded kerma and bone marrow radiation dose, age at time of exposure, and gender. The extreme understanding and cooperation of the Japanese atomic bomb survivors, control subjects, physicians of Hiroshima and Nagasaki, government authorities, and the citizens of both cities has resulted in an epidemiological study that is almost unparalleled in medical history.

Assessment of cellular telephone and other radio frequency exposure for epidemiologic research.

Epidemiologists are now embarking on the evaluation of the hypothesis that exposure to radio frequency energy from low-power wireless communication devices, such as portable cellular telephones, causes brain cancer and other adverse health outcomes. Even in the laboratory, exposures from radio frequency sources are difficult to quantify; their measurement in large populations for epidemiologic study is challenging. In this paper, we outline the nature and magnitude of these exposures and discuss the prospects for obtaining useful measures of exposure for epidemiologic research.

Detection and assessment of clusters of disease: an application to nuclear power plant facilities and childhood leukaemia in Sweden.

We review some recent statistical methods for examining geographic patterns of disease incidence for the presence of clusters. General methods search for clusters throughout the study area and then assess the statistical significance of any clusters detected. Focused methods check for elevated incidence rates close to prespecified locations of putative sources of hazard. We apply the methods to leukaemia incidence data for children aged 0-15 years in Sweden (1980-1990), particularly in reference to locations of nuclear power facilities. Unlike some other studies, notably in the United Kingdom, we do not find any significant clusters.