Article

Mortality among military participants at the 1957 PLUMBBOB nuclear weapons test series and from leukemia among participants at the SMOKY test

June 2016
Journal of Radiological Protection 36(3):474-489

June 2016
36(3):474-489

Authors:

Health effects following low doses of ionizing radiation are uncertain. Military veterans at the Nevada test site (NTS) during the SMOKY atmospheric nuclear weapons test in 1957 were reported to be at increased risk for leukemia in 1979, but this increase was not evaluated with respect to radiation dose. The SMOKY test was one of 30 tests in 1957 within the PLUMBBOB test series. These early studies led to public laws where atomic veterans could qualify for compensation for presumptive radiogenic diseases. A retrospective cohort study was conducted of 12219 veterans at the PLUMBBOB test series, including 3020 at the SMOKY nuclear test. Mortality follow-up was through 2010 and observed causes of death were compared with expected causes based on general population rates. Radiation dose to red bone marrow was based on individual dose reconstructions, and Cox proportional hazards models were used to evaluate dose response for all leukemias other than chronic lymphocytic leukemia (non-CLL leukemia). Vital status was determined for 95.3% of the 12 219 veterans. The dose to red bone marrow was low (mean 3.2 mGy, maximum 500 mGy). Military participants at the PLUMBBOB nuclear test series remained relatively healthy after 53 years and died at a lower rate than the general population. In contrast, and in comparison with national rates, the SMOKY participants showed significant increases in all causes of death, respiratory cancer, leukemia, nephritis and nephrosis, and accidents, possibly related in part to lifestyle factors common to enlisted men who made up 81% of the SMOKY cohort. Compared with national rates, a statistically significant excess of non-CLL leukemia was observed among SMOKY participants (Standardized Mortality Ratio = 1.89, 95% 1.24-2.75, n = 27) but not among PLUMBBOB participants after excluding SMOKY (SMR = 0.87, 95% 0.64-1.51, n = 47). Leukemia risk, initially reported to be significantly increased among SMOKY participants, remained elevated, but this risk diminished over time. Despite an intense dose reconstruction, the risk for leukemia was not found to increase with increasing levels of radiation dose to the red bone marrow. Based on a linear model, the estimated excess relative risk per mGy is -0.05 (95% CI -0.14, 0.04). An explanation for the observed excess of leukemia remains unresolved but conceivably could be related to chance due to small numbers, subtle biases in the study design and/or high tobacco use among enlisted men. Larger studies should elucidate further the possible relationship between fallout radiation, leukemia and cancer among atomic veterans.

Outcome Assessment in Epidemiological Studies of Low-Dose Radiation Exposure and Cancer Risks: Sources, Level of Ascertainment, and Misclassification

Article

Full-text available

Jul 2020
J Natl Canc Inst Monogr

Background: Outcome assessment problems and errors that could lead to biased risk estimates in low-dose radiation epidemiological studies of cancer risks have not been systematically evaluated. Methods: Incidence or mortality risks for all cancers or all solid cancers combined and for leukemia were examined in 26 studies published in 2006-2017 involving low-dose (mean dose ≤100 mGy) radiation from environmental, medical, or occupational sources. We evaluated the impact of loss to follow-up, under- or overascertainment, outcome misclassification, and changing classifications occurring similarly or differentially across radiation dose levels. Results: Loss to follow-up was not reported in 62% of studies, but when reported it was generally small. Only one study critically evaluated the completeness of the sources of vital status. Underascertainment of cancers ("false negatives") was a potential shortcoming for cohorts that could not be linked with high-quality population-based registries, particularly during early years of exposure in five studies, in two lacking complete residential history, and in one with substantial emigration. False positives may have occurred as a result of cancer ascertainment from self- or next-of-kin report in three studies or from enhanced medical surveillance of exposed patients that could lead to detection bias (eg, reporting precancer lesions as physician-diagnosed cancer) in one study. Most pediatric but few adult leukemia studies used expert hematopathology review or current classifications. Only a few studies recoded solid cancers to the latest International Classification of Diseases or International Classification of Diseases for Oncology codes. These outcome assessment shortcomings were generally nondifferential in relation to radiation exposure level except possibly in four studies. Conclusion: The majority of studies lacked information to enable comprehensive evaluation of all major sources of outcome assessment errors, although reported data suggested that the outcome assessment limitations generally had little effect on risk or biased estimates towards the null except possibly in four studies.

Issues in Interpreting Epidemiologic Studies of Populations Exposed to Low-Dose, High-Energy Photon Radiation

Article

Full-text available

Jul 2020
J Natl Canc Inst Monogr

This article addresses issues relevant to interpreting findings from 26 epidemiologic studies of persons exposed to low-dose radiation. We review the extensive data from both epidemiologic studies of persons exposed at moderate or high doses and from radiobiology that together have firmly established radiation as carcinogenic. We then discuss the use of the linear relative risk model that has been used to describe data from both low- and moderate- or high-dose studies. We consider the effects of dose measurement errors; these can reduce statistical power and lead to underestimation of risks but are very unlikely to bring about a spurious dose response. We estimate statistical power for the low-dose studies under the assumption that true risks of radiation-related cancers are those expected from studies of Japanese atomic bomb survivors. Finally, we discuss the interpretation of confidence intervals and statistical tests and the applicability of the Bradford Hill principles for a causal relationship.

Strengths and Weaknesses of Dosimetry Used in Studies of Low-Dose Radiation Exposure and Cancer

Article

Jul 2020
J Natl Canc Inst Monogr

Background: A monograph systematically evaluating recent evidence on the dose-response relationship between low-dose ionizing radiation exposure and cancer risk required a critical appraisal of dosimetry methods in 26 potentially informative studies. Methods: The relevant literature included studies published in 2006-2017. Studies comprised case-control and cohort designs examining populations predominantly exposed to sparsely ionizing radiation, mostly from external sources, resulting in average doses of no more than 100 mGy. At least two dosimetrists reviewed each study and appraised the strengths and weaknesses of the dosimetry systems used, including assessment of sources and effects of dose estimation error. An overarching concern was whether dose error might cause the spurious appearance of a dose-response where none was present. Results: The review included 8 environmental, 4 medical, and 14 occupational studies that varied in properties relative to evaluation criteria. Treatment of dose estimation error also varied among studies, although few conducted a comprehensive evaluation. Six studies appeared to have known or suspected biases in dose estimates. The potential for these biases to cause a spurious dose-response association was constrained to three case-control studies that relied extensively on information gathered in interviews conducted after case ascertainment. Conclusions: The potential for spurious dose-response associations from dose information appeared limited to case-control studies vulnerable to recall errors that may be differential by case status. Otherwise, risk estimates appeared reasonably free of a substantial bias from dose estimation error. Future studies would benefit from a comprehensive evaluation of dose estimation errors, including methods accounting for their potential effects on dose-response associations.

The Million Person Study, Whence it Came and Why

Article

Mar 2019

Purpose: The study of low dose and low-dose rate exposure is of immeasurable value in understanding the possible range of health effects from prolonged exposures to radiation. The Million Person Study of Low-Dose Health Effects (MPS) was designed to evaluate radiation risks among healthy American workers and veterans who are more representative of today’s populations than are the Japanese atomic bomb survivors exposed briefly to high-dose radiation in 1945. A million persons were needed for statistical reasons to evaluate low-dose and dose-rate effects, rare cancers, intakes of radioactive elements, and differences in risks between women and men. Methods and Materials: The MPS consists of five categories of workers and veterans exposed to radiation from 1939 to the present. The U.S. Department of Energy (DOE) Health and Mortality study began over 40 years ago and is the source of ∼360,000 workers. Over 25 years ago, the National Cancer Institute (NCI) collaborated with the U.S. Nuclear Regulatory Commission (NRC) to effectively create a database of nuclear power plant workers (∼150,000) and industrial radiographers (∼130,000). For over 30 years, the Department of Defense (DoD) collected data on aboveground nuclear weapons test participants (∼115,000). At the request of NCI in 1978, Landauer, Inc., saved their dosimetry databases which became the source of ∼250,000 medical and other workers. Results: Overall, 29 individual cohorts comprise the MPS of which 21 have been or are under active study (∼810,000 persons). The remaining eight cohorts (∼190,000 persons) will be studied as resources become available. The MPS is a national effort with critical support from the NRC, DOE, NASA, DoD, NCI, the Centers for Disease Control and Prevention (CDC), Landauer, Inc., and national laboratories. Conclusions: The MPS is designed to answer the major unanswered question in radiation risk understanding: What is the level of health effects when exposure is gradual overtime and not delivered briefly. The MPS will provide scientific understandings of prolonged exposure which will improve guidelines to protect workers and the public; improve compensation schemes for workers, veterans and the public; provide guidance for policy and decision makers; and provide evidence for or against the continued use of the linear nonthreshold dose-response model in radiation protection.

Ionising radiation as a risk factor for lymphoma: A review

Article

Full-text available

Oct 2020
J RADIOL PROT

The ability of ionising radiation to induce lymphoma is unclear. Here, we present a narrative review of epidemiological evidence of the risk of lymphoma, including chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM), among various exposed populations including atomic bombing survivors, industrial and medical radiation workers and individuals exposed for medical purposes. Overall, there is a suggestion of a positive dose dependent association between radiation exposure and lymphoma. The magnitude of this association is highly imprecise, however, with wide confidence intervals frequently including zero risk. External comparisons tend to show similar incidence and mortality rates to the general population. Currently, there is insufficient information on the impact of age-at-exposure, high versus low linear energy transfer (LET) radiation, external versus internal or acute versus chronic exposures. Associations are stronger for males than females, and stronger for non-Hodgkin lymphoma (NHL) and MM than for Hodgkin lymphoma (HL), while the risk of radiation induced CLL may be non-existent. This broad grouping of diverse diseases could potentially obscure stronger associations for certain subtypes, each with a different cell-of-origin. Additionally, the classification of malignancies as leukaemia or lymphoma may result in similar diseases being analysed separately while distinct diseases are analysed in the same category. Uncertainty in cell-of-origin means the appropriate organ for dose response analysis is unclear. Further uncertainties arise from potential confounding or bias due to infectious causes and immunosuppression. The potential interaction between radiation and other risk factors is unknown. Combined, these uncertainties make lymphoma perhaps the most challenging malignancy to study in radiation epidemiology.

Mortality among US military participants at eight aboveground nuclear weapons test series

Article

Jun 2020

Background: Approximately 235,000 military personnel participated at one of 230 U.S. atmospheric nuclear weapons tests from 1945 through 1962. At the Nevada Test Site (NTS) the atomic veterans participated in military maneuvers, observed nuclear weapons tests, or provided technical support. At the Pacific Proving Ground (PPG) they served aboard ships or were stationed on islands during or after nuclear weapons tests. Methods and Material: Participants at seven test series, previously studied with high-quality dosimetry and personnel records, and the first test at TRINITY formed the cohort of 114,270 male military participants traced for vital status from 1945 through 2010. Dose reconstructions were based on Nuclear Test Personnel Review records, Department of Defense. Standardized Mortality Ratios (SMR) and Cox and Poisson regression models were used in the analysis. Results: Most atomic veterans were enlisted men, served in the Navy at the PPG, and were born before 1930. Vital status was determined for 96.8% of the veterans; 60% had died. Enlisted men had significantly high all causes-mortality SMR (1.06); officers had significantly low all cause-mortality SMR (0.71). The pattern of risk over time showed a diminution of the “healthy soldier effect”: the all-cause mortality SMR after 50 y of follow-up was 1.00. The healthy soldier effect for all cancers also diminished over time. The all-cancer SMR was significantly high after 50 y (SMR 1.10) primarily from smoking-related cancers, attributed in part to the availability of cigarettes in military rations. The highest SMR was for mesothelioma (SMR 1.56) which was correlated with asbestos exposure in naval ships. Prostate cancer was significantly high (SMR 1.13). Ischemic heart disease was significantly low (SMR 0.84). Estimated mean doses varied by organ and were low; e.g., the mean red bone marrow dose was 6 mGy (maximum 108 mGy). Internal cohort dose-response analyses provided no evidence for increasing trends with radiation dose for leukemia (excluding chronic lymphocytic leukemia (CLL)) [ERR (95% CI) per 100 mGy -0.37 (-1.08, 0.33); n = 710], CLL, myelodysplastic syndrome, multiple myeloma, ischemic heart disease, or cancers of the lung, prostate, breast and brain. Conclusion: No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 y. The 95% confidence limits were narrow and exclude mortality risks per unit dose that are two to four times those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships.

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection

Article

Jul 2018

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes [1]. The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarizes several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukaemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modeling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognizes that the risks from LD/LDR are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

A Million Persons, A Million Dreams: A Vision For A National Center Of Radiation Epidemiology And Biology

Article

Oct 2021
INT J RADIAT BIOL

Background: Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. Materials and methods: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautical Space Agency (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. Results: The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. Conclusions: The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.

ASSESSMENT OF LYMPHOID NEOPLASM RISK FACTORS IN PEOPLE OCCUPATIONALLY EXPOSED TO PROLONGED IONIZING RADIATION

Article

Full-text available

Dec 2020

Objective : To estimate the incidence of malignant neoplasms of lymphoid tissue (MNLT) among employees of the siberian chemical combine (SCC) occupationally exposed to prolonged ionizing radiation. Material and methods . The study included 44,041 employees of the SCC, of whom 16,938 were occupationally exposed to prolonged low-intensity ionizing radiation (IR). Of 295 cases with hemoblastoses, there were 89 with occupational exposure to IR. The structure and incidence of hemoblastoses (based on the number of person-years of observation, (PYO), as well as the standardized relative risk (SRR) of their development and excess relative risk (err) per unit dose of radiation (GR) were evaluated. Calculation of SRR was carried out for the following intervals of the total dose of external exposure: 0; >0–0.05; >0.05–0.10; >0.10-0.15; >0.15–0.20; >0.20-0.30; >0.30-0.50; >0.5–1.0; ≥ 1.0 Gy. The control group consisted of occupationally non-exposed employees of the SCC. The calculation of SRR and err was performed using the poisson regression using the amfit module of the EPICURE package. Results . The incidence of MNLT among males of SCC was 17.1 per 100,000 PYO, with the highest incidence rates for Non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL) and chronic leukemia (CL) excluding CLL. Among females of the SCC, the incidence of MNLT was 21.3 per 100,000 PYO. It was found that in none of the intervals of the external exposure there was no statistically significant excess of the SRR compared with the control group. The results of ERR/GY calculation also did not demonstrate the increased risk of hemoblastosis among people occupationally exposed to IR. Conclusion . Occupational exposure in the studied dose range does not increase the risk of developing MNLT.

NCRP Report No 186 2020 Approaches for integrating information from radiation biology and epidemiology to enhance low-dose health risk assessment

Book

Jul 2020

The overall aim of this Report is to provide input for the development of biologically based dose-response (BBDR) models for radiation- induced cancers and circulatory disease that use an adverse outcome pathways and key-events approach for providing parameters for these models. These mechanistic data can be integrated with the most recent epidemiologic data to develop overall doseresponse curves for radiation-induced adverse health outcomes. This integration of the findings from radiation biology and epidemiology will enhance the risk assessment process by reducing uncertainties in estimated risk following exposure to low doses and low dose rates of ionizing radiation. For many decades the basis for setting radiation protection guidance for exposure to low absorbed doses and low absorbed-dose rates of ionizing radiation has been the estimation of the risk of radiation-induced cancer. In addition, there is ongoing discussion concerning risks of radiation-induced noncancer effects1 (particularly circulatory disease). The estimates for radiation-induced cancer have been derived primarily from exposure to higher doses and higher dose rates of ionizing radiation and assumptions on how to extrapolate to low doses and low dose rates. For the purpose of this Report, for low linear-energy transfer (LET) radiation, a low absorbed dose is <100 mGy delivered acutely, and a low absorbeddose rate is <5 mGy h–1 for any accumulated absorbed dose (NCRP 2015). This Report addresses the conclusions and recommendations from three previous National Council on Radiation Protection and Measurements (NCRP) reports and commentaries on the topic of the risks of adverse health outcomes at low doses and low dose rates of ionizing radiation (NCRP 2012, 2015, 2018a). In this context, the present Report proposes a path forward to enhance the estimation of risk at low doses and low dose rates. Such a modified approach is needed to supplement the information that can be obtained from the conduct of even large epidemiologic studies such as the One Million U.S. Workers and Veterans Study of Low-Dose Radiation Health Effects (million U.S. workers and veterans study) 1For this Report the term noncancer is restricted to somatic noncancer outcomes and does not include heritable effects. (Bouville et al. 2015; Boice et al. 2019), the International Nuclear Workers Study (Leuraud et al. 2015; Richardson et al. 2015), the European pooled study of radiation-induced cancer from pediatric computed tomography (Bernier et al. 2019), or other low-dose pooling studies (Lubin et al. 2017; Little, Kitahara et al. 2018). This Report presents such an approach based upon the integration of data from epidemiology and radiation biology. An essential component of the integration process is the use of BBDR models with parameters being developed from analyzing adverse outcome pathways and their associated key events. In principle, an adverse outcome pathway is the series of necessary steps that result in an initial molecular event leading to an adverse health outcome (for this Report, either cancer or circulatory disease). Definitions of adverse outcome pathways and key events are given in Section 2 and can be found also in recent reviews (Edwards et al. 2016; Preston 2017). Also, when considering mechanistic data underlying the induction of adverse health outcomes, it is important to distinguish between potential bioindicators and biomarkers of these outcomes. A bioindicator is a cellular alteration that is on a critical pathway to the disease endpoint itself (i.e., necessary, but not by itself sufficient for the endpoint), such as a specific mutation in a target cell that is associated with tumor formation. Thus, a bioindicator can be perceived as informing on the shape of the dose-response curve for the disease outcome or on cancer frequency itself, and therefore, is equivalent to a key event. A biomarker is a biological phenotype [e.g., chromosome alteration, deoxyribonucleic acid (DNA) adduct, gene expression change, specific metabolite] that can be used to indicate a response to an exposure at the cell or tissue level. In this regard, a biomarker is generally a measure of the potential for development of an adverse health outcome such as cancer (e.g., a predictor of exposure level). This Report expands upon this general approach of adverse outcome pathways, key events, and BBDR models to enhance the process of low-dose, low dose-rate risk estimation. The arrangement of this Report for the application of this general approach is: here is what we know, here is what we need to know, and this is how we can obtain the necessary knowledge. A synopsis of Sections 2 through 7 is given below. Section 2 (Introduction) provides an overview of current approaches to radiation risk assessment, the associated uncertainties and possible ways forward for enhancing the estimation of risks of cancer and circulatory disease at low doses and low dose rates. Section 3 (Epidemiology, Biosamples and Biomarkers: Cancer and Circulatory Disease) presents a review of the radiation epidemiologic studies for which biomarker data or biological samples were used. For noncancer effects it was clear that the only adverse health outcome for which significant data from radiation biology are available for use in BBDR models is circulatory disease and so this forms the basis for the discussion on noncancer effects. There are a large number of radiation epidemiologic studies available that are very informative for estimating risks at higher doses but that can only be used with a fairly high degree of uncertainty for predicting low-dose risks. A review of the main radiation epidemiologic studies has been provided in NCRP Commentary No. 27 (NCRP 2018a). Section 3.1 briefly describes the major epidemiologic radiation studies with associated biosamples that potentially can be employed to conduct investigations of bioindicators of the pathogenesis of radiation-induced cancer and other health endpoints. While none of the current investigations has yet been able to identify definitive bioindicators, there are several suggestions of biomarkers that merit confirmation through further investigations and might be informative in the absence of more definitive bioindicator studies. The details and references for these studies are provided in Section 3.1.3. Section 3.2 indicates that it is likely that bioindicators of radiation- induced noncancer effects at low doses will be restricted to circulatory disease and so this is the sole topic reviewed for biomarkers associated with noncancer responses. With current knowledge, substantive biomarker information is only available in two major radiation studies: the Japanese atomic-bomb survivors, and the Mayak Production Association workers (Mayak workers), although little use has been made of this latter population in analyses to date. In summary, there is a paucity of radiation-specific bioindicators of cancer and circulatory disease and a relative lack of radiation- specific biomarkers predictive of adverse health outcomes. Thus, it is necessary to consider the mechanisms of formation of cancers and circulatory disease, especially for radiation-induced responses, to aid with the identification of bioindicators of adverse health outcomes and to a lesser extent, biomarkers of association with an adverse health outcome. Section 4 (Radiation-Induced Biological Effects Related to Cancer and Circulatory Disease) reviews the underlying mechanisms of carcinogenesis and circulatory disease with the aim of identifying potential bioindicators of the adverse health outcome, and if possible radiation-associated bioindicators of such responses. There has been an increased understanding of the underlying mechanisms of human diseases as a result of new molecular, cellular and computational approaches, further enhanced by informative experimental animal systems that model human disease. To a lesser extent such approaches have been used to better understand the etiology of radiation-induced diseases. There is a description of the types of studies that have identified pathways and potential key events in the carcinogenesis process (Section 4.1). While currently there are no fully validated bioindicators or biomarkers of radiation-induced cancer, there is a substantial and increasing body of knowledge on radiation-induced cancer mechanisms, particularly in experimental animal systems. Quantification of inflammation and generation of persistently elevated reactive oxygen species (ROS) holds promise as a further bioindicator that is also recognized as an enabling hallmark of cancer in the context of Hanahan and Weinberg (2011). In addition, cell-survival parameters can be of importance in mechanistic models of carcinogenesis. The use of data from experimental animal systems provides opportunities to demonstrate the added value of building and applying mechanistic models of radiation-induced cancer. There are additional opportunities to apply similar models in some human radiation-induced cancers, most notably thyroid, where some work utilizing knowledge of the CLIP2 marker is already available. The incorporation of quantitative mechanistic data into appropriate cancer models (discussed in Sections 5 and 6) is likely to increase the precision of estimated risks, particularly at low-dose levels and so continued efforts to identify and validate bioindicators of radiation- induced cancers will assist in refining risk estimation. Section 4.2 outlines the biology of circulatory disease, a significant radiation-induced noncancer disease2 and the one which currently offers the best opportunity for bioindicator identification given the mechanistic data already available. The complex inflammatory processes underlying most major types of circulatory disease are reviewed, specifically those associated with atherosclerosis. The possible ways that low-dose radiation exposure and other 2NCRP (2018a) stated that radiation-induced cardiovascular disease (a circulatory disease) remains an area where further investigation is necessary. Although there is evidence that cardiovascular disease may be a factor at exposures lower than previously estimated, that evidence was not yet sufficient to allow for development of an approach to including cardiovascular disease in NCRP’s overall system of radiation protection published in NCRP (2018b). biological stressors might affect the circulatory system are also reviewed. While it is not possible yet to identify bioindicators of radiation-induced circulatory disease, it appears feasible to build upon the rapidly increasing knowledge of the mechanisms of formation of circulatory disease to develop adverse outcome pathways and at least some of the associated key events. Section 5 (Biologically Based Dose-Response Models) assesses biomathematical models of chronic disease, especially those for cancer and circulatory disease (with particular emphasis in circulatory disease on models of atherosclerosis). First, general material outlining the overall goals of biomathematical models is presented, followed by discussion of modeling considerations, particularly application of specific models using human, animal or cell data to cancer and circulatory disease. Biologically based modeling of radiation- induced cancers of the breast, colon, lung, and thyroid gland have been conducted. After considerations of some general features of BBDR models of cancer development in Section 5.1, a number of BBDR models and their application to various human and animal datasets are presented in Section 5.2. Despite some shortcomings (e.g., the fact that different models might explain the available data using different mechanistic assumptions), multiple pathway models are considered a promising conceptual approach to developing a general model framework for the complex process of carcinogenesis in various tissues. In certain cases, multiple pathway models may allow predictions that can be validated against experimental data. Circulatory disease models are considered in Section 5.3. These are less well developed than those that have been constructed to model cancer. A number of candidate models of atherosclerosis are considered. Atherosclerosis is the disease process underlying the main types of circulatory disease, specifically ischemic heart disease (IHD) and stroke, which is thought to have a largely inflammatory etiology. A number of atherosclerosis models, which share certain features, have been proposed for these inflammatory processes, specifically the adhesion and transport of monocytes through the epithelial cell layer, and diffusion through the intima. However, it is not yet clear what the radiation-associated mechanisms may be for most types of circulatory disease. Having identified the types of BBDR models that could possibly be used to enhance the estimation of low-dose, low dose-rate radiation adverse health outcomes, it is necessary to determine whether there is a generalized model that can be used for: all radiationinduced cancer types, or circulatory disease as a class. It was concluded that it would be unlikely that a single model structure could be used for describing cancer and circulatory disease. Also, it appears likely that there may be different responses even for different types of circulatory disease. The concept of a generalized model is discussed in Section 6 (Proposed Generalized Model Framework of Cancer and Circulatory Disease). It is proposed that a form of multistage clonal expansion model would be appropriate for integrating data from epidemiology and radiation biology for estimating low-dose, low dose-rate cancer risk. The parameters for such a model structure are proposed to be developed from an adverse outcome pathways and key-events approach. In such an approach the key events are considered to be bioindicators of the adverse health outcome itself. In support of this proposal to utilize generalized multistage clonal expansion models, there has been considerable recent discussion on the use of such parameterized models for environmental chemicals (OECD 2020). The Organization for Economic Co-operation and Development (OECD 2020) website provides a considerable amount of information on developing adverse outcome pathways and their use in risk assessment and ultimately in risk management practice. This general approach is also described and applied in the research program of the U.S. Environmental Protection Agency (EPA 2018). A description of biologically detailed models of specific cancers that have been applied with some levels of success is provided to indicate the viability of the use of BBDR models for estimating adverse health outcomes at low doses and low dose rates. While not definitive at this time, the approach certainly has a real likelihood of being successful. Section 7 (Research Needs) provides specific examples of research activities, both large and small that are designed for developing adverse outcome pathways and their associated key events. These include epidemiologic, human sample, laboratory animal, cellular, and molecular studies. Such research activities include investigating some general but critical responses, in order to derive greater insight into the parameters of most importance for further model development. Currently, one can envisage the following to be of high relevance: • target cell population numbers and characteristics; • survival parameters for these populations after radiation exposure; • target gene(s) critical for pathogenesis and their mutation or epimutation frequency as a function of radiation dose; • proliferation characteristics in normal and mutation-carrying cell populations; and • timing and frequency of acquisition of further mutational events in key genes and the impact of these on survival and proliferation characteristics. For enhanced model development, it is necessary to more fully identify the mechanisms of cancer development in response to radiation. The following are of importance in this regard: • Mechanisms in the development of a radiation-induced disease may differ from those in sporadic disease. • Does radiation initiate or accelerate the same processes that lead to sporadic disease, or are distinct molecular pathways involved? • BBDR models have the potential to address such questions if appropriate bioindicators become available for specific types of cancer or other diseases. • For transcriptomics, proteomics, metabolomics and epigenomics, adequate BBDR models ideally might require measurements at several time points because the profiles of phenotypic alterations may differ by stage in the pathogenesis of a disease. Clearly, the overarching need is the furthering of research targeted at the underlying mechanisms of radiation-induced adverse health outcomes (cancer and noncancer disease) leading to the identification of truly informative bioindicators of the apical endpoint (i.e., the adverse health outcome). The framework for such an approach can be the characterization of adverse outcome pathways for specific outcomes and the identification of key events from the initial event to adverse health outcome. In this context, a key-event or informative bioindicator is a true surrogate for the adverse health outcome. This approach will require the integration of data from epidemiology and radiation biology to maximize the information for estimating low-dose responses for adverse health outcomes. A particularly important result will be the ability to better describe the form of the dose-response curve for different types of radiation- induced cancer, for example, and thereby avoid the need to rely on application of the linear-nonthreshold (LNT) model without sufficient biological substantiation. A concerted effort will be needed; this is going to require a well-defined and quite extensive research effort. The need for this effort is recognized by many in the risk assessment and risk management arena.

Evaluation of Confounding and Selection Bias in Epidemiologic Studies of Populations Exposed to Low-Dose, High-Energy Photon Radiation

Article

Full-text available

Jul 2020
J Natl Canc Inst Monogr

Background: Low-dose, penetrating photon radiation exposure is ubiquitous, yet our understanding of cancer risk at low doses and dose rates derives mainly from high-dose studies. Although a large number of low-dose cancer studies have been recently published, concern exists about the potential for confounding to distort findings. The aim of this study was to describe and assess the likely impact of confounding and selection bias within the context of a systematic review. Methods: We summarized confounding control methods for 26 studies published from 2006 to 2017 by exposure setting (environmental, medical, or occupational) and identified confounders of potential concern. We used information from these and related studies to assess evidence for confounding and selection bias. For factors in which direct or indirect evidence of confounding was lacking for certain studies, we used a theoretical adjustment to determine whether uncontrolled confounding was likely to have affected the results. Results: For medical studies of childhood cancers, confounding by indication (CBI) was the main concern. Lifestyle-related factors were of primary concern for environmental and medical studies of adult cancers and for occupational studies. For occupational studies, other workplace exposures and healthy worker survivor bias were additionally of interest. For most of these factors, however, review of the direct and indirect evidence suggested that confounding was minimal. One study showed evidence of selection bias, and three occupational studies did not adjust for lifestyle or healthy worker survivor bias correlates. Theoretical adjustment for three factors (smoking and asbestos in occupational studies and CBI in childhood cancer studies) demonstrated that these were unlikely to explain positive study findings due to the rarity of exposure (eg, CBI) or the relatively weak association with the outcome (eg, smoking or asbestos and all cancers). Conclusion: Confounding and selection bias are unlikely to explain the findings from most low-dose radiation epidemiology studies.

An overview update in chemical, biological and nuclear weapons and their effects in human health

Article

May 2019

Sex-Specific Lung Cancer Risk among Radiation Workers in the Million Person Study and TB-Fluoroscopy Patients

Article

Jan 2019

Background: The study of Japanese atomic bomb survivors, exposed briefly to radiation, finds the risk of radiation-induced lung cancer to be nearly three times greater for women than for men. Because protection standards for astronauts are based on individual lifetime risk projections, this sex-specific difference limits the time women can spend in space. Populations exposed to chronic or fractionated radiation were evaluated to learn whether similar differences exist when exposures occur gradually over years. Methods and Materials: Five occupational cohorts within the Million Person Study of Low-Dose Health Effects (MPS) and a Canadian Fluoroscopy Cohort Study (CFCS) of tuberculosis patients who underwent frequent chest fluoroscopic examinations are evaluated. Included are male and female workers at the Mound nuclear facility, nuclear power plants (NPP), and industrial radiographers (IR). Workers at the Mallinckrodt Chemical Works and military participants at aboveground nuclear weapons tests provide information on the risk among males. Cox proportional hazards and Poisson regression models were used to estimate sex-specific radiation risks for lung cancer and to compare any differences. Results: Overall, 15,065 lung cancers occurred among the 443,684 subjects studied: 50,111 women and 395,573 men. The mean cumulative dose to the lung was 166.3 mGy (range 6 to 1,055 mGy) with the highest among the TB-fluoroscopy patients (mean 1,055 mGy). Mean lung dose for women in the worker cohorts was generally 4 times lower than for men. Of the 12 estimates of radiation-related risk, only one, for male IRs, showed a significant elevation (ERR 0.09; 95% CI 0.02-0.16, at 100 mGy). In contrast, the dose response for male NPP workers was negative (ERR -0.05; 95% CI -0.10, 0.01, at 100 mGy). Combined, these two cohorts provided little evidence for a radiation effect among males (ERR 0.01; 95% CI -0.04, 0.06, at 100 mGy). There was no significant dose response among females within any cohort. There was no difference in the sex-specific estimates of lung cancer risk. Conclusions: There was little evidence that chronic or fractionated exposures increased the risk of lung cancer. There were no differences in the risks of lung cancer between men and women. However, the sex-specific analyses are limited because of small numbers of women and relatively low doses. A more definitive study is ongoing of medical radiation workers which includes 85,000 women and 85,000 men (overall mean dose 82 mGy, max 1,140 mGy). Additional understanding will come from the ongoing follow-up of the CFCS.

Recent Epidemiologic Studies and the Linear No-Threshold Model For Radiation Protection-Considerations Regarding NCRP Commentary 27

Article

Feb 2019

National Council on Radiation Protection and Measurements Commentary 27 examines recent epidemiologic data primarily from low-dose or low dose-rate studies of low linear-energy-transfer radiation and cancer to assess whether they support the linear no-threshold model as used in radiation protection. The commentary provides a critical review of low-dose or low dose-rate studies, most published within the last 10 y, that are applicable to current occupational, environmental, and medical radiation exposures. The strengths and weaknesses of the epidemiologic methods, dosimetry assessments, and statistical modeling of 29 epidemiologic studies of total solid cancer, leukemia, breast cancer, and thyroid cancer, as well as heritable effects and a few nonmalignant conditions, were evaluated. An appraisal of the degree to which the low-dose or low dose-rate studies supported a linear no-threshold model for radiation protection or on the contrary, demonstrated sufficient evidence that the linear no-threshold model is inappropriate for the purposes of radiation protection was also included. The review found that many, though not all, studies of solid cancer supported the continued use of the linear no-threshold model in radiation protection. Evaluations of the principal studies of leukemia and low-dose or low dose-rate radiation exposure also lent support for the linear no-threshold model as used in protection. Ischemic heart disease, a major type of cardiovascular disease, was examined briefly, but the results of recent studies were considered too weak or inconsistent to allow firm conclusions regarding support of the linear no-threshold model. It is acknowledged that the possible risks from very low doses of low linear-energy-transfer radiation are small and uncertain and that it may never be possible to prove or disprove the validity of the linear no-threshold assumption by epidemiologic means. Nonetheless, the preponderance of recent epidemiologic data on solid cancer is supportive of the continued use of the linear no-threshold model for the purposes of radiation protection. This conclusion is in accord with judgments by other national and international scientific committees, based on somewhat older data. Currently, no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes than the linear no-threshold model.

Health Impacts of Low-Dose Ionizing Radiation: Current Scientific Debates and Regulatory Issues

Article

Full-text available

Sep 2018

Health impacts of low-dose ionizing radiation are significant in important fields such as X-ray imaging, radiation therapy, nuclear power, and others. However, all existing and potential applications are currently challenged by public concerns and regulatory restrictions. We aimed to assess the validity of the linear no-threshold (LNT) model of radiation damage, which is the basis of current regulation, and to assess the justification for this regulation. We have conducted an extensive search in PubMed. Special attention has been given to papers cited in comprehensive reviews of the United States (2006) and French (2005) Academies of Sciences and in the United Nations Scientific Committee on Atomic Radiation 2016 report. Epidemiological data provide essentially no evidence for detrimental health effects below 100 mSv, and several studies suggest beneficial (hormetic) effects. Equally significant, many studies with in vitro and in animal models demonstrate that several mechanisms initiated by low-dose radiation have beneficial effects. Overall, although probably not yet proven to be untrue, LNT has certainly not been proven to be true. At this point, taking into account the high price tag (in both economic and human terms) borne by the LNT-inspired regulation, there is little doubt that the present regulatory burden should be reduced.

The Past Informs the Future: An Overview of the Million Worker Study and the Mallinckrodt Chemical Works Cohort

Article

Apr 2018
HEALTH PHYS

The purpose of this paper is to present an overview of ongoing work on the Million Worker Study (MWS), highlighting some of the key methods and progress so far as exemplified by the study of workers at the Mallinckrodt Chemical Works (MCW). The MWS began nearly 25 y ago and continues in a stepwise fashion, evaluating one study cohort at a time. It includes workers from U.S. Department of Energy (DOE) Manhattan Project facilities, U.S. Nuclear Regulatory Commission (NRC) regulated nuclear power plants, industrial radiographers, U.S. Department of Defense (DoD) nuclear weapons test participants, and physicians and technologists working with medical radiation. The purpose is to fill the major gap in radiation protection and science: What is the risk when exposure is received gradually over time rather than briefly as for the atomic bomb survivors? Studies published or planned in 2018 include leukemia (and dosimetry) among atomic veterans, leukemia among nuclear power plant workers, mortality among workers at the MCW, and a comprehensive National Council on Radiation Protection and Measurements (NCRP) Report on dosimetry for the MWS. MCW has a singular place in history: the 40 tons (T) of uranium oxide produced at MCW were used by Enrico Fermi on 2 December 1942 to produce the first manmade sustained and controlled nuclear reaction, and the atomic age was born. Seventy-six years later, the authors followed the over 2,500 MCW workers for mortality and reconstructed dose from six sources of exposure: external gamma rays from the radioactive elements in pitchblende; medical x rays from occupationally required chest examinations; intakes of pitchblende (uranium, radium, and silica) measured by urine samples; radon breath analyses and dust surveys overseen by Robley Evans and Merril Eisenbud; occupational exposures received before and after employment at MCW; and cumulative radon concentrations and lung dose from the decay of radium in the work environment. The unique exposure reconstructions allow for multiple evaluations, including estimates of silica dust. The study results are relevant today. For example, NASA is interested that radium, deposited in the brain, releases high-LET alpha particles - the only human analogue, though limited, for high energy, high-Z particles (galactic cosmic rays) traveling through space that might affect astronauts on Mars missions. Don't discount the past; it's the prologue to the future!

Innovation: Technical and social

Article

Mar 2017

Michael Charles Thorne

Effects of ionizing radiation on reproduction and development

Chapter

Jan 2022

Roger O. McClellan

The discovery of X-rays by Roentgen in 1895 was quickly followed by expanded use of ionizing radiation in diagnostic and therapeutic medicine. It is now a key component of modern medicine and should be celebrated as one of the major scientific achievements of the last century. A second era involving radiation began in 1938 with the discovery of nuclear fission. This quickly led to development of the atomic bomb. Atomic bombs were dropped in 1945 on Hiroshima and Nagasaki, Japan, demonstrating the tremendous destructive power of the blast wave, thermal radiation, and ionizing radiation that cause substantial morbidity and mortality. The Atomic Bomb Casualty Commission, now the Radiation Effects Research Foundation was created to follow the (a) survivors who were in the cities when they were bombed, (b) individuals exposed in utero and born to survivors, and (c) an F1 population born to survivors. These cohorts have been studied to the present time. A small dose-related increase in cancer and chronic cardiovascular and respiratory diseases has been observed. Some dose-related health effects were observed in individuals exposed in utero. Detailed studies failed to identify heritable effects. A study using thousands of mice irradiated with high doses of radiation indicated a small heritable effect. Radiation protection standards for workers in the public put in place in the early 1940s have been highly effective at limiting health effects from ionizing radiation. There is an ongoing controversy over the appropriate dose–response model for ionizing radiation; a low-dose, a linear, no threshold model, or a threshold model. Concern for potential radiation exposures have been a major factor limiting expanded use of nuclear reactors to generate electricity, a carbon-free option for producing energy. This is remarkable since ionizing radiation as a hazardous agent has been more extensively studied than any other hazardous agent leading to effective standards.

Mortality from Leukemia, Cancer and Heart Disease among U.S. Nuclear Power Plant Workers, 1957-2011

Article

Oct 2021

Background The aim of the Million Person Study (MPS) of Low Dose Health Effects is to examine the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors. Nuclear power plant (NPP) workers comprise nearly 15 percent of the MPS. Leukemia, selected cancers, Parkinson’s disease, ischemic heart disease (IHD) and other causes of death are evaluated. Methods and Material The U.S. Nuclear Regulatory Commission’s Radiation Exposure Information and Reporting System (REIRS) and the Landauer, Inc. dosimetry databases identified 135,193 NPP workers first monitored 1957-1984. Annual personal dose equivalents [Hp(10)] were available for each worker. Radiation records from all places of employment were sought. Vital status was determined through 2011. Mean absorbed doses to red bone marrow (RBM), esophagus, lung, colon, brain and heart were estimated by adjusting the recorded Hp(10) for each worker by scaling factors, accounting for exposure geometry and energy of the incident gamma radiation. Standardized mortality ratios (SMR) were calculated. Radiation risks were estimated using Cox proportional hazards models. Results Nearly 50% of workers were employed for more than 20 years. The mean duration of follow-up was 30.2 y. Overall, 29,076 total deaths occurred, 296 from leukemia other than chronic lymphocytic leukemia (CLL), 3,382 from lung cancer, 140 from Parkinson’s disease and 5,410 from IHD. The mean dose to RBM was 37.9 mGy (maximum 1.0 Gy; percent >100 mGy was 9.2%), 43.2 mGy to lung, 43.7 mGy to colon, 33.2 mGy to brain, and 43.9 mGy to heart. The SMRs (95% CI) were 1.06 (0.94;1.19) for leukemia other than CLL, 1.10 (1.07;1.14) for lung cancer, 0.90 (0.76;1.06) for Parkinson’s disease, and 0.80 (0.78; 0.82) for IHD. The excess relative risk (ERR) per 100 mGy for leukemia other than CLL was 0.15 (90% CI 0.001; 0.31). For all solid cancers the ERR per 100 mGy (95% CI) was 0.01 (-0.03; 0.05), for lung cancer -0.04 (-0.11; 0.02), for Parkinson’s disease 0.24 (-0.02; 0.50), and for IHD -0.01 (-0.06; 0.04). Conclusion Prolonged exposure to radiation increased the risk of leukemia other than CLL among NPP workers. There was little evidence for a radiation-association for all solid cancers, lung cancer or ischemic heart disease. Increased precision will be forthcoming as the different cohorts within the MPS are combined, such as industrial radiographers and medical radiation workers who were assembled and evaluated in like manner.

Valid versus invalid radiation cancer risk assessment methods illustrated using Swiss population data

Article

Sep 2021

After the nuclear accident in Fukushima, the public interest in radiation related cancer-risk assessment increased. However, interpretations of results from epidemiological studies and comprehension of cancer risk assessment methods can be unclear and involve questions about correctness and validity of the approaches. To shed some light on this potential lack of clarity, valid versus invalid radiation cancer risk assessments methods are illustrated here using Swiss population data. This involves a comparison of the cancer risk assessment method based on collective dose and the cumulative risk assessment method, where the latter is recommended with regard on uncertainties and risk of misinterpretation. Further, risk assessment in different dose ranges is discussed and it is concluded that below 100 mSv it cannot be appropriately stated that an adequate strength of evidence of a causal relationship between cancer and radiation is provided, because of the large uncertainties in this dose range. However, the linear non-threshold (LNT) model can be used to model the dose response, because it represents a prudent and parsimonious model, that fits the data well and lies within the given uncertainties. Additionally, treatments of uncertainties in the risk models are illustrated. The EU-project CONFIDENCE software is applied here to obtain example radiation related lifetime cancer risks for exposures of 20 mSv and 5 mSv. Furthermore, the impact of different dosimetry errors on the uncertainties in the cancer lifetime risk calculation is analysed, by including different standard deviations (SD) and by comparing the sampling of the doses from a normal and a lognormal distribution. Using the normal distribution, for females exposed to 20 mSv, the 95% confidence interval (CI) on the cancer lifetime risk increases, when compared to using a SD of 4 mSv, by a factor of 1.5 using a SD of 8 mSv and by a factor of 1.7 using a SD of 10 mSv. The corresponding factors for males for the same exposure are 1.3 and 1.5 respectively. For exposure to 5 mSv, the 95% CIs on the risk increase by a factor of 1.2 for females and 1.4 for men for a SD of 2 mSv using the normal distribution compared to the lognormal distribution and by a factor of 1.5 and 1.8 for a SD of 3 mSv compared to a SD of 1 mSv respectively. Furthermore, differences in the resulting 95% CI on the risk, using different distributions for the dose sampling are visible.

Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Summary Bias Assessment and Meta-Analysis

Article

Full-text available

Jul 2020

Background Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases. Methods Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006–2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia. Results Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers. Conclusions Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.

Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Rationale and Framework for the Monograph and Overview of Eligible Studies

Article

Full-text available

Jul 2020
J Natl Canc Inst Monogr

Whether low-dose ionizing radiation can cause cancer is a critical and long-debated question in radiation protection. Since the Biological Effects of Ionizing Radiation report by the National Academies in 2006, new publications from large, well-powered epidemiological studies of low doses have reported positive dose-response relationships. It has been suggested, however, that biases could explain these findings. We conducted a systematic review of epidemiological studies with mean doses less than 100 mGy published 2006-2017. We required individualized doses and dose-response estimates with confidence intervals. We identified 26 eligible studies (eight environmental, four medical, and 14 occupational), including 91 000 solid cancers and 13 000 leukemias. Mean doses ranged from 0.1 to 82 mGy. The excess relative risk at 100 mGy was positive for 16 of 22 solid cancer studies and 17 of 20 leukemia studies. The aim of this monograph was to systematically review the potential biases in these studies (including dose uncertainty, confounding, and outcome misclassification) and to assess whether the subset of minimally biased studies provides evidence for cancer risks from low-dose radiation. Here, we describe the framework for the systematic bias review and provide an overview of the eligible studies.

Epidemiological Studies of Low-Dose Ionizing Radiation and Cancer: Summary Bias Assessment and Meta-Analysis

Article

Full-text available

Jul 2020
J Natl Canc Inst Monogr

Background: Ionizing radiation is an established carcinogen, but risks from low-dose exposures are controversial. Since the Biological Effects of Ionizing Radiation VII review of the epidemiological data in 2006, many subsequent publications have reported excess cancer risks from low-dose exposures. Our aim was to systematically review these studies to assess the magnitude of the risk and whether the positive findings could be explained by biases. Methods: Eligible studies had mean cumulative doses of less than 100 mGy, individualized dose estimates, risk estimates, and confidence intervals (CI) for the dose-response and were published in 2006-2017. We summarized the evidence for bias (dose error, confounding, outcome ascertainment) and its likely direction for each study. We tested whether the median excess relative risk (ERR) per unit dose equals zero and assessed the impact of excluding positive studies with potential bias away from the null. We performed a meta-analysis to quantify the ERR and assess consistency across studies for all solid cancers and leukemia. Results: Of the 26 eligible studies, 8 concerned environmental, 4 medical, and 14 occupational exposure. For solid cancers, 16 of 22 studies reported positive ERRs per unit dose, and we rejected the hypothesis that the median ERR equals zero (P = .03). After exclusion of 4 positive studies with potential positive bias, 12 of 18 studies reported positive ERRs per unit dose (P = .12). For leukemia, 17 of 20 studies were positive, and we rejected the hypothesis that the median ERR per unit dose equals zero (P = .001), also after exclusion of 5 positive studies with potential positive bias (P = .02). For adulthood exposure, the meta-ERR at 100 mGy was 0.029 (95% CI = 0.011 to 0.047) for solid cancers and 0.16 (95% CI = 0.07 to 0.25) for leukemia. For childhood exposure, the meta-ERR at 100 mGy for leukemia was 2.84 (95% CI = 0.37 to 5.32); there were only two eligible studies of all solid cancers. Conclusions: Our systematic assessments in this monograph showed that these new epidemiological studies are characterized by several limitations, but only a few positive studies were potentially biased away from the null. After exclusion of these studies, the majority of studies still reported positive risk estimates. We therefore conclude that these new epidemiological studies directly support excess cancer risks from low-dose ionizing radiation. Furthermore, the magnitude of the cancer risks from these low-dose radiation exposures was statistically compatible with the radiation dose-related cancer risks of the atomic bomb survivors.

Radiation epidemiology and low dose health effects following low-LET radiation

Article

Jul 2019

Radiation epidemiology is the study of human disease following radiation exposure to populations. Epidemiologic studies of radiation-exposed populations have been conducted for nearly 100 years, starting with the radium dial painters in the 1920s and most recently with large-scale studies of radiation workers. As radiation epidemiology has become increasingly sophisticated it is used for the setting of radiation protection standards as well as to guide the compensation programs in place for nuclear weapons workers, nuclear weapons test participants, and other occupationally exposed workers in the United States and elsewhere. It is known with high assurance that radiation effects at levels above 100-150 mGy can be detected as evidenced in multiple population studies conducted around the world. The challenge for radiation epidemiology is evaluating the effects at low doses, below about 100 mGy of low-LET radiation, and assessing the risks following low-dose-rate exposures over years. The weakness of radiation epidemiology in directly studying low dose and low-dose rate exposures is that the signal, i.e. the excess numbers of cancers associated with low-level radiation exposure, is so very small that it cannot be seen against the very high natural occurrence of cancer in the population, i.e., a lifetime risk of incidence reaching up to about 38% (i.e., 1 in 3 persons will develop a cancer in their lifetime). Thus, extrapolation models are used for the management of risk at low doses and low-dose rates, but having adequate information from low-dose and low dose-rate studies would be highly desirable. An overview of recently conducted radiation epidemiologic studies which evaluate risk following low-level radiation exposures is presented. Future improvements in risk assessment for radiation protection may come from increasingly informative epidemiologic studies, melded with mechanistic radiobiologic understanding of adverse outcome pathways, with both incorporated into biologically-based models.

Biomarkers of Exposure and Responses to Ionizing Radiation

Chapter

Jan 2019

Roger O. McClellan

NCRP 54th Annual Meeting, Radiation Protection Responsibility in Medicine: Tenforde Topical Lecture and Fostering Innovations Q & A (Questions for Roy E. Shore [T.S. Tenforde Lecturer], Ehsan Samei, Keith J. Strauss, and X. George Xu)

Article

Feb 2019

Kathryn Held

NCRP Vision for the Future and Program Area Committee Activities in 2018

Article

Feb 2019

Boice, J.D., Jr

The National Council on Radiation Protection and Measurements' (NCRP) congressional charter aligns with our vision for the future: to improve radiation protection for the public and workers. This vision is embodied within NCRP's ongoing initiatives: preparedness for nuclear terrorism, increasing the number of radiation professionals critically needed for the nation, providing new guidance for comprehensive radiation protection in the United States, addressing the protection issues surrounding the ever-increasing use of ionizing radiation in medicine (the focus of this year's annual meeting), assessing radiation doses to aircrew related to higher altitude and longer flights, providing guidance on emerging radiation issues such as the radioactive waste from hydraulic fracturing, focusing on difficult issues such as high-level waste management, and providing better estimates of radiation risks at low doses within the framework of the Million Person Study of Low-Dose Radiation Health Effects. Cutting-edge initiatives included a reevaluation of the science behind recommendations for lens of the eye dose, recommendations for emergency responders on dosimetry after a major radiological incident, guidance to the National Aeronautics and Space Administration with regard to possible central nervous system effects from galactic cosmic rays (the high-energy, high-mass ions bounding through space), reevaluating the population exposure to medical radiation, and addressing whether the linear no-threshold model is still the best available for purposes of radiation protection (not for risk assessment). To address these initiatives and goals, NCRP has seven program area committees on biology and epidemiology, operational concerns, emergency response and preparedness, medicine, environmental issues and waste management, dosimetry, and communications. The NCRP vision for the future will continue and increase under the leadership of President-Elect Dr. Kathryn D. Held (Massachusetts General Hospital and Harvard Medical School, and current NCRP executive director and chief science officer). The NCRP quest to improve radiation protection for the public is hindered only by limited resources, both human capital and financial.

Asbestos Exposure and Mesothelioma Mortality among Atomic Veterans

Article

Dec 2018

Background: During the Cold War the United States (U.S.) conducted 230 above-ground atmospheric nuclear weapons tests between 1945 and 1962 at the Nevada Test Site and the Pacific Proving Grounds. These tests involved over 250,000 military personnel. Asbestos was used on the naval vessels for insulation in the boiler room, engine room, and other areas. This is the first quantitative assessment of asbestos-related mesothelioma, including cancers of the pleura and peritoneum, among military personnel who participated in above-ground nuclear weapons testing. Methods: Approximately 114,000 atomic veterans were selected for an epidemiological study because they were in one of eight series of weapons tests that were associated with somewhat higher personnel exposures than the other tests and because they have been previously studied. We were able to categorize specific jobs into potential for asbestos exposure based on a detailed database of the military activities of the atomic veterans, developed using historical records provided by the Defense Threat Reduction Agency. Standardized mortality ratios (SMR) were calculated by service, rank(officer/enlisted) and ratings (occupation code and work location aboard ship) after 65 years of follow-up… Results: Mesothelioma deaths were significantly increased overall (SMR 1.56; 95% CI 1.32-1.82; n= 153). This increase was seen only among those serving in the Pacific Proving Ground (SMR 1.97; 95% CI 1.65-2.34; n= 134), enlisted men (SMR 1.81; 95% CI 1.53-2.13; n= 145) and the 70,309 navy personnel (SMR 2.15; 95% CI 1.80-2.56; n= 130). No increased mortality rates were seen among the other services: army (SMR 0.45), air force (SMR 0.85) or marines (SMR 0.75). Job categories with the highest potential for asbestos exposure (machinist’s mates, boiler technicians, water tender, pipe fitters, and fireman) had an of SMR 6.47. Job categories with lower potential (SMR =1.35) or no potential (SMR =1.28) for asbestos exposure had non-significantly elevated mesothelioma mortality. Conclusions: Although jobs with high potential for exposure to asbestos products were held by only 20% of the enlisted naval population, sailors with these jobs (machinist’s mate, pipe fitter, boiler technician, water tender and fireman) experienced 55% of mesothelioma deaths. The significantly higher mortality rate overall was explained by asbestos exposure among enlisted naval personnel in this low-dose radiation exposed cohort.

50 Years of the Radiation Exposure Information and Reporting System and Importance to the Million Person Study

Article

Oct 2018

Purpose: As the Radiation Exposure Information and Reporting System (REIRS) celebrates 50 years of existence, this is an appropriate time to reflect on the innovative and novel system and how it has shaped the study of occupational radiation exposure. It is also fitting to appreciate the vision and initiative of the individuals who recognized the future value of the collection and analysis of this information to better inform regulations, policies, and epidemiologic studies, and thus contribute to the protection of workers and the public from the adverse health effects of radiation exposure. Conclusions: REIRS has evolved and expanded over its 50-year history and has played a central role in providing the radiation exposure monitoring records for the Million Person Study for individuals monitored as NRC licensees and at DOE facilities. REIRS has played two major functions in epidemiologic studies. First, it has provided dosimetry information on individual workers in occupational studies to ensure nearly complete ascertainment of career doses. Second, REIRS was used as the primary data source for large cohorts within the Million Person Study: nuclear power plant workers (n∼140,000) and industrial radiographers (n∼130,000). The legacy that REIRS continues to uphold is a model for creating and maintaining a successful tool throughout decades of political, technological, and demographic change.

Outline of NCRP Commentary No. 27 “Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection”

Article

Full-text available

Aug 2018

For over four decades, a linear nonthreshold (LNT) model has been used for radiation protection purposes. In the United States of America, the National Council on Radiation Protection and Measurements (NCRP) established Scientific Committee 1-25 in 2015 to prepare a commentary to review recent epidemiologic data from studies with low doses or low dose rates and from the Life Span Study of atomic-bomb survivors to determine whether these epidemiologic studies broadly support the LNT model. In May 2018, NCRP published Commentary No. 27 “Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection”, noting that the ongoing development of science requires a constant reassessment of prior and emerging evidence to assure that the approach to radiation protection is optimal, even if not necessarily perfect. Based on the current epidemiological data, the NCRP concluded that the LNT model (perhaps with excess risk estimates reduced by a dose and dose rate effectiveness factor) should continue to be utilized for radiation protection purposes. The Commentary will be used to support the work of NCRP Council Committee 1 who are charged to develop current radiation protection guidance for the United States, ultimately updating and expanding the basic radiation protection recommendations of NCRP Report No. 116 published in 1993. This review provides an outline and summary of the key points of NCRP Commentary No. 27.

NCRP Vision for the Future and Program Area Committee Activities in 2017

Article

Feb 2018

John D. Boice

The National Council on Radiation Protection and Measurements' (NCRP) vision for the future is to improve radiation protection for the general public and workers. This vision is embodied within NCRP's ongoing initiatives: Preparedness for nuclear terrorism, increasing the number of radiation professionals critically needed for the nation, providing new guidance for radiation protection in the United States, addressing the protection issues surrounding the ever-increasing use of ionizing radiation in medicine, assessing the radiation doses to aircrew due to higher altitude and longer flights, providing guidance on emerging radiation issues such as the radioactive waste from hydraulic fracturing, focusing on difficult issues such as high-level waste management, and providing better estimates of radiation risks at low doses within the framework of the Million Person Study of Low Dose Radiation Health Effects. Cutting-edge initiatives include a re-evaluation of the science behind recommendations for lens of the eye dose, recommendations for emergency responders on dosimetry after a major radiological incident, guidance to the National Aeronautics and Space Administration with regard to possible central nervous system effects from galactic cosmic rays (the high-energy, high-mass particles bounding through space), re-evaluating the population exposure to medical radiation, and addressing whether the linear non-threshold model is still the best available for purposes of radiation protection (not for risk assessment). To address these initiatives and goals, NCRP has seven Program Area Committees on biology and epidemiology, operational concerns, emergency response and preparedness, medicine, environmental issues and waste management, dosimetry, and communications. The NCRP vision for the future received a quantum boost in 2016 when Dr. Kathryn D. Held (Massachusetts General Hospital and Harvard Medical School) accepted the position of NCRP Executive Director and Chief Science Officer. The NCRP quest to improve radiation protection for the public is hindered only by limited resources, both human capital and financial.

Radiological Weapons

Chapter

Aug 2017

Charles L Sanders

The time from the first discovery in nuclear physics to testing the first atomic bomb was only fifty years. Radiation hazards from fallout of atmospheric nuclear bomb testing have been greatly exaggerated and are for the most part non-existent. Radiation doses received by most from radiological ‘dirty’ bombs would be within the radiation hormesis range.Widespread radioactive fallout from possible use of nuclear weapons is not as devastating as most believe. Most could survive the effects of nuclear war by following simple instructions.

The linear nonthreshold (LNT) model as used in radiation protection: an NCRP update

Article

May 2017
INT J RADIAT BIOL

John D. Boice

Methods and materials: Recent studies after the BEIR VII Report (NRC 2006) are being critically reviewed and include atomic bomb survivors, Mayak workers, atomic veterans, populations on the Techa River, U.S. radiological technologists, the U.S. Million Person Study, international workers (INWORKS), Chernobyl cleanup workers, children given CT exams, and tuberculosis-fluoroscopy patients. Methodologic limitations, dose uncertainties and statistical approaches (and modeling assumptions) are being systematically evaluated. Results: The review of studies continues and will be published as an NCRP Commentary in 2017. Most studies reviewed to date are consistent with a straight line dose response but there are a few exceptions. In the past, the scientific consensus process has worked in providing practical and prudent guidance. So pragmatic judgment is anticipated. The evaluations are ongoing and the extensive NCRP review process has just begun, so no decisions or recommendations are in stone. Conclusions: The march of science requires a constant assessment of emerging evidence to provide an optimum, though not necessarily perfect, approach to radiation protection. Alternatives to the LNT model may be forthcoming, e.g., an approach that couples the best epidemiology with biologically-based models of carcinogenesis, focusing on chronic (not acute) exposure circumstances. Currently for the practical purposes of radiation protection, the LNT hypothesis reigns supreme as the best of the rest, but new epidemiology and radiobiology might change these conclusions. Stay tuned!

Space: The Final Frontier—Research Relevant to Mars

Article

Apr 2017

John D. Boice

A critically important gap in knowledge surrounds the health consequences of exposure to radiation received gradually over time. Much is known about the health effects of brief high-dose exposures, such as from the atomic bombings in Japan, but the concerns today focus on the frequent low-dose exposures received by members of the public, workers, and, as addressed in this paper, astronauts. Additional guidance is needed by the National Aeronautics and Space Administration (NASA) for planning long-term missions where the rate of radiation exposure is gradual over years and the cumulative amounts high. The direct study of low doses and low-dose rates is of immeasurable value in understanding the possible range of health effects from gradual exposures and in providing guidance for radiation protection, not only of workers and the public but also astronauts. The ongoing Million Person Study (MPS) is 10 times larger than the study of the Japanese atomic bomb survivors of 86,000 survivors with estimated doses. The number of workers with >100 mSv career dose is substantially greater. The large study size, broad range of doses, and long follow-up indicate substantial statistical ability to quantify the risk of exposures that are received gradually over time. The study consists of 360,000 U.S. Department of Energy workers from the Manhattan Project; 150,000 nuclear utility workers from the inception of the nuclear age; 115,000 atomic veterans who participated in above-ground atmospheric tests at the Nevada Test Site and the Bikini and Enewetak Atolls and Johnston Island in the Pacific Proving Grounds (PPG); 250,000 radiologists and medical workers; and 130,000 industrial radiographers. NASA uses an individual risk-based system for radiation protection in contrast to the system of dose limits for occupational exposures used by terrestrial-based organizations. The permissible career exposure limit set by NASA for each astronaut is a 3% risk of exposure-induced death (REID) from cancer at a 95% confidence level to account for uncertainties in risk projections. The large size of the MPS will reduce the uncertainty in the risk estimates, narrowing the 95% confidence interval, and thus allow more time in space for astronauts. Further differences between men and women in their response to radiation can be more fully examined, and non-cancer outcomes, such as neurological disorders and cardiovascular disease, can be evaluated in a way not hitherto possible.

Shared Dosimetry Error in Epidemiological Dose-Response Analyses

Article

Full-text available

Mar 2015
PLOS ONE

Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed.

Drinking and other risk taking behaviors of enlisted male soldiers in the US Army

Article

Full-text available

Jan 2002
Work

High-risk drinking is among the top three prevention priorities of the Department of Defense. Research suggests that enlisted male soldiers are particularly at risk for unhealthy drinking behaviors. 292,023 enlisted male soldiers who responded to a Health Risk Appraisal (HRA) survey between 1990 and 1998 were dichotomized into high and low-risk drinking groups. Logistic regression analysis showed that high-risk drinkers wore seatbelts less frequently, were more likely to drive > 15 mph over the speed limit, and to smoke more than 20 cigarettes/day. This high-risk group was predominately young (< 25), Caucasian, high school educated or less, and most likely employed as infantrymen or craftsworkers. The two highest risk occupational groups (infantrymen and craftsworkers) differ from each other, and from other Army occupations. Intervention programs should include safe driving habits and smoking cessation, as well as high-risk drinking, and should be tailored to the specific needs of the group at highest risk.

Follow up of mortality and incidence of cancer 1952-98 in men from the UK who participated in the UK's atmospheric nuclear weapon tests and experimental programmes

Article

Full-text available

Apr 2003

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. 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. 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. 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.

The R Project in Statistical Computing

Article

Feb 2001

Brian D Ripley

Leukemia Among Participants in Military Maneuvers at a Nuclear Bomb Test

Article

Oct 1980

Glyn G. Caldwell

Preliminary studies indicate that nine cases of leukemia have occurred among 3,224 men who participated in military maneuvers during the 1957 nuclear test explosion "Smoky." This represents a significant increase over the expected incidence of 3.5 cases. They included four cases of acute myelocytic leukemia, three of chronic myelocytic leukemia, and one each of hairy cell and acute lymphocytic leukemia. At time of diagnosis, patient ages ranged from 21 to 60 years (mean, 41.8 years) and the interval from time of nuclear test to diagnosis from two to 19 years (mean, 14.2 years). Film-badge records, which are available for eight of the nine men, indicated gamma radiation exposure levels ranging from 0 to 2,977 mrem (mean, 1,033 mrem). Mean film-badge gamma dose for the entire Smoky cohort was 466.2 mrem. (JAMA 244:1575-1578, 1980)

Well Body, Well Earth

Article

Dec 1984

Glyn G. Caldwell

As the title of this book implies, the earth and the human body are associated holistically for good or ill. In general, the authors' ideas are appealing, because if we destroy the balance of nature by polluting the earth, we increase the likelihood that the earth's illness will boomerang and lead us to extinction. Furthermore, the authors urge that the time for change is now and that change will come from personal life-style modification, local environmental action, and nationwide or international political pressure. In places, the book seems to advocate a return to the "good old days" when humankind communed with nature, lived as hunters and gatherers, and had minimal technology to pollute the earth. Unfortunately for the authors' thesis, life spans were usually only three or four decades, species became extinct without human interference, and the chemicals, technology, and resultant pollution from producing books such as this did not

Mortality and Cancer Frequency Among Military Nuclear Test (Smoky) Participants, 1957 Through 1979

Article

Aug 1983

Glyn G. Caldwell

Follow-up of health status has been completed through 1979 for 3,072 (95.5%) of 3,217 nuclear test participants on military maneuvers during the 1957 nuclear test "Smoky." In these participants, 112 cases of cancer were diagnosed, compared with 117.5 cases expected. During the same follow-up period (1957 through 1979), 64 persons died of cancer, compared with an expected 64.3. Statistically significantly increased frequency of occurrence and mortality was found only for leukemia. The amount of cumulative gamma radiation exposure for 1957 ranged from 0 to 10,397 mrem as measured by individual personnel film badges. Although uncertainty remains about the exact amount of radiation exposure, the lack of a significant increase after 22 years in either the incidence of or the mortality from any other cancer and the apparent lack of a dose effect by unit lead to the consideration that the leukemia findings may be attributable either to chance, to factors other than radiation, or to some combination of risk factors possibly including radiation.(JAMA 1983;250:620-624)

Dose Reconstruction for the Million Worker Study

Article

Feb 2015

The primary aim of the epidemiologic study of one million U.S. radiation workers and veterans [the Million Worker Study (MWS)] is to provide scientifically valid information on the level of radiation risk when exposures are received gradually over time and not within seconds, as was the case for Japanese atomic bomb survivors. The primary outcome of the epidemiologic study is cancer mortality, but other causes of death such as cardiovascular disease and cerebrovascular disease will be evaluated. The success of the study is tied to the validity of the dose reconstruction approaches to provide realistic estimates of organ-specific radiation absorbed doses that are as accurate and precise as possible and to properly evaluate their accompanying uncertainties. The dosimetry aspects for the MWS are challenging in that they address diverse exposure scenarios for diverse occupational groups being studied over a period of up to 70 y. The dosimetric issues differ among the varied exposed populations that are considered: atomic veterans, U.S. Department of Energy workers exposed to both penetrating radiation and intakes of radionuclides, nuclear power plant workers, medical radiation workers, and industrial radiographers. While a major source of radiation exposure to the study population comes from external gamma- or x-ray sources, for some of the study groups, there is a meaningful component of radionuclide intakes that requires internal radiation dosimetry assessments. Scientific Committee 6-9 has been established by the National Council on Radiation Protection and Measurements (NCRP) to produce a report on the comprehensive organ dose assessment (including uncertainty analysis) for the MWS. The NCRP dosimetry report will cover the specifics of practical dose reconstruction for the ongoing epidemiologic studies with uncertainty analysis discussions and will be a specific application of the guidance provided in NCRP Report Nos. 158, 163, 164, and 171. The main role of the Committee is to provide guidelines to the various groups of dosimetrists involved in the MWS to ensure that certain dosimetry criteria are considered: calculation of annual absorbed doses in the organs of interest, separation of low and high linear-energy transfer components, evaluation of uncertainties, and quality assurance and quality control. It is recognized that the MWS and its approaches to dosimetry are a work in progress and that there will be flexibility and changes in direction as new information is obtained with regard to both dosimetry and the epidemiologic features of the study components. This paper focuses on the description of the various components of the MWS, the available dosimetry results, and the challenges that have been encountered. It is expected that the Committee will complete its report in 2016.

Military Participants at U.S. Atmospheric Nuclear Weapons Testing—Methodology for Estimating Dose and Uncertainty

Article

Apr 2014
RADIAT RES

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 making 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.

Implications of Radiation Dose and Exposed Populations on Radiation Protection in the 21st Century

Article

Feb 2014
HEALTH PHYS

John Boice

Radiation is in the public eye because of Fukushima, computed tomography examinations, airport screenings, and possible terrorist attacks. What if the Boston Marathon pressure cooker had also contained a radioactive source? Nuclear power may be on the resurgence. Because of the increasing uses of radiation, the increases in population exposures, and the increasing knowledge of radiation effects, constant vigilance is needed to keep up with the changing times. Psychosocial disorders associated with the inappropriate (but real) fear of radiation need to be recognized as radiation detriments. Radiation risk communication, radiation education, and communication must improve at all levels: to members of the public, to the media, to other scientists, and to radiation professionals. Stakeholders must continue to be involved in all radiation protection initiatives. Finally, we are at a crisis as the number of war babies (me) and baby boomers (you?) who are also radiation professionals continues its rapid decline, and there are few in the pipeline to fill the current and looming substantial need: "The old road is rapidly agin'" (Dylan). NCRP has begun the WARP initiative-Where Are the Radiation Professionals?-an attempt to rejuvenate the pipeline of future professionals before the trickle becomes tiny drops. A Workshop was held in July 2013 with government agencies, military, private sector, universities, White House representatives, and societies to develop a coordinated and national action plan. A "Manhattan Project" is needed to get us "Back to the Future" in terms of the funding levels that existed in years past that provided the necessary resources to train, engage, and retain (a.k.a., jobs) the radiation professionals needed for the nation. If we don't keep swimmin' (Disney's Nemo) we'll "sink like a stone" (Dylan).Introduction of Implications of Radiation Dose and Exposed Populations (Video 2:06, http://links.lww.com/HP/A25).

Radiation Exposure of U.S. Military Individuals

Article

Feb 2014
HEALTH PHYS

The U.S. military consists of five armed services: the Army, Navy, Marine Corps, Air Force, and Coast Guard. It directly employs 1.4 million active duty military, 1.3 million National Guard and reserve military, and 700,000 civilian individuals. This paper describes the military guidance used to preserve and maintain the health of military personnel while they accomplish necessary and purposeful work in areas where they are exposed to radiation. It also discusses military exposure cohorts and associated radiogenic disease compensation programs administered by the U.S. Department of Veterans Affairs, the U.S. Department of Justice, and the U.S. Department of Labor. With a few exceptions, the U.S. military has effectively employed ionizing radiation since it was first introduced during the Spanish-American War in 1898. The U.S military annually monitors 70,000 individuals for occupational radiation exposure: ∼2% of its workforce. In recent years, the Departments of the Navy (including the Marine Corps), the Army, and the Air Force all have a low collective dose that remains close to 1 person-Sv annually. Only a few Coast Guard individuals are now routinely monitored for radiation exposure. As with the nuclear industry as a whole, the Naval Reactors program has a higher collective dose than the remainder of the U.S. military. The U.S. military maintains occupational radiation exposure records on over two million individuals from 1945 through the present. These records are controlled in accordance with the Privacy Act of 1974 but are available to affected individuals or their designees and other groups performing sanctioned epidemiology studies.Introduction of Radiation Exposure of U.S. Military Individuals (Video 2:19, http://links.lww.com/HP/A30).

Regression Models and Life-Tables (With Discussion)

Article

Nov 1971

David Cox

The analysis of censored failure times is considered. It is assumed that on each individual are available values of one or more explanatory variables. The hazard function (age‐specific failure rate) is taken to be a function of the explanatory variables and unknown regression coefficients multiplied by an arbitrary and unknown function of time. A conditional likelihood is obtained, leading to inferences about the unknown regression coefficients. Some generalizations are outlined.

The Incidence of Leukemia, Lymphoma and Multiple Myeloma among Atomic Bomb Survivors: 1950–2001

Article

Feb 2013
RADIAT RES

A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This article presents the analyses of radiation effects on leukemia, lymphoma and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose-response relationship and, to the extent the data allowed, to investigate variation in the excess risks with gender, attained age, exposure age and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a nonlinear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this nonlinearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence that the radiation-associated excess leukemia risks, especially for acute myeloid leukemia, had persisted throughout the follow-up period out to 55 years after the bombings. As in earlier analyses, there was a weak suggestion of a radiation dose response for non-Hodgkin lymphoma among men, with no indication of such an effect among women. There was no evidence of radiation-associated excess risks for either Hodgkin lymphoma or multiple myeloma.

Computational methods for case-cohort studies

Article

Feb 2007
COMPUT STAT DATA AN

Computational methods, which can be implemented using standard Cox regression software, are given for fitting “exact” pseudolikehood estimates and robust and asymptotic variance estimators from case-cohort data. These methods are based on the computational approach of Therneau and Li [1999. Computing the Cox model for case cohort designs. Lifetime Data Anal. 5, 99–112] but will be less subject to small sample bias. Further, it is shown how to accommodate time-dependent covariates and estimate absolute risk. Extensions to stratified case-cohort sampled data are also provided. The methods are illustrated in analyses of case-cohort samples from a study of radiation exposure from fluoroscopy and breast cancer using SAS software.

ICRP Publication 116. Conversion coefficients for radiological protection quantities for external radiation exposures

Article

Apr 2010
Ann ICRP

OCMAP-PLUS: A program for the comprehensive analysis of occupational Cohort data

Article

Apr 1998

The Occupational Cohort Mortality Analysis Program (OCMAP) has been redesigned for optimal microcomputer use and extended to include new computing algorithms. The new program, OCMAP-PLUS, offers a comprehensive, flexible, and efficient analysis of incidence or mortality rates and standardized measures in relation to multiple and diverse work history and exposure measures. New features include executable code, minimization of memory requirements, disk file storage of person-day arrays, stratified analyses by geographic area, employment status and up to eight exposure variables, a data imputation algorithm for study members with unknown race, and enhanced algorithms for constructing several time-dependent exposure measures. New modules create grouped data files for Poisson and logistic regression and risk set files for use in relative risk regression analysis. The Mortality and Population Data System (MPDS) provides external comparison rates and proportional mortalities. Analysis from two recent cohort mortality studies illustrate several new features.

Using the Whole Cohort in the Analysis of Case-Cohort Data

Article

May 2009

Case-cohort data analyses often ignore valuable information on cohort members not sampled as cases or controls. The Atherosclerosis Risk in Communities (ARIC) study investigators, for example, typically report data for just the 10%–15% of subjects sampled for substudies of their cohort of 15,972 participants. Remaining subjects contribute to stratified sampling weights only. Analysis methods implemented in the freely available R statistical system (http://cran.r-project.org/) make better use of the data through adjustment of the sampling weights via calibration or estimation. By reanalyzing data from an ARIC study of coronary heart disease and simulations based on data from the National Wilms Tumor Study, the authors demonstrate that such adjustment can dramatically improve the precision of hazard ratios estimated for baseline covariates known for all subjects. Adjustment can also improve precision for partially missing covariates, those known for substudy participants only, when their values may be imputed with reasonable accuracy for the remaining cohort members. Links are provided to software, data sets, and tutorials showing in detail the steps needed to carry out the adjusted analyses. Epidemiologists are encouraged to consider use of these methods to enhance the accuracy of results reported from case-cohort analyses.

An Evaluation of the Effect of Military Service on Mortality: Quantifying the Healthy Soldier Effect

Article

Jan 2009

The healthy soldier effect denotes the proposition that military populations are likely to be healthier than other populations. A systematic review was conducted which aimed to quantify the magnitude of the healthy soldier effect. Studies containing mortality rates of military personnel were identified from multiple electronic databases. Studies were included in the meta-analyses if they reported all-cause, cancer, or external-cause mortality in a military population and compared the rates to the general population. Fifty-nine studies were initially identified and 12 were included in the meta-analyses. The overall meta-standardized mortality ratios (SMRs) for all-cause mortality for deployed veterans was 0.76 (95% confidence interval [CI]: 0.65-0.89) and 0.73 (95% CI: 0.56-1.97) for non-deployed veterans based on a mean follow-up of 7.0 and 2.4 years, respectively; for cancer mortality, the SMRs were 0.78 (95% CI: 0.63-0.98) for deployed veterans and 0.75 (95% CI: 0.50-1.14) for non-deployed veterans based on 6.7 and 3.1 years follow-up, respectively; for external-cause mortality, the SMRs were 0.90 (95% CI: 0.72-1.13) for deployed veterans and 0.80 (95% CI: 0.63-1.01) for non-deployed veterans based on 4.8 and 2.0 years follow-up, respectively. Military personnel do display a healthy soldier effect that decreases their risk of mortality compared to the general population. The overall healthy soldier effect estimated ranges from 10% to 25%, depending on the cause of death studied and the period of follow-up.

Mortality and cancer incidence of Australian participants in the British nuclear tests in Australia

Article

Oct 2008
OCCUP ENVIRON MED

To investigate the mortality and cancer incidence of Australian nuclear test participants, and to identify any association with exposure to ionising radiation. A retrospective cohort study was carried out in which the mortality and cancer incidence rates of participants (n = 10,983) were compared with rates in the general male Australian population. Dose reconstructions were carried out by a panel of health physicists. Mortality and cancer rates were compared with the general population and between groups of subjects categorised by assessed radiation exposure. All-cause mortality was not raised. Mortality and incidence were significantly raised for cancers of the head and neck, lung, colon and rectum, and prostate, and for all cancers combined. For oesophageal cancer, melanoma, all leukaemias and non-chronic lymphatic leukaemia (non-CLL leukaemia), incidence was significantly raised, but mortality was non-significantly raised. No association was found between radiation exposure and overall cancer incidence or mortality, or with any cancer or cancer deaths occurring in excess. There is no evidence that the excess cancers and cancer deaths were caused by radiation exposure at the test sites. Possible contributing factors are high smoking prevalence and demographic differences from the Australian population with whom rates were compared. Asbestos is a likely contributor to some cancers in naval personnel.

Army rank and subsequent mortality by cause: 23 year follow up

Article

Jul 1977
AM J EPIDEMIOL

Mortality among veterans has been studied in relation to military rank at separation in a series of 85,491 men discharged from the US Army in 1946 and traced through 1969. It was found that although the mortality of privates was very close to expectation based on population rates, non-commissioned officers had a 23% advantage and commissioned officers about a 40% advantage. The relative advantage of the veterans who had higher rank held not only for deaths from all causes but also for most of the specific causes examined and there was only a small tendency for the differences to diminish with the passage of time during the 23-year period of follow-up.

Tri-service Health Questionnaire-1989

Article

Jul 1991

L H Lodge

An anonymous, self administered health questionnaire survey of the habits and attitudes of servicemen in the 3 Services was conducted. The overall response rate was 75%. This paper reports the results of questions on smoking. The Army had the greatest percentage of smokers, smoked most heavily and had the worst attitude to smoking of the 3 Services. The RAF had the best results in these fields. There was a higher percentage of smoker, who smoke more heavily in Germany/seadraft than UK/shoredraft. There was a rank gradient in percentage smokers, with the lowest ranks smoking the most. A sizeable proportion of the smoking population wish to give up, have tried to do so and feel their Medical Officer should be interested in their smoking habits. A reduction in prevalence of cigarette smoking to less than 30% within 5 years is recommended as a Tri-service Health Policy Goal, with the Army, Tri-Service 16-20 year olds and Private-Corporal rank equivalents and recruits, as specific target groups for intervention. The health promotion strategy should include concerted anti-smoking advice from Medical Officers.

Practical Considerations in Choosing between the Case-Cohort and Nested Case-Control Designs

Article

Apr 1991
EPIDEMIOLOGY

Sholom Wacholder

Follow up of New Zealand participants in British atmospheric nuclear weapons tests in the Pacific

Article

Jun 1990

To study the health of Royal New Zealand Navy personnel who participated in atmospheric nuclear weapons tests conducted by the United Kingdom at Malden Island and Christmas Island in 1957 and 1958. Blinded, controlled follow up of up to 30 years. New Zealand. 528 Men known to have participated in the tests and a control group of 1504 men who were in the Royal New Zealand Navy during the same period but did not participate in the tests. Mortality and incidence of cancer. Follow up for the period 1957-87 was 94% complete in test participants and 91% complete in the controls. There were 70 deaths among test participants and 179 deaths among controls, yielding a relative risk of 1.08 (90% confidence interval 0.85 to 1.38, p = 0.29). The relative risk of death from causes other than cancer was 0.96 (0.71 to 1.29, p = 0.59) whereas the relative risk of death from cancer was 1.38 (0.90 to 2.10, p = 0.09) and of the incidence of cancer was 1.12 (0.78 to 1.60, p = 0.29). For cancers other than haematological malignancies the relative risk was 1.14 (0.69 to 1.83, p = 0.31) for mortality and 1.01 (0.67 to 1.50, p = 0.48) for incidence. There were seven deaths from haematological cancers among test participants (relative risk 3.25, 90% confidence interval 1.12 to 9.64, p = 0.02), including four leukaemias (5.58, 1.04 to 41.6, p = 0.03). The relative risk for incidence of haematological cancers was 1.94 (0.74 to 4.84, p = 0.10) and that for leukaemia was 5.51 (1.03 to 41.1, p = 0.03). There were no cases of multiple myeloma in the test participants during the follow up period, but the expected number was only 0.3. Although the numbers are small, the findings for leukaemia are similar to those for British participants in the nuclear weapons test programme. Some leukaemias, and possibly some other haematological cancers, may have resulted from participation in this programme. There is little evidence of an increased risk for non-haematological cancers, and there is no evidence of an increased risk for causes of death other than cancer.

Cigarette Smoking and Leukemia

Article

Sep 1989

Components and modifiers of the healthy worker effect: Evidence from three occupational cohorts and implications for industrial compensation

Article

Jan 1989
AM J EPIDEMIOL

Howe, G. R. (NCIC Epidemiology Unit, McMurrich Building, U. of Toronto, Toronto, Ontario M5S1A8, Canada), A. M. Chiarelli, and J. P. Lindsay. Components and modifiers of the healthy worker effect: evidence from three occupational cohorts and implications for industrial compensation. Am J Epidemiol 1988; 128:1364–75. The authors examined the components and modifiers of the healthy worker effect using mortality data from three occupational cohorts: the employees of Atomic Energy of Canada Limited followed between 1950 and 1981, a 10% sample of the Canadian labor force followed between 1965 and 1979, and workers at the Eldorado Resources Limited Beaverlodge uranium mine followed between 1950 and 1980. Two important components of the healthy worker effect have been identified in these cohorts, namely, initial selection of and continuing employment of healthy individuals. There is less evidence for a contribution from the existence of differential risk factors among employed individuals as compared with the general population. The healthy worker effect is, however, substantially modified by time since employment, sex, age, specific cause of death, and specific occupation. Because of this variation, it is inappropriate to account for the healthy worker effect by a single parameter, and all of the above factors must be taken into account in any appropriate analysis. When the only available comparison group for an occupational cohort is the general population, the healthy worker effect is unlikely to have any substantial influence on the process of assessing causality for any observed association or attributing cause in an individual case. This would be particularly true for cancer, and even more so for lung cancer, a disease often assocfated with industrial compensation cases.

Effects of selection on mortality

Article

Dec 1974
AM J EPIDEMIOL

The effect of the bias of medical selection on subsequent mortality by cause, was examined in a series of 85,491 white male World War II U.S. Army veterans who have been followed for a period of 23 yr, 1947 to 1969. The results indicate that the selection process for military service exerted a profound effect on mortality of Army veterans after separation from service. Generally, the mortality rates are well below those of the general population within the first few years of discharge, but thereafter gradually approach those of the parent population. The effect of the bias of selection on subsequent mortality rates may persist even after 23 yr from Army discharge. The effect of the bias varies considerably according to the nature of the cause of death.

Polycythemia vera among participants of a nuclear weapons test

Article

Sep 1984

Two cases of polycythemia vera and two cases of suspected polycythemia vera were found among 3,217 nuclear test participants present during the detonation of the nuclear device, "Smoky," on Aug 31, 1957, and traced through December 1981. The observed occurrence of four cases of polycythemia vera in a group this size significantly exceeds that expected. However, the small individual whole-body doses of radiation reported for these four participants makes the association with ionizing radiation tenuous, although this was the only known unusual risk factor.

Leukemia Among Participants in Military Maneuvers at a Nuclear Bomb Test: A Preliminary Report

Article

Nov 1980

Cancer mortality risk among military participants of a 1958 atmospheric nuclear weapons test

Article

Apr 1995

This study was undertaken to determine if Navy veterans who participated in an atmospheric nuclear test in 1958 were at increased risk of death from certain cancers. Cancer mortality risk of 8554 Navy veterans who participated in an atmospheric nuclear test in the Pacific was compared with that of 14,625 Navy veterans who did not participate in any test. Radiation dosage information was obtained from film badges for 88% of the test participants. The median radiation dose for the test participants was 388 mrem (3.88 millisieverts [mSv]). Among participants who received the highest radiation dose (> 1000 mrem, or 10 mSv), an increased mortality risk for all causes (relative risk [RR] = 1.23; 95% confidence interval [CI] = 1.04, 1.45), all cancers (RR = 1.42; 95% CI = 1.03, 1.96), and liver cancer (RR = 6.42; 95% CI = 1.17, 35.3) was observed. The risk for cancer of the digestive organs was elevated among test participants (rate ratio = 1.47; 95% CI = 1.06, 2.04) but with no significant dose-response trend. Many of the cancers of a priori interest were not significantly elevated in the overall test participant group or in the group that received the highest radiation dose. Most of the cancers suspected of being radiogenic were not significantly elevated among the test participants. Nevertheless, increased risks for certain cancers cannot be ruled out at this time. Veterans who participated in the nuclear weapons tests should continue to be monitored.

Mortality of veteran participants in the CROSSROADS nuclear test

Article

Jul 1997

Operation CROSSROADS, conducted at Bikini Atoll in 1946, was the first post World War II test of nuclear weapons. Mortality experience of 40,000 military veteran participants in CROSSROADS was compared to that of a similar cohort of nonparticipating veterans. All-cause mortality of the participants was slightly increased over nonparticipants by 5% (p < .001). Smaller increases in participant mortality for all malignancies (1.4%, p = 0.26) or leukemia (2.0%, p = 0.9) were not statistically significant. These results do not support a hypothesis that radiation had increased participant cancer mortality over that of nonparticipants.

Analysis of Case-Cohort Designs

Article

Jan 2000
J CLIN EPIDEMIOL

The case-cohort design is most useful in analyzing time to failure in a large cohort in which failure is rare. Covariate information is collected from all failures and a representative sample of censored observations. Sampling is done without respect to time or disease status, and, therefore, the design is more flexible than a nested case-control design. Despite the efficiency of the methods, case-cohort designs are not often used because of perceived analytic complexity. In this article, we illustrate computation of a simple variance estimator and discuss model fitting techniques in SAS. Three different weighting methods are considered. Model fitting is demonstrated in an occupational exposure study of nickel refinery workers. The design is compared to a nested case-control design with respect to analysis and efficiency in a small simulation. In this example, case-cohort sampling from the full cohort was more efficient than using a comparable nested case-control design.

Trends in U.S. Smoking Rates in Occupational Groups: The National Health Interview Survey 1987–1994

Article

Jul 2004

It is unknown if reductions in U.S. adult smoking rates are uniform across occupational groups. The National Health Interview Survey (NHIS) is a multistage area probability cross-sectional survey of the U.S. civilian population. Data on occupational and smoking status were collected on 141122 adult participants from the 1987, 1988, and 1990 -1994 NHIS annual surveys. Overall smoking rates ranged from 58% in roofers to 4% in physicians, with higher rates found among blue collar professions. There were reductions in smoking from 1987-1994 within 72% of occupational groups; 19 of these downward trends were significant and occurred exclusively within white collar professions. Blue collar workers continue to smoke in large numbers, whereas white collar workers report lower rates along with corresponding significant downward trends in rates among selected occupational groups. The development of effective smoking prevention strategies targeting blue collar groups is needed.

Epidemiological studies of UK test veterans: II. Mortality and cancer incidence

Article

Oct 2004

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.

Leukemia among persons present at an atmospheric nuclear test (SMOKY)

Jan 1979
361-362

Centers for Disease Control and Prevention. Leukemia among persons present at an atmospheric nuclear test (SMOKY). MMWR. 1979; 28:361-362.

A review of the Dose Reconstruction Program of the Defense Threat Reduction Agency

Jan 2003

National Research
Council

National Research Council. A review of the Dose Reconstruction Program of the Defense Threat Reduction Agency. Washington, DC: National Academies Press; 2003.

Atomic bombs, asbestos, and healthy warriors

Jan 2014
21-23

J D Boice

Boice JD Jr. Atomic bombs, asbestos, and healthy warriors. Health Phys News. 2014; XLII:21-23. [Accessed May 2, 2016] http://ncrponline.org/wp-content/themes/ncrp/PDFs/BOICE-HPnews/ 20_Atomic_Veterans_Jan2014.pdf.

Mortality of Nuclear Weapons Test Participants

Jan 1985

C D Robinette
S Jablon
T L Preston

Robinette, CD.; Jablon, S.; Preston, TL. Mortality of Nuclear Weapons Test Participants. Washington, DC: National Academies Press; 1985.

The Five Series Study: Mortality of Military Participants in U.S. Nuclear Weapons Tests

Jan 2000

S Thaul
W F Page
H Crawford
H O'maonaigh

Thaul, S.; Page, WF.; Crawford, H.; O'Maonaigh, H. The Five Series Study: Mortality of Military Participants in U.S. Nuclear Weapons Tests. Washington, DC: National Academies Press; Institute of Medicine; 2000.

MD: CDC, National Center for Health Statistics

May 2016

Disease Centers
Control
Prevention

Centers for Disease Control and Prevention. National Death Index. Hyattsville, MD: CDC, National Center for Health Statistics; http://www.cdc.gov/nchs/data/ndi/ ndi_users_guide_chapter4.pdf [Accessed May 2, 2016]

National Program of Cancer Registries (NPCR) Registry Plus ™ Link Plus. http://www.cdc.gov/cancer Military participants at U.S. atmospheric nuclear weapons testing-Methodology for estimating dose and uncertainty

Jan 2014
RADIAT RES
471-484

Disease Centers
Control
Prevention
Je
Hl Beck
Jw Aanenson
Ha Grogan
Hj Mohler
Ss Mohler
Pg Voillequé

Centers for Disease Control and Prevention. [Accessed May 2, 2016] National Program of Cancer Registries (NPCR). Registry Plus ™ Link Plus. http://www.cdc.gov/cancer/npcr/tools/registryplus/ lp.htm 17. Till JE, Beck HL, Aanenson JW, Grogan HA, Mohler HJ, Mohler SS, Voillequé PG. Military participants at U.S. atmospheric nuclear weapons testing-Methodology for estimating dose and uncertainty. Radiat Res. 2014; 181:471-484. [PubMed: 24758578]

An evaluation of the effect of military service on mortality: quantifying the healthy soldier effect

Jan 2008
ANN EPIDEMIOL
928-936

R Mclaughlin
L Nielson
M Waller

McLaughlin R, Nielson L, Waller M. An evaluation of the effect of military service on mortality: quantifying the healthy soldier effect. Ann Epidemiol. 2008; 18:928-936. [PubMed: 19041592]

DC: Historical Branch, Office of the Quartermaster General

Jan 1958
1946-1953

F A Koehler

Koehler, FA. Special Rations for the Armed Forces, 1946-53. Vol. Chapter 1. Washington DC: Historical Branch, Office of the Quartermaster General; 1958. QMC Historical Studies, Series II, No. 6http://archiveis/u9eRO [Accessed May 2, 2016]

Conversion coefficients for radiological protection quantities for external radiation exposures

Jan 2010
Ann ICRP
1-257

ICRP Publication 116. Conversion coefficients for radiological protection quantities for external radiation exposures. Ann ICRP. 2010; 40:1-257.

Low-Dose Radiation Research Act of 2015

Jan 2015

HR. [Accessed May 2, 2016] Low-Dose Radiation Research Act of 2015. 2015. https:// www.congress.gov/bill/114th-congress/house-bill/35

Defense Threat Reduction Agency

May 2016

Defense Threat Reduction Agency. [Accessed May 2, 2016] Operation PLUMBBOB. Fact Sheet. http://www.dtra.mil/Portals/61/Documents/NTPR/1-Fact_Sheets/19_PLUMBBOB.pdf

Mortality among military participants at the 1957 PLUMBBOB nuclear weapons test series and from leukemia among participants at the SMOKY test

Abstract

No full-text available

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