Adjusting for smoking status or a reliable surrogate such as socioeconomic status (SES) is critically important in occupational epidemiology studies when any smoking-related cancer or cardiovascular ...disease is an outcome of interest. Sometimes, however, data on smoking patterns or individual-level smoking surrogates such as job title, education, pay scale or other measures of SES are not readily available in occupational cohorts.
To obtain a surrogate measure for missing smoking or individual-level SES data, we demonstrate a method used to obtain and geocode residential address histories which were then linked to area-level SES measures from the United States Census in three test samples and then in a full cohort of workers from the Mound nuclear weapons facility in Dayton, Ohio, USA. The mean educational attainment of the Census Block Group was used to derive a categorical estimate of educational attainment which was compared to self-reported (SR) education available from Mound worker histories using Kappa statistics. Lung cancer mortality patterns between area-derived (AD) and SR education were investigated using Standardized Mortality Ratios (SMR) and Cox Proportional Hazards models with stratification or adjustment by either SR or AD education.
Home address histories were obtained from linkages of individual worker data to online resources. In the test cohorts, mean educational attainment was the Census Block Group measure found to have the largest magnitude association with individual-level SES measures. Among 7251 Mound workers, 5685 (78.4%) had at least one residential address match (mean 4.9 addresses) identified. The SR and AD educational attainment measures were highly correlated (weighted Kappa coefficient 0.10, p < .0001). SMR patterns by SR and AD educational attainment were similar, with steadily decreasing mortality with increased educational attainment by either measure. Cox models for lung cancer using AD education produced similar results as those using SR education as an adjustment factor.
When individual-level SES indicators are not available for statistical adjustment, area-level SES measures can serve as a reliable surrogate when investigating outcomes that are affected by lifestyle factors such as smoking.
Element-specific biokinetic models are used to reconstruct doses to systemic tissues from internal emitters. Typically, a systemic model for a radionuclide explicitly depicts only its dominant ...repositories. Remaining tissues and fluids are aggregated into a pool called Other tissue in which the radionuclide is assumed to be uniformly distributed. In the systemic biokinetic models used in radiation protection, the brain usually is addressed as an implicit mass fraction of Other tissue rather than an explicitly depicted repository. Due to increasing interest in radiation effects on the brain, efforts are underway to improve brain dosimetry for internal radiation sources.
We assessed potential improvements in brain dosimetry for internal emitters by explicitly modeling brain kinetics rather than treating the brain as a mass fraction of Other tissue. We selected 10 elements for which brain kinetics can be modeled using published biokinetic data. Injection dose coefficients were calculated for a relatively long-lived radioisotope of each element using each of two versions of the ICRP's latest systemic biokinetic model for the element, the original version and a modified version differing only in the treatment of brain. If the ICRP model contained an explicit brain pool, the modified version depicted brain instead as a mass fraction of Other tissue. If the ICRP model included brain in Other tissue, the modified version included an explicit brain pool with kinetics based on best available brain-specific data.
The result for a given radionuclide is expressed as a ratio A:B, where A and B are the dose coefficients based on the versions of the model with and without an explicit brain pool, respectively. The following ratios A:B were obtained for the 10 radionuclides addressed here:
241
Am, 0.13;
207
Bi, 0.57;
234
U, 0.81;
239
Pu, 0.96;
203
Hg (vapor), 1.4;
134
Cs, 1.5;
54
Mn, 1.7;
210
Po, 1.7;
226
Ra, 1.9;
210
Pb, 3.3. These ratios indicate that a dose estimate for brain based on a biokinetic model with brain implicitly contained in Other tissue may substantially underestimate or substantially overestimate a dose estimate that reflects best available brain-specific biokinetic data. Of course, the reliability of the latter estimate depends on the quality of the underlying biokinetic data.
Where feasible, the brain should be depicted explicitly in biokinetic models used in epidemiological studies addressing adverse effects of ionizing radiation.
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.
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.
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-causes mortality SMR (0.71). The pattern of risk over time showed a diminution of the 'healthy soldier effect': the all-causes mortality SMR after 50 years 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 years (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 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.
No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 years. The 95% confidence limits were narrow and excluded mortality risks per unit dose that are two to four times higher than those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships.
Radium dial workers: back to the future Martinez, Nicole E.; Jokisch, Derek W.; Dauer, Lawrence T. ...
International journal of radiation biology,
04/2022, Volume:
98, Issue:
4
Journal Article
Peer reviewed
Open access
This paper reviews the history of the radium dial workers in the United States, summarizes the scientific progress made since the last evaluation in the early 1990s, and discusses current progress in ...updating the epidemiologic cohort and applying new dosimetric models for radiation risk assessment.
The discoveries of radiation and radioactivity led quickly to medical and commercial applications at the turn of the 20th century, including the development of radioluminescent paint, made by combining radium with phosphorescent material and adhesive. Workers involved with the painting of dials and instruments included painters, handlers, ancillary workers, and chemists who fabricated the paint. Dial painters were primarily women and, prior to the mid to late 1920s, would use their lips to give the brush a fine point, resulting in high intakes of radium. The tragic experience of the dial painters had a significant impact on industrial safety standards, including protection measures taken during the Manhattan Project. The dial workers study has formed the basis for radiation protection standards for intakes of radionuclides by workers and the public.
The mortality experience of 3,276 radium dial painters and handlers employed between 1913 and 1949 is being determined through 2019. The last epidemiologic follow-up was 30 years ago when most of these workers were still alive. Nearly 65% were born before 1920, 37.5% were teenagers when first hired, and nearly 50% were hired before 1930 when the habit of placing brushes in mouths essentially stopped. Comprehensive dose reconstruction techniques are being applied to estimate organ doses for each worker related to the intake of
226
Ra,
228
Ra, and associated photon exposures. Time dependent dose-response analyses will estimate lifetime risks for specific causes of death.
The study of radium dial workers is part of the Million Person Study of low-dose health effects that is designed to evaluate radiation risks among healthy American workers and veterans. Despite being one of the most important and influential radiation effects studies ever conducted, shifting programmatic responsibilities and declining funding led to the termination of the radium program of studies in the early 1990s. Renewed interest and opportunity have arisen. With scientific progress made in dosimetric methodology and models, the ability to perform a study over the entire life span, and the potential applicability to other scenarios such as medicine, environmental contamination and space exploration, the radium dial workers have once again come to the forefront.
Following the Fukushima accident, the International Commission on Radiological Protection (ICRP) convened a task group to compile lessons learned from the nuclear reactor accident at the Fukushima ...Daiichi nuclear power plant in Japan, with respect to the ICRP system of radiological protection. In this memorandum the members of the task group express their personal views on issues arising during and after the accident, without explicit endorsement of or approval by the ICRP. While the affected people were largely protected against radiation exposure and no one incurred a lethal dose of radiation (or a dose sufficiently large to cause radiation sickness), many radiological protection questions were raised. The following issues were identified: inferring radiation risks (and the misunderstanding of nominal risk coefficients); attributing radiation effects from low dose exposures; quantifying radiation exposure; assessing the importance of internal exposures; managing emergency crises; protecting rescuers and volunteers; responding with medical aid; justifying necessary but disruptive protective actions; transiting from an emergency to an existing situation; rehabilitating evacuated areas; restricting individual doses of members of the public; caring for infants and children; categorising public exposures due to an accident; considering pregnant women and their foetuses and embryos; monitoring public protection; dealing with 'contamination' of territories, rubble and residues and consumer products; recognising the importance of psychological consequences; and fostering the sharing of information. Relevant ICRP Recommendations were scrutinised, lessons were collected and suggestions were compiled. It was concluded that the radiological protection community has an ethical duty to learn from the lessons of Fukushima and resolve any identified challenges. Before another large accident occurs, it should be ensured that inter alia: radiation risk coefficients of potential health effects are properly interpreted; the limitations of epidemiological studies for attributing radiation effects following low exposures are understood; any confusion on protection quantities and units is resolved; the potential hazard from the intake of radionuclides into the body is elucidated; rescuers and volunteers are protected with an ad hoc system; clear recommendations on crisis management and medical care and on recovery and rehabilitation are available; recommendations on public protection levels (including infant, children and pregnant women and their expected offspring) and associated issues are consistent and understandable; updated recommendations on public monitoring policy are available; acceptable (or tolerable) 'contamination' levels are clearly stated and defined; strategies for mitigating the serious psychological consequences arising from radiological accidents are sought; and, last but not least, failures in fostering information sharing on radiological protection policy after an accident need to be addressed with recommendations to minimise such lapses in communication.
To present the methodology used to determine vital status and obtain cause of death (COD) within the Million Person Study of Low-Dose Health Effects (MPS). Data sources and vital status tracing ...techniques used to obtain vital status and COD for six (n = 424,238 subjects) of the ∼20+ cohorts under study are described.
A multistage approach using multiple sources of vital status information was used to determine vital status (or 'trace') study participants from as early as 1940 to the present. Mortality records from state departments of vital statistics and the Social Security Administration Death Master File (SSA-DMF) were matched to study participants by Social Security Number (SSN), full name, date of birth (DOB), and/or sex using deterministic and probabilistic algorithms. The National Death Index (NDI) and SSA Service for Epidemiological Researchers (SSA-SER) were used to obtain COD (after 1978) and verification of alive status, respectively. Online public records and ancestry services, death certificates, and specialized mortality sources were also utilized.
For the MPS cohorts traced to date (nuclear power plant workers, industrial radiographers, atomic veterans, and workers at Rocketdyne/Atomics International, Mound nuclear facility, and Mallinckrodt Chemical Works), vital status was confirmed for over 90% of all study subjects in all but one cohort (88%). The ascertainment of COD was over 96% for all cohorts.
A hallmark of a high-quality epidemiologic cohort mortality study is a low percentage of subjects with unknown vital status and a low percentage of deaths without a COD. The sources and methods used for vital status tracing and COD determination for the MPS have been successful and should be useful for other investigators tracing large, historic study populations. Some of the approaches would be applicable for use in all cohort studies using regional-specific mortality data or modifications to the approach.
The purpose of this study was to identify germline single nucleotide polymorphisms (SNPs) that optimally predict radiation-associated contralateral breast cancer (RCBC) and to provide new biological ...insights into the carcinogenic process. Fifty-two women with contralateral breast cancer and 153 women with unilateral breast cancer were identified within the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study who were at increased risk of RCBC because they were ≤ 40 years of age at first diagnosis of breast cancer and received a scatter radiation dose > 1 Gy to the contralateral breast. A previously reported algorithm, preconditioned random forest regression, was applied to predict the risk of developing RCBC. The resulting model produced an area under the curve (AUC) of 0.62 (p = 0.04) on hold-out validation data. The biological analysis identified the cyclic AMP-mediated signaling and Ephrin-A as significant biological correlates, which were previously shown to influence cell survival after radiation in an ATM-dependent manner. The key connected genes and proteins that are identified in this analysis were previously identified as relevant to breast cancer, radiation response, or both. In summary, machine learning/bioinformatics methods applied to genome-wide genotyping data have great potential to reveal plausible biological correlates associated with the risk of RCBC.
Abstract Background Women with germline BRCA1 or BRCA2 ( BRCA1 / BRCA2 ) mutations are at very high risk of developing breast cancer, including asynchronous contralateral breast cancer (CBC). BRCA1 / ...BRCA2 genes help maintain genome stability and assist in DNA repair. We examined whether the risk of CBC associated with radiation treatment was higher among women with germline BRCA1 / BRCA2 mutations than among non-carriers. Methods A population-based, nested case–control study was conducted within a cohort of 52,536 survivors of unilateral breast cancer (UBC). Cases were 603 women with CBC and controls were 1199 women with UBC individually matched on age at diagnosis, race, year of first diagnosis and cancer registry. All women were tested for BRCA1 and BRCA2 mutations. Radiation absorbed dose from the initial radiotherapy (RT) to the CBC location within the contralateral breast was reconstructed from measurements in a tissue-equivalent phantom and details available in the therapy records. Findings Among women treated with radiation, the mean radiation dose was 1.1 Gy (range = 0.02–6.2 Gy). Risk of developing CBC was elevated among women who carried a deleterious BRCA1 / BRCA2 mutation (rate ratio, RR = 4.5, confidence interval, CI = 3.0–6.8), and also among those treated with RT (RR = 1.2, CI = 1.0–1.6). However, among mutation carriers, an incremental increase in risk associated with radiation dose was not statistically significant. Interpretation Multiplicative interaction of RT with mutation status would be reflected by a larger association of RT with CBC among carriers than among non-carriers, but this was not apparent. Accordingly, there was no clear indication that carriers of deleterious BRCA / BRCA2 mutations were more susceptible to the carcinogenic effects of radiation than non-carriers. These findings are reassuring and have important clinical implications for treatment decisions and the clinical management of patients harbouring deleterious BRCA1 / BRCA2 mutations. Funding All work associated with this study was supported by the U.S. National Cancer Institute R01CA097397, U01CA083178.
The risk of mesothelioma, including cancers of the pleura and peritoneum, was examined within two large cohorts of workers monitored for exposure to ionizing radiation.
Mortality was assessed among ...253,632 workers routinely monitored for external radiation, including 30,724 industrial radiographers (IR) at shipyards, 142,583 workers at nuclear power plants (NPP), and 83,441 IR who had not worked at an NPP or shipyard. Follow-up was from 1969 through 2011. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were computed; observed numbers of deaths from mesothelioma (including cancers of the pleura and peritoneum) and asbestosis were compared with numbers expected based on age-, sex-, and calendar year-specific national mortality rates. Job history and quantitative asbestos exposure data were unavailable, but work at a shipyard was taken as a surrogate for the likelihood of exposure. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mesothelioma in relation to estimated cumulative radiation exposure to the lung.
The mean duration of follow-up was 25.3 years (max 42 years). The mean cumulative lung dose was 28.6 mGy (7.3% > 250 mGy). Nearly 20% of the workers had died by 2011. A total of 421 mesothelioma deaths were found (75% occurring after 1999) with increased SMRs among workers monitored in shipyards (SMR 9.97; 95% CI 8.50-11.63) and for NPP workers (SMR 5.55; 95% CI 4.88-6.29), but not for IR who had not worked in shipyards (SMR 1.15; 95% CI 0.53-2.19). Likewise, deaths from asbestosis (n = 189) were also increased for shipyard and NPP workers (SMR = 18.1 and 9.2, respectively), but not among workers who never worked at a shipyard or NPP (SMR = 0.70; n = 1). Radiation dose to the lung was not associated with a statistically meaningful dose-response trend for mesothelioma in the combined cohorts (HR at 100 mGy = 1.10; 95% CI 0.96-1.27; p = .18), nor was mesothelioma risk associated with radiation exposure among IR who had not worked in a shipyard and assumed minimally exposed to asbestos.
An elevated rate of death from mesothelioma was observed in two radiation-exposed occupational groups with potential for asbestos exposure. The increased risk of death from asbestosis, combined with little evidence of a rising trend in mesothelioma mortality with increasing radiation exposure, suggests that the mesothelioma (and asbestosis) excess in these workers was due to asbestos exposure in shipyards and power plants and not to occupational low-dose radiation.
A substantial body of epidemiologic literature addresses risks associated with occupational radiation exposure but comparing results between studies is often difficult as different statistical models ...are commonly used. It is unclear whether different methods produce similar results for estimates of radiation risk when applied to the same data. The goal of this study was to compare the radiation risk estimates for leukemia other than chronic lymphocytic leukemia (non-CLL) and ischemic heart disease (IHD) produced by both Cox and Poisson regression models for time-dependent dose-response analyses of occupational exposure.
For brevity, this methods paper presents the results from one cohort, the Nuclear Power Plant workers (NPP), though the evaluation considered five cohorts of varying size and exposure as part of the Million Worker Study. Cox Proportional Hazards models, with age as the underlying timescale for hazard, were conducted using three computer software programs: SAS, R, and Epicure. Doses lagged 2 years for non-CLL and 10 years for ischemic heart disease were treated as time-dependent exposures at the annual level and were examined both in categories and as a continuous term. Hazard ratios (HR) and 95% confidence intervals (CI) were reported for each model in SAS and R, while the Peanuts program of Epicure was utilized to produce Excess Relative Risk (ERR) estimates and 95% CI. All models were adjusted for gender and year of birth. Four piece-wise exponential Poisson models (log-linear regression for rate) were developed with varying cutpoints for age strata from very fine to broad categories using both R and the Amfit program in Epicure for ERR estimates.
Comparable estimates of risk (both RR and ERR) were observed from Cox and Poisson models, regardless of software utilized, as long as appropriately narrow categories of age were utilized to control the confounding of age in Poisson models. The ERR estimates produced in Epicure tended to agree very closely with the HR or RR estimates, and the statistical software program used had no impact to risk estimates for the same model.
As computational power is no longer the burden today as it has been in the past, the results of this evaluation support the use of the Cox proportional hazards or the ungrouped Poisson approach to analyzing time-dependent dose-response relationships to ensure that maximum control over the confounding of age is achieved in studies of mortality for cohorts occupationally exposed to radiation.
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