Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 43 Records) |
Query Trace: Daniels RD [original query] |
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Cancer mortality after low dose exposure to ionising radiation in workers in France, the United Kingdom, and the United States (INWORKS): cohort study
Richardson DB , Leuraud K , Laurier D , Gillies M , Haylock R , Kelly-Reif K , Bertke S , Daniels RD , Thierry-Chef I , Moissonnier M , Kesminiene A , Schubauer-Berigan MK . Bmj 2023 382 e074520 OBJECTIVE: To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer. DESIGN: Multinational cohort study. SETTING: Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS). PARTICIPANTS: 309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years. MAIN OUTCOME MEASURES: Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer. RESULTS: The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos. CONCLUSIONS: This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world's most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings. |
Ionizing radiation and solid cancer mortality among US nuclear facility workers
Kelly-Reif K , Bertke SJ , Daniels RD , Richardson DB , Schubauer-Berigan MK . Int J Epidemiol 2023 52 (4) 1015-1024 BACKGROUND: The risk of solid cancers from low-level protracted ionizing radiation is not well characterized. Nuclear workers provide valuable information on the effects of ionizing radiation in contemporary exposure scenarios relevant to workers and the public. METHODS: We evaluated the association between penetrating ionizing radiation exposure and solid cancer mortality among a pooled cohort of nuclear workers in the USA, with extended follow-up to examine cancers with long latencies. This analysis includes 101 363 workers from five nuclear facilities, with 12 069 solid cancer deaths between 1944 and 2016. The association between cumulative equivalent dose measured in sieverts (Sv) and solid cancer subtypes were modelled as the excess relative rate per Sv (ERR Sv-1) using Cox regression. RESULTS: For the association between ionizing radiation exposure and all solid cancer mortality we observed an elevated rate (ERR Sv-1=0.19; 95% CI: -0.10, 0.52), which was higher among a contemporary sub-cohort of workers first hired in 1960 or later (ERR Sv-1= 2.23; 95% CI: 1.13, 3.49). Similarly, we observed an elevated rate for lung cancer mortality (ERR Sv-1= 0.65; 95% CI: 0.09, 1.30) that was higher among contemporary hires (ERR Sv-1= 2.90; 95% CI: 1.00, 5.26). CONCLUSIONS: Although concerns remain about confounding, measurement error and precision, this analysis strengthens the evidence base indicating there are radiogenic risks for several solid cancer types. |
All-cause and cause-specific mortality in a cohort of WTC-exposed and non-WTC-exposed firefighters
Singh A , Zeig-Owens R , Cannon M , Webber MP , Goldfarb DG , Daniels RD , Prezant DJ , Boffetta P , Hall CB . Occup Environ Med 2023 80 (6) 297-303 OBJECTIVE: To compare mortality rates in World Trade Center (WTC)-exposed Fire Department of the City of New York (FDNY) firefighters with rates in similarly healthy, non-WTC-exposed/non-FDNY firefighters, and compare mortality in each firefighter cohort with the general population. METHODS: 10 786 male WTC-exposed FDNY firefighters and 8813 male non-WTC-exposed firefighters from other urban fire departments who were employed on 11 September 2001 were included in the analyses. Only WTC-exposed firefighters received health monitoring via the WTC Health Programme (WTCHP). Follow-up began 11 September 2001 and ended at the earlier of death date or 31 December 2016. Death data were obtained from the National Death Index and demographics from the fire departments. We estimated standardised mortality ratios (SMRs) in each firefighter cohort versus US males using demographic-specific US mortality rates. Poisson regression models estimated relative rates (RRs) of all-cause and cause-specific mortality in WTC-exposed versus non-WTC-exposed firefighters, controlling for age and race. RESULTS: Between 11 September 2001 and 31 December 2016, there were 261 deaths among WTC-exposed firefighters and 605 among non-WTC-exposed. Both cohorts had reduced all-cause mortality compared with US males (SMR (95% CI)=0.30 (0.26 to 0.34) and 0.60 (0.55 to 0.65) in WTC-exposed and non-WTC-exposed, respectively). WTC-exposed firefighters also had lower rates of all-cause mortality (RR=0.54, 95% CI=0.49 to 0.59) and cancer-specific, cardiovascular-specific and respiratory disease-specific mortality compared with non-WTC-exposed firefighters. CONCLUSION: Both firefighter cohorts had lower than expected all-cause mortality. Fifteen years post 11 September 2001, mortality was lower in WTC-exposed versus non-WTC-exposed firefighters. Lower mortality in the WTC-exposed suggests not just a healthy worker effect, but additional factors such as greater access to free health monitoring and treatment that they receive via the WTCHP. |
Firefighting and cancer: A meta-analysis of cohort studies in the context of cancer hazard identification
DeBono NL , Daniels RD , Beane Freeman LE , Graber JM , Hansen J , Teras LR , Driscoll T , Kjaerheim K , Demers PA , Glass DC , Kriebel D , Kirkham TL , Wedekind R , Filho AM , Stayner L , Schubauer-Berigan MK . Saf Health Work 2023 14 (2) 141-152 Objective: We performed a meta-analysis of epidemiological results for the association between occupational exposure as a firefighter and cancer as part of the broader evidence synthesis work of the IARC Monographs program. Methods: A systematic literature search was conducted to identify cohort studies of firefighters followed for cancer incidence and mortality. Studies were evaluated for the influence of key biases on results. Random-effects meta-analysis models were used to estimate the association between ever-employment and duration of employment as a firefighter and risk of 12 selected cancers. The impact of bias was explored in sensitivity analyses. Results: Among the 16 included cancer incidence studies, the estimated meta-rate ratio, 95% confidence interval (CI), and heterogeneity statistic (I2) for ever-employment as a career firefighter compared mostly to general populations were 1.58 (1.14–2.20, 8%) for mesothelioma, 1.16 (1.08–1.26, 0%) for bladder cancer, 1.21 (1.12–1.32, 81%) for prostate cancer, 1.37 (1.03–1.82, 56%) for testicular cancer, 1.19 (1.07–1.32, 37%) for colon cancer, 1.36 (1.15–1.62, 83%) for melanoma, 1.12 (1.01–1.25, 0%) for non-Hodgkin lymphoma, 1.28 (1.02–1.61, 40%) for thyroid cancer, and 1.09 (0.92–1.29, 55%) for kidney cancer. Ever-employment as a firefighter was not positively associated with lung, nervous system, or stomach cancer. Results for mesothelioma and bladder cancer exhibited low heterogeneity and were largely robust across sensitivity analyses. Conclusions: There is epidemiological evidence to support a causal relationship between occupational exposure as a firefighter and certain cancers. Challenges persist in the body of evidence related to the quality of exposure assessment, confounding, and medical surveillance bias. © 2023 Occupational Safety and Health Research Institute |
End-stage renal disease incidence in a cohort of US firefighters from San Francisco, Chicago, and Philadelphia
Pinkerton LE , Bertke S , Dahm MM , Kubale TL , Siegel MR , Hales TR , Yiin JH , Purdue MP , Beaumont JJ , Daniels RD . Am J Ind Med 2022 65 (12) 975-984 BACKGROUND: Firefighters perform strenuous work in hot environments, which may increase their risk of chronic kidney disease. The purpose of this study was to evaluate the risk of end-stage renal disease (ESRD) and types of ESRD among a cohort of US firefighters compared to the US general population, and to examine exposure-response relationships. METHODS: ESRD from 1977 through 2014 was identified through linkage with Medicare data. ESRD incidence in the cohort compared to the US population was evaluated using life table analyses. Associations of all ESRD, systemic ESRD, hypertensive ESRD, and diabetic ESRD with exposure surrogates (exposed days, fire runs, and fire hours) were examined in Cox proportional hazards models adjusted for attained age (the time scale), race, birth date, fire department, and employment duration. RESULTS: The incidence of all ESRD was less than expected (standardized incidence ratio (SIR) = 0.79; 95% confidence interval = 0.69-0.89, observed = 247). SIRs for ESRD types were not significantly increased. Positive associations of all ESRD, systemic ESRD, and hypertensive ESRD with exposed days were observed: however, 95% confidence intervals included one. CONCLUSIONS: We found little evidence of increased risk of ESRD among this cohort of firefighters. Limitations included the inability to evaluate exposure-response relationships for some ESRD types due to small observed numbers, the limitations of the surrogates of exposure, and the lack of information on more sensitive outcome measures for potential kidney effects. |
Scientific value of the sub-cohort of children in the World Trade Center Health Registry
Brackbill RM , Butturini E , Cone JE , Ahmadi A , Daniels RD , Farfel MR , Kubale T . Int J Environ Res Public Health 2022 19 (19) The World Trade Center Health Registry (WTCHR) was established in 2002 as a public health resource to monitor the health effects from the World Trade Center (WTC) disaster. We evaluated the representativeness of the WTC youth population (<18 years on 11 September 2001) by comparing the distributions of age, gender, race/ethnic groups, and income to 2000 census data for the matched geographic area, including distance from disaster. There were 2379 WTCHR enrolled children living in Lower Manhattan south of Canal Street on 11 September 2001, along with 752 enrolled students who attended school in Lower Manhattan but were not area residents. The WTCHR sub-group of children who were residents was similar to the geographically corresponding census population on age and sex. Black and Hispanic children are moderately overrepresented at 0.9% and 2.4% in the WTCHR compared to 0.8% and 1.7% in census population, respectively, while lower-income households are slightly under-represented, 28.8% in the WTCHR and 30.8% for the corresponding census information. Asian children appear underrepresented at 3.0% participation compared to 6.3% in the census. While the demographics of WTCHR youth are somewhat skewed, the gaps are within expected patterns of under-representation observed in other longitudinal cohorts and can be effectively addressed analytically or through targeted study design. |
Nonmalignant respiratory disease mortality in male Colorado Plateau uranium miners, 1960-2016
Kelly-Reif K , Bertke S , Daniels RD , Richardson DB , Schubauer-Berigan MK . Am J Ind Med 2022 65 (10) 773-782 BACKGROUND: To evaluate trends of nonmalignant respiratory disease (NMRD) mortality among US underground uranium miners on the Colorado Plateau, and to estimate the exposure-response association between cumulative radon progeny exposure and NMRD subtype mortality. METHODS: Standardized mortality ratios (SMRs) and excess relative rates per 100 working level months (excess relative rate [ERR]/100 WLM) were estimated in a cohort of 4021 male underground uranium miners who were followed from 1960 through 2016. RESULTS: We observed elevated SMRs for all NMRD subtypes. Silicosis had the largest SMR (n = 52, SMR = 41.4; 95% confidence interval [CI]: 30.9, 54.3), followed by other pneumoconiosis (n = 49, SMR = 39.6; 95% CI: 29.6, 52.3) and idiopathic pulmonary fibrosis (IPF) (n = 64, SMR = 4.77; 95% CI 3.67, 6.09). SMRs for silicosis increased with duration of employment; SMRs for IPF increased with duration of employment and calendar period. There was a positive association between cumulative radon exposure and silicosis with evidence of modification by smoking (ERR/100 WLM(≥10 pack-years) = 0.78; 95% CI: 0.05, 24.6 and ERR/100 WLM(<10 pack-years) = 0.01; 95% CI: -0.03, 0.52), as well as a small positive association between radon and IPF (ERR/100 WLM = 0.06, 95% CI: 0.00, 0.24); these associations were driven by workers with prior employment in hard rock mining. CONCLUSIONS: Uranium mining workers had excess NMRD mortality compared with the general population; this excess persisted throughout follow-up. Exposure-response analyses indicated a positive association between radon exposure and IPF and silicosis, but these analyses have limitations due to outcome misclassification and missing information on occupational co-exposures such as silica dust. |
The World Trade Center Health Program: Twenty years of health effects research
Daniels RD , Kubale TL , Reissman DB , Howard J . Am J Ind Med 2021 64 (10) 797-802 It has been 20 years since the devastating terrorist attacks on September 11, 2001. Thousands were injured or killed during the attacks and many more are at risk of adverse health stemming from physical, psychological, and emotional stressors born out of the attacks. Private, federal, state, and local resources were gathered soon after the attacks to address impacts to the community, including the health and well-being of both responders and survivors. Many of these efforts are now largely consolidated under the federally mandated World Trade Center (WTC) Health Program. This program provides medical monitoring and treatment of qualifying conditions among the 9/11-exposed population and supports related physical and mental health research. In this commentary, we describe the WTC Health Program, with emphasis on the health-effects research it has funded since inception in 2011. We describe sentinel research publications, and how science has impacted the program. We provide examples relating studies in this special issue to important roles in the WTC Health Program research agenda. Finally, we provide a perspective on future research needs. |
Cancer incidence in World Trade Center-exposed and non-exposed male firefighters, as compared with the US adult male population: 2001-2016
Webber MP , Singh A , Zeig-Owens R , Salako J , Skerker M , Hall CB , Goldfarb DG , Jaber N , Daniels RD , Prezant DJ . Occup Environ Med 2021 78 (10) 707-714 OBJECTIVE: To compare cancer incidence in Fire Department of the City of New York (FDNY) firefighters who worked at the World Trade Center (WTC) site to incidence in a population of non-WTC-exposed firefighters, the Career Firefighter Health Study (CFHS) cohort, and to compare rates from each firefighter cohort to rates in demographically similar US males. METHODS: FDNY (N=10 786) and CFHS (N=8813) cohorts included male firefighters who were active on 11 September 2001 (9/11) and were followed until death or 31 December 2016. Cases were identified from 15 state cancer registries. Poisson regression models assessed cancers in each group (FDNY and CFHS) versus US males, and associations between group and cancer rates; these models estimated standardised incidence ratios (SIRs) and adjusted relative rates (RRs), respectively. Secondary analyses assessed surveillance bias and smoking history. RESULTS: We identified 915 cancer cases in 841 FDNY firefighters and 1002 cases in 909 CFHS firefighters. FDNY had: higher rates for all cancers (RR=1.13; 95% CI 1.02 to 1.25), prostate (RR=1.39; 95% CI 1.19 to 1.63) and thyroid cancer (RR=2.53; 95% CI 1.37 to 4.70); younger median ages at diagnosis (55.6 vs 59.4; p<0.001, all cancers); and more cases with localised disease when compared with CFHS. Compared with US males, both firefighter cohorts had elevated SIRs for prostate cancer and melanoma. Control for surveillance bias in FDNY reduced most differences. CONCLUSIONS: Excess cancers occurred in WTC-exposed firefighters relative to each comparison group, which may partially be explained by heightened surveillance. Two decades post-9/11, clearer understanding of WTC-related risk requires extended follow-up and modelling studies (laboratory or animal based) to identify workplace exposures in all firefighters. |
The World Trade Center Health Program: Petitions for adding qualifying health conditions
Daniels RD , Carreón T , Bilics JA , Reissman DB , Howard J . Am J Ind Med 2021 64 (10) 885-892 The federally mandated World Trade Center Health Program provides limited health benefits for qualifying health conditions related to the 9/11 terrorist attacks. A qualifying health condition is an illness or health condition for which the member's exposure to airborne toxins, any other hazard, or any other adverse condition resulting from the 9/11 terrorist attacks is considered substantially likely to be a significant factor in aggravating, contributing to, or causing the illness or health condition. These qualifying health conditions are listed in federal regulations. The regulations also provide a process for amending this list. This commentary describes the methods developed for adding health conditions to the list of qualifying health conditions and discusses changes to the list that have occurred during the Program's 2011-2020 period. |
Lung Cancer Mortality and Styrene Exposure in the Reinforced Plastics Boatbuilding Industry: Evaluation of Healthy Worker Survivor Bias
Bertke SJ , Keil A , Daniels RD . Am J Epidemiol 2021 190 (9) 1784-1792 The evidence of styrene as a human lung carcinogen has been inconclusive. Occupational cohorts within the reinforced plastics industry are an ideal population to study this association due to relatively high levels of exposure to styrene and lack of concomitant exposures to other known carcinogens. However, healthy worker survivor bias (HWSB), where healthier workers stay employed longer and thus have higher exposure potential, is a likely source of confounding bias for exposure-response associations, in part due to styrene's acute effects. We studied a cohort of 5163 boatbuilders exposed to styrene in Washington state employed between 1959 and 1978; prior regression analyses demonstrated little evidence for an exposure-response between styrene exposure and lung cancer mortality. Based on estimates of necessary components of HWSB, we found evidence for a potentially large HWSB. Using g-estimation of a structural nested model to account for HWSB we estimated that one year of exposure >30 ppm accelerates time to lung cancer death by 2.3 years (95% Confidence intervals=1.53, 2.94). Our results suggest possibly strong HWSB in our small cohort and indicate that large, influential studies of styrene exposed workers may suffer similar biases, warranting a re-assessment of the evidence of long-term health effects of styrene exposure. |
Risk of cancer associated with low-dose radiation exposure: comparison of results between the INWORKS nuclear workers study and the A-bomb survivors study
Leuraud K , Richardson DB , Cardis E , Daniels RD , Gillies M , Haylock R , Moissonnier M , Schubauer-Berigan MK , Thierry-Chef I , Kesminiene A , Laurier D . Radiat Environ Biophys 2021 60 (1) 23-39 The Life Span Study (LSS) of Japanese atomic bomb survivors has served as the primary basis for estimates of radiation-related disease risks that inform radiation protection standards. The long-term follow-up of radiation-monitored nuclear workers provides estimates of radiation-cancer associations that complement findings from the LSS. Here, a comparison of radiation-cancer mortality risk estimates derived from the LSS and INWORKS, a large international nuclear worker study, is presented. Restrictions were made, so that the two study populations were similar with respect to ages and periods of exposure, leading to selection of 45,625 A-bomb survivors and 259,350 nuclear workers. For solid cancer, excess relative rates (ERR) per gray (Gy) were 0.28 (90% CI 0.18; 0.38) in the LSS, and 0.29 (90% CI 0.07; 0.53) in INWORKS. A joint analysis of the data allowed for a formal assessment of heterogeneity of the ERR per Gy across the two studies (P = 0.909), with minimal evidence of curvature or of a modifying effect of attained age, age at exposure, or sex in either study. There was evidence in both cohorts of modification of the excess absolute risk (EAR) of solid cancer by attained age, with a trend of increasing EAR per Gy with attained age. For leukemia, under a simple linear model, the ERR per Gy was 2.75 (90% CI 1.73; 4.21) in the LSS and 3.15 (90% CI 1.12; 5.72) in INWORKS, with evidence of curvature in the association across the range of dose observed in the LSS but not in INWORKS; the EAR per Gy was 3.54 (90% CI 2.30; 5.05) in the LSS and 2.03 (90% CI 0.36; 4.07) in INWORKS. These findings from different study populations may help understanding of radiation risks, with INWORKS contributing information derived from cohorts of workers with protracted low dose-rate exposures. |
Epidemiological studies of low-dose ionizing radiation and cancer: Summary bias assessment and meta-analysis
Hauptmann M , Daniels RD , Cardis E , Cullings HM , Kendall G , Laurier D , Linet MS , Little MP , Lubin JH , Preston DL , Richardson DB , Stram DO , Thierry-Chef I , Schubauer-Berigan MK , Gilbert ES , Berrington de Gonzalez A . J Natl Cancer Inst Monogr 2020 2020 (56) 188-200 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. |
A workshop on cognitive aging and impairment in the 9/11-exposed population
Daniels RD , Clouston SAP , Hall CB , Anderson KR , Bennett DA , Bromet EJ , Calvert GM , Carreón T , DeKosky ST , Diminich ED , Finch CE , Gandy S , Kreisl WC , Kritikos M , Kubale TL , Mielke MM , Peskind ER , Raskind MA , Richards M , Sano M , Santiago-Colón A , Sloan RP , Spiro A 3rd , Vasdev N , Luft BJ , Reissman DB . Int J Environ Res Public Health 2021 18 (2) The terrorist attacks on 11 September 2001 potentially exposed more than 400,000 responders, workers, and residents to psychological and physical stressors, and numerous hazardous pollutants. In 2011, the World Trade Center Health Program (WTCHP) was mandated to monitor and treat persons with 9/11-related adverse health conditions and conduct research on physical and mental health conditions related to the attacks. Emerging evidence suggests that persons exposed to 9/11 may be at increased risk of developing mild cognitive impairment. To investigate further, the WTCHP convened a scientific workshop that examined the natural history of cognitive aging and impairment, biomarkers in the pathway of neurodegenerative diseases, the neuropathological changes associated with hazardous exposures, and the evidence of cognitive decline and impairment in the 9/11-exposed population. Invited participants included scientists actively involved in health-effects research of 9/11-exposed persons and other at-risk populations. Attendees shared relevant research results from their respective programs and discussed several options for enhancements to research and surveillance activities, including the development of a multi-institutional collaborative research network. The goal of this report is to outline the meeting's agenda and provide an overview of the presentation materials and group discussion. |
Ischaemic heart and cerebrovascular disease mortality in uranium enrichment workers
Anderson JL , Bertke SJ , Yiin J , Kelly-Reif K , Daniels RD . Occup Environ Med 2020 78 (2) 105-111 OBJECTIVE: Linear and non-linear dose-response relationships between radiation absorbed dose to the lung from internally deposited uranium and external sources and circulatory system disease (CSD) mortality were examined in a cohort of 23 731 male and 5552 female US uranium enrichment workers. METHODS: Rate ratios (RRs) for categories of lung dose and linear excess relative rates (ERRs) per unit lung dose were estimated to evaluate the associations between lung absorbed dose and death from ischaemic heart disease (IHD) and cerebrovascular disease. RESULTS: There was a suggestion of modestly increased IHD risk in workers with internal uranium lung dose above 1 milligray (mGy) (RR=1.4, 95% CI 0.76 to 2.3) and a statistically significantly increased IHD risk with external dose exceeding 150 mGy (RR=1.3, 95% CI 1.1 to 1.6) compared with the lowest exposed groups. ERRs per milligray were positive for IHD and uranium internal dose and for both outcomes per gray external dose, although the CIs generally included the null. CONCLUSIONS: Non-linear dose-response models using restricted cubic splines revealed sublinear responses at lower internal doses, suggesting that linear models that are common in radioepidemiological cancer studies may poorly describe the association between uranium internal dose and CSD mortality. |
Epidemiological studies of low-dose ionizing radiation and cancer: Rationale and framework for the monograph and overview of eligible studies
Berrington de Gonzalez A , Daniels RD , Cardis E , Cullings HM , Gilbert E , Hauptmann M , Kendall G , Laurier D , Linet MS , Little MP , Lubin JH , Preston DL , Richardson DB , Stram D , Thierry-Chef I , Schubauer-Berigan MK . J Natl Cancer Inst Monogr 2020 2020 (56) 97-113 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. |
Strengths and weaknesses of dosimetry used in studies of low-dose radiation exposure and cancer
Daniels RD , Kendall GM , Thierry-Chef I , Linet MS , Cullings HM . J Natl Cancer Inst Monogr 2020 2020 (56) 114-132 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. |
Exposure-response assessment of cancer mortality in styrene-exposed boatbuilders
Daniels RD , Bertke SJ . Occup Environ Med 2020 77 (10) 706-712 OBJECTIVES: To improve exposure estimates and reexamine exposure-response relationships between cumulative styrene exposure and cancer mortality in a previously studied cohort of US boatbuilders exposed between 1959 and 1978 and followed through 2016. METHODS: Cumulative styrene exposure was estimated from work assignments and air-sampling data. Exposure-response relationships between styrene and select cancers were examined in Cox proportional hazards models matched on attained age, sex, race, birth cohort and employment duration. Models adjusted for socioeconomic status (SES). Exposures were lagged 10 years or by a period maximising the likelihood. HRs included 95% profile-likelihood CIs. Actuarial methods were used to estimate the styrene exposure corresponding to 10(-4) extra lifetime risk. RESULTS: The cohort (n= 5163) contributed 201 951 person-years. Exposures were right-skewed, with mean and median of 31 and 5.7 ppm-years, respectively. Positive, monotonic exposure-response associations were evident for leukaemia (HR at 50 ppm-years styrene = 1.46; 95% CI 1.04 to 1.97) and bladder cancer (HR at 50 ppm-years styrene =1.64; 95% CI 1.14 to 2.33). There was no evidence of confounding by SES. A working lifetime exposure to 0.05 ppm styrene corresponded to one extra leukaemia death per 10 000 workers. CONCLUSIONS: The study contributes evidence of exposure-response associations between cumulative styrene exposure and cancer. Simple risk projections at current exposure levels indicate a need for formal risk assessment. Future recommendations on worker protection would benefit from additional research clarifying cancer risks from styrene exposure. |
Cancer mortality update with an exposure response analysis among styrene-exposed workers in the reinforced plastics boatbuilding industry
Bertke SJ , Yiin JH , Daniels RD . Am J Ind Med 2018 61 (7) 566-571 BACKGROUND: There is sparse and inconsistent evidence of an association between styrene exposure and cancer. METHODS: This study examines mortality patterns in a previously studied cohort of 5201 workers employed in two Washington boat-building facilities, extending follow-up 5 years. Standardized mortality ratios (SMR) were calculated using state rates as referent. Cox regression calculated rate ratios (RR) per year employed in styrene-exposed exposed jobs. RESULTS: No excess deaths from lymphohematopoietic cancers (LHCs) were observed (SMR: 0.99, 95%CI: 0.74-1.30) when compared to the referent population; however, the relative risk increased with duration of employment in internal analyses. Conversely, lung cancer mortality was significantly elevated (SMR: 1.24, 95%CI: 1.08-1.41), but there was no evidence of a dose-response relationship. CONCLUSION: We found evidence that occupational exposure to styrene was associated with increased LHC risk, while no such association was observed for lung cancer. |
Occupational asthma risk from exposures to toluene diisocyanate: A review and risk assessment
Daniels RD . Am J Ind Med 2018 61 (4) 282-292 BACKGROUND: Toluene Diisocyanate (TDI) is a known respiratory sensitizer linked to occupational asthma (OA). To better manage worker risks, an appropriate characterization of the TDI-OA dose-risk relationship is needed. METHODS: The literature was reviewed for data suitable for dose-response modeling. Previous study data were fit to models to derive prospective occupational exposure limits (OELs), using benchmark dose (BMD) and low-dose extrapolation approaches. RESULTS: Data on eight TDI-exposed populations were suitable for analysis. There were 118 OA cases in a population contributing 13 590 person-years. The BMD-based OEL was 0.4 ppb. The OEL based on low-dose extrapolation to working lifetime extra risk of 1/1000 was 0.3 ppb. CONCLUSIONS: This study synthesized epidemiologic data to characterize the TDI-OA dose-risk relationship. This approach yielded prospective OEL estimates below recent recommendations by the American Conference of Governmental Industrial Hygienists, but given significant study limitations, this should be interpreted with caution. Confirmatory research is needed. |
Response to Goodman et al
Pinkerton LE , Yiin JH , Daniels RD , Fent KW . Am J Ind Med 2017 60 (2) 223-225 We thank the Journal for providing us the opportunity to respond to the letter from Goodman et al. [2017] regarding the conclusions of our mortality study among toluene diisocyanate (TDI)-exposed workers [Pinkerton et al., 2016]. | | Goodman et al. [2017] point out that exposure measurement error can result in a bias towards the null or away from the null. We agree and did not assert otherwise. Rather, in our paper, we pointed out that exposure measurement error is among several possible explanations for the lack of an observed positive association of cumulative TDI exposure, based on inhalation, with lung and larynx cancer [Pinkerton et al., 2016]. | | Goodman et al. [2017] also raise the possibility of positive confounding by smoking because our risk estimate for other smoking-related cancers in the overall cohort is imprecise and chronic obstructive pulmonary disease (COPD) mortality, which is more strongly related to smoking, was elevated in the cohort compared to the general population. The standardized mortality ratio for other smoking-related cancers was 1.06 (95% confidence interval, 0.85–1.31), which is evidence against large differences in smoking patterns between the cohort and general population. Although Goodman et al. [2017] state that even slight differences could account for an elevated number of respiratory deaths, other data indicate that smoking is unlikely to fully explain our findings [Siemiatycki et al., 1988]. We caution against using the findings for COPD mortality to assess potential differences in smoking between the cohort and general population because other investigators have reported associations of TDI exposure with chronic bronchitis [Jones et al., 1992] and decline in pulmonary function [Diem et al., 1982]. |
Site-specific solid cancer mortality following exposure to ionizing radiation: a cohort study of workers (INWORKS)
Richardson DB , Cardis E , Daniels RD , Gillies M , Haylock R , Leuraud K , Laurier D , Moissonnier M , Schubauer-Berigan MK , Thierry-Chef I , Kesminiene A . Epidemiology 2017 29 (1) 31-40 BACKGROUND: There is considerable scientific interest in associations between protracted low-dose exposure to ionizing radiation and the occurrence of specific types of cancer. METHODS: Associations between ionizing radiation and site-specific solid cancer mortality were examined among 308,297 nuclear workers employed in France, the United Kingdom, and the United States. Workers were monitored for external radiation exposure and follow-up encompassed 8.2 million person-years. Radiation-mortality associations were estimated using a maximum likelihood method and using a Markov chain Monte Carlo method, the latter used to fit a hierarchical regression model to stabilize estimates of association. RESULTS: The analysis included 17,957 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using a maximum likelihood method to quantify associations between radiation dose and site-specific cancer, we obtained positive point estimates for oral, esophagus, stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura, bone and connective tissue, skin, ovary, testis, and thyroid cancer; in addition, we obtained negative point estimates for cancer of the liver and gallbladder, prostate, bladder, kidney, and brain. Most of these estimated coefficients exhibited substantial imprecision. Employing a hierarchical model for stabilization had little impact on the estimated associations for the most commonly observed outcomes, but for less frequent cancer types the stabilized estimates tended to take less extreme values and have greater precision than estimates obtained without such stabilization. CONCLUSIONS: The results provide further evidence regarding associations between low-dose radiation exposure and cancer. |
Mortality from circulatory diseases and other non-cancer outcomes among nuclear workers in France, the United Kingdom and the United States (INWORKS)
Gillies M , Richardson DB , Cardis E , Daniels RD , O'Hagan JA , Haylock R , Laurier D , Leuraud K , Moissonnier M , Schubauer-Berigan MK , Thierry-Chef I , Kesminiene A . Radiat Res 2017 188 (3) 276-290 Positive associations between external radiation dose and non-cancer mortality have been made in a number of published studies, primarily of populations exposed to high-dose, high-dose-rate ionizing radiation. The goal of this study was to determine whether external radiation dose was associated with non-cancer mortality in a large pooled cohort of nuclear workers exposed to low-dose radiation accumulated at low dose rates. The cohort comprised 308,297 workers from France, United Kingdom and United States. The average cumulative equivalent dose at a tissue depth of 10 mm [Hp(10)] was 25.2 mSv. In total, 22% of the cohort were deceased by the end of follow-up, with 46,029 deaths attributed to non-cancer outcomes, including 27,848 deaths attributed to circulatory diseases. Poisson regression was used to investigate the relationship between cumulative radiation dose and non-cancer mortality rates. A statistically significant association between radiation dose and all non-cancer causes of death was observed [excess relative risk per sievert (ERR/Sv) = 0.19; 90% CI: 0.07, 0.30]. This was largely driven by the association between radiation dose and mortality due to circulatory diseases (ERR/Sv = 0.22; 90% CI: 0.08, 0.37), with slightly smaller positive, but nonsignificant, point estimates for mortality due to nonmalignant respiratory disease (ERR/Sv = 0.13; 90% CI: -0.17, 0.47) and digestive disease (ERR/Sv = 0.11; 90% CI: -0.36, 0.69). The point estimate for the association between radiation dose and deaths due to external causes of death was nonsignificantly negative (ERR = -0.12; 90% CI: <-0.60, 0.45). Within circulatory disease subtypes, associations with dose were observed for mortality due to cerebrovascular disease (ERR/Sv = 0.50; 90% CI: 0.12, 0.94) and mortality due to ischemic heart disease (ERR/Sv = 0.18; 90% CI: 0.004, 0.36). The estimates of associations between radiation dose and non-cancer mortality are generally consistent with those observed in atomic bomb survivor studies. The findings of this study could be interpreted as providing further evidence that non-cancer disease risks may be increased by external radiation exposure, particularly for ischemic heart disease and cerebrovascular disease. However, heterogeneity in the estimated ERR/Sv was observed, which warrants further investigation. Further follow-up of these cohorts, with the inclusion of internal exposure information and other potential confounders associated with lifestyle factors, may prove informative, as will further work on elucidating the biological mechanisms that might cause these non-cancer effects at low doses. |
Radon in US workplaces: A review
Daniels RD , Schubauer-Berigan MK . Radiat Prot Dosimetry 2017 176 (3) 1-9 Exposure to naturally occurring radon is unavoidable and is second only to smoking as a direct cause of lung cancer in the USA. The literature for existing information on US occupations that are prone to increased radon exposures was reviewed. Current recommendations and applicable protective standards against occupational radon exposure that are applicable to US workers are discussed. Exposure varied widely among several working populations, most of whom were employed in industries that were unrelated to the uranium fuel cycle. Radon protection standards differed among agencies and have not changed since the height of domestic uranium production in the 1970s. In contrast, European countries are adopting recommendations by the International Commission on Radiation Protection to set a reference level near a derived annual exposure of about one working level month, which is 25% of the level currently established for US miners. |
Examining temporal effects on cancer risk in the International Nuclear Workers' Study (INWORKS)
Daniels RD , Bertke SJ , Richardson DB , Cardis E , Gillies M , O'Hagan JA , Haylock R , Laurier D , Leuraud K , Moissonnier M , Thierry-Chef I , Kesminiene A , Schubauer-Berigan MK . Int J Cancer 2016 140 (6) 1260-1269 The paper continues the series of publications from the International Nuclear Workers Study cohort (INWORKS) that comprises 308,297 workers from France, the United Kingdom and the United States, providing 8.2 million person-years of observation from a combined follow-up period (at earliest 1944 to at latest 2005). These workers' external radiation exposures were primarily to photons, resulting in an estimated average career absorbed dose to the colon of 17.4 milligray. The association between cumulative ionizing radiation dose and cancer mortality was evaluated in general relative risk models that describe modification of the excess relative risk (ERR) per gray (Gy) by time since exposure and age at exposure. Methods analogous to a nested-case control study using conditional logistic regression of sampled risks sets were used. Outcomes included: all solid cancers, lung cancer, leukemias excluding chronic lymphocytic, acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma. Significant risk heterogeneity was evident in chronic myeloid leukemia with time since exposure, where we observed increased ERR per Gy estimates shortly after exposure (2-10 year) and again later (20-30 years). We observed delayed effects for acute myeloid leukemia although estimates were not statistically significant. Solid cancer excess risk was restricted to exposure at age 35+ years and also diminished for exposure 30 years prior to attained age. Persistent or late effects suggest additional follow-up may inform on lifetime risks. However, cautious interpretation of results is needed due to analytical limitations and a lack of confirmatory results from other studies. This article is protected by copyright. All rights reserved. |
The International Nuclear Workers Study (Inworks): A Collaborative epidemiological study to improve knowledge about health effects of protracted low-dose exposure
Laurier D , Richardson DB , Cardis E , Daniels RD , Gillies M , O'Hagan J , Hamra GB , Haylock R , Leuraud K , Moissonnier M , Schubauer-Berigan MK , Thierry-Chef I , Kesminiene A . Radiat Prot Dosimetry 2016 173 21-25 INWORKS is a multinational cohort study, gathering 308 297 workers in the nuclear industry in France, the United Kingdom and the United States of America, with detailed individual monitoring data for external exposure to ionising radiation. Over a mean duration of follow-up of 27 y, the number of observed deaths was 66 632, including 17 957 deaths due to solid cancers, 1791 deaths due to haematological cancers and 27 848 deaths due to cardiovascular diseases. Mean individual cumulative external dose over the period 1945-2005 was 25 mSv. Analyses demonstrated a significant association between red bone marrow dose and the risk of leukaemia (excluding chronic lymphocytic leukaemia) and between colon dose and the risk of solid cancers. INWORKS assembled some of the strongest evidence to strengthen the scientific basis for the protection of adults from low dose, low-dose rate, exposures to ionising radiation. |
Mortality in a combined cohort of uranium enrichment workers
Yiin JH , Anderson JL , Daniels RD , Bertke SJ , Fleming DA , Tollerud DJ , Tseng CY , Chen PH , Waters KM . Am J Ind Med 2016 60 (1) 96-108 OBJECTIVE: To examine the patterns of cause-specific mortality and relationship between internal exposure to uranium and specific causes in a pooled cohort of 29,303 workers employed at three former uranium enrichment facilities in the United States with follow-up through 2011. METHODS: Cause-specific standardized mortality ratios (SMRs) for the full cohort were calculated with the U.S. population as referent. Internal comparison of the dose-response relation between selected outcomes and estimated organ doses was evaluated using regression models. RESULTS: External comparison with the U.S. population showed significantly lower SMRs in most diseases in the pooled cohort. Internal comparison showed positive associations of absorbed organ doses with multiple myeloma, and to a lesser degree with kidney cancer. CONCLUSION: In general, these gaseous diffusion plant workers had significantly lower SMRs than the U.S. POPULATION: The internal comparison however, showed associations between internal organ doses and diseases associated with uranium exposure in previous studies. |
Post-9/11 cancer incidence in World Trade Center-exposed New York City firefighters as compared to a pooled cohort of firefighters from San Francisco, Chicago and Philadelphia (9/11/2001-2009)
Moir W , Zeig-Owens R , Daniels RD , Hall CB , Webber MP , Jaber N , Yiin JH , Schwartz T , Liu X , Vossbrinck M , Kelly K , Prezant DJ . Am J Ind Med 2016 59 (9) 722-30 BACKGROUND: We previously reported a modest excess of cancer in World Trade Center (WTC)-exposed firefighters versus the general population. This study aimed to separate the potential carcinogenic effects of firefighting and WTC exposure by comparing to a cohort of non-WTC-exposed firefighters. METHODS: Relative rates (RRs) for all cancers combined and individual cancer subtypes from 9/11/2001 to 12/31/2009 were modeled using Poisson regression comparing 11,457 WTC-exposed firefighters to 8,220 urban non-WTC-exposed firefighters. RESULTS: Compared with non-WTC-exposed firefighters, there was no difference in the RR of all cancers combined for WTC-exposed firefighters (RR = 0.96, 95%CI: 0.83-1.12). Thyroid cancer was significantly elevated (RR = 3.82, 95%CI: 1.07-20.81) from 2001 to 2009; this was attenuated (RR = 3.43, 95%CI: 0.94-18.94) and non-significant when controlling for possible surveillance bias. Prostate cancer was elevated during the latter half (2005-2009; RR = 1.38, 95%CI: 1.01-1.88). CONCLUSIONS: Further follow-up is needed to assess the relationship between WTC exposure and cancers with longer latency periods. |
Mortality among workers exposed to toluene diisocyanate in the US polyurethane foam industry: Update and exposure-response analyses
Pinkerton LE , Yiin JH , Daniels RD , Fent KW . Am J Ind Med 2016 59 (8) 630-43 BACKGROUND: Mortality among 4,545 toluene diisocyante (TDI)-exposed workers was updated through 2011. The primary outcome of interest was lung cancer. METHODS: Life table analyses, including internal analyses by exposure duration and cumulative TDI exposure, were conducted. RESULTS: Compared with the US population, all cause and all cancer mortality was increased. Lung cancer mortality was increased but was not associated with exposure duration or cumulative TDI exposure. In post hoc analyses, lung cancer mortality was associated with employment duration in finishing jobs, but not in finishing jobs involving cutting polyurethane foam. CONCLUSIONS: Dermal exposure, in contrast to inhalational exposure, to TDI is expected to be greater in finishing jobs and may play a role in the observed increase in lung cancer mortality. Limitations include the lack of smoking data, uncertainty in the exposure estimates, and exposure estimates that reflected inhalational exposure only. Am. J. Ind. Med. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. |
A study update of mortality in workers at a phosphate fertilizer production facility
Yiin JH , Daniels RD , Kubale TL , Dunn KL , Stayner LT . Am J Ind Med 2015 59 (1) 12-22 OBJECTIVE: To evaluate the mortality experience among 3,199 workers employed 1951-1976 at a phosphate fertilizer production plant in central Florida with follow-up through 2011. METHODS: Cause-specific standardized mortality ratios (SMRs) for the full cohort were calculated with the U.S. population as referent. Lung cancer and leukemia risks were further analyzed using conditional logistic regression. RESULTS: The mortality due to all-causes (SMR = 1.07, 95% confidence interval [CI] 1.02-1.13, observed deaths [n] = 1,473), all-cancers (SMR = 1.16, 95%CI 1.06-1.28, n = 431), and a priori outcomes of interests including lung cancer (SMR = 1.32, 95%CI = 1.13-1.53, n = 168) and leukemia (SMR = 1.74, 95%CI = 1.11-2.62, n = 23) were statistically significantly elevated. Regression modeling on employment duration or estimated radiation scores did not show exposure-response relation with lung cancer or leukemia mortality. CONCLUSION: SMR results showed increased lung cancer and leukemia mortality in a full cohort of the phosphate fertilizer production facility. There was, however, no exposure-response relation observed among cases and matched controls. Am. J. Ind. Med. (c) 2015 Wiley Periodicals, Inc. |
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