Abstract
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.
Applications for fluoropolymers and PFOA include surface coatings for stain, oil, and water resistance on household products, carpets, textiles, and food packaging; personal care products; seals; ...coatings for cables and wires; and construction materials. Since the previous classification of PFOA (as “possibly carcinogenic to humans”, Group 2B) by the IARC Monographs in 2014,2 many new studies have investigated the association between exposure to PFOA and cancer in experimental animals and humans, as well as mechanistic endpoints relevant to the key characteristics of carcinogens. ...PFOA induces oxidative stress, modulates receptor-mediated effects (via PPARα, CAR/PXR, and PPARγ), and alters cell proliferation, cell death, and nutrient and energy supply in human primary cells and experimental systems. For testicular cancer, additional evidence was a positive association in an ecological analysis conducted by the Working Group of available data on orchiectomies from the Veneto region of Italy, and a US study finding no associations.9 For all other cancers, the evidence was “inadequate”, as there were only sporadic positive findings.
Abstract
The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent ...experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert advisory group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs program. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating, and integrating evidence to identify causes of human cancer. The advancements adopted include the strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals, and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention.
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 ...IARCMonographs program.
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.
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.
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.
ObjectivesTo summarise the rationale, workflow and recommendations for the conduct of exposure assessment critiques in key human studies evaluated for International Agency for Research on Cancer ...(IARC) Monographs on the Identification of Carcinogenic Hazards.MethodsApproaches to evaluating exposure assessment quality in human cancer and mechanistic studies were reviewed according to the precepts outlined in the IARC Monographs Preamble, using two agents as case studies. Exposure assessment ‘domains’, that is, salient aspects of exposure assessment for the agent under evaluation, were selected for review across the key human studies.ResultsThe case studies of night shift work (volume 124) and 1,1,1-trichloroethane (volume 130) used a common approach, tailored to the agents’ specific exposure scenarios, to evaluate exposure assessment quality. Based on the experiences of IARC Working Groups to date, the implementation of exposure assessment critique requires the need for agent-specific knowledge, consideration of the validity of time-varying exposure metrics related to duration and intensity, and transparent, concise reviews that prioritise the most important strengths and limitations of exposure assessment methods used in human studies.ConclusionsExposure assessment has not historically been a fully appreciated component for evaluating the quality of epidemiological studies in cancer hazard identification. Exposure assessment critique in key human cancer and mechanistic studies is now an integral part of IARC Monographs evaluations and its conduct will continue to evolve as new agents are evaluated. The approaches identified here should be considered as a potential framework by others when evaluating the exposure assessment component of epidemiological studies for systematic reviews.
Recent animal studies have suggested the potential for wide-ranging health effects resulting from exposure to carbon nanotubes and nanofibers (CNT/F). To date, no studies in the US have directly ...examined the relationship between occupational exposure and potential human health effects.
Our goal was to measure CNT/F exposures among US workers with representative job types, from non-exposed to highly exposed, for an epidemiologic study relating exposure to early biologic effects.
108 participants were enrolled from 12 facilities across the US. Personal, full-shift exposures were assessed based on the mass of elemental carbon (EC) at the respirable and inhalable aerosol particle size fractions, along with quantitatively characterizing CNT/F and estimating particle size via transmission electron microscopy (TEM). Additionally, sputum and dermal samples were collected and analyzed to determine internal exposures and exposures to the hands/wrists.
The mean exposure to EC was 1.00 μg/m3 at the respirable size fraction and 6.22 μg/m3 at the inhalable fraction. Analysis by TEM found a mean exposure of 0.1275 CNT/F structures/cm3, generally to agglomerated materials between 2 and 10 μm. Internal exposures to CNT/F via sputum analysis were confirmed in 18% of participants while ∼70% had positive dermal exposures.
We demonstrated the occurrence of a broad range of exposures to CNT/F within 12 facilities across the US. Analysis of collected sputum indicated internal exposures are currently occurring within the workplace. This is an important first step in determining if exposures in the workforce have any acute or lasting health effects.
Expert Working Groups explicitly describe how they were able—or not—to rule out these sources of error with reasonable confidence, as seen in recent evaluations of night shift work,4 opium ...consumption5 and aniline.6 Many approaches to evaluating the direction and magnitude of biases in observational epidemiology have been described in the scientific literature—some new,7 and some existing for decades.8 To make these methodological developments more easily accessible to those conducting cancer hazard identification, the Monographs programme and the National Cancer Institute’s Division of Cancer Epidemiology and Genetics convened a scientific workshop of global experts in cancer epidemiology and in statistical and epidemiological methodology. ...attendees outlined approaches that researchers could adopt to assess the impacts of each source of bias in their own studies. The workshop materials will result in the publication of a new volume in the IARC Scientific Publications series Statistical Methods in Cancer Research, which includes the landmark publications on cohort and case–control studies authored by Breslow and Day.9 10 The new Scientific Publication, expected in early 2024, will summarise methods for bias assessment to support cancer hazard identification, illustrate these methods with examples and discuss how these methods could also be incorporated into future published studies to better inform cancer hazard and risk assessments. Funding This work was supported by the International Agency for Research on Cancer (IARC) and by the National Cancer Institute’s Intramural Research Program, Division of Cancer Epidemiology and Genetics.
Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals along ...with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up.
Here, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (> 0.5 µg/m
) and Low (< 0.1 µg/m
) inhalable CNT/F exposures in the industrial setting. Peptide biomarker model building and refinement employed linear regression and partial least squared discriminant analyses. Top-ranked peptides were then sequence identified and evaluated for pathological-relevance.
In total, 41 peptides were found to be highly discriminatory after model building with a strong linear correlation to personal CNT/F exposure. The top-five peptide model offered ideal prediction with high accuracy (Q
= 0.99916). Unsupervised validation affirmed 43.5% of the serum peptidomic variance was attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers.
The serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks.
Correspondence to Dr Kaitlin Kelly-Reif, Division of Field Studies and Engineering, National Institute for Occupational Safety and Health, Cincinnati, Ohio, USA; kkelly-reif@cdc.gov The US Radiation ...Exposure Compensation Act (RECA) is a government compensation programme, which provides partial restitution to individuals whose health was affected by nuclear weapons testing or uranium industry employment. Details on cohort inclusion criteria, vital status, mortality ascertainment, outcome definition and standard population rates are reported in a previous study.2 We calculated standardised mortality ratios (SMRs) and corresponding 95% CIs overall and by decade of calendar period (1960–1969, …, 2000–2009, 2010–2016) for silicosis, interstitial pulmonary fibrosis (IPF) and pneumoconiosis, which are compensable for uranium miners under RECA. A recent study from the large international Pooled Uranium Miner Analysis showed that miners first hired 1965 or later experience elevated lung cancer (observed=856, SMR=1.34; 95% CI 1.26 to 1.44).5 Clinical data also indicate that workers employed after 1971 have a high burden of respiratory disease.6 The examination of non-malignant respiratory mortality rates in the Colorado Plateau cohort indicates that uranium mining conditions still cause a considerable health burden to workers that will continue into the foreseeable future.
Studies of uranium miners on the US Colorado Plateau have identified associations between exposure to radon progeny and risk of lung cancer. This study added 15 years of mortality follow-up for the ...4,137 miners (primarily white or American Indian) in the Colorado Plateau cohort. The cohort experienced 209 new lung cancer deaths. For white miners, the standardized mortality ratio for lung cancer compared with the regional population was 3.99 (95% confidence interval: 3.43, 4.62) for the period 1991–2005. For American Indian miners, the lung cancer standardized mortality ratio was 3.27 (95% confidence interval: 2.19, 4.73). These standardized mortality ratios have not declined substantially since the 1980s. Internally standardized rate ratios by radon exposure category over the entire follow-up period are similar to those based on earlier follow-up, although estimates within smoking categories demonstrated improved precision. The apparent interaction between radon and smoking in causing lung cancer remains submultiplicative but greater than additive. Mortality rates from silicosis remain highly elevated in the cohort. Elevated mortality rates were observed from interstitial pulmonary fibrosis, multiple myeloma, and non-Hodgkin lymphoma. Significant trends were observed with increased radon exposure in silicosis and pulmonary fibrosis mortality and in the incidence of diabetes-related end-stage renal disease among white miners.
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