Purpose: The linear nonthreshold (LNT) model has been used in radiation protection for over 40 years and has been hotly debated. It relies heavily on human epidemiology, with support from ...radiobiology. The scientific underpinnings include NCRP Report No. 136 ('Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation'), UNSCEAR 2000, ICRP Publication 99 (2004) and the National Academies BEIR VII Report (2006). NCRP Scientific Committee 1-25 is reviewing recent epidemiologic studies focusing on dose-response models, including threshold, and the relevance to radiation protection.
Methods and materials: Recent studies after the BEIR VII Report are being critically reviewed and include atomic-bomb survivors, Mayak workers, atomic veterans, populations on the Techa River, U.S. radiological technologists, the U.S. Million Person Study, international workers (INWORKS), Chernobyl cleanup workers, children given computerized tomography scans, and tuberculosis-fluoroscopy patients. Methodologic limitations, dose uncertainties and statistical approaches (and modeling assumptions) are being systematically evaluated.
Results: The review of studies continues and will be published as an NCRP commentary in 2017. Most studies reviewed to date are consistent with a straight-line dose response but there are a few exceptions. In the past, the scientific consensus process has worked in providing practical and prudent guidance. So pragmatic judgment is anticipated. The evaluations are ongoing and the extensive NCRP review process has just begun, so no decisions or recommendations are in stone.
Conclusions: The march of science requires a constant assessment of emerging evidence to provide an optimum, though not necessarily perfect, approach to radiation protection. Alternatives to the LNT model may be forthcoming, e.g. an approach that couples the best epidemiology with biologically-based models of carcinogenesis, focusing on chronic (not acute) exposure circumstances. Currently for the practical purposes of radiation protection, the LNT hypothesis reigns supreme as the best of the rest, but new epidemiology and radiobiology might change these conclusions. Stay tuned!
Understanding the health consequences of exposure to radiation received gradually over time is critically needed. The National Aeronautics and Space Administration (NASA) bases its safety standards ...on the acute exposures received by Japanese atomic bomb survivors. Such a brief exposure differs appreciably from the chronic radiation received during a two to three year mission to Mars. NASA also applies an individual risk-based system for radiation protection that accounts for age, sex, smoking history, and individual life styles. Because the Japanese life span study (LSS) reports women to be at 2 to 3 times greater lifetime risk of developing cancer than men, female astronauts are allowed less time in space. Another concern is the potential behavioral and cognitive impairments from galactic cosmic radiation (GCR) impinging on the nervous system that might jeopardize the mission, and, possibly, lead to dementia later in life. GCR are high-velocity heavy ions traveling through space. There are no human circumstances/analogs similar to GCR that can provide direct information on the possible effects of such high-LET exposure to brain tissue. The MPS provides a more representative group (healthy men and women) for risk estimates than the 1945 Japanese population exposed briefly to the atomic bombs. The permissible career exposure limit set by NASA for each astronaut is a 3% risk of exposure-induced death (REID) from cancer at a 95% confidence level to account for uncertainties in risk projections. Because the MPS is 10 times larger than the LSS, the 95% confidence levels will be narrower and thus allow more time in space, all things being equal. Sex-specific differences in radiation risk can be examined more fully in the MPS with over 250,000 women compared with about 32,000 women in the LSS. Non-cancer outcomes such as neurological disorders also can be evaluated following low-dose rate exposures to high-LET alpha particles. Workers at several nuclear facilities had intakes of radionuclides, such as plutonium, that exposed brain tissue to alpha particles (Helium nuclei) for life. Such workers are being evaluated for mortality from dementia and other motor neuron diseases; can be evaluated for clinically diagnosed incidences of these conditions; and, though challenging, could be interviewed and ask to take cognition tests. Ischemic heart disease is also under study. The MPS, thus, provides another line of human inquiry to assist in decision-making and policy guidance for space missions beyond earth orbit.
These studies were undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on ovarian function and reproductive outcomes. We reviewed the ...frequency of acute ovarian failure, premature menopause, live birth, stillbirth, spontaneous and therapeutic abortion and birth defects in the participants in the Childhood Cancer Survivor Study (CCSS). Acute ovarian failure (AOF) occurred in 6.3% of eligible survivors. Exposure of the ovaries to high-dose radiation (especially over 10 Gy), alkylating agents and procarbazine, at older ages, were significant risk factors for AOF. Premature nonsurgical menopause (PM) occurred in 8% of participants versus 0.8% of siblings (rate ratio = 13.21; 95% CI, 3.26 to 53.51; P < .001). Risk factors for PM included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score, and a diagnosis of Hodgkin's lymphoma. One thousand two hundred twenty-seven male survivors reported they sired 2,323 pregnancies, and 1,915 female survivors reported 4,029 pregnancies. Offspring of women who received uterine radiation doses of more than 5 Gy were more likely to be small for gestational age (birthweight < 10 percentile for gestational age; 18.2% v 7.8%; odds ratio = 4.0; 95% CI, 1.6 to 9.8; P = .003). There were no differences in the proportion of offspring with simple malformations, cytogenetic syndromes, or single-gene defects. These studies demonstrated that women treated with pelvic irradiation and/or increasing alkylating agent doses were at risk for acute ovarian failure, premature menopause, and small-for-gestational-age offspring. There was no evidence for an increased risk of congenital malformations. Survivors should be generally reassured although some women have to consider their potentially shortened fertile life span in making educational and career choices.
Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and ...quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal.
The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautics and Space Administration (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized.
The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure.
The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.
The potential health consequences of the Trinity nuclear weapon test of 16 July 1945 at Alamogordo, New Mexico, are challenging to assess. Population data are available for mortality but not for ...cancer incidence for New Mexico residents for the first 25 y after the test, and the estimates of radiation dose to the nearby population are lower than the cumulative dose received from ubiquitous natural background radiation. Despite the estimates of low population exposures, it is believed by some that cancer rates in counties near the Trinity test site (located in Socorro County) are elevated compared with other locations across the state. Further, there is a concern about adverse pregnancy outcomes and genetic diseases (transgenerational or heritable effects) related to population exposure to fallout radiation. The possibility of an intergenerational effect has long been a concern of exposed populations, e.g., Japanese atomic bomb survivors, survivors of childhood and adolescent cancer, radiation workers, and environmentally exposed groups. In this paper, the likelihood of discernible transgenerational effects is discounted because (1) in all large-scale comprehensive studies of exposed populations, no heritable genetic effects have been demonstrated in children of exposed parents; (2) the distribution of estimated doses from Trinity is much lower than in other studied populations where no transgenerational effects have been observed; and (3) there is no evidence of increased cancer rates among the scientific, military, and professional participants at the Trinity test and at other nuclear weapons tests who received much higher doses than New Mexico residents living downwind of the Trinity site.
From 1986 to 1991, 4831 men from Estonia were sent to clean up radioactively contaminated areas near Chernobyl (Chornobyl). Their cancer incidence during 1986 to 2019 was compared to that of the male ...population of Estonia. The cohort of cleanup workers was linked to national population and cancer registers based on unique personal identification numbers. Nineteen (0.4%) workers could not be traced. A total of 4812 men contributing 120 770 person‐years of follow‐up were eligible for the analyses. Standardized incidence ratios (SIR) and adjusted relative risks (ARR, expressed as ratios of SIRs) with 95% confidence intervals (CI) were calculated. A total of 687 incident cancer cases were registered in the cohort (SIR 1.11, 95% CI 1.03‐1.19). Presumptive radiation‐related cancers combined were in excess, but not when smoking‐ and alcohol‐related cancers were excluded (SIR 0.92, 95% CI 0.71‐1.18). For smoking‐related cancers, the SIR was 1.24 (95% CI 1.13‐1.36) and for alcohol‐related cancer the SIR was 1.53 (95% CI 1.31‐1.75). Less educated workers had a higher risk of all cancers (ARR = 1.21, 95% CI 1.02‐1.44) and smoking‐related cancers (ARR = 1.42, 95% CI 1.14‐1.76). An elevated risk of alcohol‐related cancers was evident 15 to 24 years (vs <15 years) after return from the Chernobyl area. This updated register‐based follow‐up of Chernobyl cleanup workers from Estonia revealed an excess of radiation‐related cancer sites combined, but the excess was not apparent after excluding cancers associated with smoking and alcohol.
What's new?
After the 1986 Chernobyl nuclear reactor explosion, nearly 5000 men from Estonia were sent to clean up the radioactively contaminated areas. Here, the authors present their cancer incidence during 34‐year follow‐up compared with that of the male population of Estonia. This updated register‐based study found no evidence of increased cancer risk due to protracted radiation exposure among the cleanup workers. In contrast, increased risks were apparent for cancer sites related to tobacco smoking and alcohol consumption. Correction added on 24‐June 2023, after first online publication: the What's New? was revised to improve readability
Children with cancer receive mutagenic treatments, which raises concern about the potential transmissibility of germline damage to their offspring. This question has been inadequately studied to date ...because of a lack of detailed individual treatment exposure assessment such as gonadal radiation doses.
Within the Childhood Cancer Survivor Study, we performed a retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female childhood cancer survivors. We quantified chemotherapy with alkylating agents and radiotherapy doses to the testes and ovaries and related these exposures to risk of congenital anomalies using logistic regression.
One hundred twenty-nine children had at least one anomaly (prevalence = 2.7%). For children whose mothers were exposed to radiation or alkylating agents versus neither, the prevalence of anomalies was 3.0% versus 3.5% (P = .51); corresponding figures were 1.9% versus 1.7% (P = .79) for the children of male survivors. Neither ovarian radiation dose (mean, 1.19 Gy; odds ratio OR = 0.59; 95% CI, 0.20 to 1.75 for 2.50+ Gy) nor testicular radiation dose (mean, 0.48 Gy; OR = 1.01; 95% CI, 0.36 to 2.83 for 0.50+ Gy) was related to risk of congenital anomalies. Treatment with alkylating agents also was not significantly associated with anomalies in the children of male or female survivors.
Our findings offer strong evidence that the children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parent's exposure to mutagenic cancer treatments. This information is important for counseling cancer survivors planning to have children.
A critically important gap in knowledge surrounds the health consequences of exposure to radiation received gradually over time. Much is known about the health effects of brief high-dose exposures, ...such as from the atomic bombings in Japan, but the concerns today focus on the frequent low-dose exposures received by members of the public, workers, and, as addressed in this paper, astronauts. Additional guidance is needed by the National Aeronautics and Space Administration (NASA) for planning long-term missions where the rate of radiation exposure is gradual over years and the cumulative amounts high. The direct study of low doses and low-dose rates is of immeasurable value in understanding the possible range of health effects from gradual exposures and in providing guidance for radiation protection, not only of workers and the public but also astronauts. The ongoing Million Person Study (MPS) is 10 times larger than the study of the Japanese atomic bomb survivors of 86,000 survivors with estimated doses. The number of workers with >100 mSv career dose is substantially greater. The large study size, broad range of doses, and long follow-up indicate substantial statistical ability to quantify the risk of exposures that are received gradually over time. The study consists of 360,000 U.S. Department of Energy workers from the Manhattan Project; 150,000 nuclear utility workers from the inception of the nuclear age; 115,000 atomic veterans who participated in above-ground atmospheric tests at the Nevada Test Site and the Bikini and Enewetak Atolls and Johnston Island in the Pacific Proving Grounds (PPG); 250,000 radiologists and medical workers; and 130,000 industrial radiographers. NASA uses an individual risk-based system for radiation protection in contrast to the system of dose limits for occupational exposures used by terrestrial-based organizations. The permissible career exposure limit set by NASA for each astronaut is a 3% risk of exposure-induced death (REID) from cancer at a 95% confidence level to account for uncertainties in risk projections. The large size of the MPS will reduce the uncertainty in the risk estimates, narrowing the 95% confidence interval, and thus allow more time in space for astronauts. Further differences between men and women in their response to radiation can be more fully examined, and non-cancer outcomes, such as neurological disorders and cardiovascular disease, can be evaluated in a way not hitherto possible.
The study of Japanese atomic bomb survivors, exposed briefly to radiation, finds the risk of radiation-induced lung cancer to be nearly three times greater for women than for men. Because protection ...standards for astronauts are based on individual lifetime risk projections, this sex-specific difference limits the time women can spend in space. Populations exposed to chronic or fractionated radiation were evaluated to learn whether similar differences exist when exposures occur gradually over years.
Five occupational cohorts within the Million Person Study of Low-Dose Health Effects (MPS) and a Canadian Fluoroscopy Cohort Study (CFCS) of tuberculosis patients who underwent frequent chest fluoroscopic examinations are evaluated. Included are male and female workers at the Mound nuclear facility, nuclear power plants (NPP), and industrial radiographers (IR). Workers at the Mallinckrodt Chemical Works and military participants at aboveground nuclear weapons tests provide information on the risk among males. Cox proportional hazards and Poisson regression models were used to estimate sex-specific radiation risks for lung cancer and to compare any differences.
Overall, 15,065 lung cancers occurred among the 443,684 subjects studied: 50,111 women and 395,573 men. The mean cumulative dose to the lung was 166.3 mGy (range 6 to 1,055 mGy) with the highest among the TB-fluoroscopy patients (mean 1,055 mGy). Mean lung dose for women in the worker cohorts was generally 4 times lower than for men. Of the 12 estimates of radiation-related risk, only one, for male IRs, showed a significant elevation (ERR 0.09; 95% CI 0.02-0.16, at 100 mGy). In contrast, the dose response for male NPP workers was negative (ERR −0.05; 95% CI −0.10, 0.01, at 100 mGy). Combined, these two cohorts provided little evidence for a radiation effect among males (ERR 0.01; 95% CI −0.04, 0.06, at 100 mGy). There was no significant dose-response among females within any cohort. There was no difference in the sex-specific estimates of lung cancer risk.
There was little evidence that chronic or fractionated exposures increased the risk of lung cancer. There were no differences in the risks of lung cancer between men and women. However, the sex-specific analyses are limited because of small numbers of women and relatively low doses. A more definitive study is ongoing of medical radiation workers which include 85,000 women and 85,000 men (overall mean dose 82 mGy, max 1,140 mGy). Additional understanding will come from the ongoing follow-up of the CFCS.
The Childhood Cancer Survivor Study (CCSS) is a comprehensive multicenter study designed to quantify and better understand the effects of pediatric cancer and its treatment on later health, including ...behavioral and sociodemographic outcomes. The CCSS investigators have published more than 100 articles in the scientific literature related to the study. As with any large cohort study, high standards for methodologic approaches are imperative for valid and generalizable results. In this article we describe methodological issues of study design, exposure assessment, outcome validation, and statistical analysis. METHODS for handling missing data, intrafamily correlation, and competing risks analysis are addressed; each with particular relevance to pediatric cancer survivorship research. Our goal in this article is to provide a resource and reference for other researchers working in the area of long-term cancer survivorship.
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