The study of low dose and low-dose rate exposure is of immeasurable value in understanding the possible range of health effects from prolonged exposures to radiation. The Million Person Study (MPS) ...of low-dose health effects was designed to evaluate radiation risks among healthy American workers and veterans who are more representative of today's populations than are the Japanese atomic bomb survivors exposed briefly to high-dose radiation in 1945. A million persons were needed for statistical reasons to evaluate low-dose and dose-rate effects, rare cancers, intakes of radioactive elements, and differences in risks between women and men.
The MPS consists of five categories of workers and veterans exposed to radiation from 1939 to the present. The U.S. Department of Energy (DOE) Health and Mortality study began over 40 years ago and is the source of ∼360,000 workers. Over 25 years ago, the National Cancer Institute (NCI) collaborated with the U.S. Nuclear Regulatory Commission (NRC) to effectively create a cohort of nuclear power plant workers (∼150,000) and industrial radiographers (∼130,000). For over 30 years, the Department of Defense (DoD) collected data on aboveground nuclear weapons test participants (∼115,000). At the request of NCI in 1978, Landauer, Inc., (Glenwood, IL) saved their dosimetry databases which became the source of a cohort of ∼250,000 medical and other workers.
Overall, 29 individual cohorts comprise the MPS of which 21 have been or are under active study (∼810,000 persons). The remaining eight cohorts (∼190,000 persons) will be studied as resources become available. The MPS is a national effort with critical support from the NRC, DOE, National Aeronautics and Space Administration (NASA), DoD, NCI, the Centers for Disease Control and Prevention (CDC), the Environmental Protection Agency (EPA), Landauer, Inc., and national laboratories.
The MPS is designed to address the major unanswered question in radiation risk understanding: What is the level of health effects when exposure is gradual over time and not delivered briefly. The MPS will provide scientific understandings of prolonged exposure which will improve guidelines to protect workers and the public; improve compensation schemes for workers, veterans and the public; provide guidance for policy and decision makers; and provide evidence for or against the continued use of the linear nonthreshold dose-response model in radiation protection.
Mortality was studied in a cohort of 4831 men from Estonia who participated in the environmental cleanup of the radioactively contaminated areas around Chernobyl in 1986–1991. Their mortality in ...1986–2020 was compared with the mortality in the Estonian male population. A total of 1503 deaths were registered among the 4812 traced men. The all-cause standardized mortality ratio (SMR) was 1.04 (95% CI 0.99–1.09). All-cancer mortality was elevated (SMR 1.16, 95% CI 1.03–1.28). Radiation-related cancers were in excess (SMR 1.20, 95% CI 1.03–1.36); however, the excesses could be attributed to tobacco and alcohol consumption. For smoking-related cancers, the SMR was 1.20 (95% CI 1.06–1.35) and for alcohol-related cancers the SMR was 1.56 (95% CI 1.26–1.86). Adjusted relative risks (ARR) of all-cause mortality were increased among workers who stayed in the Chernobyl area ≥ 92 days (ARR 1.20, 95% CI 1.08–1.34), were of non-Estonian ethnicity (ARR 1.33, 95% CI 1.19–1.47) or had lower (basic or less) education (ARR 1.63, 95% CI 1.45–1.83). Suicide mortality was increased (SMR 1.31, 95% CI 1.05–1.56), most notably among men with lower education (ARR 2.24, 95% CI 1.42–3.53). Our findings provide additional evidence that unhealthy behaviors such as alcohol and smoking play an important role in shaping cancer mortality patterns among Estonian Chernobyl cleanup workers. The excess number of suicides suggests long-term psychiatric and substance use problems tied to Chernobyl-related stressors, i.e., the psychosocial impact was greater than any direct carcinogenic effect of low-dose radiation.
Summary Background The reproductive implications of mutagenic treatments given to children with cancer are not clear. By studying the risk of untoward pregnancy outcomes, we indirectly assessed the ...risk of transmission of germline damage to the offspring of survivors of childhood cancer who were given radiotherapy and chemotherapy. Methods We did a retrospective cohort analysis, within the Childhood Cancer Survivor Study (CCSS), of the risk of stillbirth and neonatal death among the offspring of men and women who had survived childhood cancer. Patients in CCSS were younger than 21 years at initial diagnosis of an eligible cancer, were treated at 25 US institutions and one Canadian institution, and had survived for at least 5 years after diagnosis. We quantified the chemotherapy given to patients, and the preconception radiation doses to the testes, ovaries, uterus, and pituitary gland, and related these to the risk of stillbirth or neonatal death using Poisson regression analysis. Findings Among 1148 men and 1657 women who had survived childhood cancer, there were 4946 pregnancies. Irradiation of the testes (16 1% of 1270; adjusted relative risk 0·8 95% CI 0·4–1·6; mean dose 0·53 Gy SD 1·40) and pituitary gland (17 3% of 510, 1·1 0·5–2·4 for more than 20·00 Gy; mean dose 10·20 Gy 13·0 for women), and chemotherapy with alkylating drugs (26 2% of 1195 women, 0·9 0·5–1·5; ten 1% of 732 men, 1·2 0·5–2·5) were not associated with an increased risk of stillbirth or neonatal death. Uterine and ovarian irradiation significantly increased risk of stillbirth and neonatal death at doses greater than 10·00 Gy (five 18% of 28, 9·1 3·4–24·6). For girls treated before menarche, irradiation of the uterus and ovaries at doses as low as 1·00–2·49 Gy significantly increased the risk of stillbirth or neonatal death (three 4% of 69, 4·7 1·2–19·0). Interpretation Our findings do not support concern about heritable genetic changes affecting the risk of stillbirth and neonatal death in the offspring of men exposed to gonadal irradiation. However, uterine and ovarian irradiation had serious adverse effects on the offspring that were probably related to uterine damage. Careful management is warranted of pregnancies in women given high doses of pelvic irradiation before puberty. Funding Westlakes Research Institute, National Cancer Institute, and Children's Cancer Research Fund.
Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide ...and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.
Background: Although second primary cancers are a leading cause of death among men with testicular cancer, few studies have quantified risks among long-term survivors. Methods: Within 14 ...population-based tumor registries in Europe and North America (1943–2001), we identified 40 576 1-year survivors of testicular cancer and ascertained data on any new incident solid tumors among these patients. We used Poisson regression analysis to model relative risks (RRs) and excess absolute risks (EARs) of second solid cancers. All statistical tests were two-sided. Results: A total of 2285 second solid cancers were reported in the cohort. The relative risk and EAR decreased with increasing age at testicular cancer diagnosis (P<.001); the EAR increased with attained age (P<.001) but the excess RR decreased. Among 10-year survivors diagnosed with testicular cancer at age 35 years, the risk of developing a second solid tumor was increased (RR = 1.9, 95% confidence interval CI = 1.8 to 2.1). Risk remained statistically significantly elevated for 35 years (RR = 1.7, 95% CI = 1.5 to 2.0; P<.001). We observed statistically significantly elevated risks, for the first time, for cancers of the pleura (malignant mesothelioma; RR = 3.4, 95% CI = 1.7 to 5.9) and esophagus (RR = 1.7, 95% CI = 1.0 to 2.6). Cancers of the lung (RR = 1.5, 95% CI = 1.2 to 1.7), colon (RR = 2.0, 95% CI = 1.7 to 2.5), bladder (RR = 2.7, 95% CI = 2.2 to 3.1), pancreas (RR = 3.6, 95% CI = 2.8 to 4.6), and stomach (RR = 4.0, 95% CI = 3.2 to 4.8) accounted for almost 60% of the total excess. Overall patterns were similar for seminoma and nonseminoma patients, with lower risks observed for nonseminoma patients treated after 1975. Statistically significantly increased risks of solid cancers were observed among patients treated with radiotherapy alone (RR = 2.0, 95% CI = 1.9 to 2.2), chemotherapy alone (RR = 1.8, 95% CI = 1.3 to 2.5), and both (RR = 2.9, 95% CI = 1.9 to 4.2). For patients diagnosed with seminomas or nonseminomatous tumors at age 35 years, cumulative risks of solid cancer 40 years later (i.e., to age 75 years) were 36% and 31%, respectively, compared with 23% for the general population. Conclusions: Testicular cancer survivors are at statistically significantly increased risk of solid tumors for at least 35 years after treatment. Young patients may experience high levels of risk as they reach older ages. The statistically significantly increased risk of malignant mesothelioma in testicular cancer survivors has, to our knowledge, not been observed previously in a cohort of patients treated with radiotherapy.
Radiation is one of the most important stressors related to missions in space beyond Earth’s orbit. Epidemiologic studies of exposed workers have reported elevated rates of Parkinson’s disease. The ...importance of cognitive dysfunction related to low-dose rate radiation in humans is not defined. A meta-analysis was conducted of six cohorts in the Million Person Study (MPS) of low-dose health effects to learn whether there is consistent evidence that Parkinson’s disease is associated with radiation dose to brain.
The MPS evaluates all causes of death among U.S. radiation workers and veterans, including Parkinson’s disease. Systematic and consistent methods are applied to study all categories of workers including medical radiation workers, industrial radiographers, nuclear power plant workers, atomic veterans, and Manhattan Projects workers at the Los Alamos National Laboratory and at Rocky Flats. Consistent methods for all cohorts are used to estimate organ-specific doses and to obtain vital status and cause of death.
The meta-analysis include 6 cohorts within the MPS, consisting of 517,608 workers and 17,219,001 person-years of observation. The mean dose to brain ranged from 6.9 to 47.6 mGy and the maximum dose from 0.76 to 2.7 Gy. Five of the 6 cohorts revealed positive associations with Parkinson’s disease. The overall summary estimate from the meta-analysis was statistically significant based on 1573 deaths due to Parkinson’s disease. The summary excess relative risk at 100 mGy was 0.17 (95% CI: 0.05; 0.29).
Parkinson’s disease was positively associated with radiation in the MPS cohorts indicating the need for careful evaluation as to causality in other studies, delineation of possible mechanisms, and assessing possible implications for space travel as well as radiation protection guidance for terrestrial workers.
Background: Many women develop breast cancer after treatment for Hodgkin lymphoma (HL) at a young age. We estimated this future risk, taking into account age and calendar year of HL diagnosis, HL ...treatment information, population breast cancer incidence rates, and competing causes of death. Methods: Relative risks of breast cancer for categories defined by radiation dose to the chest (0, 20–<40 Gy, or ≥40 Gy) and use of alkylating agents (yes or no) were estimated from a case–control study conducted within an international population-based cohort of 3817 female 1-year survivors of HL diagnosed at age 30 years or younger from January 1, 1965, through December 31, 1994. To compute cumulative absolute risks of breast cancer, we used modified standardized incidence ratios to relate cohort breast cancer risks to those in the general population, enabling application of population-based breast cancer rates, and we allowed for competing risks by using population-based mortality rates in female HL survivors. Results: Cumulative absolute risks of breast cancer increased with age at end of follow-up, time since HL diagnosis, and radiation dose. For an HL survivor who was treated at age 25 years with a chest radiation dose of at least 40 Gy without alkylating agents, estimated cumulative absolute risks of breast cancer by age 35, 45, and 55 years were 1.4% (95% confidence interval CI = 0.9% to 2.1%), 11.1% (95% CI = 7.4% to 16.3%), and 29.0% (95% CI = 20.2% to 40.1%), respectively. Cumulative absolute risks were lower in women treated with alkylating agents. Conclusions: Breast cancer projections varied considerably by type of HL therapy, time since HL diagnosis, and age at end of follow-up. These estimates are applicable to HL survivors treated with regimens of the past and can be used to counsel such patients and plan management and preventive strategies. Projections should be used with caution, however, in patients treated with more recent approaches, including limited-field radiotherapy and/or ovary-sparing chemotherapy.
Estimates of radiation risks following prolonged exposures at low doses and low-dose rates are uncertain. Medical radiation workers are a major component of the Million Person Study (MPS) of low-dose ...health effects. Annual personal dose equivalents, H
P
(10), for individual workers are available to facilitate dose-response analyses for lung cancer, leukemia, ischemic heart disease (IHD) and other causes of death.
The Landauer, Inc. dosimetry database identified 109,019 medical and associated radiation workers first monitored 1965-1994. Vital status and cause of death were determined through 2016. Mean absorbed doses to red bone marrow (RBM), lung, heart, and other organs were estimated by adjusting the recorded H
P
(10) for each worker by scaling factors, accounting for exposure geometry, the energy of the incident photon radiation, sex of the worker and whether an apron was worn. There were 4 exposure scenarios: general radiology characterized by low-energy x-ray exposure with no lead apron use, interventional radiologists/cardiologists who wore aprons, nuclear medicine personnel and radiation oncologists exposed to high-energy photon radiation, and other workers. Standardized mortality ratio (SMR) analyses were performed. Cox proportional hazards models were used to estimate organ-specific radiation risks.
Overall, 11,433 deaths occurred (SMR 0.60; 95%CI 0.59,0.61), 126 from leukemia other than chronic lymphocytic leukemia (CLL), 850 from lung cancer, and 1654 from IHD. The mean duration of monitoring was 23.7 y. The excess relative rate (ERR) per 100 mGy was estimated as 0.10 (95% CI −0.34, 0.54) for leukemia other than CLL, 0.15 (0.02, 0.27) for lung cancer, and −0.10 (-0.27, 0.06) for IHD. The ERR for lung cancer was 0.16 (0.01, 0.32) among the 55,218 male workers and 0.09 (-0.19, 0.36) among the 53,801 female workers; a difference that was not statistically significant (p-value = 0.23).
Medical radiation workers were at increased risk for lung cancer that was higher among men than women, although this difference was not statistically significant. In contrast, the study of Japanese atomic bomb survivors exposed briefly to radiation in 1945 found females to be nearly 3 times the radiation risk of lung cancer compared with males on a relative scale. For medical workers, there were no statistically significant radiation associations with leukemia excluding CLL, IHD or other specific causes of death. Combining these data with other cohorts within the MPS, such as nuclear power plant workers and nuclear submariners, will enable more precise estimates of radiation risks at relatively low cumulative doses.
The National Council on Radiation Protection and Measurements' (NCRP) congressional charter aligns with our vision for the future: to improve radiation protection for the public and workers. This ...vision is embodied within NCRP's ongoing initiatives: preparedness for nuclear terrorism, increasing the number of radiation professionals critically needed for the nation, providing new guidance for comprehensive radiation protection in the United States, addressing the protection issues surrounding the ever-increasing use of ionizing radiation in medicine (the focus of this year's annual meeting), assessing radiation doses to aircrew related to higher altitude and longer flights, providing guidance on emerging radiation issues such as the radioactive waste from hydraulic fracturing, focusing on difficult issues such as high-level waste management, and providing better estimates of radiation risks at low doses within the framework of the Million Person Study of Low-Dose Radiation Health Effects. Cutting-edge initiatives included a reevaluation of the science behind recommendations for lens of the eye dose, recommendations for emergency responders on dosimetry after a major radiological incident, guidance to the National Aeronautics and Space Administration with regard to possible central nervous system effects from galactic cosmic rays (the high-energy, high-mass ions bounding through space), reevaluating the population exposure to medical radiation, and addressing whether the linear no-threshold model is still the best available for purposes of radiation protection (not for risk assessment). To address these initiatives and goals, NCRP has seven program area committees on biology and epidemiology, operational concerns, emergency response and preparedness, medicine, environmental issues and waste management, dosimetry, and communications. The NCRP vision for the future will continue and increase under the leadership of President-Elect Dr. Kathryn D. Held (Massachusetts General Hospital and Harvard Medical School, and current NCRP executive director and chief science officer). The NCRP quest to improve radiation protection for the public is hindered only by limited resources, both human capital and financial.
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