In its 2012 report on tissue reactions, the International Commission on Radiological Protection (ICRP) made several key assumptions regarding radiation risk to the lens of the eye, including that ...radiation-related minor opacities will progress to become vision-impairing cataracts, that protracted irradiation confers as much risk per unit dose as an acute exposure, and that there is a dose threshold for cataract effects at about 0.5Gy. The few studies available provide only limited support for the ICRP assumption that radiation-related minor opacities are predictive of vision-impairing cataracts; further longitudinal data are clearly needed. In keeping with the ICRP assumption, there is currently no compelling evidence for diminished cataractogenic effects at low dose rates, i.e., the data are compatible with a dose-rate effectiveness factor (DREF) of unity but the uncertainties are large enough that other values of DREF cannot be ruled out. Most available epidemiologic data suggest there is a dose threshold somewhere between several hundred mGy and one Gy for lens opacities. The new studies of medical and occupational exposures that have evaluated groups with low doses tend to confirm there is little or no excess risk at doses under 100mGy, while new studies of interventional cardiologist personnel who often have substantial doses to the lens of the eye have shown elevated opacity risks. Thus occupations that have high lens doses should receive remedial attention to prevent lens opacity risk.
A marked increase in leukemia risks was the first and most striking late effect of radiation exposure seen among the Hiroshima and Nagasaki atomic bomb survivors. This article presents analyses of ...radiation effects on leukemia, lymphoma and multiple myeloma incidence in the Life Span Study cohort of atomic bomb survivors updated 14 years since the last comprehensive report on these malignancies. These analyses make use of tumor- and leukemia-registry based incidence data on 113,011 cohort members with 3.6 million person-years of follow-up from late 1950 through the end of 2001. In addition to a detailed analysis of the excess risk for all leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia (neither of which appear to be radiation-related), we present results for the major hematopoietic malignancy types: acute lymphoblastic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia, adult T-cell leukemia, Hodgkin and non-Hodgkin lymphoma and multiple myeloma. Poisson regression methods were used to characterize the shape of the radiation dose-response relationship and, to the extent the data allowed, to investigate variation in the excess risks with gender, attained age, exposure age and time since exposure. In contrast to the previous report that focused on describing excess absolute rates, we considered both excess absolute rate (EAR) and excess relative risk (ERR) models and found that ERR models can often provide equivalent and sometimes more parsimonious descriptions of the excess risk than EAR models. The leukemia results indicated that there was a nonlinear dose response for leukemias other than chronic lymphocytic leukemia or adult T-cell leukemia, which varied markedly with time and age at exposure, with much of the evidence for this nonlinearity arising from the acute myeloid leukemia risks. Although the leukemia excess risks generally declined with attained age or time since exposure, there was evidence that the radiation-associated excess leukemia risks, especially for acute myeloid leukemia, had persisted throughout the follow-up period out to 55 years after the bombings. As in earlier analyses, there was a weak suggestion of a radiation dose response for non-Hodgkin lymphoma among men, with no indication of such an effect among women. There was no evidence of radiation-associated excess risks for either Hodgkin lymphoma or multiple myeloma.
The prevailing belief for some decades has been that human radiation-related cataract occurs only after relatively high doses; for instance, the ICRP estimates that brief exposures of at least ...0.5–2 Sv are required to cause detectable lens opacities and 5 Sv for vision-impairing cataracts. For protracted exposures, the ICRP estimates the corresponding dose thresholds as 5 Sv and 8 Sv, respectively. However, several studies, especially in the last decade, indicate that radiation-associated opacities occur at much lower doses. Several studies suggest that medical or environmental radiation exposure to the lens confers risk of opacities at doses well under 1 Sv. Among Japanese A-bomb survivors, risks for cataracts necessitating lens surgery were seen at doses under 1 Gy. The confidence interval on the A-bomb dose threshold for cataract surgery prevalence indicated that the data are compatible with a dose threshold ranging from none up to only 0.8 Gy, similar to the dose threshold for minor opacities seen among Chernobyl clean-up workers with primarily protracted exposures. Findings from various studies indicate that radiation risk estimates are probably not due to confounding by other cataract risk factors and that risk is seen after both childhood and adult exposures. The recent data are instigating reassessments of guidelines by various radiation protection bodies regarding permissible levels of radiation to the eye. Among the future epidemiological research directions, the most important research need is for adequate studies of vision-impairing cataract after protracted radiation exposure.
Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of ...contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population‐based case‐control study of women with breast cancer where cases (N = 1,521) had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24–2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR = 1.54, 95% CI 1.18–1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR = 1.50, 95% CI 1.08–2.08; p‐trend = 0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.
What's new?
Do alcohol and smoking contribute to the risk of developing breast cancer … a second time? Both are risk factors for first breast cancer, and this study set out to identify their impact on contralateral breast cancer risk. The authors set up a case‐control study, where cases had developed cancer in both breasts at different times, and controls had developed cancer in only one breast. They found that alcohol use and smoking after first diagnosis did increase the risk of developing cancer in the second breast, and recommending lifestyle changes could reduce their risk.
Exposure to ionizing radiation is ubiquitous, and it is well established that moderate and high doses cause ill-health and can be lethal. The health effects of low doses or low dose-rates of ionizing ...radiation are not so clear. This paper describes a project which sets out to summarize, as a restatement, the natural science evidence base concerning the human health effects of exposure to low-level ionizing radiation. A novel feature, compared to other reviews, is that a series of statements are listed and categorized according to the nature and strength of the evidence that underpins them. The purpose of this restatement is to provide a concise entrée into this vibrant field, pointing the interested reader deeper into the literature when more detail is needed. It is not our purpose to reach conclusions on whether the legal limits on radiation exposures are too high, too low or just right. Our aim is to provide an introduction so that non-specialist individuals in this area (be they policy-makers, disputers of policy, health professionals or students) have a straightforward place to start. The summary restatement of the evidence and an extensively annotated bibliography are provided as appendices in the electronic supplementary material.
Background In utero exposure to radiation is known to increase risks of childhood cancers, and childhood exposure is associated with increased risks of adult-onset cancers. However, little is known ...about whether in utero exposure to radiation increases risks of adult-onset cancers. Methods Solid cancer incidence rates were examined among survivors of the atomic bombings of Hiroshima and Nagasaki who were in utero (n = 2452) or younger than 6 years (n = 15388) at the time of the bombings. Poisson regression was used to estimate and compare the levels and temporal patterns of the radiation-associated excess risks of first primary solid cancers among these survivors at ages 12–55. All statistical tests were two-sided. Results There were 94 eligible cancers in the in utero group and 649 in the early childhood group. The excess relative risk (ERR) increased with dose for both in utero (age 50, ERR = 1.0 per Sv, 95% confidence interval CI = 0.2 to 2.3 per Sv) and early childhood (age 50, ERR = 1.7 per Sv, 95% CI = 1.1 to 2.5 Sv) exposures. The ERR declined (P = .046) with increasing attained age in the combined cohort. Excess absolute rates (EARs) increased markedly with attained age among those exposed in early childhood but exhibited little change in the in utero group. At age 50, the estimated EARs per 10000 person-years per Sv were 6.8 (95% CI = <0 to 49) for those exposed in utero and 56 (95% CI = 36 to 79) for those exposed as young children. Conclusions Both the in utero and early childhood groups exhibited statistically significant dose-related increases in incidence rates of solid cancers. The apparent difference in EARs between the two groups suggests that lifetime risks following in utero exposure may be considerably lower than for early childhood exposure, but further follow-up is needed.
The atomic bomb and other studies have established with certainty that moderate-to-high doses of radiation cause many types of solid cancer and leukemia. Moving down the dose range to the vicinity of ...100-200 mSv, the risks become fuzzy and then unknown at low doses on the order of 10-20 mSv. Nor have low-dose experimental studies provided definitive answers: some have suggested there may be adverse biological effects in the range of 5-50 mSv, while others support a "no risk" interpretation. Epidemiologic data contain intrinsic "noise" (variation by known and unknown factors related to genetics, lifestyle, other environmental exposures, sociodemographics, diagnostic accuracy, etc.) so are generally too insensitive to provide compelling answers in the low-dose range. However, there have been recent provocative reports regarding risk from relatively low-dose occupational and medical radiation exposures that warrant careful consideration. Summaries of the largest studies with low-dose or low dose-rate radiation exposure provide suggestive evidence of risk for solid cancer and stronger evidence for leukemia risk. Recently, interest in health endpoints other than cancer also has risen sharply, in particular the degree of cardiovascular and cataract risk following doses under 1 Sv. Data regarding cardiovascular disease are limited and fuzzy, with suggestions of inconsistencies, and the risk at low doses is essentially unknown. The evidence of cataract risk after low dose-rate exposures among those conducting interventional medical radiological procedures is becoming strong. The magnitude of radiation impacts on human health requires fuller documentation, especially for low-dose or low dose-rate exposures. From the epidemiologic vantage point, this will require longer observation of existing irradiated cohorts and development of new informative cohorts, improved accuracy in dose assessments, more attention to confounding variables, and more biosamples from irradiated groups to enable translational radiobiological studies. Introduction of Radiation Impacts on Human Health (Video 2:02, http://links.lww.com/HP/A35).
The overall aim of this contribution to the 'Second Bill Morgan Memorial Special Issue' is to provide a high-level review of a recent report developed by a Committee for the National Council on ...Radiation Protection and Measurements (NCRP) titled 'Approaches for Integrating Information from Radiation Biology and Epidemiology to Enhance Low-Dose Health Risk Assessment'. It derives from previous NCRP Reports and Commentaries that provide the case for integrating data from radiation biology studies (available and proposed) with epidemiological studies (also available and proposed) to develop Biologically-Based Dose-Response (BBDR) models. In this review, it is proposed for such models to leverage the adverse outcome pathways (AOP) and key events (KE) approach for better characterizing radiation-induced cancers and circulatory disease (as the example for a noncancer outcome). The review discusses the current state of knowledge of mechanisms of carcinogenesis, with an emphasis on radiation-induced cancers, and a similar discussion for circulatory disease. The types of the various informative BBDR models are presented along with a proposed generalized BBDR model for cancer and a more speculative one for circulatory disease. The way forward is presented in a comprehensive discussion of the research needs to address the goal of enhancing health risk assessment of exposures to low doses of radiation. The use of an AOP/KE approach for developing a mechanistic framework for BBDR models of radiation-induced cancer and circulatory disease is considered to be a viable one based upon current knowledge of the mechanisms of formation of these adverse health outcomes and the available technical capabilities and computational advances. The way forward for enhancing low-dose radiation risk estimates will require there to be a tight integration of epidemiology data and radiation biology information to meet the goals of relevance and sensitivity of the adverse health outcomes required for overall health risk assessment at low doses and dose rates.
To examine the incidence of clinically important cataracts in relation to lens radiation doses between 0 and approximately 3 Gy to address risks at relatively low brief doses.
Informed consent was ...obtained, and human subjects procedures were approved by the ethical committee at the Radiation Effects Research Foundation. Cataract surgery incidence was documented for 6066 atomic bomb survivors during 1986-2005. Sixteen risk factors for cataract, such as smoking, hypertension, and corticosteroid use, were not confounders of the radiation effect on the basis of Cox regression analysis. Radiation dose-response analyses were performed for cataract surgery incidence by using Poisson regression analysis, adjusting for demographic variables and diabetes mellitus, and results were expressed as the excess relative risk (ERR) and the excess absolute risk (EAR) (ie, measures of how much radiation multiplies ERR or adds to EAR the risk in the unexposed group).
Of 6066 atomic bomb survivors, 1028 underwent a first cataract surgery during 1986-2005. The estimated threshold dose was 0.50 Gy (95% confidence interval CI: 0.10 Gy, 0.95 Gy) for the ERR model and 0.45 Gy (95% CI: 0.10 Gy, 1.05 Gy) for the EAR model. A linear-quadratic test for upward curvature did not show a significant quadratic effect for either the ERR or EAR model. The linear ERR model for a 70-year-old individual, exposed at age 20 years, showed a 0.32 (95% CI: 0.09, 0.53) corrected excess risk at 1 Gy. The ERR was highest for those who were young at exposure.
These data indicate a radiation effect for vision-impairing cataracts at doses less than 1 Gy. The evidence suggests that dose standards for protection of the eye from brief radiation exposures should be 0.5 Gy or less.
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