Leveraging Advances in Modern Science to Revitalize Low-Dose Radiation Research in the United States (2022) / Chapter Skim
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From page 127... ...
Section 5.5 provides the timeline and cost estimates for implementing the recommended research agenda, and Section 5.6 compares the committee's recommended agenda to those of other entities. 5.1 LOW-DOSE RADIATION RESEARCH CHALLENGES AND OVERVIEW OF RESEARCH PRIORITIES The committee addressed Charge 2 of its Statement of Task by listing challenges for epidemiological and biological research as well as some that are common to both research approaches (see Box 5.1)
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• Establishment of cause-effect relationships, although an important goal of low-dose radiation epidemiological studies, is often challenged by study design conditions which could result in a number of possible explanations for the observed associations or lack thereof. In the absence of an inte grated mechanistic understanding, epidemiological studies are unable to make strong judgments as to whether an observed association represents a cause-effect relationship between low-dose radiation exposure and the adverse health outcome.
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• Lack of incorporation of measurement and data science with computer tech nology with sufficient sensitivity and specificity to detect the subtle biological and related effects of low-dose and low-dose-rate radiation exposure. a This list was informed by Dale Preston (Hirosoft International)
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The committee recommended research program leverages advances in modern science and sets ambitious goals for revitalized low-dose radiation research in the United States: to improve understanding of adverse human health effects from exposures at doses and dose rates experienced by the U.S. population, to identify mechanisms for induction of these health effects, to develop improved risk models for doses and dose rates at which direct measurement of risks is not possible or limited, and to develop more individualized risk estimates.
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In addition, research in radioecology, in the psychological effects following low-dose radiation exposures, and in radiation risk communication are not included in the recommended strategic agenda but are topics that are worth exploring by the low-dose radiation program in the future.
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populations. E2 Improve estimation of risks for cancer More precisely define health outcomes to enable exclusion of diseases B1–B4; I1–I3 and non-cancer health outcomes from caused by other effects, identifying easily measured signatures low-dose and low-dose-rate external and that can serve as disease surrogates by improving dosimetry and internal radiation exposures.
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I2 Harmonized databases to support Develop accessible databases that document exposure levels, rates, E1–E3; B1–B4 biological and epidemiological studies. types, and durations as well as cell, molecular, and health outcomes for human populations and experimental models.
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Scientific and Decision-Making Value Powerful analytical tools are now available or are being developed that allow more accurate measurement of radiation exposures and exposure rates and more precise definition of the adverse health effects that may arise due to radiation exposures. Application of these tools in epidemiological studies of human populations will improve investigations of adverse health effects that may be caused by low-dose and low-dose-rate exposures.
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. Current Status and Promising Research Directions Epidemiological studies aiming to directly quantify the adverse health effects that result from low-dose and low-dose-rate radiation exposures, either internal or external, will require careful selection and detailed characterization of study populations that allow examination of lifetime risks of radiation exposures.
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for disease occurrence needed for low-dose and low-dose-rate epidemiological studies requires significant effort and resources. However, assembly of informative, new cohorts may become feasible in the future by employing more efficient sampling methods and by taking advan tage of more precise information about radiation exposures and disease phenotypes that inform on etiology that is expected to be captured in future, computationally accessible electronic medical records (EMRs)
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, above, is the issue of confounding. Without the benefit of random assignment, comparison groups in epidemiological studies may differ with respect to factors other than radiation exposure.
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They may quantify individual characteristics (e.g., genetic, epigenetic, and im mune status) that may influence risk of developing adverse health outcomes from low-dose and low-dose-rate radiation exposures.
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Even less is known about the levels of risk for health outcomes other than cancer, including cardiovascular disease, neurological disorders, immune dysfunction, cataracts, and heritable genetic effects. However, if such risks exist at low doses and dose rates, they could lead to substantial changes in risk-benefit analyses for activities that involve low-dose radiation exposures.
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. Evidence from a range of exposure scenarios at higher doses consistently demonstrates elevated cancer risks for nearly all tissues based on data from the atomic bombing survivors (Grant et al., 2017)
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, ideally with respect to factors relevant to etiology and that are not influenced by treatment strategies that may change over time or with economic status. Quantitative health outcomes and molecular surrogates thereof that are suggested by epidemiological studies at higher doses or that have been shown in laboratory model studies to be related to low-dose and low-dose-rate radiation exposure might be given special attention.
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Scientific and Decision-Making Value Several factors may influence an individual's sensitivity to radiation and therefore need to be considered in risk assessment and risk management. Age at exposure has been shown to modify the radiation dose-response relationship for some cancer types.
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Variation in individual response to radiation is a topic of growing importance for radiological protection (Rajaraman et al., 2018; Wojcik et al., 2018) and of an ongoing ICRP task group.9 Current Status and Promising Research Directions Evidence for inherited genetic susceptibility to radiation response derives largely from rare genetic syndromes in which individuals demonstrate hypersensitivity to the killing effects of radiation and frequently have increased risk for developing cancer, such as ataxia-telangiectasia, Nijmegen breakage syndrome, and others (Pollard and Gatti, 2009)
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It is currently also unclear if the immunological changes following low-dose radiation exposures actually link to the same long-term and late clinical disease outcomes as high-dose radiation exposures or if other outcomes are more relevant (Boerma et al., 2022)
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. Whether these findings are consistent for tobacco and radiation exposures on other outcomes also associated with tobacco exposure (e.g., bladder cancer and cardiovascular disease)
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Laboratory model-based studies tend to be better controlled, adequately statistically powered, and less prone to confounding, therefore substantially strengthening the evidence for disease causation and the underlying dose-response relationships, provided they accurately model the disease pathogenesis following irradiation. The following sections suggest several aspects of mechanism-based biological research that may increase understanding of how low-dose and low-dose-rate radiation exposures lead to adverse health effects, including development of improved laboratory models (see Section 5.3.1)
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Extrapolation from experimental data to possible effects in humans is considered more reliable when similar molecular responses and/or outcomes are observed in a variety of model systems. Integration of the information gained from laboratory models and from epidemiological studies will improve understanding of the mechanisms underlying low-dose and low-dose-rate radiation-induced adverse health outcomes, improve risk estimates for the low-dose and low-dose-rate exposures experienced by the U.S.
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Processes that appear important can then be promoted for assessment in animal models and eventually for association with radiation exposure in epidemiological studies. Mice are the animal species most commonly used for studies of physiology and disease formation, and several strains have been exceedingly well characterized biologically and genetically.
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