The Future of Low Dose Radiation Research in the United States Proceedings of a Symposium (2019) / Chapter Skim
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4 Current and Future Directions of Low Dose Radiation Research
4 Current and Future Directions of Low Dose Radiation Research
Pages 35-58
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From page 35... ...
However, many have questioned whether epidemiology has reached its limit in characterizing disease risks at low doses of radiation because often the background levels of the same diseases are high and because risks at low levels of radiation are expected to be low. A new era of large-scale radiation epidemiology studies of medically, environmentally, and occupationally exposed populations has improved our understanding of risks at low doses of radiation (Kitahara et al., 2015)
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Dr. Bob Ullrich provided additional explanations of why low dose radiation risk studies using the RERF cohorts are difficult.
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Dr. Ullrich noted that continuing follow-up of the atomic bombing survivors offers additional opportunities to refine site-specific cancer risk estimates and to understand the joint effects of radiation and other factors on cancer risk, but also to produce new knowledge as the time of followup and statistical power increase.
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From page 38... ...
He noted that the launching of some of the major occupational studies of radiation workers occurred with the anticipation that potential risks, if any, could not be revealed using these study designs. That did not end up being the case and, instead, occupational studies proved useful in quantifying the risks associated with protracted radiation exposures and can help strengthen the foundation for radiation protection standards for millions of workers worldwide who are externally exposed to ionizing radiation on the job.
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These studies generally involve unselected populations that include men and women of all ages who typically received low and often chronic exposures. There are several studies of populations with environmental radiation exposures for which individual dose estimates are available.
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nuclear workers Cancer mortality 119,195 10,877 20 mSv 0.01 –0.02 to 0.05 Schubauer-Berigan et al., 2015 UK national registry Cancer incidence 174,451 11,133 25 mSv 0.03 0.004 to 0.05 Muirhead et al., 2009 of radiation workers French nuclear Cancer mortality 59,004 2,536 26 mSv 0.04 –0.04 to 0.13* Fournier et al., 2016 workers INWORKS Cancer mortality 308,297 17,957 21 mGy 0.05 0.018 to 0.079*
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summarized studies on medically exposed cohorts and their contributions toward clarifying long-term health risks of protracted radiation exposures from diagnostic medical imaging procedures. She noted that historical cohort studies from the 1910s to the 1960s such as the Massachusetts and Canadian fluoroscopy cohorts showed increases in breast cancer risk among women exposed repeatedly over many years to medical radiation for tuberculosis (Boice et al., 1991; Howe, 1995; Howe and McLaughlin, 1996)
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Utah Fallout Case-Control Leukemia 939 4,302 2.9 cases 4.5 (–0.4; 14) Stevens et al., 1990 2.7 controls Nuclear Power Plant Accidents Three Mile Island Cohort Solid incidence 1,643 21,494 0 –1 (–1; 30)
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Nair et al., 2009 Taiwan Buildings Cohort Cancer 117 6,242 48 0.19 (0.01; 0.31) Hwang et al., 2008 NOTE: CI = confidence interval; ERR = excess relative risk.
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Dr. Berrington de González explained that this new era of epidemiological studies of low dose radiation facilitated by electronic record linkage and pooling of cohorts is promising in addressing critical gaps in knowledge of the long-term health risks of low dose radiation.
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DOE's low dose radiation research program supported almost exclusively radiation biology research.
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. The large investments in animal radiation research and the increasing interest in low dose radiation studies have stimulated recent efforts to archive data and tissue samples around the world and make them accessible 3 SCID mice are immunodeficient mice that are able to accept human hematopoietic stem cells harvested from human bone marrow or thymus.
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Dr. Woloschak noted that the increasing sensitivity and reliability of techniques in biology and the increasing ability to produce different radiation doses, dose rates, and radiation qualities in experimental designs will help enhance findings in low dose radiation research.
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Incorporation of state-of-the-art approaches and models into low dose radiation research offers exciting opportunities to engage scientists in multidisciplinary research and to make breakthroughs in a variety of areas, from basic mechanistic science to practical applications including risk estimation and potential targets for risk reduction. 4.2.3 Epigenetic Alterations from Low Dose Radiation Dr.
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presents his laboratory's work on epigenetic alterations following low dose radiation exposures to the Agouti viable yellow (Avy) isogenic strain of mice.
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• Is the linear no-threshold model potentially inappropriate for esti mating human risk from low doses of ionizing radiation? 4.3 NEW DIRECTIONS This section summarizes presentations that took place at the symposium on scientific advances and emerging analytical technologies that have the potential to revolutionize radiation research and provide important insights about the causality of health risks associated with low dose and low dose rate radiation exposures.
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This roadmap took into account factors such as assay reproducibility, sensitivity, and specificity for radiation exposure. It was then used to summarize the current status of proposed biomarkers for epidemiological studies investigating low dose health effects.
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Dr. Gray noted that most of the above-mentioned technologies have been applied to human tissues and can be considered for use in the assessment of radiation health effects.
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presenting on technological advancements that could be incorporated in low dose radiation research. Seated at the table from left to right are Dr.
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Dr. Gawad said that initial work is needed to see if single-cell genomics is currently sensitive enough to detect changes induced by exposure to low doses of mutagens, such as low dose radiation.
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Dr. Formenti noted that the abscopal effect opens the door for research in the ability of radiotherapy to enhance responses to immunotherapy by "turning the tumor into an individualized cancer vaccine." Experiments in syngeneic mouse models7 that mimic the setting of advanced human cancers have demonstrated promising outcomes of combining radiation therapy with immunotherapy (Demaria et al., 2005)
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For instance, it is unknown whether scattered dose to the rest of the body following radiation therapy contributes to systemic effects.
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Dr. Blakely and colleagues see several opportunities for studying the effects of low dose radiation on the microbiome: • To identify radiation biomarkers that assess levels and types of radiation exposure; • To identify host gene, protein, and microbial targets for develop ment of medical treatments; • To provide the evidence needed to predict disease risk after radia tion exposure and by incorporating individual variability in genes, environment, and lifestyle for each person; and • To define the mechanism by which radiation exposure affects health risk using multi-scale and multi-omics "systems biology" approaches across different model systems.
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58 THE FUTURE OF LOW DOSE RADIATION RESEARCH Recognizing the complex interplay between host genetics and exposures on the microbial and metabolic composition of the gut, researchers at Lawrence Berkeley National Laboratory have used a population-based mouse model known as the "Collaborative Cross" (Mao et al., 2015; Snijders et al., 2016) to start answering questions about the mediating effect of the microbiome on radiation exposure–associated immune sensitivity.
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