Radiation Carcinogenesis Risk Assessments for Never-smokers.
ABSTRACT Cigarette smoking, which is presently associated with more than 20% of adult deaths in the United States, is a large confounder to radiation risk estimates derived from epidemiology data. Astronauts and other exposed groups are classified as never-smokers (NS), defined as lifetime use of less than 100 cigarettes. In the past, radiation risk estimates have been made using average U.S. population rates for cancer and all causes of death, which may lead to overestimation of radiation risks for NS. In this report, age- and gender-specific radiation carcinogenesis risk calculations for NS and the average U.S. population are compared. Lung is the major tissue site for smoking and radiation-related cancer. However, other radiogenic cancers where tobacco has been shown to increase population cancer rates are esophagus, oral cavity, salivary gland, bladder, stomach, liver, colorectal, and leukemia. After adjusting U.S. cancer rates to remove smoking effects, radiation risks for lung and other cancers were estimated using the multiplicative risk model and a mixture model, with weighted contributions for additive and multiplicative risk transfer. Radiation mortality risks for NS were reduced compared to the average U.S. population by more than 20% and 50% in the mixture model and multiplicative transfer models, respectively. The authors discuss possible mechanisms of cancer risks from radiation and tobacco that suggest multiplicative effects could occur. These results suggest that improved understanding of possible synergisms between cancer initiators and promoters, such as radiation and tobacco, would greatly improve risk estimates and reduce uncertainties for differentially exposed groups, including NS.
- SourceAvailable from: Francis A Cucinotta
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- "). DEVCAN provides age, sex and tissue specific incidence and mortality data to ages 95+. Corrections for never-smokers for cancer and circulatory risks were made as described previously (Cucinotta et al., 2013a, 2012). "
ABSTRACT: The prediction of the risks of cancer and other late effects from space radiation exposure carries large uncertainties mostly due to the lack of information on the risks from high charge and energy (HZE) particles and other high linear energy transfer (LET) radiation. In our recent work new methods were used to consider NASA's requirement to protect against the acceptable risk of no more than 3% probability of cancer fatality estimated at the 95% confidence level. Because it is not possible that a zero-level of uncertainty could be achieved, we suggest that an acceptable uncertainty level should be defined in relationship to a probability distribution function (PDF) that only suffers from modest skewness with higher uncertainty allowed for a normal PDF. In this paper, we evaluate PDFs and the number or "safe days" in space, which are defined as the mission length where risk limits are not exceeded, for several mission scenarios at different acceptable levels of uncertainty. In addition, we briefly discuss several important issues in risk assessment including non-cancer effects, the distinct tumor spectra and lethality found in animal experiments for HZE particles compared to background or low LET radiation associated tumors, and the possibility of non-targeted effects (NTE) modifying low dose responses and increasing relative biological effectiveness (RBE) factors for tumor induction. Each of these issues skew uncertainty distributions to higher fatality probabilities with the potential to increase central values of risk estimates in the future. Therefore they will require significant research efforts to support space exploration within acceptable levels of risk and uncertainty. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.Life sciences and space research 04/2015; 5. DOI:10.1016/j.lssr.2015.04.002
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- "Studies in lung tissue are of significance as this organ is the first target for environmental alpha particle emitters such as uranium and radon, which are responsible for a significant fraction of lung cancer incidence in non-smokers . For astronauts, lung cancer development poses a significant risk for death as a consequence of extended space missions . Additionally, the radiosensitivity of this organ is dose-limiting for radiation therapy and a source for acute and long-term complications in the treatment of multiple thoracic cancers , . "
ABSTRACT: We report the functional and temporal relationship between cellular phenotypes such as oxidative stress, p38MAPK-dependent responses and genomic instability persisting in the progeny of cells exposed to sparsely ionizing low-Linear Energy Transfer (LET) radiation such as X-rays or high-charge and high-energy (HZE) particle high-LET radiation such as 56Fe ions. We found that exposure to low and high-LET radiation increased reactive oxygen species (ROS) levels as a threshold-like response induced independently of radiation quality and dose. This response was sustained for two weeks, which is the period of time when genomic instability is evidenced by increased micronucleus formation frequency and DNA damage associated foci. Indicators for another persisting response sharing phenotypes with stress-induced senescence, including beta galactosidase induction, increased nuclear size, p38MAPK activation and IL-8 production, were induced in the absence of cell proliferation arrest during the first, but not the second week following exposure to high-LET radiation. This response was driven by a p38MAPK-dependent mechanism and was affected by radiation quality and dose. This stress response and elevation of ROS affected genomic instability by distinct pathways. Through interference with p38MAPK activity, we show that radiation-induced stress phenotypes promote genomic instability. In contrast, exposure to physiologically relevant doses of hydrogen peroxide or increasing endogenous ROS levels with a catalase inhibitor reduced the level of genomic instability. Our results implicate persistently elevated ROS following exposure to radiation as a factor contributing to genome stabilization.PLoS ONE 10/2014; 9(10):e108234. DOI:10.1371/journal.pone.0108234 · 3.23 Impact Factor
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ABSTRACT: The number of individuals exposed to particle radiations in cancer treatment worldwide is increasing rapidly, and space agencies are developing plans for long duration, deep space missions in which humans could be exposed to significant levels of radiation from charged particles. Hence, the NCRP 47th Annual Meeting on "Scientific and Policy Challenges of Particle Radiations in Medical Therapy and Space Missions" was a timely opportunity to showcase the current scientific knowledge regarding charged particles, enhance cross-fertilization between the oncology and space scientific communities, and identify common needs and challenges to both communities as well as ways to address those challenges. This issue of Health Physics contains papers from talks presented at that meeting and highlights provocative questions and the ample opportunities for synergism between space and particle-therapy research to further understanding of the biological impacts of particle radiations.Health physics 11/2012; 103(5):681-4. DOI:10.1097/HP.0b013e318264b2f5 · 0.77 Impact Factor