Radon and Leukemia in the Danish Study: Another Source of Dose

Harley, Naomi H.; Robbins, Elliott

doi:10.1097/hp.0b013e3181ad8018

Cited by 28 publications

(22 citation statements)

References 19 publications

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“…For example, progenitor cells in the less exposed neighborhood of the investigated part of the epithelium can support the maintenance of cell count by proliferating and migrating into the highly exposed area. Furthermore, stem cells from bone marrow possibly present in the bronchial epithelium (Harley and Robbins 2009;Massberg et al 2007) can also help tissue maintenance.…”

Section: Area Ratio (%)mentioning

confidence: 99%

Mutation induction by inhaled radon progeny modeled at the tissue level

Madas

Balásházy

2011

Radiat Environ Biophys

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The observable responses of living systems to ionizing radiation depend on the level of biological organization studied. Understanding the relationships between the responses characteristic of the different levels of organization is of crucial importance. The main objective of the present study is to investigate how some cellular effects of radiation manifest at the tissue level by modeling mutation induction due to chronic exposure to inhaled radon progeny. For this purpose, a mathematical model of the bronchial epithelium was elaborated to quantify cell nucleus hits and cell doses. Mutagenesis was modeled considering endogenous as well as radiation-induced DNA damages and cell cycle shortening due to cell inactivation. The model parameters describing the cellular effects of radiation are obtained from experimental data. Cell nucleus hits, cell doses, and mutation induction were computed for the activity hot spots of the large bronchi at different exposures. Results demonstrate that the mutagenic effect of densely ionizing radiation is dominated by cell cycle shortening due to cell inactivation and not by DNA damages. This suggests that radiation burdens of non-progenitor cells play a significant role in mutagenesis in case of protracted exposures to densely ionizing radiation. Mutation rate as a function of dose rate exhibits a convex shape below a threshold. This threshold indicates the exhaustion of the tissue regeneration capacity of local progenitor cells. It is suggested that progenitor cell hyperplasia occurs beyond the threshold dose rate, giving a possible explanation of the inverse dose-rate effect observed in the epidemiology of lung cancer among uranium miners.

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Section: Area Ratio (%)mentioning

confidence: 99%

Mutation induction by inhaled radon progeny modeled at the tissue level

Madas

Balásházy

2011

Radiat Environ Biophys

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“…Whole-body γ-ray doses have been found to significantly increase risks of leukemia in survivors of atomic bombings in Japan (Hsu et al, 2013), risks of leukemia, NHL and MM in the U.K. radiation workers (Muirhead et al, 2009), and risks of leukemia and NHL in Chornobyl cleanup workers (Kesminiene et al, 2008; Zablotska et al, 2013). Less is known about the effects of radon decay alpha particles on the bone marrow, but a recent study (Harley and Robbins, 2009) reported that the bronchial mucosa has an abundance of circulating lymphocytes, thus suggesting that RDP exposures could be associated with hematologic cancers originating from these cells.…”

Section: Discussionmentioning

confidence: 99%

Leukemia, lymphoma and multiple myeloma mortality (1950–1999) and incidence (1969–1999) in the Eldorado uranium workers cohort

Zablotska

Lane

Frost³

et al. 2014

Environmental Research

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Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932–1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation.

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“…Results from previous studies on the possible effect of exposure of indoor radon on risk of childhood leukemia have been largely negative but still inconclusive. The potential dose pathway for the association, in addition to the exposure of the red bone marrow, has been suggested to be through the exposure of lymphocytes within the tracheobronchial epithelium (23). Studies in Norway, France, the UK, and Switzerland showed no association, but a Danish case-control study with complete residential histories and a statistical model with 40% r 2 reported an elevated risk (24)(25)(26)(27)(28).…”

Section: Health Effects Of Indoor Radonmentioning

confidence: 99%

Predicting residential radon concentrations in Finland: Model development, validation, and application to childhood leukemia

Nikkilä¹,

Arvela²,

Mehtonen³

et al. 2019

Scand J Work Environ Health

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Indoor radon prediction models were created based on ~80 000 measurements and modern machine learning methods were used in modelling. The performance of the models was comparable to the previously published ones. We observed a non-significant risk of childhood leukemia from indoor radon. However, the modelling involves some uncertainties.Nikkilä A, Arvela H, Mehtonen J, Raitanen J, Heinäniemi M, Auvinen A. Predicting residential radon concentrations in Finland: Model development, validation, and application to childhood leukemia.Objectives Inhaled radon gas is a known alpha-emitting carcinogen linked especially to lung cancer. Studies on higher concentrations of indoor radon and childhood leukemia have conflicting but largely negative results. In this study, we aimed to create a sophisticated statistical model to predict indoor radon concentrations and apply it to a Finnish childhood leukemia case-control dataset.Methods Prediction was based on ~80 000 indoor radon measurements, which were linked to national registries for potential indoor radon predictors based on the literature. In modelling, we used classical methods, random forests and deep neural networks. We had 1093 cases and 3279 controls from a nationwide case-control study. We estimated odds ratio (OR) for childhood leukemia using conditional logistic regression adjusted for potential confounders. ResultsThe r 2 of the final log-linear model was 0.21 for houses and 0.20 for apartments. Using random forest method, we were able to obtain slightly better fit for both houses (r 2 = 0.28) and apartments (r 2 = 0.23). In a risk analysis based on the case-control data with log-linear model, we observed a non-significant (P=0.54) increase with predicted radon concentrations [OR for the 2 nd quartile 1.08, 95% confidence interval (CI) 0.77-1.50, OR 1.10 with 95% CI 0.79-1.53 for the 3 rd , and 1.29 with 95% CI 0.93-1.77 for the highest quartile].Conclusions Our modelling and the previously published models performed similarly but involves major uncertainties, and the results should be interpreted with caution. We observed a slight non-significant increase in risk of childhood leukemia related to higher average indoor radon concentrations.

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Radon and Leukemia in the Danish Study: Another Source of Dose

Cited by 28 publications

References 19 publications

Mutation induction by inhaled radon progeny modeled at the tissue level

Mutation induction by inhaled radon progeny modeled at the tissue level

Leukemia, lymphoma and multiple myeloma mortality (1950–1999) and incidence (1969–1999) in the Eldorado uranium workers cohort

Predicting residential radon concentrations in Finland: Model development, validation, and application to childhood leukemia

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