D. Laurier

Lung Cancer Risk from Radon and Progeny and Statement on Radon

Recent epidemiological studies of the association between lung cancer and exposure to radon and its decay products are reviewed. Particular emphasis is given to pooled case-control studies of residential exposures, and to cohorts of underground miners exposed to relatively low levels of radon. The residential and miner epidemiological studies provide consistent estimates of the risk of lung cancer, with significant associations observed at average annual concentrations of approximately 200 Bq/m³ and cumulative occupational levels of approximately 50 working level months (WLM), respectively. Based on recent results from combined analyses of epidemiological studies of miners, a lifetime excess absolute risk of 5 × 10⁻⁴ per WLM [14 × 10⁻⁵ per (mJh/m³)] should now be used as the nominal probability coefficient for radon- and radon-progeny-induced lung cancer, replacing the previous Publication 65 (ICRP, 1993) value of 2.8 × 10⁻⁴ per WLM [8 × 10⁻⁵ per (mJh/m³)]. Current knowledge of radon-associated risks for organs other than the lungs does not justify the selection of a detriment coefficient different from the fatality coefficient for radon-induced lung cancer. Publication 65 (ICRP, 2003) recommended that doses from radon and its progeny should be calculated using a dose conversion convention based on epidemiological data. It is now concluded that radon and its progeny should be treated in the same way as other radionuclides within the ICRP system of protection; that is, doses from radon and its progeny should be calculated using ICRP biokinetic and dosimetric models. ICRP will provide dose coefficients per unit exposure to radon and its progeny for different reference conditions of domestic and occupational exposure, with specified equilibrium factors and aerosol characteristics.

Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS): an international cohort study

Summary Background There is much uncertainty about the risks of leukaemia and lymphoma after repeated or protracted low-dose radiation exposure typical of occupational, environmental, and diagnostic medical settings. We quantified associations between protracted low-dose radiation exposures and leukaemia, lymphoma, and multiple myeloma mortality among radiation-monitored adults employed in France, the UK, and the USA. Methods We assembled a cohort of 308 297 radiation-monitored workers employed for at least 1 year by the Atomic Energy Commission, AREVA Nuclear Cycle, or the National Electricity Company in France, the Departments of Energy and Defence in the USA, and nuclear industry employers included in the National Registry for Radiation Workers in the UK. The cohort was followed up for a total of 8·22 million person-years. We ascertained deaths caused by leukaemia, lymphoma, and multiple myeloma. We used Poisson regression to quantify associations between estimated red bone marrow absorbed dose and leukaemia and lymphoma mortality. Findings Doses were accrued at very low rates (mean 1·1 mGy per year, SD 2·6). The excess relative risk of leukaemia mortality (excluding chronic lymphocytic leukaemia) was 2·96 per Gy (90% CI 1·17–5·21; lagged 2 years), most notably because of an association between radiation dose and mortality from chronic myeloid leukaemia (excess relative risk per Gy 10·45, 90% CI 4·48–19·65). Interpretation This study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukaemia. Funding Centers for Disease Control and Prevention, Ministry of Health, Labour and Welfare of Japan, Institut de Radioprotection et de Sûreté Nucléaire, AREVA, Electricité de France, National Institute for Occupational Safety and Health, US Department of Energy, US Department of Health and Human Services, University of North Carolina, Public Health England.

Human exposure to high natural background radiation: what can it teach us about radiation risks?

Natural radiation is the major source of human exposure to ionising radiation, and its largest contributing component to effective dose arises from inhalation of (222)Rn and its radioactive progeny. However, despite extensive knowledge of radiation risks gained through epidemiologic investigations and mechanistic considerations, the health effects of chronic low-level radiation exposure are still poorly understood. The present paper reviews the possible contribution of studies of populations living in high natural background radiation (HNBR) areas (Guarapari, Brazil; Kerala, India; Ramsar, Iran; Yangjiang, China), including radon-prone areas, to low dose risk estimation. Much of the direct information about risk related to HNBR comes from case-control studies of radon and lung cancer, which provide convincing evidence of an association between long-term protracted radiation exposures in the general population and disease incidence. The success of these studies is mainly due to the careful organ dose reconstruction (with relatively high doses to the lung), and to the fact that large-scale collaborative studies have been conducted to maximise the statistical power and to ensure the systematic collection of information on potential confounding factors. In contrast, studies in other (non-radon) HNBR areas have provided little information, relying mainly on ecological designs and very rough effective dose categorisations. Recent steps taken in China and India to establish cohorts for follow-up and to conduct nested case-control studies may provide useful information about risks in the future, provided that careful organ dose reconstruction is possible and information is collected on potential confounding factors.

Risk of cancer from occupational exposure to ionising radiation: retrospective cohort study of workers in France, the United Kingdom, and the United States (INWORKS).

Study question Is protracted exposure to low doses of ionising radiation associated with an increased risk of solid cancer? Methods In this cohort study, 308 297 workers in the nuclear industry from France, the United Kingdom, and the United States with detailed monitoring data for external exposure to ionising radiation were linked to death registries. Excess relative rate per Gy of radiation dose for mortality from cancer was estimated. Follow-up encompassed 8.2 million person years. Of 66 632 known deaths by the end of follow-up, 17 957 were due to solid cancers. Study answer and limitations Results suggest a linear increase in the rate of cancer with increasing radiation exposure. The average cumulative colon dose estimated among exposed workers was 20.9 mGy (median 4.1 mGy). The estimated rate of mortality from all cancers excluding leukaemia increased with cumulative dose by 48% per Gy (90% confidence interval 20% to 79%), lagged by 10 years. Similar associations were seen for mortality from all solid cancers (47% (18% to 79%)), and within each country. The estimated association over the dose range of 0-100 mGy was similar in magnitude to that obtained over the entire dose range but less precise. Smoking and occupational asbestos exposure are potential confounders; however, exclusion of deaths from lung cancer and pleural cancer did not affect the estimated association. Despite substantial efforts to characterise the performance of the radiation dosimeters used, the possibility of measurement error remains. What this study adds The study provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality. Although high dose rate exposures are thought to be more dangerous than low dose rate exposures, the risk per unit of radiation dose for cancer among radiation workers was similar to estimates derived from studies of Japanese atomic bomb survivors. Quantifying the cancer risks associated with protracted radiation exposures can help strengthen the foundation for radiation protection standards. Funding, competing interests, data sharing Support from the US Centers for Disease Control and Prevention; Ministry of Health, Labour and Welfare of Japan; Institut de Radioprotection et de Sûreté Nucléaire; AREVA; Electricité de France; US National Institute for Occupational Safety and Health; US Department of Energy; and Public Health England. Data are maintained and kept at the International Agency for Research on Cancer.

Ionizing radiation biomarkers for potential use in epidemiological studies

Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.

Radon Exposure And The Risk Of Leukemia: A Review Of Epidemiological Studies

Since the 1990s, several authors estimated that radon inhalation may deliver a small amount of irradiation to the red bone marrow, and consequently may increase the risk of leukemia in humans. The objective of this review is to conduct a critical analysis of epidemiologic results currently available concerning the relationship between radon exposure and the risk of leukemia. Nineteen ecological studies, six miner cohort studies, and eight case-control studies published between 1987 and 2000 are included in this review. The limitations associated with each of these studies are discussed. The results of the ecological studies are relatively concordant and suggest an association between radon concentrations and the risk of leukemia at a geographic level. But these ecological studies present important limitations, and some are only crude analyses. Moreover, the results of the cohort and case-control studies, based on individual data, do not show any significant association between radon exposure and leukemia risk. Our conclusion is that the overall epidemiologic results currently available do not provide evidence for an association between radon exposure and leukemia.

Childhood leukemia around French nuclear power plants—The geocap study, 2002–2007

The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case–control study included the 2,753 cases diagnosed in mainland France over 2002–2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the 19 NPPs. The study used distance to NPPs and a dose‐based geographic zoning (DBGZ), based on the estimated dose to bone marrow related to NPP gaseous discharges. An odds ratio (OR) of 1.9 [1.0–3.3], based on 14 cases, was evidenced for children living within 5 km of NPPs compared to those living 20 km or further away, and a very similar association was observed in the concomitant incidence study (standardized incidence ratio (SIR) = 1.9 [1.0–3.2]). These results were similar for all the 5‐year‐age groups. They persisted after stratification for several contextual characteristics of the municipalities of residence. Conversely, using the DBGZ resulted in OR and SIR close to one in all of the dose categories. There was no increase in AL incidence over 1990–2001 and over the entire 1990–2007 period. The results suggest a possible excess risk of AL in the close vicinity of French NPPs in 2002–2007. The absence of any association with the DBGZ may indicate that the association is not explained by NPP gaseous discharges. Overall, the findings call for investigation for potential risk factors related to the vicinity of NPP and collaborative analysis of multisite studies conducted in various countries.

Epidemiological studies of leukaemia in children and young adults around nuclear facilities: a critical review

The existence of an increased risk of childhood leukaemia near nuclear installations is a recurrent issue. A review of the related epidemiological literature is presented here. Results for 198 nuclear sites throughout 10 countries were included in the review. In addition to local studies, 25 multi-site studies have been published for eight countries. A large variability was noticed in the quality of the data as well as in the definition of the study population and in the methods of analysis. Many studies present important limits that make the results difficult to interpret. The review confirms that some clusters of childhood leukaemia cases exist locally. However, results based on multi-site studies around nuclear installations do not indicate an increased risk globally. Many studies were launched to investigate possible origins of the observed clusters around specific sites, but up to now, none of the proposed hypotheses have explained them.

An update of cancer mortality among the French cohort of uranium miners: Extended follow-up and new source of data for causes of death

The follow-up of the French cohort of uranium miners has been extended to 1994, and a new source of information for causes of death has been used. The paper presents the new results regarding the risk of death among the cohort, and analyses the impact of the methodological changes on these results. The extension of the follow-up results in a substantial increase in statistical power compared with previous analysis (+25% for person-years and +74% for the number of deaths). The use of the National Mortality Database as the principal source for causes of death allows to reduce the potential bias in the calculation of standardized mortality ratios (SMR). As a consequence, an excess risk of deaths from laryngeal cancer, suggested in the first analysis, is not confirmed. The analysis shows the existence of an excess risk of deaths from lung cancer among French uranium miners (85 observed deaths, SMR = 1.9, 95% confidence interval CI: 1.5–2.3), and an increase of this risk with cumulative exposure to radon (excess relative risk per 100 working level month = 0.6, 95% CI: 0.1–1.2). These results confirm the existence of a risk of death from lung cancer in a population chronically exposed to relatively low levels of radon.

Lung cancer risk in the French cohort of uranium miners

The French cohortof uranium miners includes 5098 miners,and 125 lung cancer deaths have been observed. The relationship between radon exposure and risk of lung cancer is estimated using relative risk models, which allow investigation of time dependent modifying factors such as the period of exposure, time since exposure and exposure rate. A linear exposure-response relationship is observed. The main modifier is the period of exposure before or after 1956: the excess relative risk after introduction of ventilation in the French mines is eight times higher than before. The decrease in risk with time since exposure and exposure rate disappears when period of exposure is taken into account. Compared to most of the uranium miner studies, this cohort constitutes a population exposed to low levels and low rates of radon for a long duration. The extension of the French cohort leads to an important increase in its statistical power. Exposure rate effect will be further investigated, in the framework of a European collaborative research project aiming at the synthesis of the effects of radon exposure at low dose and low dose rate.