Radiation-exposed Populations Research Articles

Exaggeration of consequences of low-dose radiation exposures with special reference to cataracts

Publications overestimating the medical and ecological sequels of a slight anthropogenic increase in the radiation background have been reviewed recently with examples of different organs and pathological conditions. The overestimation contributed to the strangulation of atomic energy. The use of nuclear energy for electricity production is on the agenda today due to the increasing energy needs of humankind. Apparently, certain scientific writers acted in the interests of fossil fuel producers. Health risks and environmental damage are maximal for coal and oil, lower for natural gas, and much lower for atomic energy. This letter is an addition to previously published materials, this time focused on studies of cataracts in radiation-exposed populations in Russia. Selection and self-selection bias are of particular significance. Apparently, the self-reporting rate correlates with dose estimates and/or with professional awareness about radiation-related risks among nuclear workers or radiologic technologists, the latter being associated with their work experience/duration and hence with the accumulated dose. Individuals informed of their higher doses would more often seek medical advice and receive more attention from medics. As a result, lens opacities are diagnosed in exposed people earlier than in the general population. This explains dose-effect correlations proven for the incidence of cataracts but not for the frequency of cataract surgeries. Along the same lines, various pathological conditions are more often detected in exposed people. Ideological bias and the trimming of statistics have not been unusual in the Russian medical sciences. It is known that ionizing radiation causes cataracts; however, threshold levels associated with risks are understudied. In particular, thresholds for chronic and fractionated exposures are uncertain and may be underestimated.

Nicotinamide riboside intervention alleviates hematopoietic system injury of ionizing radiation-induced premature aging mice.

Radiotherapy destroys cancer cells and inevitably harms normal human tissues, causing delayed effects of acute radiation exposure (DEARE) and accelerating the aging process in most survivors. However, effective methods for preventing premature aging induced by ionizing radiation are lacking. In this study, the premature aging mice of DEARE model was established after 6 Gy total body irradiation (TBI). Then the therapeutic effects and mechanism of nicotinamide riboside on the premature aging mice were evaluated. The results showed that 6 Gy TBI induced premature aging of the hematopoietic system in mice. Nicotinamide riboside treatment reversed aging spleen phenotypes by inhibiting cellular senescence and ameliorated serum metabolism profiles. Further results demonstrated that nicotinamide riboside supplementation alleviated the myeloid bias of hematopoietic stem cells and temporarily restored the regenerative capacity of hematopoietic stem cells probably by mitigating the reactive oxygen species activated GCN2/eIF2α/ATF4 signaling pathway. The results of this study firstly indicate that nicotinamide riboside shows potential as a DEARE therapeutic agent for radiation-exposed populations and patients who received radiotherapy.

Dose estimates and their uncertainties for use in epidemiological studies of radiation-exposed populations in the Russian Southern Urals.

Many residents of the Russian Southern Urals were exposed to radioactive environmental pollution created by the operations of the Mayak Production Association in the mid- 20th century. There were two major releases: the discharge of about 1x1017 Bq of liquid waste into the Techa River between 1949 and 1959; and the atmospheric release of 7.4 * 1016 Bq as a result an explosion in the radioactive waste-storage facility in 1957. The releases into the Techa River resulted in the exposure of more than 30,000 people who lived in riverside villages between 1950 and 1961. The 1957 accident contaminated a larger area with the highest exposure levels in an area that is called the East Urals Radioactive Trace (EURT). Current epidemiologic studies of the exposed populations are based on dose estimates obtained using a Monte-Carlo dosimetry system (TRDS-2016MC) that provides multiple realizations of the annual doses for each cohort member. These dose realizations provide a central estimate of the individual dose and information on the uncertainty of these dose estimates. In addition, the correlation of individual annual doses over realizations provides important information on shared uncertainties that can be used to assess the impact of shared dose uncertainties on risk estimate uncertainty.This paper considers dose uncertainties in the TRDS-2016MC. Individual doses from external and internal radiation sources were reconstructed for 48,036 people based on environmental contamination patterns, residential histories, individual 90Sr body-burden measurements and dietary intakes. Dietary intake of 90Sr resulted in doses accumulated in active bone marrow (or simply, marrow) that were an order of magnitude greater than those in soft tissues. About 84% of the marrow dose and 50% of the stomach dose was associated with internal exposures. The lognormal distribution is well-fitted to the individual dose realizations, which, therefore, could be expressed and easily operated in terms of geometric mean (GM) and geometric standard deviation (GSD). Cohort average GM for marrow and stomach cumulative doses are 0.21 and 0.03 Gy, respectively. Cohort average dose uncertainties in terms of GSD are as follows: for marrow it is 2.93 (90%CI: 2.02-4.34); for stomach and the other non-calcified tissues it is 2.32 (90% CI: 1.78-2.9).

Epidemiology of Thyroid Cancer.

Epidemiology of Thyroid Cancer.

Occupational radiation exposure and excess additive risk of cataract incidence in a cohort of US radiologic technologists

ObjectivesPrevious analyses of cataract in radiation-exposed populations have assessed relative risk; radiogenic excess additive risk (EAR), arguably of more public health importance, has not been estimated. Previous analysis of a...

Radiation epidemiology and health effects following low-level radiation exposure

Radiation epidemiology is the study of human disease following radiation exposure to populations. Epidemiologic studies of radiation-exposed populations have been conducted for nearly 100 years, starting with the radium dial painters in the 1920s and most recently with large-scale studies of radiation workers. As radiation epidemiology has become increasingly sophisticated it is used for setting radiation protection standards as well as to guide the compensation programmes in place for nuclear weapons workers, nuclear weapons test participants, and other occupationally exposed workers in the United States and elsewhere. It is known with high assurance that radiation effects at levels above 100–150 mGy can be detected as evidenced in multiple population studies conducted around the world. The challenge for radiation epidemiology is evaluating the effects at low doses, below about 100 mGy of low-linear energy transfer radiation, and assessing the risks following low dose-rate exposures over years. The weakness of radiation epidemiology in directly studying low dose and low dose-rate exposures is that the signal, i.e. the excess numbers of cancers associated with low-level radiation exposure, is so very small that it cannot be seen against the very high background occurrence of cancer in the population, i.e. a lifetime risk of incidence reaching up to about 38% (i.e. 1 in 3 persons will develop a cancer in their lifetime). Thus, extrapolation models are used for the management of risk at low doses and low dose rates, but having adequate information from low dose and low dose-rate studies would be highly desirable. An overview of recently conducted radiation epidemiologic studies which evaluate risk following low-level radiation exposures is presented. Future improvements in risk assessment for radiation protection may come from increasingly informative epidemiologic studies, combined with mechanistic radiobiologic understanding of adverse outcome pathways, with both incorporated into biologically based models.

Genetic characterization of medullary thyroid cancer in childhood survivors of the Chernobyl accident

BackgroundRadiation-associated fusion oncogenes play a direct role in papillary thyroid cancer development and pathogenic fusions have recently been reported in medullary thyroid cancer. To date, no studies have evaluated oncogenic events in medullary thyroid cancer in a radiation-exposed population. MethodsSomatic and germline alterations, including RET fusions, were evaluated in paired medullary thyroid cancer tumor and normal samples from the Chernobyl Tissue Bank, a heavily screened population affected by the Chernobyl disaster. ResultsTissue was available for 49 individuals. The median age of diagnosis was 26 years (range 9 to 43 years); 16 were radiation-exposed at a median age of 6 (range 2 days to 17 years). A total of 21 patients harbored germline RET mutations (codons 634[13], 918[5], 790[1], 609[1], and 620[1]); 4 had family history. Sporadic medullary thyroid cancer was identified in 27 patients (RET[18], KRAS[1], RET+KRAS[1], TP53[1], wild type [6]), with 1 RET fusion (1/49;2%). The age at operation for patients with hereditary medullary thyroid cancer was not different than sporadic medullary thyroid cancer (23.5 vs 28 years, P = .063). In sporadic medullary thyroid cancer, radiation was not associated with a difference in age at operation, tumor size, or tumor stage (P > .05). ConclusionIn a heavily screened cohort, genetic analysis revealed germline RET mutations in previously unrecognized probands and a remarkable number of sporadic medullary thyroid cancer cases with a young age at presentation.

RBPI21 (Opebacan) Promotes Rapid Trilineage Hematopoietic Recovery in a Murine Model of High-Dose Total Body Irradiation.

The complexity of providing adequate care after radiation exposure has drawn increasing attention. While most therapeutic development has focused on improving survival at lethal radiation doses, acute hematopoietic syndrome (AHS) occurs at substantially lower exposures. Thus, it is likely that a large proportion of such a radiation-exposed population will manifest AHS of variable degree and that the medical and socioeconomic costs of AHS will accrue. Here, we examined the potential of rBPI21 (opebacan), used without supportive care, to accelerate hematopoietic recovery after radiation where expected survival was substantial (42-75%) at 30 days). rBPI21 administration was associated with accelerated recovery of hematopoietic precursors and normal marrow cellularity, with increases in megakaryocyte numbers particularly marked. This translated into attaining normal trilineage peripheral blood counts 2-3 weeks earlier than controls. Elevations of hematopoietic growth factors observed in plasma and the marrow microenvironment suggest the mechanism is likely multifactorial and not confined to known endotoxin-neutralizing and cytokine down-modulating activities of rBPI21 . These observations deserve further exploration in radiation models and other settings where inadequate hematopoiesis is a prominent feature. These experiments also model the potential of therapeutics to limit the allocation of scarce resources after catastrophic exposures as an endpoint independent of lethality mitigation. This article is protected by copyright. All rights reserved.

Altered molecular profile in thyroid cancers from patients affected by the Three Mile Island nuclear accident.

In 1979, Three Mile Island (TMI) nuclear power plant experienced a partial meltdown with release of radioactive material. The effects of the accident on thyroid cancer (TC) in the surrounding population remain unclear. Radiation-induced TCs have a lower incidence of single nucleotide oncogenic driver mutations and higher incidence of gene fusions. We used next generation sequencing (NGS) to identify molecular signatures of radiation-induced TC in a cohort of TC patients residing near TMI during the time of the accident. Case series. We identified 44 patients who developed papillary thyroid carcinoma between 1974 and 2014. Patients who developed TC between 1984 and 1996 were at risk for radiation-induced TC, patients who developed TC before 1984 or after 1996 were the control group. We used targeted NGS of paired tumor and normal tissue from each patient to identify single nucleotide oncogenic driver mutations. Oncogenic gene fusions were identified using quantitative reverse transcription polymerase chain reaction. We identified 15 patients in the at-risk group and 29 patients in the control group. BRAFV600E mutations were identified in 53% patients in the at-risk group and 83% patients in the control group. The proportion of patients with BRAF mutations in the at-risk group was significantly lower than predicted by the The Cancer Genome Atlas cohort. Gene fusion or somatic copy number alteration drivers were identified in 33% tumors in the at-risk group and 14% of tumors in the control group. Findings were consistent with observations from other radiation-exposed populations. These data raise the possibility that radiation released from TMI may have altered the molecular profile of TC in the population surrounding TMI. 4 Laryngoscope, 127:S1-S9, 2017.

Association of chromosome translocation rate with low dose occupational radiation exposures in U.S. radiologic technologists.

Chromosome translocations are a well-recognized biological marker of radiation exposure and cancer risk. However, there is uncertainty about the lowest dose at which excess translocations can be detected, and whether there is temporal decay of induced translocations in radiation-exposed populations. Dosimetric uncertainties can substantially alter the shape of dose-response relationships; although regression-calibration methods have been used in some datasets, these have not been applied in radio-occupational studies, where there are also complex patterns of shared and unshared errors that these methods do not account for. In this article we evaluated the relationship between estimated occupational ionizing radiation doses and chromosome translocation rates using fluorescent in situ hybridization in 238 U.S. radiologic technologists selected from a large cohort. Estimated cumulative red bone marrow doses (mean 29.3 mGy, range 0-135.7 mGy) were based on available badge-dose measurement data and on questionnaire-reported work history factors. Dosimetric assessment uncertainties were evaluated using regression calibration, Bayesian and Monte Carlo maximum likelihood methods, taking account of shared and unshared error and adjusted for overdispersion. There was a significant dose response for estimated occupational radiation exposure, adjusted for questionnaire-based personal diagnostic radiation, age, sex and study group (5.7 translocations per 100 whole genome cell equivalents per Gy, 95% CI 0.2, 11.3, P = 0.0440). A significant increasing trend with dose continued to be observed for individuals with estimated doses <100 mGy. For combined estimated occupational and personal-diagnostic-medical radiation exposures, there was a borderline-significant modifying effect of age (P = 0.0704), but little evidence (P > 0.5) of temporal decay of induced translocations. The three methods of analysis to adjust for dose uncertainty gave similar results. In summary, chromosome translocation dose-response slopes were detectable down to <100 mGy and were compatible with those observed in other radiation-exposed populations. However, there are substantial uncertainties in both occupational and other (personal-diagnostic-medical) doses that may be imperfectly taken into account in our analysis.

Background stratified Poisson regression analysis of cohort data

Background stratified Poisson regression is an approach that has been used in the analysis of data derived from a variety of epidemiologically important studies of radiation-exposed populations, including uranium miners, nuclear industry workers, and atomic bomb survivors. We describe a novel approach to fit Poisson regression models that adjust for a set of covariates through background stratification while directly estimating the radiation-disease association of primary interest. The approach makes use of an expression for the Poisson likelihood that treats the coefficients for stratum-specific indicator variables as 'nuisance' variables and avoids the need to explicitly estimate the coefficients for these stratum-specific parameters. Log-linear models, as well as other general relative rate models, are accommodated. This approach is illustrated using data from the Life Span Study of Japanese atomic bomb survivors and data from a study of underground uranium miners. The point estimate and confidence interval obtained from this 'conditional' regression approach are identical to the values obtained using unconditional Poisson regression with model terms for each background stratum. Moreover, it is shown that the proposed approach allows estimation of background stratified Poisson regression models of non-standard form, such as models that parameterize latency effects, as well as regression models in which the number of strata is large, thereby overcoming the limitations of previously available statistical software for fitting background stratified Poisson regression models.

Estimates of the potential risk of radiation-related cancer from screening in the UK

Estimates of the potential risk of radiation-related cancer from screening in the UK

Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation

Although ionizing radiation induces germline mutations in animals, human studies of radiation-exposed populations have not detected an effect. We conducted a case-control study of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation, to investigate gonadal radiation exposure of parents from medical sources before their child's conception. Parents of 206 cases from nine North American institutions and 269 controls participated; fathers of 184 cases and 223 friend and relative controls and mothers of 204 cases and 260 controls provided information in telephone interviews on their medical radiation exposure. Cases provided DNA for RB1 mutation testing. Of common procedures, lower gastrointestinal (GI) series conferred the highest estimated dose to testes and ovaries. Paternal history of lower GI series was associated with increased risk of retinoblastoma in the child [matched odds ratio (OR) = 3.6, 95% confidence interval (CI) = 1.2-11.2, two-sided p = 0.02], as was estimated total testicular dose from all procedures combined (OR for highest dose=3.9, 95% CI = 1.2-14.4, p = 0.02). Maternal history of lower GI series was also associated with increased risk (OR = 7.6, 95% CI = 2.8-20.7, p < 0.001) as was the estimated total dose (OR for highest dose = 3.0, 95% CI = 1.4-7.0, p = 0.005). The RB1 mutation spectrum in cases of exposed parents did not differ from that of other cases. Some animal and human data support our findings of an association of gonadal radiation exposure in men and women with new germline RB1 mutation detectable in their children, although bias, confounding, and/or chance may also explain the results.

Ionizing Radiation and Kidney Cancer among Japanese Atomic Bomb Survivors

Understanding of the role of radiation as a cause of kidney cancer remains limited. The most common types of kidney cancer are renal cell carcinoma and renal pelvis carcinoma. It has been posited that these entities differ in their degree of radiogenicity. Recent analyses of cancer incidence and mortality in the Life Span Study (LSS) of Japanese atomic bomb survivors have examined associations between ionizing radiation and renal cell carcinoma, but these analyses have not reported results for cancer of the renal pelvis and ureters. This paper reports the results of analyses of kidney cancer incidence during the period 1958-1998 among 105,427 atomic bomb survivors. Poisson regression methods were used to derive estimates of associations between radiation dose (in sievert, Sv) and cancer of the renal parenchyma (n = 167), and cancer of the renal pelvis and ureter (n = 80). Heterogeneity by cancer site was tested by joint modeling of cancer risks. Radiation dose was positively associated with cancers of the renal pelvis and ureter [excess relative rate (ERR)/Sv = 1.65; 90% confidence interval (CI): 0.37, 3.78]. The magnitude of this association was larger than the estimated association between radiation dose and cancer of the renal parenchyma (ERR/Sv = 0.27; 90% CI = -0.19, 0.98). While the association between radiation and cancer of the renal parenchyma was of greater magnitude at ages <55 years (ERR/Sv = 2.82; 90% CI = 0.45, 8.89) than at older attained ages (ERR/Sv = -0.11; 90% CI = nd, 0.53), the association between radiation and cancers of the renal pelvis and ureter varied minimally across these categories of attained age. A test of heterogeneity of type-specific risks provides modest support for the conclusion that risks vary by kidney cancer site (LRT = 2.34, 1 d.f., P = 0.13). Since some studies of radiation-exposed populations examine these sites in aggregate, results were also derived for the combined category of cancer of the renal parenchyma, renal pelvis and ureters. Overall, there was a positive association between radiation and the combined category of cancer of the renal parenchyma, renal pelvis and ureters (ERR/Sv = 0.60, 90% CI: 0.09, 1.30). Updated follow-up of the LSS cohort provides substantial additional information on the association between radiation and cancer of the renal pelvis and ureter, a site not examined in recent reports on analyses of these data. The results are suggestive of differences between the different regions of the kidney in sensitivity to the carcinogenic effects of ionizing radiation.

Health risks of low photon energy imaging

The major health risk associated with low photon energy imaging is thought to be the induction of cancer as a consequence of the radiation exposure and this is the focus of this paper. Low photon energy imaging typically involves exposure to a low dose (<50 mGy) of low linear energy transfer (LET) radiation delivered at high dose-rate. Since epidemiologic data cannot provide an accurate assessment of risk at the doses used in imaging, risk estimates are currently made by fitting a linear response to intermediate and high dose data for cancer induction in radiation-exposed human populations. This method assumes a linear no-threshold (LNT) response and implies that no dose of radiation is safe. This assumption is not borne out by many laboratory studies of cancer-related endpoints that would suggest that the risk at low doses is much less than would be estimated from linear extrapolation from intermediate to high doses. It is also well recognised that the dose-response from many epidemiologic studies could equally well be fit by threshold models. Through the study of radiation-induced neoplastic transformation in vitro J-shaped dose-response curves for a variety of low LET radiations, including those used in low photon energy imaging, have been demonstrated. The relative risks calculated from this data compare remarkably well with those for breast cancer and leukemia incidence in radiation-exposed populations. From this it is concluded that the LNT hypothesis is likely to overestimate the risk of cancer induction by low photon energy imaging, at least for certain tumors.

UNDERSTANDING ESTIMATION OF TIME AND AGE EFFECT-MODIFICATION OF RADIATION-INDUCED CANCER RISKS AMONG ATOMIC-BOMB SURVIVORS

In radiation risk assessment based on follow-up data, estimation of the excess relative cancer rate involves evaluation of effect-modification by time-related factors such as age at exposure, time since exposure, and attained age. Because these variables are collinear, the regression coefficients purportedly measuring effect-modification of the radiation-related excess relative rate by time and age factors generally differ from the individual effects of these factors. For example, depending on whether it is an age-at-exposure/attained-age effect-modification model or an age-at-exposure/time-since-exposure model which is used, the regression coefficient for the effect of changes in age at exposure on the excess relative rate per Gray measures the combined effects of changes in both age at exposure and time since exposure, or of age at exposure and attained age, respectively, rather than the individual effect of changes in age at exposure, which is of interest for scientific purposes. Such insights should be integrated when reporting and interpreting estimates for time-related risk modification in cohort studies of radiation-exposed populations. Cancer incidence data for the Life Span Study of atomic-bomb survivors are used for illustration in parallel to theory. In summary, model coefficients for time-since-exposure, age-at-exposure, and attained-age effects on radiation-induced cancer risks among atomic-bomb survivors and in other cohort studies estimate combined effects (estimable combined effects are explicated). An appropriate unequivocal display of results for effect-modification is suggested. Goodness of fit appears unreliable for sorting out the most significant effect-modifiers. For example, a model including only one of the effect-modifiers may provide a fit similar to a model including the other two effect-modifiers, even when only the latter are actually related to effect-modification. Also, due to collinearity between these effect-modifier variables, all three models with two of the effect-modifiers necessarily show equivalent fits.

Prevalence of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Its Malignant Progression in Radiation-Exposed Population.

The prevalence of Monoclonal Gammopathy of Undetermined Significance (MGUS) in Japanese population and that in radiation-exposed population have not been accurately determined. We performed a M-protein screening to determine the prevalence of MGUS and a cohort study to determine the probability of progression from MGUS to multiple myeloma (MM) in a large Japanese population exposed to radiation. In this study, if we could find any effects of radiation-exposure on outcomes, we may provide etiological clues for MGUS and its progression to MM, or, even if we could not, we may provide the Japanese-specific prevalence of MGUS and its progression. The target population included atomic bomb survivors living in Nagasaki City as of October 1, 1988 (N=71,062; median age 58 years at 1988; range 42 to 97). The screening process consisted of agarose-gel electrophoresis, immuno-electrophoresis and quantitative immunoglobulin. General laboratory test and physical examination were also conducted. Serum samples were obtained from 52,525 subjects (73.9% of population) during October 1, 1988 to March 31, 2004. We identified 1,087 cases of MGUS among screened subjects. The crude prevalence of MGUS was 2.1% (95%CI, 1.9 to 2.2) in all subjects, and was 2.4% when limited subjects 50 years or older at 1988. MGUS prevalence increased by age same as many previous studies had reported. The prevalence was significantly higher in men than in women (2.8% vs. 1.6%, odds ratio 1.7, 95%CI, 1.5–1.9). To investigate the effect of radiation-exposure on occurrence of MGUS, a multiple logistic regression analysis, adjusted for age-at-1988 and sex, were performed including three radiation exposed-states: exposed within 1.5km from the atomic bomb hypocenter, 1.5–3.0km, and beyond 3.0km. There was a significant interaction between age-at-1988 and the exposed distance. We suspected that age at exposed to radiation might influence the occurrence of MGUS. Therefore, we performed multiple logistic regressions separately by dichotomized exposed age at 1945, under 20 years or 20 years or more, including sex, age-at-1988 (every 10 years as continuous data), and exposed distance category as covariates. In both age groups, male sex and the aging were strong risk factors of occurrence of MGUS. The exposed distance was not affected in exposed age 20 years or more at 1945. However, in exposed age under 20 years at 1945, MGUS prevalence was higher in those exposed within 1.5km than those beyond 3.0km (adjusted OR=1.4, 95%CI, 1.7–2.4, p<0.0001). Among MGUS cases, 38 cases developed to MM during the follow-up. Overall cumulative risk of MM from MGUS was 8% during the average follow-up period 4.6 years. The estimated cumulative risk of developing MM was not different in sex, exposed age, and exposed distance, though those exposed proximally tend to develop to MM earlier than those exposed distally. Our results suggest that the higher radiation exposure at the younger age may affect the occurrence of MGUS beyond the effect of aging and sex on it, but the effect was weak for the progression from MGUS to MM. Further population-based studies for people exposed to radiation and external analyses are needed to confirm these findings.

Increased T-cell Receptor Mutation Frequency in Radiation-Exposed Residents Living Near the Semipalatinsk Nuclear Test Site

From 1949 to 1989, 488 nuclear explosions were carried out in Semipalatinsk, and the cancer risk is increased in this region. Measuring somatic-cell mutation frequencies may be a useful tool for evaluating cancer risk within radiation-exposed populations. Here, we report the first evidence of increased T-cell receptor (TCR) mutations in peripheral blood from radiation-exposed residents of Semipalatinsk. The TCR mutation frequency in the highly exposed residents (Dolon and Sarzhal) was significantly higher than in the control group (Kokpekti). There was no statistically significant difference between the control group and the weakly exposed group (Kaynar and Semipalatinsk-city). The TCR mutation assay appeared to be a useful biological dosimeter even after a period of 40 years since radiation exposure. This may be the result of specific conditions, such as the presence of internal exposure.

Occupational X‐ray examinations and lung cancer risk

Occupational X-ray examination programs have been conducted in many countries to screen for occupational and nonoccupational respiratory diseases, resulting in widespread exposure to X-radiation. We conducted a multicentre case-control study of lung cancer in the Czech Republic, Hungary, Poland, Romania, Russia and Slovakia, including 2,589 cases and 2,859 controls enrolled during 1998-2002. We collected detailed information on occupational X-ray examinations, occupations and tobacco smoking. We calculated odds ratios of lung cancer via multiple logistic regression after adjustment for age, sex, center and tobacco smoking. Among controls 24.9% reported no X-ray examination, 62.9% reported 1-30 examinations and 12.2% reported more than 30 examinations. When we chose individuals with no examination as the reference group, the odds ratios of lung cancer were 1.21 (95% confidence interval [CI] 0.99-1.48), 1.33 (95% CI 1.08-1.64), 1.49 (95% CI 1.18-1.87), 1.52 (95% CI 1.17-1.99) and 2.15 (95% CI 1.50-3.08) for 1-10, 11-20, 21-30, 31-40 and more than 40 examinations, respectively (p-value of test for linear trend <0.0001). The association between X-ray examinations and lung cancer risk was strong in countries with low prevalence of exposure and absent in countries with high prevalence of exposure. Odds ratios for X-ray examinations were lower among smokers than among nonsmokers. The magnitude of the increased risk observed is higher than expected on the basis of other studies of radiation-exposed populations. Although the association we detected between X-ray examinations and lung cancer risk may reflect a carcinogenic effect of repeated exposure to low-level ionizing radiation, reporting bias and particularly uncontrolled confounding by occupational exposure to carcinogens are also likely explanations of the results.

Remembrance: Gilbert Wheeler Beebe, 1912–2003

FIGUREFigureGilbert Beebe died on March 3, 2003, 1 month short of his 91st birthday and 2 days after working a full Saturday at the office. Gil was renowned as a radiation epidemiologist. He conducted ground-breaking studies of mortality and morbidity among persons exposed to the atomic bombings in Japan and to the Chernobyl reactor accident in Ukraine. His 70 years as a statistician/epidemiologist spanned several careers. Gil first worked at the National Committee on Maternal Health, where he conducted an important study of contraceptive services in economically depressed areas. From there he went to the office of the Surgeon General of the Army, and then to the National Academy of Sciences (NAS). Gil and others (including Michael DeBakey) had been advocating an ongoing follow-up system based on military and medical records, and it was at the NAS that Gil created the Medical Follow-up Agency (MFUA) to accomplish that. While at NAS, Gil worked with Seymour Jablon to organize the Atomic Bomb Casualty Commission (ABCC) research program to study the late health effects of radiation exposure in Japanese A-bomb survivors. Later known as the Life Span Study, this remains the most important source of information on radiation-related risk of cancer and other long-term health effects in humans. At age 65, Gil began his fifth career at the National Cancer Institute, where he worked for 25 years. After the Chernobyl accident, Gil led international studies of thyroid cancer and leukemia among radiation-exposed populations in Belarus and Ukraine. When Gil retired from NCI in 2002, he continued to work 6 days a week as Scientist Emeritus. Gil’s family, friends, and colleagues honored him last year at the National Academy of Sciences first annual Beebe Symposium. Throughout his careers, Gil was the right man in the right place. His work ethic and wisdom, combined with creativity and unusual intellectual generosity, made him a wonderful role model for 3 generations of radiation epidemiologists and statisticians. He patiently listened to others, suggested new ideas, and stimulated young investigators. Gil loved work—one would probably say he was a workaholic—and yet he found time to raise 4 children, participate in community group discussions, and attend office celebrations (typically arriving with a few bottles of wine). Gil added a special presence to his environment, wherever he was. Without fanfare, Gil Beebe created a remarkable legacy in the fields of epidemiology and radiation and in the scientific community at large. We will miss him.