Exposure to ionizing radiation and brain cancer incidence: The Life Span Study cohort

BackgroundIonizing radiation is a cause of cancer. This paper examines the effects of radiation dose and age at exposure on the incidence of brain cancer using data from the Life Span Study (LSS) of atomic bomb survivors.MethodsThe Radiation Effects Research Foundation website provides demographic details of the LSS population, estimated radiation doses at time of bomb in 1945, person years of follow-up and incident cancers from 1958 to 1998. We modelled brain cancer incidence using background-stratified Poisson regression, and compared the excess relative risk (ERR) per Gray (Gy) of brain dose with estimates from follow-up studies of children exposed to diagnostic CT scans.ResultsAfter exposure to atomic bomb radiation at 10 years of age the estimated ERR/Gy was 0.91 (90%CI 0.53, 1.40) compared with 0.07 (90%CI −0.27, 0.56) following exposure at age 40. Exposure at 10 years of age led to an estimated excess of 17 brain tumors per 100,000 person year (pyr) Gy by 60 years of age. These LSS estimates are substantially less than estimates based on follow-up of children exposed to CT scans.ConclusionEstimates of ERR/Gy for brain cancers in the LSS and haemangioma cohorts seem much smaller than estimates of risk for young persons in the early years after exposure to CT-scans. This could be due to reverse causation bias in the CT cohorts, diagnostic error, measurement error with radiation doses, loss of early follow-up in the LSS, or non-linearity of the dose-response curve.     

Time variations in the risk of cancer following irradiation in childhood

The Japanese atomic bomb survivors and three other cohorts of children exposed to radiation are analyzed, and evidence is found for a reduction in the radiation-induced relative risk of cancers other than leukemia with time following exposure. Multiplicative adjustments to the excess risk either of the form exp[-delta.(time since exposure)] or of the form [time since exposure] gamma give equivalent goodness of fit. Using the former type of adjustment an annual overall reduction of 6.9-8.6% in excess relative risk is indicated (depending on the year after which this reduction might take effect). Using the second type of multiplier an adjustment to the excess relative risk varying between [time after exposure]-2.0 and [time after exposure]-3.2 fits best overall. All these reductions are statistically significant at the 5% level. There is no significant variation by cohort, by sex, by cancer type, or by age at exposure group in the degree of annual reduction in excess relative risk. Although time-adjusted relative and absolute risk models give equivalently good fits within each cohort, there is significant variation between cohorts in the degree of increase of risk with time in the absolute risk formulation, in contrast to the lack of such heterogeneity for the relative risk formulation. It is shown that if the range of observed reductions in relative risk is assumed to operate 40 or more years after exposure in the youngest age groups, the calculated UK population risks would be reduced by 30-45% compared to those based on a constant relative risk model.     

Cancer mortality risk among workers at the Mayak nuclear complex

At present, direct data on risk from protracted or fractionated radiation exposure at low dose rates have been limited largely to studies of populations exposed to low cumulative doses with resulting low statistical power. We evaluated the cancer risks associated with protracted exposure to external whole-body gamma radiation at high cumulative doses (the average dose is 0.8 Gy and the highest doses exceed 10 Gy) in Russian nuclear workers. Cancer deaths in a cohort of about 21,500 nuclear workers who began working at the Mayak complex between 1948 and 1972 were ascertained from death certificates and autopsy reports with follow-up through December 1997. Excess relative risk models were used to estimate solid cancer and leukemia risks associated with external gamma-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing gamma-ray dose (P < 0.001). Under a linear dose-response model, the excess relative risk for lung, liver and skeletal cancers as a group (668 deaths) adjusted for plutonium exposure is 0.30 per gray (P < 0.001) and 0.08 per gray (P < 0.001) for all other solid cancers (1062 deaths). The solid cancer dose-response functions appear to be nonlinear, with the excess risk estimates at doses of less than 3 Gy being about twice those predicted by the linear model. Plutonium exposure was associated with increased risks both for lung, liver and skeletal cancers (the sites of primary plutonium deposition) and for other solid cancers as a group. A significant dose response, with no indication of plutonium exposure effects, was found for leukemia. Excess risks for leukemia exhibited a significant dependence on the time since the dose was received. For doses received within 3 to 5 years of death the excess relative risk per gray was estimated to be about 7 (P < 0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External gamma-ray exposures significantly increased risks of both solid cancers and leukemia in this large cohort of men and women with occupational radiation exposures. Risks at doses of less than 1 Gy may be slightly lower than those seen for doses arising from acute exposures in the atomic bomb survivors. As dose estimates for the Mayak workers are improved, it should be possible to obtain more precise estimates of solid cancer and leukemia risks from protracted external radiation exposure in this cohort.     

Effects of radiation on incidence of primary liver cancer among atomic bomb survivors.

We describe the radiation risk for primary liver cancers between 1958 and 1987 in a cohort of atomic bomb survivors in Hiroshima and Nagasaki, Japan. The analysis is based on a comprehensive pathology review of known or suspected liver neoplasms that generated 518 incident, first primary cases, mostly hepatocellular carcinoma. Excess relative risk from atomic bomb radiation was linear: 0.81 per sievert weighted liver dose (95% CI [0.32, 1.43]; P < 0.001). Males and females had similar relative risk so that, given a threefold higher background incidence in males, the radiation-related excess incidence was substantially higher in males. Excess risk peaked for those with age at exposure in the early 20s; there was essentially no excess risk in those exposed before age 10 or after age 45. Whether this was due to a difference in sensitivity or possible confounding by other factors could not be addressed retrospectively in the full cohort. A paucity of cholangiocarcinoma and hemangiosarcoma cases suggested that they are not significantly associated with whole-body radiation exposure, as they are with the internal alpha-particle-emitting radiological contrast medium Thorotrast. Because most of the radiation-related excess cases occurred among males, it is important to ascertain what factors put men at greater risk of radiation-related liver cancer.     

Are cancer risks associated with exposures to ionising radiation from internal emitters greater than those in the Japanese A-bomb survivors?

After ingestion or inhalation of radionuclides, internal organs of the human body will be exposed to ionising radiation. Current risk estimates of radiation-associated cancer from internal emitters are largely based on extrapolation of risk from high-dose externally exposed groups. Concerns have been expressed that extrapolated risk estimates from internal emitters are greatly underestimated, by factors of ten or more, thus implying a severe underestimation of the true risks. Therefore, data on cancer mortality and incidence in a number of groups who received exposure predominantly from internal emitters are examined and excess relative risks per Sv are compared with comparable (age at exposure, time since exposure, gender) matched subsets of the Japanese atomic bomb survivor cohort. Risks are examined separately for low LET and high LET internal emitters. There are eight studies informative for the effects of internal low LET radiation exposure and 12 studies informative for the effects of internal high LET radiation. For 11 of the 20 cancer endpoints (subgroups of particular study cohorts) examined in the low LET internal emitter studies, the best estimate of the excess relative risk is greater than the corresponding estimate in the Japanese atomic bomb survivors and for the other nine it is less. For four of these 20 studies, the relative risk is significantly (2-sided P < 0.05) different from that in the Japanese atomic bomb survivors, in three cases greater than the atomic bomb survivor relative risk and in one case less. Considering only those six low LET studies/endpoints with 100 or more deaths or cases, for four out of six studies/endpoints the internal emitter risk is greater than that in the Japanese atomic bomb survivors. For seven of the 24 cancer endpoints examined in the high LET internal emitter studies the best estimate of the ERR in the internal emitter study is greater than the corresponding estimate in the Japanese atomic bomb survivors and for the other 17 it is less. For six studies, the relative risk is significantly (2-sided P < 0.05) different from that in the Japanese atomic bomb survivors, in one case greater than the atomic bomb survivor relative risk and in five cases less. Considering only those eight high LET studies/endpoints with 100 or more deaths or cases, for five out of eight studies/endpoints the internal emitter risk is greater than that in the Japanese atomic bomb survivors. These results suggest that excess relative risks in the internal emitter studies do not appreciably differ from those in the Japanese atomic bomb survivors. However, there are substantial uncertainties in estimates of risks in the internal emitter studies, particularly in relation to lung cancer associated with radon daughter (alpha particle) exposure, so a measure of caution should be exercised in these conclusions.     

Radiation dose associated with renal failure mortality: a potential pathway to partially explain increased cardiovascular disease mortality observed after whole-body irradiation

Whole-body and thoracic ionizing radiation exposure are associated with increased cardiovascular disease (CVD) risk. In atomic bomb survivors, radiation dose is also associated with increased hypertension incidence, suggesting that radiation dose may be associated with chronic renal failure (CRF), thus explaining part of the mechanism for increased CVD. Multivariate Poisson regression was used to evaluate the association of radiation dose with various definitions of chronic kidney disease (CKD) mortality in the Life Span Study (LSS) of atomic bomb survivors. A secondary analysis was performed using a subsample for whom self-reported information on hypertension and diabetes, the two biggest risk factors for CRF, had been collected. We found a significant association between radiation dose and only our broadest definition of CRF among the full cohort. A quadratic dose excess relative risk model [ERR/Gy(2) = 0.091 (95% CI: 0.05, 0.198)] fit minimally better than a linear model. Within the subsample, association was also observed only with the broadest CRF definition [ERR/Gy(2) = 0.15 (95% CI: 0.02, 0.32)]. Adjustment for hypertension and diabetes improved model fit but did not substantially change the ERR/Gy(2) estimate, which was 0.17 (95% CI: 0.04, 0.35). We found a significant quadratic dose relationship between radiation dose and possible chronic renal disease mortality that is similar in shape to that observed between radiation and incidence of hypertension in this population. Our results suggest that renal dysfunction could be part of the mechanism causing increased CVD risk after whole-body irradiation, a hypothesis that deserves further study.     

The outcome of local radiation injuries: 14 years of follow-up after the Chernobyl accident

The Chernobyl nuclear power plant accident on April 26, 1986 was the largest in the history of the peaceful use of nuclear energy. Of the 237 individuals initially suspected to have been significantly exposed to radiation during or in the immediate aftermath of the accident, the diagnosis of acute radiation sickness (ARS) could be confirmed in 134 cases on the basis of clinical symptoms. Of these, 54 patients suffered from cutaneous radiation syndrome (CRS) to varying degrees. Among the 28 patients who died from the immediate consequences of accidental radiation exposure, acute hemopoietic syndrome due to bone marrow failure was the primary cause of death only in a minority. In 16 of these 28 deaths, the primary cause was attributed to CRS. This report describes the characteristic cutaneous sequelae as well as associated clinical symptoms and diseases of 15 survivors of the Chernobyl accident with severe localized exposure who were systematically followed up by our groups between 1991 and 2000. All patients presented with CRS of varying severity, showing xerosis, cutaneous telangiectasias and subungual splinter hemorrhages, hemangiomas and lymphangiomas, epidermal atrophy, disseminated keratoses, extensive dermal and subcutaneous fibrosis with partial ulcerations, and pigmentary changes including radiation lentigo. Surprisingly, no cutaneous malignancies have been detected so far in those areas that received large radiation exposures and that developed keratoses; however, two patients first presented in 1999 with basal cell carcinomas on the nape of the neck and the right lower eyelid, areas that received lower exposures. During the follow-up period, two patients were lost due to death from myelodysplastic syndrome in 1995 and acute myelogenous leukemia in 1998, respectively. Other radiation-induced diseases such as dry eye syndrome (3/15), radiation cataract (5/15), xerostomia (4/15) and increased FSH levels (7/15) indicating impaired fertility were also documented. This study, which analyzes 14 years in the clinical course of a cohort of patients with a unique exposure pattern, corroborates the requirement for long-term, if not life-long, follow-up not only in atomic bomb survivors, but also after predominantly local radiation exposure.     

Cancer morbidity and mortality among the liquidators of the Chernobyl accident: estimation of radiation risks

The work focuses on the results of the analysis of the cancer incidence among the Chernobyl emergency workers residing in Russia during 1991-2001. The analysis is based on the data for the cohort of male emergency workers from 6 regions of Russia including 55718 persons with documented external radiation doses in the range of 0.001-0.3 Gy who worked within the 30-km zone in 1986-1987. The mean age at exposure for these persons was 34.8 years old and the mean external radiation dose 0.13 Gy. In this cohort 1370 cases of solid cancer were diagnosed. Three follow-up periods were considered: 1991-1995, 1996-2001 and 1991-2001. The second follow-up period was chosen to allow for a minimum latency period of 10 years. Risk assessments were performed for two control groups: the first control group ("external") represented incidence rates for corresponding ages in Russia in general and the second control group ("internal") consisted of emergency workers. The estimated standardized incidence ratio (SIR) is in good agreement with that of the control within 95% CI. The values of the excess relative risk per unit dose 1 Gy (ERR/Gy) for solid malignant neoplasms have been estimated to be 0.33 (95% CI: -0.39, 1.22) (internal control) for the follow-up period 1991-2001 and 0.19 (95% CI: -0.66, 1.27) for 1996-2001. The analysis of cancer morbidity was carried out for the cohort of 29003 emergency workers who took part in liquidation of the consequences of the Chernobyl accident from 26 April 1986 to 25 April 1987. It was shown that the excess relative risk of cancer deaths per unit dose 1 Sv (ERR/Sv) is equal to 1.52 (95% CI: 0.20, 2.85).     

Thyroid cancer risk in Belarus after the Chernobyl accident: Comparison with external exposures

Within the time period 1990–1993, childhood thyroid cancer incidence due to the Chernobyl accident increased dramatically in Belarus, especially with regard to the birth cohort January 1, 1971, to May 31, 1986. This rise subsequently slowed down, i.e. during the period 1994–1996. The respective data were analysed and compared with the results of an analysis on the time dependence of thyroid cancer incidence in a pooled cohort of persons who had been exposed during childhood to external radiation with high dose rates. Concerning the period of 5–10 years following exposure, the excess absolute cancer risk per unit thyroid dose in the latter (external) exposure group was found to exceed the one in the Belarus group by a factor of two. This difference, however, is not statistically significant. The age-adjusted average excess absolute risk per unit thyroid dose for the period of 5–50 years following external childhood exposure was found to be 8 female and 14 male cases per 10⁴ person-year · Gy, which is a factor about 2.5 times higher than for the non-adjusted risk in the pooled cohort, as reported by Ron et al. in 1995. Assessments of future excess thyroid cancer cases due to the Chernobyl accident were done on the basis of the time dependence of thyroid cancer risk following external exposure. The thyroid cancer incidence among the birth cohort considered in Belarus and for a period starting from the cessation of the available observation data (1 January 1997) and extending to 50 years after the Chernobyl accident has been estimated to be about 15,000 cases, with an uncertainty range of 5000–45,000 cases. According to our calculations, 80% of these cases exceed the baseline risk under enhanced thyroid surveillance. Received: 8 June 1999 / Accepted in revised form: 20 November 1999     

Twenty years after the Chernobyl accident: solid cancer incidence in various groups of the Ukrainian population

Several major international studies such as those performed on the A-bomb survivors, have shown a clear linkage between the exposure to ionizing radiation and the occurrence of various cancer types including leukemia. While these studies are mostly characterized by high dose rates, studies on populations exposed after the Chernobyl accident are in most cases characterized by low dose rates which are typical for occupational radiation protection. Here, data on more than 60,000 Ukrainian workers who participated in recovery operation works in Chernobyl in 1986–1987, more than 50,000 evacuees from the city of Prypyat and the 30 km zone, and about 360,000 residents of most contaminated territories are presented, which cover a period of observation from 1980 to 2004. For all cancers combined, statistically significant higher incidence rates than the national rates were found only for the recovery workers (standardized incidence ratio (SIR) 117.2%, 95% confidence interval: 114.1–120.3), while those for the other investigated groups were lower. In all groups under study a significant increase of thyroid cancer incidence rates has been registered. This increase appears to be associated, at least partly, with the fallout of radioiodine, and it was found not only in children, but also in adolescents and adults. For example, the most significant excess was found for male recovery workers corresponding to a factor of 8.0. It is important to keep in mind, however, that the contribution of confounding factors such as an intensified thyroid screening after the Chernobyl accident could not be quantified, in the present study. For female recovery workers there was also an excess of breast cancer over the national rates (SIR 190.6%; 95% confidence interval: 163.6–217.7%). An analysis of the two other groups (evacuees and residents of contaminated territories) gave controversial results: relative to the local standard there was a statistically significant excess, while comparison with the national level did not substantiate this conclusion.     

Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases

This is the 14th report in a series of periodic general reports on mortality in the Life Span Study (LSS) cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation to investigate the late health effects of the radiation from the atomic bombs. During the period 1950-2003, 58% of the 86,611 LSS cohort members with DS02 dose estimates have died. The 6 years of additional follow-up since the previous report provide substantially more information at longer periods after radiation exposure (17% more cancer deaths), especially among those under age 10 at exposure (58% more deaths). Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, and effect modification by gender, age at exposure, and attained age. The risk of all causes of death was positively associated with radiation dose. Importantly, for solid cancers the additive radiation risk (i.e., excess cancer cases per 10(4) person-years per Gy) continues to increase throughout life with a linear dose-response relationship. The sex-averaged excess relative risk per Gy was 0.42 [95% confidence interval (CI): 0.32, 0.53] for all solid cancer at age 70 years after exposure at age 30 based on a linear model. The risk increased by about 29% per decade decrease in age at exposure (95% CI: 17%, 41%). The estimated lowest dose range with a significant ERR for all solid cancer was 0 to 0.20 Gy, and a formal dose-threshold analysis indicated no threshold; i.e., zero dose was the best estimate of the threshold. The risk of cancer mortality increased significantly for most major sites, including stomach, lung, liver, colon, breast, gallbladder, esophagus, bladder and ovary, whereas rectum, pancreas, uterus, prostate and kidney parenchyma did not have significantly increased risks. An increased risk of non-neoplastic diseases including the circulatory, respiratory and digestive systems was observed, but whether these are causal relationships requires further investigation. There was no evidence of a radiation effect for infectious or external causes of death.     

Lithuanian cohort of Chernobyl cleanup workers: Cancer incidence follow-up 1986–2012

BackgroundCancer risks following radiation exposure in adulthood after Chernobyl are less studied compared to those after exposure in childhood. We aimed to evaluate cancer risk in the Lithuanian cohort of Chernobyl cleanup workers 26 years after their exposure in Chernobyl.MethodsStudy population (6707 men) was followed for cancer incidence upon return from Chernobyl till the end of 2012 by linkage procedure with the Lithuanian Cancer Registry and for migration and death – with Central Population Registry. The site-specific cancer risk in the cohort was estimated by calculating the standardised incidence ratio (SIR) with 95 % confidence interval (CI).ResultsA total of 596 cancer cases was observed in the cohort, against 584 expected (SIR 1.02; 95 % CI 0.94, 1.11). Only incidence of mouth and pharynx cancers was increased compared to the expected (SIR 1.41; 95 % CI 1.07, 1.86). Nevertheless, an increased risk of thyroid cancer was observed among cleanup workers who were younger than 30 years when entering the Chernobyl zone (SIR 2.90; 95 % CI 1.09, 7.72), whose radiation dose was above 100 milisievert (mSv) (SIR 3.13; 95 % CI 1.30, 7.52) and who had shorter duration of stay (SIR 2.30; 95 % CI 1.03, 5.13).ConclusionsOur findings are consistent with those observed in other cohorts of workers, namely, the increased risk of cancer sites related to behavioural factors. The increased risk of thyroid cancer among cleanup workers who were younger than 30 years when entering Chernobyl and whose radiation dose was above 100 mSv cannot exclude the association with the radiation exposure in Chernobyl.     

Analysis of thyroid cancer data from the Ukraine after ’Chernobyl’ using a two-mutation carcinogenesis model

The thyroid cancer data of children in the northern regions of the Ukraine after the reactor accident at Chernobyl were combined with thyroid dose measurements in the same regions and analysed using a two- mutation carcinogenesis model. The best fit was obtained for radiation acting as an initiating agent, i.e. on the first mutation of the model. The observed relatively high increase of thyroid cancer incidence after 1990 in children exposed to radiation released after the reactor accident could be ascribed to the high thyroid doses and the relatively low background thyroid cancer incidence in children. The maximum annual incidence is predicted to occur fairly soon after the reactor accident, i.e. about 10 years. For adults, the predicted relative increase of annual thyroid cancers is much lower than for children younger than 20 years. The modelling results are used to derive risk estimates for radiation-induced thyroid cancer. These risk estimates are dependent on age at exposure, follow-up time and the background thyroid cancer incidence. The calculated excess absolute risk for a population of all ages is about one-third of that currently used by ICRP, but for children the calculated absolute risks are about a factor of 3 higher than derived in other epidemiological studies. The model results indicate that the excess absolute radiation risk per unit dose for children is about the same as or a little lower than that for adults. Received: 11 May 1999 / Accepted: 30 December 1999     

Mortality from solid cancers other than lung,liver, and bone in relation to external dose among plutonium and non-plutonium workers in the Mayak Worker Cohort

Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts.     

Radiation effects on breast cancer risk: a pooled analysis of eight cohorts

Breast cancer incidence rates after radiation exposure in eight large cohorts are described and compared. The nature of the exposures varies appreciably, ranging from a single or a small number of high-dose-rate exposures (Japanese atomic bomb survivors, U.S. acute post-partum mastitis patients, Swedish benign breast disease patients, and U.S. infants with thymic enlargement) to highly fractionated high-dose-rate exposures (two U.S. tuberculosis cohorts) and protracted low-dose-rate exposure (two Swedish skin hemangioma cohorts). There were 1,502 breast cancers among 77,527 women (about 35,000 of whom were exposed) with 1.8 million woman-years of follow-up. The excess risk depends linearly on dose with a downturn at high doses. No simple unified summary model adequately describes the excess risks in all groups. Excess risks for the thymus, tuberculosis, and atomic bomb survivor cohorts have similar temporal patterns, depending on attained age for relative risk models and on both attained age and age at exposure for excess rate models. Excess rates were similar in these cohorts, whereas, related in part to the low breast cancer background rates for Japanese women, the excess relative risk per unit dose in the bomb survivors was four times that in the tuberculosis or thymus cohorts. Excess rates were higher for the mastitis and benign breast disease cohorts. The hemangioma cohorts showed lower excess risks suggesting ameliorating dose-rate effects for protracted low-dose-rate exposures. For comparable ages at exposure (approximately 0.5 years), the excess risk in the hemangioma cohorts was about one-seventh that in the thymus cohort, whose members received acute high-dose-rate exposures. The results support the linearity of the radiation dose response for breast cancer, highlight the importance of age and age at exposure on the risks, and suggest a similarity in risks for acute and fractionated high-dose-rate exposures with much smaller effects from low-dose-rate protracted exposures. There is also a suggestion that women with some benign breast conditions may be at elevated risk of radiation-associated breast cancer.     

Investigation on circular asymmetry of geographical distribution in cancer mortality of Hiroshima atomic bomb survivors based on risk maps: analysis of spatial survival data

While there is a considerable number of studies on the relationship between the risk of disease or death and direct exposure from the atomic bomb in Hiroshima, the risk for indirect exposure caused by residual radioactivity has not yet been fully evaluated. One of the reasons is that risk assessments have utilized estimated radiation doses, but that it is difficult to estimate indirect exposure. To evaluate risks for other causes, including indirect radiation exposure, as well as direct exposure, a statistical method is described here that evaluates risk with respect to individual location at the time of atomic bomb exposure instead of radiation dose. In addition, it is also considered to split the risks into separate risks due to direct exposure and other causes using radiation dose. The proposed method is applied to a cohort study of Hiroshima atomic bomb survivors. The resultant contour map suggests that the region west to the hypocenter has a higher risk compared to other areas. This in turn suggests that there exists an impact on risk that cannot be explained by direct exposure.     

Analysis of a Hormesis Effect in the Leukemia-Caused Mortality Among Atomic Bomb Survivors

Yakovlev and Polig (1996) developed a mechanistically motivated stochastic model of radiation carcinogenesis allowing for cell death. The key feature of the model is that it allows for radiation-induced cell killing to compete with the process of tumor promotion. This model describes and explains a wide range of experimental findings documented in the radiobiological literature, including the inverse dose-rate effect and radiation hormesis. The model has successfully been applied to various sets of experimental and epidemiological data to gain quantitative insight into the processes of tumorigenesis induced by radiation and chemical carcinogens. In this paper, we discuss the most recent application of the Yakovlev-Polig model to the analysis of epidemiological data on the mortality caused by radiation-induced leukemia (all types) among the atomic bomb survivors (Hiroshima and Nagasaki). Nonparametric estimates of the hazard function for leukemia latency time were obtained for three different dose groups identified in the Hiroshima cohort. The behavior of these estimates suggests the presence of the hormesis-type effect in relation to leukemia-caused mortality. A parsimonious version of the mechanistic model yields parametric estimates that are in good agreement with their nonparametric counterparts. Using the parametric model, we corroborated the presence of a moderate hormesis effect in the Hiroshima data. However, we have been unable to uncover the same effect with the Nagasaki cohort of the atomic bomb survivors.     

Latent period in induction of radiogenic solid tumors in the cohort of emergency workers

The paper presents estimates for the latent period of the induction of radiogenic solid cancers among Chernobyl emergency workers (males) living in six central regions of Russia. The analysis is based on medical and dosimetry data gathered by the National Radiation and Epidemiological Registry over the time period from 1986 to 2005. The cohort includes 59,770 persons who stayed in the exposure zone (30-km zone around the Chernobyl nuclear power plant) in 1986–1987. There were 2,718 cases of solid tumors identified during the follow-up time in this cohort. The mean radiation dose in the cohort is 0.13 Gy. The radiation risk and latent period were estimated using the method of maximum likelihood. The excess relative risk per unit dose was found to be 0.96 (95% confidence interval (CI): 0.3–1.7) and the minimum latent period for induction of solid tumors is 4.0 years (95% CI: 3.3–4.9).     

Thyroid cancer incidence among Chernobyl emergency workers: follow-up period 1986-2003

A vast amount of research articles devoted to the increase in childhood thyroid cancer incidence in the most contaminated by radionuclides territories of Belarus, Russia and Ukraine affected by the Chernobyl accident were published recent years. However, the amount of research studies of thyroid cancer incidence among the Chernobyl emergency workers (liquidators) is quite scanty. In the article results of the study of thyroid cancer incidence in the cohort of the Chernobyl liquidators (103427 persons) residing in 6 administrative regions of Russia (North-West, Volgo-Vyatsky, Central-Chernozemny, Povolzhsky, North-Caucasus and Urals) are described and discussed. For the period 1986-2003 eighty seven cases of thyroid cancer were detected in the cohort. Statistically significant excess of the incidence among liquidators over baseline incidence, SIR = 3.39 (95% CI: 2.73; 4.16), among men of Russia has been found. The highest thyroid cancer incidence (SIR = 6.49) was registered among liquidators who had been involved in mitigation works during April-July 1986. At the same time no statistically significant relationship between the incidence rate and external radiation dose, ERR = 1.68 (95% CI: -0.95; 6.46), was detected.     

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

BackgroundComparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer.MethodsWe analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases.ResultsFrom multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH_1Gy) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH_1Gy = 0.038 (95 % CI: −0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH_1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH_1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001.ConclusionThere is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors.ImpactA direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.