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.     

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.     

Relative risks of radiation-associated cancer: comparison of second cancer in therapeutically irradiated populations with the Japanese atomic bomb survivors

In this paper the radiation-associated relative risks of second primary cancer incidence in groups treated for first primary cancer by radiotherapy are compared with radiation-associated relative risk estimates in the Japanese atomic bomb survivor cancer incidence data. For four cancer sites, namely lung cancer, bone cancer, ovarian cancer and leukaemia, the relative risks in the comparable (age at exposure, time since exposure, sex matched) subsets of the Japanese data are significantly greater than those in the majority of second cancer studies. Even when the differences between the relative risks in the Japanese atomic bomb survivors and the medical series do not approach conventional levels of statistical significance, relative risks tend to be higher in the Japanese data than in the second cancer studies. At least for leukaemia, the discrepancy between the Japanese and second cancer risks can be largely explained by cell- sterilisation effects. There are few indications of modification of radiation-associated second cancer relative risk among those treated with adjuvant chemotherapy, nor are there strong indications of modification of radiation- associated relative risk by heritable genetic factors. If anything, there is evidence that second cancer relative excess risks are lower among those patients with cancer-prone disorders than among non-susceptible patients. However, the higher underlying cancer risk in some of these medically exposed populations should also be considered, in particular for those with cancer-prone conditions, so that the absolute excess risk is sometimes higher than in the Japanese data. Received: 14 May 1999 / Accepted in revised form: 17 September 1999     

Projection of cancer risks from the Japanese atomic bomb survivors to the England and Wales population taking into account uncertainty in risk parameters

Generalized relative risk models, with adjustments to the relative risk for time after exposure and age at exposure and incorporating a linear-quadratic dose response, were fitted to the latest (Life Span Study Report 12) Japanese atomic bomb survivor cancer mortality data using Bayesian Markov Chain Monte Carlo methods, taking account of random errors in the DS86 dose estimates. The resulting uncertainty distributions in the relative risk model parameters were used to derive uncertainties in population cancer risks for a current UK population. Following an assumed administered dose of 1 Sv, leukaemia mortality risks were estimated to be 1.93×10^–2 Sv^–1 (95% CI 1.14, 3.38), or 0.44 years of life lost Sv^–1 (95% CI 0.22, 0.94). Following an assumed administered dose of 1 Sv, solid cancer mortality risks were calculated to be 10.36×10^–2 Sv^–1 (95% CI 8.41, 12.42), or 1.38 years of life lost Sv^–1 (95% CI 1.11, 1.68). In general, solid cancer risks were very similar to those predicted by classical likelihood-based methods; however, leukaemia risks were somewhat higher, by 10–35%, than those predicted by classical likelihood-based methods. This is so in both cases, irrespective of whether or not adjustments are made in these likelihood-based fits for the effects of measurement errors, and the discrepancy for leukaemia tends to be greater at higher doses. Overall, cancer risks predicted by Bayesian Markov Chain Monte Carlo methods are similar to those derived by classical likelihood-based methods and which form the basis of established estimates of radiation-induced cancer risk. Received: 28 September 1999 / Accepted: 21 August 2000     

Radon-associated lung cancer risk among French uranium miners: modifying factors of the exposure–risk relationship

Radon is classified as a known pulmonary carcinogen in humans. A better understanding of the effects of low exposure and time-dependent factors, modifying the lung cancer risk is of continued interest. We present analyses of the exposure–risk relationship in the French cohort of uranium miners updated until 1999 and including five additional years of follow-up. These new analyses provide a better opportunity to look at low radon exposures with longer follow-up intervals, and allow consideration of new modifying factors, such as physical activity, mine location and job type. The cohort includes 5,086 miners, and 159 lung cancer deaths have been observed among these over a follow-up of more than 30 years. The exposure–risk relationship was estimated using excess relative risk models, which allow investigation of several modifying factors such as period of exposure, time since exposure, age at exposure, duration of exposure, exposure rate, job type, mine type and physical activity. The analysis confirms the association between radon exposure and lung cancer risk (ERR per 100 WLM = 0.58, P < 0.01). Period of exposure and physical activity appear as major modifying factors. Higher risks are observed for hard physical activity works. The effect of hard physical activity persists when the period of exposure is taken into account (ERR per 100 WLM = 2.95, P < 0.01).     

Leukemia incidence in the Russian cohort of Chernobyl emergency workers

Of all potentially radiogenic cancers, leukemia, a type of cancer of the blood, has the highest risk attributable to ionizing radiation. Despite this, the quantitative estimation of radiation risk of a leukemia demands studying very large exposed cohorts, because of the very low level of this disease in unexposed populations and because of the tendency for its radiation risk to decrease with time. At present, the Japanese cohort of atomic bomb survivors is still the primary source of data that allows analysis of radiation-induced leukemia and the underlying dose–response relationship. The second large cohort that would allow to study radiation-induced leukemia is comprised of individuals who were exposed due to the accident of the Chernobyl nuclear power plant in 1986. The objective of the present study was to estimate radiation risks of leukemia incidence among the Russian cohort of Chernobyl emergency workers, for different time periods after the accident. Twenty-five years after the Chernobyl accident and based on the results of the present study, one can conclude that the radiation risk of leukemia incidence derived from the Russian cohort of Chernobyl emergency workers is similar to that derived from the cohort of atomic bomb survivors: The time-averaged excess relative risk per Gray (ERR Gy⁻¹) equals 4.98 for the Russian cohort and 3.9 for the life span study (LSS) cohort; excess absolute risk decreases with time after exposure at an annual rate of 9% for the Russian cohort, and of 6.5% for the LSS cohort. Thus, the excess in risk of leukemia incidence in a population due to a single exposure is restricted in time after exposure by the period of about 15 years.     

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.     

Solid cancer incidence in atomic bomb survivors: 1958-1998

This is the second general report on radiation effects on the incidence of solid cancers (cancers other than malignancies of the blood or blood-forming organs) among members of the Life Span Study (LSS) cohort of Hiroshima and Nagasaki atomic bomb survivors. The analyses were based on 17,448 first primary cancers (including non-melanoma skin cancer) diagnosed from 1958 through 1998 among 105,427 cohort members with individual dose estimates who were alive and not known to have had cancer prior to 1958. Radiation-associated relative risks and excess rates were considered for all solid cancers as a group, for 19 specific cancer sites or groups of sites, and for five histology groups. Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, how these risks vary with gender, age at exposure, and attained age, and the evidence for inter-site variation in the levels and patterns of the excess risk. For all solid cancers as a group, it was estimated that about 850 (about 11%) of the cases among cohort members with colon doses in excess of 0.005 Gy were associated with atomic bomb radiation exposure. The data were consistent with a linear dose response over the 0- to 2-Gy range, while there was some flattening of the dose response at higher doses. Furthermore, there is a statistically significant dose response when analyses were limited to cohort members with doses of 0.15 Gy or less. The excess risks for all solid cancers as a group and many individual sites exhibit significant variation with gender, attained age, and age at exposure. It was estimated that, at age 70 after exposure at age 30, solid cancer rates increase by about 35% per Gy (90% CI 28%; 43%) for men and 58% per Gy (43%; 69%) for women. For all solid cancers as a group, the excess relative risk (ERR per Gy) decreases by about 17% per decade increase in age at exposure (90% CI 7%; 25%) after allowing for attained-age effects, while the ERR decreased in proportion to attained age to the power 1.65 (90% CI 2.1; 1.2) after allowing for age at exposure. Despite the decline in the ERR with attained age, excess absolute rates appeared to increase throughout the study period, providing further evidence that radiation-associated increases in cancer rates persist throughout life regardless of age at exposure. For all solid cancers as a group, women had somewhat higher excess absolute rates than men (F:M ratio 1.4; 90% CI 1.1; 1.8), but this difference disappears when the analysis was restricted to non-gender-specific cancers. Significant radiation-associated increases in risk were seen for most sites, including oral cavity, esophagus, stomach, colon, liver, lung, non-melanoma skin, breast, ovary, bladder, nervous system and thyroid. Although there was no indication of a statistically significant dose response for cancers of the pancreas, prostate and kidney, the excess relative risks for these sites were also consistent with that for all solid cancers as a group. Dose-response estimates for cancers of the rectum, gallbladder and uterus were not statistically significant, and there were suggestions that the risks for these sites may be lower than those for all solid cancers combined. However, there was emerging evidence from the present data that exposure as a child may increase risks of cancer of the body of the uterus. Elevated risks were seen for all of the five broadly classified histological groups considered, including squamous cell carcinoma, adenocarcinoma, other epithelial cancers, sarcomas and other non-epithelial cancers. Although the data were limited, there was a significant radiation-associated increase in the risk of cancer occurring in adolescence and young adulthood. In view of the persisting increase in solid cancer risks, the LSS should continue to provide important new information on radiation exposure and solid cancer risks for at least another 15 to 20 years.     

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.     

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.     

Radiation Effects on Mortality from Solid Cancers Other than Lung,Liver, and Bone Cancer in the Mayak Worker Cohort: 1948–2008

Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948–2008. The cohort of Mayak Production Association (PA) workers in Russia offers a unique opportunity to study the effects of prolonged low dose rate external gamma exposures and exposure to plutonium in a working age population. We examined radiation effects on the risk of mortality from solid cancers excluding sites of primary plutonium deposition (lung, liver, and bone surface) among 25,757 workers who were first employed in 1948–1982. During the period 1948–2008, there were 1,825 deaths from cancers other than lung, liver and bone. Using colon dose as a representative external dose, a linear dose response model described the data well. The excess relative risk per Gray for external gamma exposure was 0.16 (95% CI: 0.07 – 0.26) when unadjusted for plutonium exposure and 0.12 (95% CI 0.03 – 0.21) when adjusted for plutonium dose and monitoring status. There was no significant effect modification by sex or attained age. Plutonium exposure was not significantly associated with the group of cancers analyzed after adjusting for monitoring status. Site-specific risks were uncertainly estimated but positive for 13 of the 15 sites evaluated with a statistically significant estimate only for esophageal cancer. Comparison with estimates based on the acute exposures in atomic bomb survivors suggests that the excess relative risk per Gray for prolonged external exposure in Mayak workers may be lower than that for acute exposure but, given the uncertainties, the possibility of equal effects cannot be dismissed.     

Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent

Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory results. In this case–control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5′-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer risk. For women ≤50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in the analyses of cancer-associated polymorphisms.     

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.     

Studies of the mortality of atomic bomb survivors. Report 12, part II. Noncancer mortality: 1950-1990.

This report updates the data on noncancer mortality for 86,572 atomic bomb survivors with dose estimates in the Radiation Effects Research Foundation's Life Span Study cohort. The primary analyses are based on more than 27,000 noncancer disease deaths that occurred in the cohort between October 1, 1950, and December 31, 1990, 30% more than in the previous report. The present analyses strengthen earlier findings of a statistically significant increase in noncancer disease death rates with radiation dose. Increasing trends are observed for diseases of the circulatory, digestive and respiratory systems. Rates for those exposed to 1 Sv are elevated about 10%, a relative increase that is considerably smaller than that for cancer. However, estimates of the number of radiation-related noncancer deaths in the cohort to date (140 to 280) are 50 to 100% of the number for solid cancer. The data do not yet clarify the shape of the dose response. There is no significant evidence against linearity, but the data are statistically consistent with curvilinear dose-response functions that posit essentially zero risk for doses below 0.5 Sv. Similarly, while the data are consistent with substantial variation in the excess relative risk with age at exposure or attained age, there is no statistically significant dependence on these factors. In view of the small relative risks and the lack of understanding of biological mechanisms, we emphasize consideration of whether the findings could be explained by misclassification, confounding or selection effects. Based on available data, we conclude that such factors are unlikely to fully explain the observed dose response. A significant dose response is also seen for deaths from blood diseases with an excess relative risk that is several times greater than that seen for solid cancer. Particular attention is paid to the possibility that this apparent effect is a consequence of the attribution of leukemia or other cancer deaths to noncancer blood diseases. We find that misclassification does not explain this excess risk. As in earlier reports, suicide rates tend to decrease with increasing dose.     

Risks of leukemia in Japanese atomic bomb survivors, in women treated for cervical cancer, and in patients treated for ankylosing spondylitis.

The dose-response relationship for radiation-induced leukemia was examined in a pooled analysis of three exposed populations: Japanese atomic bomb survivors, women treated for cervical cancer, and patients irradiated for ankylosing spondylitis. A total of 383 leukemias were observed among 283,139 study subjects. Considering all leukemias apart from chronic lymphocytic leukemia, the optimal relative risk model had a dose response with a purely quadratic term representing induction and an exponential term consistent with cell sterilization at high doses; the addition of a linear induction term did not improve the fit of the model. The relative risk decreased with increasing time since exposure and increasing attained age, and there were significant (P < 0.00001) differences in the parameters of the model between datasets. These differences were related in part to the significant differences (P = 0.003) between the models fitted to the three main radiogenic leukemia subtypes (acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia). When the three datasets were considered together but the analysis was repeated separately for the three leukemia subtypes, for each subtype the optimal model included quadratic and exponential terms in dose. For acute myeloid leukemia and chronic myeloid leukemia, there were reductions of relative risk with increasing time after exposure, whereas for acute lymphocytic leukemia the relative risk decreased with increasing attained age. For each leukemia subtype considered separately, there was no indication of a difference between the studies in the relative risk and its distribution as a function of dose, age and time (P > 0.10 for all three subtypes). The nonsignificant indications of differences between the three datasets when leukemia subtypes were considered separately may be explained by random variation, although a contribution from differences in exposure dose-rate regimens, inhomogeneous dose distribution within the bone marrow, inadequate adjustment forcell sterilization effects, or errors in dosimetry could have played a role.     

Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.     

Studies of mortality of atomic bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950-1997

This continues the series of general reports on mortality in the cohort of atomic bomb survivors followed up by the Radiation Effects Research Foundation. This cohort includes 86,572 people with individual dose estimates, 60% of whom have doses of at least 5 mSv. We consider mortality for solid cancer and for noncancer diseases with 7 additional years of follow-up. There have been 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases during the 47-year follow-up. Of these, 19% of the solid cancer and 15% of the noncancer deaths occurred during the latest 7 years. We estimate that about 440 (5%) of the solid cancer deaths and 250 (0.8%) of the noncancer deaths were associated with the radiation exposure. The excess solid cancer risks appear to be linear in dose even for doses in the 0 to 150-mSv range. While excess rates for radiation-related cancers increase throughout the study period, a new finding is that relative risks decline with increasing attained age, as well as being highest for those exposed as children as noted previously. A useful representative value is that for those exposed at age 30 the solid cancer risk is elevated by 47% per sievert at age 70. There is no significant city difference in either the relative or absolute excess solid cancer risk. Site-specific analyses highlight the difficulties, and need for caution, in distinguishing between site-specific relative risks. These analyses also provide insight into the difficulties in interpretation and generalization of LSS estimates of age-at-exposure effects. The evidence for radiation effects on noncancer mortality remains strong, with risks elevated by about 14% per sievert during the last 30 years of follow-up. Statistically significant increases are seen for heart disease, stroke, digestive diseases, and respiratory diseases. The noncancer data are consistent with some non-linearity in the dose response owing to the substantial uncertainties in the data. There is no direct evidence of radiation effects for doses less than about 0.5 Sv. While there are no statistically significant variations in noncancer relative risks with age, age at exposure, or sex, the estimated effects are comparable to those seen for cancer. Lifetime risk summaries are used to examine uncertainties of the LSS noncancer disease findings.     

FISH chromosome aberration analysis on retired radiation workers from the Sellafield nuclear facility

Chromosome analysis using fluorescence in situ hybridization was undertaken on 294 retired workers from the British Nuclear Fuels plc facility at Sellafield, 95 with external occupational exposure <50 mSv, 108 with 50-499 mSv, and 91 with >500 mSv. In univariate analyses, external dose (P <10-s) and age (P = 0.0075) were significantly associated with translocation frequency, but no effect was found for smoking status. In a multivariate analysis with age and external dose as continuous variables, the slopes were 0.017 +/- 0.0075 x 10(-2) translocations per cell per year for age (P = 0.024) and 1.11+/- 0.190 x 10(-2) translocations per cell per sievert for external dose (P < 10(-5)). The dose response for translocation induction for occupational workers is similar to the linear component of in vitro dose-response curves, thus supporting the use of translocation frequency for retrospective biological dosimetry in situations of chronic low-dose exposure occurring over many years. The dose response obtained in this study is lower than the linear component of the dose response for stable chromosome aberrations obtained for the Japanese atomic bomb survivors. Thus, if chromosome aberration levels are indicative of cancer risk, this would suggest that low-dose risks derived from the Japanese atomic bomb survivor data will overestimate the risks associated with the occupational exposure encountered by the men in this study.     

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.