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PubMed1994

Relationship of five anthropometric measurements at age 18 to radiation dose among atomic bomb survivors exposed in utero.

Five body measurements--standing height, body weight, sitting height, chest circumference and intercristal diameter--of 18-year-old atomic bomb survivors exposed in utero in Hiroshima and Nagasaki were analyzed in relation to DS86 uterine dose. Age in utero was divided into four periods: 0-7, 8-15, 16-25 and > or = 26 weeks. This categorization is based upon the study of radiation-induced brain damage. The linear regression analyses for these five variables showed significant decreases with increasing dose. The regression coefficients were -2.65 cm/Gy for standing height, -2.46 kg/Gy for body weight, -0.92 cm/Gy for sitting height, -1.37 cm/Gy for chest circumference and -0.32 cm/Gy for intercristal diameter. The multivariate test statistic for the overall dose effect on five body measurements was significant, but the interaction between dose and gestational period was not significant. Principal-component analysis was applied to the five variables. For the first-component scores, the dose effect was significant, but the interaction between dose and gestational period was not significant. For the second-component scores, the dose effect was significant specifically at 0-7 weeks. The radiation dose effect on the second principal component found at 0-7 weeks of gestation suggests that malformations occur in this period.

Adolescent↗
PubMed1993

Stable chromosome aberrations among A-bomb survivors: an update.

Analysis of data on stable chromosome aberrations collected between 1968 and 1985 by the Radiation Effects Research Foundation (RERF) on 1703 individuals exposed to A-bomb radiation in Hiroshima and Nagasaki, Japan, reveals different dose-response relationships in the two cities, as well as significant effects of both time of assay and age at exposure. In Hiroshima, the proportion of cells with aberrations increased by 0.080 per sievert at low doses, assuming a constant neutron radiation RBE of 10 relative to gamma radiation, for assays performed during the latest period (1981-1985). In Nagasaki, the low-dose increase was 0.0126 per sievert. There was evidence that radiation exposure was more effective for producing stable aberrations at some younger ages at exposure, although the interpretation of this interaction is difficult. Modeling neutron and gamma-ray components of dose separately in a way which allows the neutron RBE to vary with dose yielded an estimated low-dose limiting value of RBE of 707 (95% confidence bound 200-infinity), with a low-dose response of approximately 0.008 aberrations per sievert. This RBE is much higher than the published RBEs for induction of aberrations in vitro. The high estimated RBE and the differences in dose response by city both are suggestive of systematic dose estimation errors in which either neutrons were underestimated in Hiroshima or gamma rays were overestimated in Nagasaki.

Adolescent↗
PubMed1993

Dose survival of G0 lymphocytes irradiated in vitro: a test for a possible population bias in the cohort of atomic bomb survivors exposed to high doses.

This study was intended to test for a possible early selective loss of relatively radiosensitive individuals from those atomic bomb survivors exposed to high doses using an in vitro X-ray dose-survival assay of peripheral blood lymphocytes. The assay was reasonably reproducible since the coefficient of variation (CV) was 8.2% for the mean D10 (the dose required to kill 90% of cells) of 3.39 Gy after 15 repeat tests for one control donor during the study period. The CV for single tests for 201 survivors was essentially the same, i.e., 7.7% with a mean D10 of 3.37 Gy, indicating very little heterogeneity of lymphocyte radiosensitivity among individuals. Linear regression analysis of D10 on the DS86 dose showed no evidence for the consistent change in average D10 values among the survivors exposed to high doses. The results might imply that the G0 lymphocytes do not express full variations in radiosensitivity and may not be suitable for quantitative measurements of relative radiosensitivity. Alternatively, the very small variation in lymphocyte radiosensitivity may be real and detection of the rare individuals with altered radiosensitivity may require much larger-scale testing. Therefore, no conclusive answer to the question of population bias was provided for the survivors.

Adult↗
PubMed1993

Noncancer disease incidence in the atomic bomb survivors: 1958-1986.

Using the longitudinal data of the Adult Health Study (AHS) cohort collected during 1958-1986, we examined for the first time the relationship between exposure to ionizing radiation and the incidence of 19 nonmalignant disorders in the A-bomb survivors. Affected individuals were ascertained through the three-digit codes of the International Classification of Diseases which are encoded in the AHS database subsequent to diagnoses made on the basis of general laboratory tests, physical examinations, and history-taking conducted during biennial AHS examinations. The disease onset time was estimated using the mid-point between the AHS examination data when the disease was initially reported and the previously attended disease-free examination date. Dosimetry System 86 organ doses judged to be most appropriate were used. Tests of dose effects were performed assuming a linear relative risk model with stratified background incidence. For the entire study period, significant excess risk was detected for uterine myoma (P < 0.001), chronic liver disease and cirrhosis (P = 0.006), and thyroid disease (P < 0.0001), defined broadly as the presence of one or more of certain noncancerous thyroid conditions. The incidence of myocardial infarction was shown to be increased (P = 0.03) in later years (1968-1986) among the younger heavily exposed AHS subjects, confirming the results of the recent Life Span Study (LSS) noncancer mortality report on coronary heart disease. The findings for uterine myoma may serve as additional evidence indicating benign tumor growth as a possible consequence of radiation exposure. Our results indicating the involvement of radiation in the development of liver diseases are consistent with the report of increased mortality from liver cirrhosis with radiation dose in the LSS cohort. An effect of age at exposure was detected for nonmalignant thyroid disease (P = 0.02), with an increased risk for those exposed who were under 20 years of age, but not for older survivors. Thus the AHS data suggest that thyroid glands in the young are more radiosensitive not only to the development of malignancies, but also to the development of nonmalignant disorders as well. The findings hold independently of the dose effects observed for thyroid cancer. This study also shows that for the period 1958-1986 new occurrences of lens opacity are not increased with radiation dose (P = 0.39) in the AHS subjects.

Adult↗
PubMed1993

Study of the titers of anti-Epstein-Barr virus antibodies in the sera of atomic bomb survivors.

Antibody titers to Epstein-Barr virus antigens were determined in the sera of 372 atomic bomb survivors to evaluate the effect of the previous radiation exposure on immune competence against the latent infection of the virus. The proportion of persons with high titers (> or = 1:40) of IgG antibodies to the early antigen was significantly elevated in the exposed survivors. Furthermore, the distribution of IgM titers against the viral capsid antigen was significantly affected by radiation dose with an increased occurrence of titers of 1:5 and 1:10 in the exposed persons, although the dose effect was only marginally suggestive when persons with rheumatoid factor were eliminated from the analysis. These results suggest that reactivation of Epstein-Barr virus in the latent stage occurs more frequently in the survivors, even though this might not be affected by the radiation dose. Otherwise, there was neither an increased trend in the prevalence of high titers (> or = 1:640) of IgG antibodies to the viral capsid antigen among the exposed people nor a correlation between the radiation exposure and distributions of titers of IgA antibodies to the viral capsid antigen or antibodies to the anti-Epstein-Barr virus-associated nuclear antigen.

Adult↗
PubMed1993

A longitudinal study of growth and development of stature among prenatally exposed atomic bomb survivors.

Growth retardation due to exposure to the atomic bomb has been evaluated using repeated measurements of stature from 10 to 18 years of age. A highly significant growth retardation due to the DS86 uterine dose was observed in all trimesters combined and in the first and second trimesters of pregnancy. In the first trimester, all parameter estimates based on a linear (L) or linear-quadratic (L-Q) dose-response relationship were negative in relation to the DS86 uterine dose. The positive dose estimate in the second trimester is small and close to the control level. Statistically significant difference was determined by a multivariate test statistic examining whether or not a set of two- or three-parameter estimates including a constant term related to an L or L-Q dose-response relationship was different from zero. A radiation-related growth retardation was demonstrable as a longitudinal result of the repeated measurements of stature. The dose effect in the third trimester was not significant under either the L or the L-Q model. The relationship between birth weights and repeated measurements of stature in adolescence is discussed based on the results obtained by a growth curve analysis.

Adolescent↗
PubMed1993

Joint analysis of site-specific cancer risks for the atomic bomb survivors.

Statistical methods are presented for joint analysis of site-specific cancer risks for the atomic bomb survivors. Previous analyses of these data have been made either without regard to cancer type, excluding leukemia, or separately for types or classes of cancers. Clearly, analyses without regard to cancer type are less than satisfactory. The primary advantages of joint, rather than separate, analyses are that: (1) models can be fitted with some parameters common to cancer types and others type-specific; (2) significance tests can be used to compare type-specific risks; and (3) through consideration of more comprehensive models, a clearer understanding may be obtained of the modifying effects of sex, age at exposure, and time since exposure. Joint analysis is straightforward, entailing primarily the incorporation of another factor, cancer type, in the usual cross-tabulation of the data for analysis. The use of these methods is illustrated in an analysis of three classes of cancer studied by the National Research Council's BEIR V Committee: digestive, respiratory, and other solid tumors. Based on this analysis, some criticism is made of the BEIR V preferred models. The proposed methods are applicable to models for either relative or absolute risks, and results using both types of models are given. Although some of the gains from joint analysis are apparent from the results here, it will be important to use these methods with a more suitable choice of cancer classes and for cancer incidence data where the diagnoses are more accurate.

Age Factors↗
PubMed1995

Lack of effects of atomic bomb radiation on genetic instability of tandem-repetitive elements in human germ cells.

In a pilot study to detect the potential effects of atomic bomb radiation on germ-line instability, we screened 64 children from 50 exposed families and 60 from 50 control families for mutations at six minisatellite loci by using Southern blot analysis with Pc-1, lambda TM-18, ChdTC-15, p lambda 3, lambda MS-1, and CEB-1 probes. In the exposed families, one or both parents received a radiation dose > 0.01 Sv. Among the 64 children, only one child had parents who were both exposed. Thus, of a total of 128 gametes that produced the 64 children, 65 gametes were derived from exposed parents and 63 were from unexposed parents, the latter being included in a group of 183 unexposed gametes used for calculating mutation rates. The average parental gonadal dose for the 65 gametes was 1.9 Sv. We detected a total of 28 mutations at the p lambda g3, lambda MS-1, and CEB-1 loci, but no mutations at the Pc-1, lambda TM-18, and ChdTC-15 loci. We detected 6 mutations in 390 alleles of the 65 exposed gametes and 22 mutations in 1098 alleles of the 183 gametes from the unexposed parents. The mean mutation rate per locus per gamete in these six minisatellite loci was 1.5% in the exposed parents and 2.0% in the unexposed parents. We observed no significant difference in mutation rates in the children of the exposed and the unexposed parents (P = .37, Fisher's exact probability test).

Chromosome Mapping↗
PubMed1996

Breast cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with breast cancer mortality in the atomic bomb survivors study.

The relationship between exposure to low-linear energy transfer ionizing radiation and subsequent breast cancer mortality risk is reported based on a further 7 years of follow-up in the Canadian fluoroscopy study. Amongst 31,917 women first treated for tuberculosis in a Canadian institution between 1930 and 1952, a total of 688 breast cancer deaths were observed between 1950 and 1987. There is a strong linear trend of increasing risk with increasing dose (P < 0.0001), with the excess relative risk per sievert decreasing with age at exposure (P = 0.0003). The excess relative risk is approximately constant between 5 and 39 years after exposure, with a suggestion of a decrease between 40 and 57 years after exposure, though this could be a chance effect (P = 0.22). Combined analyses of the Canadian fluoroscopy data and the data for the atomic bomb survivors with respect to breast cancer mortality are also reported. In general the two studies are reasonably consistent, the only distinct difference being the much greater excess relative risk per sievert amongst women exposed to very high doses in the province of Nova Scotia (P, heterogeneity <0.0001). Based on the combined data sets a simple relative risk (RR) model for the effect of a dose of D sieverts at age A years is developed: RR(D) = 1.0 + 0.52D exp[-0.10(A-15)]. This model fits the combined data well, and is used to predict excess lifetime risks of breast cancer mortality after radiation exposure from routine annual mammography.

Adolescent↗
PubMed1996

Studies of the mortality of atomic bomb survivors. Report 12, Part I. Cancer: 1950-1990.

This continues the series of periodic general reports on cancer mortality in the cohort of A-bomb survivors followed by the Radiation Effects Research Foundation. The follow-up is extended by the 5 years 1986-1990, and analysis includes an additional 10,500 survivors with recently estimated radiation doses. Together these extensions add about 550,000 person-years of follow-up. The cohort analyzed consists of 86,572 subjects, of which about 60% have dose estimates of at least 0.005 Sv. During 1950-1990 there have been 3086 and 4741 cancer deaths for the less than and greater than 0.005 Sv groups, respectively. It is estimated that among these there have been approximately 420 excess cancer deaths during 1950-1990, of which about 85 were due to leukemia. For cancers other than leukemia (solid cancers), about 25% of the excess deaths in 1950-1990 occurred during the last 5 years; for those exposed as children this figure is nearly 50%. For leukemia only about 3% of the excess deaths in 1950-1990 occurred in the last 5 years. Whereas most of the excess for leukemia occurred in the first 15 years after exposure, for solid cancers the pattern of excess risk is apparently more like a life-long elevation of the natural age-specific cancer risk. Taking advantage of the lengthening follow-up, increased attention is given to clarifying temporal patterns of the excess cancer risk. Emphasis is placed on describing these patterns in terms of absolute excess risk, as well as relative risk. For example: (a) although it is becoming clearer that the excess relative risk for those exposed as children has declined over the follow-up, the excess absolute risk has increased rapidly with time; and (b) although the excess relative risk at a given age depends substantially on sex and age at exposure, the age-specific excess absolute risk depends little on these factors. The primary estimates of excess risk are now given as specific to sex and age at exposure, and these include projections of dose-specific lifetime risks for this cohort. The excess lifetime risk per sievert for solid cancers for those exposed at age 30 is estimated at 0.10 and 0.14 for males and females, respectively. Those exposed at age 50 have about one-third these risks. Projection of lifetime risks for those exposed at age 10 is more uncertain. Under a reasonable set of assumptions, estimates for this group range from about 1.0-1.8 times the estimates for those exposed at age 30. The excess life-time risk for leukemia at 1 Sv for those exposed at either 10 or 30 years is estimated as about 0.015 and 0.008 for males and females, respectively. Those exposed at age 50 have about two-thirds that risk. Excess risks for solid cancer appear quite linear up to about 3 Sv, but for leukemia apparent nonlinearity in dose results in risks at 0.1 Sv estimated at about 1/20 of those for 1.0 Sv. Site-specific risk estimates are given, but it is urged that great care be taken in interpreting these, because most of their variation can be explained simply by imprecision in the estimates.

Adolescent↗
PubMed1996

Incidence of salivary gland tumors among atomic bomb survivors, 1950-1987. Evaluation of radiation-related risk.

A wide-ranging search for benign and malignant tumors of the major and minor salivary glands among members of the Life Span Study sample of the Radiation Effects Research Foundation identified 41 malignant and 94 benign incident tumors, including 14 malignant and 12 benign tumors of the minor salivary gland, plus 10 major gland tumors of unknown behavior. Dose-response analyses found statistically significant increases in risk with increasing A-bomb dose for both cancer and benign tumors. Estimated relative risks at 1 Sv weighted tissue kerma (RR1Sv, with 90% confidence interval in parentheses) were 4.5 (2.5-8.5) for cancer and 1.7 (1.1-2.7) for benign tumors. When analyzed by histological subtype within these two broad groups, it appeared that most of the dose response for malignant tumors was provided by an exceptionally strong dose response for mucoepidermoid carcinoma [11 exposed cases with dose estimates, RR1Sv = 9.3 (3.5-30.6)], and most or all of that for benign tumors corresponded to Warthin's tumor [12 cases, RR1Sv = 4.1 (1.6-11.3)]. There was a marginal dose response for malignant tumors other than mucoepidermoid carcinoma [RR1Sv = 2.4 (0.99-5.7)] but no significant trend for benign tumors other than Warthin's tumor [RR1Sv = 1.3 (0.9-2.2)]. Re-examination of the original data from published studies of other irradiated populations may shed new light on the remarkable type specificity of the salivary tumor dose response observed in the present study.

Dose-Response Relationship, Radiation↗
PubMed1996

Cataract in atomic bomb survivors based on a threshold model and the occurrence of severe epilation.

This report re-examines the relationship of radiation dose to the occurrence of cataracts among 1742 atomic bomb survivors seen in the years 1963-1964 for whom the degree of epilation and Dosimetry System 1986 (DS86) doses are known. Of these individuals, 67 had cataracts. A relative risk model with two thresholds, one for the epilation group and the other for the no-epilation group, has been fitted to the data using a binomial odds regression approach and a constant relative biological effectiveness (RBE) for neutrons of 10. Among these models, a linear-linear (L-L) dose-response relationship with two thresholds presents the best fit. Under the L-L threshold model based on DS86 eye organ dose estimates for the epilation and no-epilation groups, the slope estimate for the epilation group was 1.6-2.0 times greater than that for the no-epilation group, but no statistical difference between the two slope estimates was noted. The estimated threshold for the epilation group was 0.86 Sv and 1.54 Sv for the no-epilation group, but again the difference between the two threshold estimates is not statistically significant. When an L-L relative risk model with two thresholds was fitted to the data assuming the dose estimates to be in error by 35%, or when the data were restricted to the 1105 individuals exposed in Japanese houses at distances of less than 2500 m, where the DS86 doses are thought to be most reliable, the results were almost the same as those for the individuals for whom unadjusted DS86 eye organ dose estimates were used.

Adult↗
PubMed1996

Biodosimetry: chromosome aberration in lymphocytes and electron paramagnetic resonance in tooth enamel from atomic bomb survivors.

One hundred enamel samples isolated from extracted teeth donated by atomic bomb survivors were subjected to free radical measurement by means of electron paramagnetic resonance (ESR). Results comparing ESR with the chromosome aberration frequency in lymphocytes of the tooth donors, and with the physically estimated DS86 dose suggested that ESR data correlated more closely with chromosome data than with the estimated DS86 doses, probably because DS86 may depend on erroneous memory in some cases.

Adult↗
PubMed1996

[Analysis of participation rates of atomic bomb survivors in health examinations].

Participation rates of atomic bomb survivors in health examinations were analyzed with a multiple logistic regression model. Rates were obtained for each stratum by sex, age group and residential ward. The effect of residential wards was considered in relation to the social indices of the wards. The effects of sex, age group and residential ward on participation rates were as follows: (1) Females had higher participation rates than males in the working age group (40-64). No sex differences were seen after age 65. (2) The participation rates had a peak around age 70 and were exceptionally high also in the youngest age group (40-44). (3) Participation rates were higher in suburban wards than in central wards. The participation rates had a negative correlation with urban characteristics while they had a positive correlation with suburban characteristics. In particular they had significant negative correlation to the number of clinics and positive correlation with voter participation rates in elections. These results suggest the need for a new type of urban health examination and reflection of the general attitude of the residents to the government.

Adult↗
PubMed1997

Cancer mortality among atomic bomb survivors exposed in utero or as young children, October 1950-May 1992.

Cancer mortality for the period from October 1950 through May 1992 was analyzed in atomic bomb survivors exposed in utero. Risk estimates for this group were also compared to those for survivors who were less than 6 years old at the time of exposure. The cohorts studied include 807 in utero survivors and 5,545 persons exposed during childhood with all members of both groups having estimated doses of at least 0.01 Sv. The comparison group includes 10,453 persons with little (<0.01 Sv) or no exposure. Analyses were limited mainly to cancer deaths occurring between the ages of 17 and 46. Only 10 cancer deaths were observed among persons exposed in utero. However, there is a significant dose response with an estimate of excess relative risk per sievert (ERR/Sv) of 2.1 (90% confidence interval of 0.2 to 6.0). This estimate does not differ significantly from that for survivors exposed during the first 5 years of life. The cancer deaths among those exposed in utero involved leukemia (2), female-specific organs (3) and digestive organs (5). Nine deaths occurred in females, where the excess risk for all solid cancers has a 90% confidence interval on the ERR/Sv of 1.6 to 17. Significant risks were found for cancers of the digestive system [90% confidence interval (CI) on the ERR/Sv of 0.7 to 20] and for female-specific cancers (90% CI on the ERR/Sv of 0.7 to 42). These risks do not differ significantly from those seen in females exposed as children. There were no deaths from solid cancer in men exposed in utero. The ERR/Sv has an upper 95% confidence bound of 2.5 which does not differ from that for exposed children, where the upper 95% confidence bound is 1.5. The sexes differ even when female-specific cancers are excluded from the comparison. Although there were only two leukemia deaths among those exposed in utero, the leukemia death rate for this group is higher than that in the comparison group (P = 0.054) with an exposure effect that is about half the magnitude and not significantly different from that seen after childhood exposure (P = 0.103). However, there is no evidence of a dose response among those exposed in utero because no high-dose leukemia deaths were observed, a result that differs considerably from that for those exposed as children. There is a need for caution in the interpretation of these data. First, the number of cancer deaths is small; second, there is unexplained significant difference in the mortality from solid cancer between the sexes; and third, the excess of leukemia in those exposed in utero is not reflected in an increasing dose response.

Adult↗
PubMed1997

Suicidal terrorist bombings in Israel--identification of human remains.

Positive identification of human remains is one of the most important tasks in mass disaster investigations. Religious and jurisdictional demands in Israel, require the identification process to be completed in the shortest possible time. In the 18 suicidal terrorist bombings that took place in Israel between the years 1993-1996, 127 victims and 19 perpetrators were killed, and their severely fragmented bodies were identified within 24 h. The efficient completion of the identification endeavor was enabled by the implementation of a variety of techniques and the close collaboration in the investigation between the different emergency and forensic agencies. This paper presents the mass disaster identification policy and techniques currently used in Israel. The importance of an interdisciplinary approach for the identification of extremely fragmented human remains from mass disasters and the creation of a central data bank of fingerprints and genetic markers is emphasized.

Adolescent↗
PubMed1997

Prevalence of uterine myoma detected by ultrasound examination in the atomic bomb survivors.

Benign tumors of several organs have been demonstrated to occur as late effects of atomic bomb exposure, and a recent addition to the list of affected organs is the uterus. The increased incidence of uterine myoma noted in Radiation Effects Research Foundation (RERF) Adult Health Study Report 7 (Wong et al., Radiat, Res. 135, 418-430, 1993), however, was based on self-reported information, optional gynecological examination and patient-requested ultrasound examination. Thus the possibility of dose-related bias in case detection was a serious concern. Therefore, the relationship between the prevalence of uterine myoma and dose to the uterus was examined after excluding as much bias as possible by asking all women who had undergone biennial examinations from December 1991 through December 1993 to undergo ultrasound examinations. Among 2506 female participants in Hiroshima, the uterus was visualized by ultrasound examination in 1190, and 238 were found to have uterine nodules. Multiple logistic analysis using Dosimetry System 1986 uterine doses revealed a significant dose response for the prevalence of uterine nodules. The odds ratio at 1 Gy was 1.61 (95% confidence interval: 1.12-2.31). It is unlikely that the observed relationship after adjusting for bladder filling, volume of the uterus, age and menopause status was the result of dose-related bias. These results support previous findings at RERF and provide further evidence that radiation exposure is one of the factors associated with uterine myoma.

Adult↗
PubMed1997

Issues in the comparison of risk estimates for the population in the Techa River region and atomic bomb survivors.

Plutonium production in the former Soviet Union began in 1949 at the Mayak Production Association located between the cities of Chelyabinsk and Ekaterinbourg in the southern Ural mountains about 1200 km east to Moscow. During the first few years of Mayak's operation, almost 30,000 people living on the banks of the Techa River received significant internal and external exposures as a consequence of the release of large quantities of radioactive materials from Mayak. Studies of levels of radioactive contamination and health effects in this population began in the early 1950s. A systematic follow-up of a fixed cohort that includes all people who were living in Techa River villages in 1949 was begun about 30 years ago. In this paper we describe the Techa River cohort, outline the nature of the exposures and discuss the status of follow-up for the period from 1950 through 1989. While noting the limitations of the current epidemiological follow-up data, we also compare the demographic and mortality structure of the Techa River cohort with the Life Span Study cohort of Japanese atomic bomb survivors. It is seen that, despite a number of limitations, the current data suggest that the risks of mortality from leukemia and other cancers increase with increasing radiation dose in the Techa River cohort. This finding suggests that, with continued improvements in the quality of the follow-up and dosimetry, the Techa River cohort has the potential to provide quantitative estimates of the risks of chronic low-dose-rate radiation exposures for an unselected general population that will be an important complement to the estimates based on the Life Span Study that are used as the primary basis for numerical assessments of radiation risk.

Environmental Exposure↗