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PubMed1991

The shape of the cancer mortality dose-response curve for the A-bomb survivors.

The shape of the dose-response curve for cancer mortality in the A-bomb survivor data is analyzed in the context of linear-quadratic models. Results are given for all cancers except leukemia as a group, for leukemia, and for combined inferences assuming common curvature. Since there is substantial information aside from these data suggesting a dose-response curve with upward curvature, the emphasis here is not on estimating the best-fitting dose-response curve, but rather on assessing the maximum curvature under linear-quadratic models which is consistent with the data. The apparent shape of the dose-response curve is substantially affected by imprecision in the dose estimates, and methods are applied to correct for this. The extent of curvature can be expressed as the factor by which linear risk estimates from these data should be divided to arrive at appropriate estimates of risk at low doses. Influential committees have in the past recommended ranges of 1.5-4 and of 2-10 for such a factor. Results here suggest that values greater than about 2.0-2.5 are at least moderately inconsistent with these data, within the context of linear-quadratic models. It is emphasized, however, that there is little direct information in these data regarding risks following low doses; the inferences here depend strongly on the assumption of a linear-quadratic model.

Dose-Response Relationship, Radiation↗
PubMed1991

Analysis of time and age patterns in cancer risk for A-bomb survivors.

This report has two aims: (1) to describe and analyze the age/time patterns of excess cancer risk in the atomic bomb survivor cohort followed up by the Radiation Effects Research Foundation (RERF), and (2) to describe statistical methods which are used in RERF's analyses of data on mortality and morbidity in the cohort. In contrast to previous analyses of the cohort cancer mortality data, substantial use is made of Japanese national cancer rates for the purpose of investigation of the age/time variations in excess risk. This analysis considers mortality from all cancers except leukemia as a group. Primary attention is given to description in terms of the age-specific excess relative risk, but the importance of appropriate descriptions of the absolute excess risk is also emphasized. When models for the excess risk allow variation with age and time, both constant relative and absolute excess risk models provide similar fits to the data. Previous reports have indicated that for a given age at exposure and sex, the excess age-specific relative risk is remarkably constant throughout the current follow-up period. Statistical analysis here indicates that for those less than about 35 years of age at exposure there is no departure from this pattern, beyond ordinary sampling variation. For those over about 35 years of age at exposure, there is modest evidence of an increasing trend in the excess relative risk, which could plausibly be attributed to effects related to minimal latent period. Some brief consideration is given to modeling the absolute excess risk as the product of an age-at-exposure and time-since-exposure effect. Interpretation of these results, particularly in regard to projections beyond the current follow-up, is discussed.

Age Factors↗
PubMed1990

[Occurrence of breast cancer, renal cancer and multiple myeloma in a Nagasaki atomic bomb survivor].

A 60-year-old female, who was exposed to the Nagasaki atomic bomb at 18 years old, had renal cancer and subsequently was found to have multiple myeloma (IgG kappa). She underwent the left mastectomy for breast cancer at 43 years old but was not given chemotherapy and radiotherapy. The karyotype of bone marrow cells was 46, XX. The estimated radiation dose was under 10 rads. While the effect of such a low-dose of radiation is considered to be almost negligible, there would be a possibility that in this case the risk of carcinogenesis was enhanced as her age advanced.

Breast Neoplasms↗
PubMed1990

Allowing for random errors in radiation dose estimates for the atomic bomb survivor data.

The presence of random errors in the individual radiation dose estimates for the A-bomb survivors causes underestimation of radiation effects in dose-response analyses, and also distorts the shape of dose-response curves. Statistical methods are presented which will adjust for these biases, provided that a valid statistical model for the dose estimation errors is used. Emphasis is on clarifying some rather subtle statistical issues. For most of this development the distinction between radiation dose and exposure is not critical. The proposed methods involve downward adjustment of dose estimates, but this does not imply that the dosimetry system is faulty. Rather, this is a part of the dose-response analysis required to remove biases in the risk estimates. The primary focus of this report is on linear dose-response models, but methods for linear-quadratic models are also considered briefly. Some plausible models for the dose estimation errors are considered, which have typical errors in a range of 30-40% of the true values, and sensitivity analysis of the resulting bias corrections is provided. It is found that for these error models the resulting estimates of excess cancer risk based on linear models are about 6-17% greater than estimates that make no allowance for dose estimation errors. This increase in risk estimates is reduced to about 4-11% if, as has often been done recently, survivors with dose estimates above 4 Gy are eliminated from the analysis.

Bias↗
PubMed1990

Phagocytic and bactericidal activities of leukocytes in whole blood from atomic bomb survivors.

This study evaluated the phagocytic and bactericidal activities of peripheral blood leukocytes from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression for age, sex, radiation exposure, city of exposure, and neutrophil counts. No significant radiation effect was observed for either blood phagocytic or bactericidal activities. The only significant variable for these functions was the neutrophil count.

Adult↗
PubMed1990

Studies of the mortality of A-bomb survivors. 9. Mortality, 1950-1985: Part 2. Cancer mortality based on the recently revised doses (DS86).

The present study, the ninth in a series that began in 1961, extends the time of surveillance 3 more years and covers the period 1950-1985. It is based on the recently revised doses, termed the DS86. The impact of the change from the T65D to the DS86 on the dose-response relationships for cancer mortality was described in the first of this series of reports. Here, the focus is on cancer mortality among the 76,000 A-bomb survivors within the LSS sample for whom DS86 doses have been estimated, with the emphasis on biological issues associated with radiation carcinogenesis. Briefly, the following is found: The excess in leukemia mortality has continued to decline with time, but remains slightly but significantly elevated in 1981-1985 in Hiroshima. For cancers other than leukemia, as a group, excess deaths continue to increase over time in direct proportion to the normal increase in natural cancer mortality with increasing age, and the relative risk seems unchanged over time within age ATB cohorts. The single exception is the cohort under 10 years of age ATB. Within this group of survivors, where the relative risk, although based on relatively few deaths, has been quite high at the higher doses, as judged by deaths before the age of 30, the risk has fallen and has remained fairly constant at a lower level thereafter. Thus the present analysis still supports, in the main, estimation of lifetime risk based on the assumption of a constant relative risk. For the same age ATD, both the relative and absolute risks are higher for younger age ATB cohorts than older ones for cancers other than leukemia. There is no statistically significant difference in excess deaths between males and females except for leukemia, though the relative risk is higher for females than for males, significantly so for cancers of the esophagus and lung, reflecting the higher background cancer rate for males. Significant dose responses are observed for leukemia, cancers of the esophagus, stomach, colon, lung, breast, ovary, and urinary bladder and multiple myeloma, as previously observed. No significant increase is demonstrable as yet for cancers of the rectum, gallbladder, pancreas, uterus, and prostate and malignant lymphoma. In the present report, cancers of the bone, pharynx, nose, and larynx, and skin except melanoma are also examined, but none of these sites show a significant increase with dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1990

Congenital malformations, stillbirths, and early mortality among the children of atomic bomb survivors: a reanalysis.

Of all the data sets pertinent to the estimation of the genetic risks to humans following exposure to ionizing radiation, potentially the most informative is that composed of the cohort of children born to atomic bomb survivors. We present here an analysis of the relationship between parental exposure history and untoward pregnancy outcomes within this cohort, using to the fullest extent possible the recently revised estimates of the doses received by their parents, the so-called DS86 doses. Available for study are 70,073 terminations, but DS86 doses have not been or presently cannot be computed on the parents of 14,770. The frequency of untoward pregnancy outcomes, defined as a pregnancy terminating in a child with a major congenital malformation, and/or stillborn, and/or dying in the first 14 days of life, increases with combined (summed) parental dose, albeit not significantly so. Under a standard linear model, when the sample of observations is restricted to those children whose parents have been assigned the newly established DS86 doses (n = 55,303), ignoring concomitant sources of variation and assuming a neutron RBE of 20, the estimated increase per sievert in the predicted frequency of untoward outcomes is 0.00354 (+/- 0.00343). After adjustment for concomitant sources of variation, the estimated increase per sievert in the proportion of such births is 0.00422 (+/- 0.00342) if the neutron RBE is assumed to be 20. A "one-hit" model with appropriate adjustments for extraneous sources of variation results in an almost identical value, namely, 0.00412 (+/- 0.00364). When the sample is extended to include parents lacking the full array of dose parameters necessary to calculate the DS86 dose, but sufficient for an empirical conversion of the previously employed T65DR dose system to its DS86 equivalent, we find under the linear model that the estimated increase per sievert in untoward pregnancy outcomes is some 31% higher than that published previously, 0.00264 (+/- 0.00277), assuming an RBE of 20, after adjustment for extraneous sources of variation. (Since a dose could not be calculated in 367 of the 70,073 outcomes, the n = 69,706). The corresponding value with the one-hit model is 0.00262 (+/- 0.00294).

Cohort Studies↗
PubMed1990

The children of parents exposed to atomic bombs: estimates of the genetic doubling dose of radiation for humans.

The data collected in Hiroshima and Nagasaki during the past 40 years on the children of survivors of the atomic bombings and on the children of a suitable control population are analyzed on the basis of the newly revised estimates of radiation doses. No statistically significant effects emerge with respect to eight different indicators. Since, however, it may confidently be assumed some mutations were induced, we have taken the data at face value and calculated the minimal gametic doubling doses of acute radiation for the individual indicators at various probability levels. An effort has also been made to calculate the most probable doubling dose for the indicators combined. The latter value is between 1.7 and 2.2 Sv. It is suggested the appropriate figure for chronic radiation would be between 3.4 and 4.5 Sv. These estimates suggest humans are less sensitive to the genetic effects of radiation than has been assumed on the basis of past extrapolations from experiments with mice.

Aneuploidy↗
PubMed1990

Perinatal loss and neurological abnormalities among children of the atomic bomb. Nagasaki and Hiroshima revisited, 1949 to 1989.

Studies of the survivors of the atomic bombing of Hiroshima and Nagasaki who were exposed to ionizing radiation in utero have demonstrated a significant increase in perinatal loss and the vulnerability of the developing fetal brain to injury. These studies have also helped to define the stages in the development of the human brain that are particularly susceptible to radiation-related damage. Exposure at critical junctures in development increases the risk of mental retardation, small head size, subsequent seizures, and poor performance on conventional tests of intelligence and in school. The most critical period, 8 through 15 weeks after fertilization, corresponds to that time in development when neuronal production increases and migration of immature neurons to their cortical sites of function occurs. The epidemiologic data are, however, too sparse to settle unequivocally the nature of the dose-response function and, in particular, whether there is or is not a threshold to damage. If a threshold does exist, it appears to be in the 0.10- to 0.20-Gy fetal-dose range in this vulnerable gestational period.

Abnormalities, Radiation-Induced↗
PubMed1989

Micro-quantity tissue digestion for metal measurements by use of a microwave acid-digestion bomb.

We describe a simple and convenient method for processing small amounts of tissue samples for trace-metal measurements by atomic absorption spectrometry, by use of a modified Parr microwave digestion bomb. Digestion proceeds rapidly (less than or equal to 90 s) in a sealed Teflon-lined vessel that eliminates contamination or loss from volatilization. Small quantities of tissue (5-100 mg dry weight) are digested in high-purity nitric acid, yielding concentrations of analyte that can be measured directly without further sample manipulation. We analyzed National Institute of Standards and Technology bovine liver Standard Reference Material to verify the accuracy of the technique. We assessed the applicability of the technique to analysis for aluminum in bone by comparison with a dry ashing procedure.

Aluminum↗
PubMed1988

Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia.

The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85% agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2%. The present study suggests that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high-dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure.

Acute Disease↗
PubMed1989

The 1983 Beirut Airport terrorist bombing. Injury patterns and implications for disaster management.

The casualty profile and results of the medical care provided for the survivors of the terrorist truck bombing of the U.S. Marine Corps facility in Beirut, Lebanon, in 1983 were reviewed to determine the factors that influenced casualty survival. This explosion resulted in 346 casualties, of whom 234 (68%) were immediately killed. The spectrum of injury was determined in 85 survivors using the Injury Severity Score (ISS). There were seven (6.3%) deaths among the 112 immediate survivors. All deaths occurred among the 19 (17%) victims who were critically injured (ISS greater than 15), giving a mortality in this population of 37 per cent. Six (86%) of the seven deaths were associated with an initial delay in treatment. Head injury was the most common fatal injury among both immediate fatalities (71.4%) and immediate survivors (57%). Thoracic injury and burns each accounted for 29 per cent of survivor deaths. Triage efficiency, as determined by the rates of overtriage (80%) and undertriage (0), did not appear adversely to affect mortality. Critical analysis of disasters such as this can contribute to improvements in preparation and casualty care in the event of future disasters.

Disasters↗
PubMed1985

Effects of atomic bomb radiation on the differentiation of B lymphocytes and on the function of concanavalin A-induced suppressor T lymphocytes.

The differentiation of peripheral blood B lymphocytes into immunoglobulin-producing cells (Ig-PC) by pokeweed mitogen (PWM) and the function of concanavalin A (Con A)-induced suppressor T lymphocytes were examined to elucidate the late effects of atomic bomb radiation. A total of 140 individuals, 70 with an exposure dose of 100 rad or more and an equal number with an exposure dose of 0 rad matched by sex and age, were selected from the Nagasaki Adult Health Study (AHS) sample. Both the differentiation of peripheral blood B lymphocytes into Ig-PC by PWM and the function of Con A-induced suppressor T lymphocytes tended to be more depressed in the exposed group than in the control group, but a statistically significant difference could not be observed between the two groups. The function of Con A-induced suppressor T lymphocytes tended to decrease with age, but a statistical significance was detected only for percentage suppression against IgM-PC.

Adult↗
PubMed1988

Reassessment of gamma doses from the atomic bombs in Hiroshima and Nagasaki.

Reassessment of gamma doses from the atomic bombs in Hiroshima and Nagasaki has been carried out with thermoluminescent measurements of ceramic materials, such as bricks and decorative tiles, which were collected from buildings that remain as they were at the time of the explosions. The thermoluminescent measurements were performed using thermoluminescent dating techniques generally used in archaeology. Annual background dose rates from natural radionuclides in the ceramic materials and from environmental radiation including cosmic rays were determined with commercially available thermoluminescent detectors. A time-zero point at the original firing of the ceramic materials was estimated from the age of the buildings given in "the register book." Total background dose was evaluated by multiplying the period between the time-zero point and the time of measurement by the annual dose rate. The resultant gamma doses in Hiroshima and Nagasaki are given as a function of distance from ground zero and are compared with the DS86 (Dosimetry System 1986) and the T65D (Tentative 1965 Dose) gamma doses.

Ceramics↗
PubMed1988

Search for mutations altering protein charge and/or function in children of atomic bomb survivors: final report.

A sample of (1) children whose parents had been proximally exposed (i.e., less than 2,000 m from the hypocenter) at the time of the atomic bombings of Hiroshima and Nagasaki and (2) a suitable comparison group have been examined for the occurrence of mutations altering the electrophoretic mobility or activity of a series of 30 proteins. The examination of the equivalent of 667,404 locus products in the children of proximally exposed persons yielded three mutations altering electrophoretic mobility; the corresponding figure for the comparison group was three mutations in 466,881 tests. The examination of a subset of 60,529 locus products for loss of enzyme activity in the children of proximally exposed persons yielded one mutation; no mutations were encountered in 61,741 determinations on the children of the comparison group. When these two series are compared, the mutation rate observed in the children of proximally exposed persons is thus 0.60 x 10(-5)/locus/generation, with 95% confidence intervals between 0.2 and 1.5 x 10(-5), and that in the comparison children is 0.64 x 10(-5)/locus/generation, with 95% intervals between 0.1 and 1.9 x 10(-5). The average conjoint gonad doses for the proximally exposed parents are estimated to be 0.437 Gy of gamma radiation and 0.002 Gy of neutron radiation. If a relative biological effectiveness of 20 is assigned to the neutron radiation, the combined total gonad dose for the parents becomes 0.477 Sv. (Organ absorbed doses are expressed in gray [1 Gy = 100 rad]; where dose is a mixture of gamma and neutron radiation, it is necessary because of the differing relative biological effectiveness of gamma and neutron radiation to express the combined gamma-neutron gonad exposures in sieverts [1 Sv = 100 rem]).

Enzymes↗
PubMed1988

The effect of changes in dosimetry on cancer mortality risk estimates in the atomic bomb survivors.

In the spring of 1986 the Radiation Effects Research Foundation (RERF) received a new atomic bomb dosimetry system. This report presents the comparisons of leukemia and nonleukemia cancer mortality risk estimates under the old and new dosimetries. In terms of total kerma (essentially whole-body gamma plus neutron exposure), risk estimates for both classes of cancer are 75-85% higher with the new dosimetry. This and other summary comparisons allow for possible nonlinearity at high estimated doses. Changes are also considered in relation to organ doses and assumptions about the relative biological effectiveness (RBE) of neutrons. Without regard to RBE, the risk estimates for total organ dose are essentially unchanged by the dosimetry revision. However, with increasing assumed values of RBE, the estimated low-LET risk decreases much less rapidly under the new dosimetry, due to the smaller neutron component. Thus at an assumed constant RBE of 10, for example, the effect of the dosimetry revision is to increase organ dose risk estimates, relative to those based on the old dosimetry, by 30% for nonleukemia and 80% for leukemia. At an RBE of 20 these increases are 72 and 136%, respectively. A number of other issues are discussed. The city difference in dose is no longer statistically significant, even at an RBE of one. Estimation of RBE is even less feasible with new dosimetry. There is substantial question of the linearity in dose response, in the sense of a leveling off at higher doses. Finally, some indication is given of how risks estimated from this dosimetry and the current data may compare to widely used estimates based largely on the RERF data with the previous dosimetry.

Humans↗
PubMed1987

Malignant and benign ovarian neoplasms among atomic bomb survivors, Hiroshima and Nagasaki, 1950-80.

For 1950-80, 194 ovarian cancer cases were ascertained among the 70,030 females of the Radiation Effects Research Foundation's Life-Span Study E-85 sample, and 106 autopsied cases with benign ovarian neoplasms were ascertained among all 3,046 autopsies performed in the same sample. On the basis of microscopic review, 66% of the cancer and 84% of the benign tumor cases were classified by histologic type. The age-adjusted ovarian cancer incidence rates showed a statistically significant increase with increased exposure dose, both in the entire exposed group (P less than .01) and in the microscopically reviewed subset (P less than .01). This dose response was only significant (P less than .01) in the latter half of the study period, 1965-80. The radiation effect was higher in the younger age group at the time of the bomb (ATB) for the specific attained age or was adjusted for attained age. In general, relative risk (greater than or equal to 100 rad vs. 0 rad) did not differ by attained age, except for the youngest age group, less than 20 years old ATB, where the relative risk tended to decrease with increased attained age, although cases were few in number and follow-up study was necessary. Estimated minimum latent period for radiation-induced ovarian cancer seemed to be 15-20 years. The proportion of autopsied cases with benign ovarian tumor increased with increasing exposure dose, both in the entire series of cases (P less than .05) and in the microscopically reviewed subset. Statistical significance, however, was not achieved in the latter group (P greater than .10). The distribution of histologic types of both cancer and benign tumor of the ovary did not vary significantly with radiation dose. The data are consistent with the hypothesis that radiation injury of the ovaries and secondary excess of gonadotropic hormones are important causative factors in the development of ovarian neoplasms.

Adult↗
PubMed1987

Serum TSH, thyroglobulin, and thyroidal disorders in atomic bomb survivors exposed in youth: 30-year follow-up study.

Follow-up examinations to determine the frequency of thyroidal disorders were conducted by the Radiation Effects Research Foundation (RERF) on individuals in Hiroshima and Nagasaki who were less than 20 yr of age at the time of exposure to the atomic bomb. Concentrations of serum thyroid stimulating hormone (TSH), thyroglobulin (TG), and anti-TG antibody 30 yr after exposure were also determined. Nontoxic uninodular goiter was found in 13 cases of the 100 + rad exposed group (n = 477) and in three cases of the nonexposed group (n = 501). The prevalence in the 100+ rad exposed group was significantly higher (chi-squared = 6.584, p less than 0.01). Thyroid cancer was found in eight exposed cases, all of whom were in the 100+ rad group, and the prevalence was significantly greater (chi-squared = 7.919, p less than 0.01). Regardless of the presence or absence of thyroid disorders, serum TSH and TG levels were not statistically different between the 100 rad + exposed and nonexposed groups. Although hypothyroidism was found in 23 of the total cases, there was no correlation between its development and exposure to ionizing irradiation.

Adolescent↗