Life Span Study Cohort Research Articles

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.

A-bomb survivors: further evidence of late effects of early deaths.

Reanalysis of A-bomb survivor data has shown the following: a) in the high-dose (> 1 Gy) subgroups of the life span study cohort of 5-y survivors, there is a significant deficit of individuals who were < 10 y or > 50 y at the time of the bomb; and b) in the cohort on in utero children, there is a significant deficit of individuals who were < 8 wk of fetal age when exposed. This paper discusses how this selection bias has affected the perception of three effects of A-bomb radiation: marrow damage, carcinogenesis, and second-generation effects.

Studies of the Mortality of A-Bomb Survivors. 9. Mortality, 1950-1985: Part 3. Noncancer Mortality Based on the Revised Doses (DS86)

Deaths in the RERF Life Span Study (LSS) sample have been determined for the years 1950-1985 and an analysis of cancer mortality with the revised DS86 doses has been described separately. In this report, we examine the relationship to dose of deaths from all diseases other than cancer. Although the evidence is still limited, there seems to be an excess risk from noncancer death at high doses (2 or 3 Gy and over). Statistically, a pure quadratic or a linear-threshold model [the estimated threshold dose is 1.4 Gy (0.6-2.8 Gy)] is found to fit better than a simple linear or linear-quadratic model. This increase in noncancer mortality is statistically demonstrable, generally, after 1965 and among the younger survivors (less than 40 at the time of the bombing), suggesting a sensitivity for this age group. For specific causes of death, an excess in relative risk at the high dose level, that is, 2 Gy or more, is seen in circulatory and digestive diseases. The relative risk is, however, much smaller than that for cancer. These findings, based as they are on death certificates, have their limitations. Most significant, perhaps, is the possible erroneous attribution of radiation-related cancer deaths to other causes. At present, the contribution such errors may make to the apparent increase in non-cancer deaths at the higher doses cannot be estimated as rigorously as is obviously desirable. However, even now, this increase does not appear to be fully explicable in terms of errors in classification. Further follow-up of mortality in this LSS cohort as well as disease revealed by the biennial physical examinations of the morbidity subsample (Adult Health Study) of the LSS cohort will be needed to confirm this suggestion of a radiation-related increase in mortality from causes other than cancer, and to determine whether it results in a demonstrable life shortening among the heavily exposed A-bomb survivors.

Thyroid Cancer: Epidemiological Study of Thyroid Cancer in A-bomb Survivors from Extended Life Span Study Cohort in Hiroshima

We analysed thyroid cancers which were diagnosed clinically or detected at autopsy during 22 years (1958 to 1979) in a sample of 75, 493 study subjects exposed in Hiroshima belonging to the extended LSS sample of the Radiation Effects Research Foundation. One hundred and twenty-five cases of clinical thyroid cancer (15 in males and 110 in females) were confirmed, giving a crude incidence rate per 100,000 person-years of 2.7 for males, 12.4 for females and 8.6 for both sexes combined. There was a significant increase of thyroid cancer with increase of atomic bomb radiation dose (thyroid tissue dose based on T65D) in females and in the sexes combined. This tendency was predominant in those exposed at less than 19 years of age. Compared to the control group, the relative risk in the ≥0.50 Gy group was higher at 4.0 for males (not significant) and at 4.3 for females (p <0.01). Latent thyroid cancer was detected in 155 cases or 3.5% (2.5% for males and 4.5% for females) of the 4, 425 cases that came to autopsy during the same period. Compared to the control group, the relative risk in the 50 + rad group was 1.7 for males (not significant), 2.0 for females (p <0.05) and 1.9 for both sexes combined (p <0.05). New data obtained from autopsy cases between 1950 and 1985 have been added.

Thyroid Cancer: Epidemiological Study of Thyroid Cancer in A-bomb Survivors from Extended Life Span Study Cohort in Hiroshima

We analysed thyroid cancers which were diagnosed clinically or detected at autopsy during 22 years (1958 to 1979) in a sample of 75,493 study subjects exposed in Hiroshima belonging to the extended LSS sample of the Radiation Effects Research Foundation. One hundred and twenty-five cases of clinical thyroid cancer (15 in males and 110 in females) were confirmed, giving a crude incidence rate per 100,000 person-years of 2.7 for males, 12.4 for females and 8.6 for both sexes combined. There was a significant increase of thyroid cancer with increase of atomic bomb radiation dose (thyroid tissue dose based on T65D) in females and in the sexes combined. This tendency was predominant in those exposed at less than 19 years of age. Compared to the control group, the relative risk in the greater than or equal to 0.50 Gy group was higher at 4.0 for males (not significant) and at 4.3 for females (p less than 0.01). Latent thyroid cancer was detected in 155 cases or 3.5% (2.5% for males and 4.5% for females) of the 4,425 cases that came to autopsy during the same period. Compared to the control group, the relative risk in the 50+ rad group was 1.7 for males (not significant), 2.0 for females (p less than 0.05) and 1.9 for both sexes combined (p less than 0.05). New data obtained from autopsy cases between 1950 and 1985 have been added.

Life table analysis with small numbers of cases: an example—multiple myeloma in hiroshima and nagasaki

Life table analysis techniques in epidemiology depend upon the asymptotic properties of the statistical test methods employed. In some instances, the statistical procedures indicate highly significant results which are, in reality, unjustified. The phenomenon may occur when the asymptotic methods are applied in situations where the cases of interest are few in number. This situation is illustrated by the 20 multiple myeloma deaths observed in the RERF Life Span Study cohort. A permutation test is applied to the life table data, although the test requires the false assumption that the censoring distribution is independent of the radiation dose. A simulation test is developed which does not require equal censoring, which has the same asymptotics as the usual test methods, and which is less likely to overestimate significance in small samples. It is found that both of these small-sample tests provide reasonable numerical solutions. In addition, the simulation test is recommended in general for analyzing life...