Greetings: 50 years of Atomic Bomb Casualty Commission-Radiation Effects Research Foundation studies.

The Atomic Bomb Casualty Commission was established in Hiroshima in 1947 and in Nagasaki in 1948 under the auspices of the U.S. National Academy of Sciences to initiate a long-term and comprehensive epidemiological and genetic study of the atomic bomb survivors. It was replaced in 1975 by the Radiation Effects Research Foundation which is a nonprofit Japanese foundation binationally managed and supported with equal funding by the governments of Japan and the United States. Thanks to the cooperation of the survivors and the contributions of a multitude of scientists, these studies flourish to this day in what must be the most successful long-term research collaboration between the two countries. Although these studies are necessarily limited to the effects of acute, whole-body, mixed gamma-neutron radiation from the atom bombs, their comprehensiveness and duration make them the most definitive descriptions of the late effects of radiation in humans. For this reason, the entire world relies heavily on these data to set radiation standards. As vital as the study results are, they still represent primarily the effects of radiation on older survivors. Another decade or two should correct this deficiency and allow us to measure definitively the human risk of heritable mutation from radiation. We look to the worldwide radiation and risk community as well as to the survivors who have contributed so much to what has been done already to accomplish this goal.

A long-term cohort study of the atomic-bomb survivors.

The Atomic Bomb Casualty Commission (ABCC), the predecessor of the Radiation Effects Research Foundation (RERF), was established in 1947 to conduct long-term, comprehensive epidemiological and genetic studies of the atomic-bomb (A-bomb) survivors. Today this study still depends upon the voluntary cooperation of several tens of thousands of survivors of the bombings of Hiroshima and Nagasaki. An in-depth follow-up study of mortality in the study population of 120,000 persons, including A-bomb survivors and controls, has continued since 1950. The study of tumor incidence was initiated through record linkage with a tumor registry system in Hiroshima and Nagasaki in 1958. In the same year, biennial medical examinations of 20,000 individuals began. Follow-up studies also have been conducted on in-utero-exposed persons and first-generation offspring of the survivors. On the basis of these studies spanning nearly half a century, we know that the occurrence of leukemia and cancers associated with A-bomb radiation is higher than among the non-exposed. Among the A-bomb survivors, radiation cataracts, hyperparathyroidism, delayed growth and development, and chromosomal aberrations also occur more often. However, to date no evidence exists of genetic effects in the children of A-bomb survivors. It should be kept in mind that such study results could never be obtained without the cooperation of A-bomb survivors.

Profiles of non-cancer diseases in atomic bomb survivors.

This article summarizes the results of a recent study of atomic bomb radiation and non-cancer diseases in the AHS (Adult Health Study) population by the RERF (Radiation Effects Research Foundation) along with a general discussion of previous studies. The association of atomic bomb radiation and CVD was examined by incidence studies and prevalence studies of various endpoints of atherosclerosis, such as MI, stroke, aortic arch calcification, isolated systolic hypertension, and pulse wave velocity, and, although the excess was small, all endpoints indicated an increase of CVD in the heavily exposed group. Because of the consistency of the results, it is almost certain that CVD is higher among atomic bomb survivors. However, all CVD risk factors associated with lifestyle had not necessarily been adjusted for in studies to date, and it is difficult at present to conclude that the increase in CVD among survivors was a direct effect of radiation. Recent studies have demonstrated almost certainly that uterine myoma is more frequent among atomic bomb survivors. It cannot, at present, be concluded that uterine myoma is caused by radiation, because there are no reported studies of other exposed populations. Further analyses including the role of confounding factors as well as molecular approaches are needed to verify this radiation effect. The relationship between atomic bomb radiation exposure and hyperparathyroidism can now be said to have been established in view of the strong dose response, the agreement with results of studies of other populations, the high risk in the younger survivors, and the biological plausibility. Future studies by molecular approaches, etc., are needed to determine the pathogenic mechanism. Among other benign tumours, a dose response has been demonstrated for tumours of the thyroid, stomach and ovary. Although fewer studies have been conducted than for cancer, a clear association between radiation and various benign tumours is emerging. Concerning the association between atomic bomb radiation exposure and chronic liver diseases, the recent incidence study of members of the AHS population demonstrated a significant dose response. Both chronic hepatitis and cirrhosis were suggested as being associated with exposure. The possibility that the increased occurrence of chronic liver diseases among the survivors may be due to hepatitis virus infection cannot be excluded, and the results of the ongoing hepatitis C virus antibody titre studies are awaited.

Mortality study of atomic-bomb survivors: implications for assessment of radiation accidents.

To determine the possible late effects of atomic-bomb radiation, the Life Span Study (LSS) cohort of about 120,000 individuals, including 93,000 atomic bomb survivors and 27,000 non-exposed controls, was established by the Radiation Effects Research Foundation (RERF). Mortality in this cohort has been under study since 1950. Deaths are routinely identified through the family registry system and ascertainment is virtually complete. Cancer incidence data for the LSS cohort are also available from the Hiroshima and Nagasaki population-based tumour registry established in 1958. The central finding of the LSS is an increase in cancer risk. Besides the well-known increase in leukaemia, increases in solid cancer such as cancers of the lung, breast, stomach and thyroid have also been demonstrated. Radiation-induced leukaemia occurred 2 to 3 years after exposure, reached its peak within 6 to 8 years after the bombing, and has since declined steadily. However, this has not been true of solid cancer. Radiation-induced solid cancer begins to appear at later ages than such cancer is normally prone to develop, and continues to increase proportionally with the increase in mortality or incidence in the control group as it ages. Survivors who were exposed in the first or second decade of life have just entered the cancer-prone age and have so far exhibited a high relative risk in association with radiation dose. Whether the elevated risk will continue or will fail with time is not yet clear. It is important to continue long-term follow-up of this cohort to document the changes with time since exposure. Beyond cancer risk, increased risk of non-cancer mortality is also suggested, although it is not conclusive.

Childhood thyroid diseases around Chernobyl evaluated by ultrasound examination and fine needle aspiration cytology.

Screening by ultrasound examination and fine-needle aspiration cytological biopsy (FNA) was conducted in five regions in Belarus, Ukraine, and Russia to investigate the prevalence of childhood thyroid diseases around Chernobyl. Gomel, Zhitomir, Kiev, and the western area of Bryansk are the administrative regions where severe radioactive contamination occurred. The subjects from Mogilev, where contamination was relatively low, served as controls. Among 55,054 subjects (26,406 boys and 28,648 girls), the prevalence of ultrasonographic thyroid abnormalities such as nodule, cyst, and abnormal echogenity was significantly higher in the regions with severe contamination than in Mogilev. Of the 1,396 children showing echographic thyroid abnormalities 197 were selected for FNA, and a sample was successfully obtained for diagnosis from 171 (51 boys and 120 girls) of the 197 subjects. The aspirate was insufficient for diagnosis in the remaining 26 subjects. Thyroid cancer was encountered in four children (2.3%) from the contaminated regions, two children being from Gomel. The other thyroid diseases were follicular neoplasm, 6.4%; adenomatous goiter, 18.7%; chronic thyroiditis, 31.0%; and cyst, 24.0%, suggesting that a major cause of thyroid nodularity is nonneoplastic changes, mainly chronic thyroiditis and cysts. These results will serve as an important data base for further analyses and suggest that childhood thyroid diseases, including both neoplasms and immunological disorders, are consequences of radioactive fallout.

[Health effects of atomic bomb radiation].

The health effects of atomic bomb radiation have been studied by the Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation (RERF) based on a fixed population of atomic bomb survivors in Hiroshima and Nagasaki which had been established in 1950. The results obtained to the present can be classified into the following three categories: (1) The effects for which a strong association with atomic bomb radiation has been found include malignant neoplasms, cataracts, chromosomal aberrations, small head size and mental retardation among the in utero exposed. (2) A weak association has been found in the several sites of cancers, some non-cancer mortalities and immunological abnormalities. (3) No association has been observed in some types of leukemia, osteosarcoma, accelerated aging, sterility and hereditary effects.

The epidemiological approach to cadmium pollution in Japan.

The study of health problems due to cadmium pollution in Japan originated from an endemic episode of Itai-itai disease in a rural area in north-central Japan after World War II. The disease was defined as osteomalacia with tubular changes in the kidney and considered to be associated with excess intake of cadmium. This episode motivated the Japanese Government to conduct health examinations on the general population in cadmium-polluted and non-polluted areas throughout the country since 1969. Although Itai-itai disease-like bone changes were rarely found, these studies revealed a higher prevalence of renal tubular dysfunction among elderly people in the cadmium-polluted areas. No significant difference was noted in cancer mortality, but mortality from cardiovascular diseases and all causes tended to be lower in cadmium-polluted areas. Clinical and pathological studies in man as well as experiments on primates have recently been made to elucidate the pathogenesis of Itai-itai disease and the health effects of cadmium. The lack of knowledge on the ecological and biological complex of cadmium resulted in the impediment of studies on this problem. The lesson from this experience is that basic research is essential for promoting the study of pollutants such as heavy metals, though pollution problems usually require urgent solutions.

Recent results of health examinations on the general population in cadmium-polluted and control areas in Japan.

Health examinations by a revised method aimed at detecting renal tubular dysfunctions more effectively were conducted on the general population aged 50 years and over in cadmium-polluted areas (1826 persons) and control areas (1611 persons) in four prefectures in Japan in 1976. Although detailed analysis of the data is not yet completed, some of the results obtained are described here. The prevalence of glucosuria and low molecular weight proteinuria, frequency of decreased % TRP, and cadmium concentrations in urine are higher in the cadmium-polluted areas than in the controls. Clinically diagnosed cases with tubular dysfunctions seem to follow the same trend as above, though these cases are very few in number and they are limited to the advanced age group. When cadmium concentration in rice is taken as an index, a dose-response relationship is not necessarity explicit in the observations by prefecture. However, suggestive data are obtained in the observation by district in one cadmium-polluted area.