Kazunori Kodama

Two longitudinal cohort studies of Japanese atomic bomb survivors-the life span study (LSS) and the adult health study (AHS)-from the Radiation Effects Research Foundation (RERF) indicate that total body irradiation doses less than 1 Gy are associated with an increased risk of cardiovascular disease (CVD), but several questions about this association remain.In particular, the diversity of heart disease subtypes and the high prevalence of other risk factors complicate the estimates of radiation effects. Subtype-specific analyses with more reliable diagnostic criteria and measurement techniques are needed. The radiation effects on CVD risk are probably tissue-reaction (deterministic) effects, so the dose-response relationships for various subtypes of CVD may be nonlinear and therefore should be explored with several types of statistical models.Subpopulations at high risk need to be identified because effects at lower radiation doses may occur primarily in these susceptible subpopulations. Whether other CVD risk factors modify radiation effects also needs to be determined. Finally, background rates for various subtypes of CVD have historically differed substantially between Japanese and Western populations, so the generalisability to other populations needs to be examined.Cardiovascular disease mechanisms and manifestations may differ between high-dose local irradiation and low-dose total body irradiation (TBI)-microvascular damage and altered metabolism from low-dose TBI, but coronary artery atherosclerosis and thrombotic myocardial infarcts at high localised doses. For TBI, doses to organs other than the heart may be important in pathogenesis of CVD, so data on renal and liver disorders, plaque instability, microvascular damage, metabolic disorders, hypertension and various CVD biomarkers and risk factors are needed. Epidemiological, clinical and experimental studies at doses of less than 1 Gy are necessary to clarify the effects of radiation on CVD risk.

To determine late health effects of radiation in atomic bomb survivors, the Radiation Effects Research Foundation has been conducting studies on the Life Span Study (LSS) population, which consists of 93 000 atomic bomb survivors and 27 000 controls. A recent report on the incidence of solid cancers estimates that at the age of 70 y, after exposure at the age of 30 y, solid-cancer rates increase by about 35 % per Gy for men and 58 % per Gy for women. The age-at-exposure is an important risk modifier. Furthermore, it seems that radiation-associated increases in cancer rates persist throughout life. In addition, radiation has similar effects upon first-primary and second-primary cancer risks. A recent report on leukemia mortality suggested that the effect of radiation on leukemia mortality persisted for more than five decades. In addition, a significant dose–response for myelodysplastic syndrome is found in Nagasaki LSS members 40–60 y after radiation exposure. In view of the nature of the continuing increase in solid cancers, the LSS should continue to provide important new information on cancer risks, as most survivors still alive today were exposed to the atomic bomb radiation under the age of 20 y and are now entering their cancer-prone years.

With the aim of accurately assessing the effects of radiation exposure in the Japanese atomic-bomb survivors, the Radiation Effects Research Foundation has, over several decades, conducted studies of the Life Span Study (LSS) cohort, comprising 93 000 atomic-bomb survivors and 27 000 controls. Solid cancer: the recent report on solid cancer incidence found that at age 70 years following exposure at age 30 years, solid cancer rates increase by about 35% Gy(-1) for men and 58% Gy(-1) for women. Age-at-exposure is an important risk modifier. In the case of lung cancer, cigarette smoking has been found to be an important risk modifier. Radiation has similar effects on first-primary and second-primary cancer risks. Finally, radiation-associated increases in cancer rates appear to persist throughout life. Leukaemia: the recent report on leukaemia mortality suggests that radiation effects on leukaemia mortality persisted for more than 50 years. Moreover, significant dose-response for myelodysplastic syndrome was observed in Nagasaki LSS members even 40-60 years after radiation exposure. Future perspective: given the continuing solid cancer increase in the survivor population, the LSS will likely continue to provide important new information on radiation exposure and solid cancer risks for another 15-20 years, especially for those exposed at a young age.

There have been few studies on cancer incidence and survival among children in Japan. Childhood cancer cases in Hiroshima City can be ascertained almost perfectly in terms of completeness and validity as both a population-based cancer registry and a tissue registry cover the whole area. We report here recent incidence and survival of childhood cancer in Hiroshima City. Subjects were cancer patients less than 15 years of age in Hiroshima City registered in the Hiroshima City Cancer Registry and/or the Hiroshima Prefecture Tumor Registry (tissue registry) between 1998 and 2000. Cancer incidence in Hiroshima City was calculated for 12 diagnostic groups according to the International Classification of Childhood Cancer, and compared with general incidence in Japan. Five-year survival was calculated by the Kaplan-Meier method. There were 63 children who had a cancer newly diagnosed during 1998-2000, with only one death-certificate-only case (1.6%). Age-standardized incidence rates (per million) were 144.3 for boys and 93.9 for girls. Leukemia was the most frequent (29%) among the 12 diagnostic groups. There were 13 cancer deaths during this period and five-year survival was 79% (95% Confidence Interval: 67%-87%). Childhood cancer incidence was slightly higher than that for all of Japan, but the relative distribution of patients by diagnostic group was compatible with the general pattern. Both of these observations might be due to the high quality of the tumor and tissue registries.