Cancer and non-cancer effects in Japanese atomic bomb survivors**Presented as an invited paper at the 21st LH Gray Conference ‘The Radiobiology—RadiationProtection Interface’, Royal College of Physicians, Edinburgh 4–6 June 2008.

Abstract

The survivors of the atomic bombings in Hiroshima and Nagasaki are a general populationof all ages and sexes and, because of the wide and well characterised range of dosesreceived, have been used by many scientific committees (International Commission onRadiological Protection (ICRP), United Nations Scientific Committee on the Effects ofAtomic Radiation (UNSCEAR), Biological Effects of Ionizing Radiations (BEIR)) as thebasis of population cancer risk estimates following radiation exposure. Leukaemia was thefirst cancer to be associated with atomic bomb radiation exposure, with preliminaryindications of an excess among the survivors within the first five years after the bombings.An excess of solid cancers became apparent approximately ten years after radiationexposure. With increasing follow-up, excess risks of most cancer types have beenobserved, the major exceptions being chronic lymphocytic leukaemia, and pancreatic,prostate and uterine cancer. For most solid cancer sites a linear dose response isobserved, although in the latest follow-up of the mortality data there is evidence (p = 0.10) for an upward curvature in the dose response for all solid cancers. The only cancer siteswhich exhibit (upward) curvature in the dose response are leukaemia, and non-melanomaskin and bone cancer. For leukaemia the dose response is very markedly upwardcurving, indeed largely describable as a pure quadratic dose response, particularlyin the low dose (0–2 Sv) range. Even 55 years after the bombings over 40% ofthe Life Span Study cohort remain alive, so continued follow-up of this group isvital for completing our understanding of long-term radiation effects in people.In general, the relative risks per unit dose among the Japanese atomic bomb survivors aregreater than those among comparable subsets in studies of medically exposed individuals.Cell sterilisation largely accounts for the discrepancy in relative risks between these twopopulations, although other factors may contribute, such as the generally higher underlyingcancer risks in the medical series than in the Japanese atomic bomb survivors. Risks amongoccupationally exposed groups such as nuclear workforces and underground miners aregenerally consistent with those observed in the Japanese atomic bomb survivors. Ingeneral, consistent patterns of variation of risk with age at exposure are also seen inall studies—risks for all cancer types diminish with increasing age at exposure.There are also excess risks of various types of non-malignant disease in the Japanese atomicbomb survivors, in particular cardiovascular, respiratory and digestive diseases. Indeed,risks are elevated to much the same degree for a number of non-malignant diseaseendpoints, suggestive of bias. However, in contrast with the cancer data, there is much lessconsistency in the pattern of risk between the atomic bomb survivors and other exposedgroups; for example, radiation-associated respiratory and digestive diseases have not beenseen in these other groups. Although cardiovascular risks have been seen elsewhere,particularly in medically exposed groups, in contrast with the cancer data there is muchless consistency in risk between studies: risks per unit dose in epidemiological studiesvary over at least two orders of magnitude, possibly as a result of confoundingfactors. In the absence of a convincing mechanistic explanation of epidemiologicalevidence, at present a cause-and-effect interpretation of the reported statisticalassociations for cardiovascular disease is unreliable but cannot be excluded. Furtherepidemiological and biological evidence will allow a firmer conclusion to be drawn.